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Sunday, October 9th

Chen, J., Reiher, W., Hermann-Luibl, C., Sellami, A., Cognigni, P., Kondo, S., Helfrich-Förster, C., Veenstra, J.A. and Wegener, C. (2016). Allatostatin A signalling in Drosophila regulates feeding and sleep and is modulated by PDF. PLoS Genet 12: e1006346. PubMed ID: 27689358 Summary: Feeding and sleep are fundamental behaviours with significant interconnections and cross-modulations. The circadian system and peptidergic signals are important components of this modulation, but still little is known about the mechanisms and networks by which they interact to regulate feeding and sleep. This study shows that specific thermogenetic activation of peptidergic Allatostatin A (AstA)-expressing posterior lateral protocerebrum (PLP) neurons and enteroendocrine cells reduces feeding and promotes sleep in the fruit fly Drosophila. The effects of AstA cell activation are mediated by AstA peptides with receptors homolog to galanin receptors subserving similar and apparently conserved functions in vertebrates. The PLP neurons are identified to be a downstream target of the neuropeptide pigment-dispersing factor (PDF), an output factor of the circadian clock. PLP neurons are contacted by PDF-expressing clock neurons, and express a functional PDF receptor demonstrated by cAMP imaging. Silencing of AstA signalling and continuous input to AstA cells by tethered PDF changes the sleep/activity ratio in opposite directions but does not affect rhythmicity. Taken together, these results suggest that pleiotropic AstA signalling by a distinct neuronal and enteroendocrine AstA cell subset adapts the fly to a digestive energy-saving state which can be modulated by PDF.

Berendes, V., Zill, S.N., Büschges, A. and Bockemühl, T. (2016). Speed-dependent interplay between local pattern-generating activity and sensory signals during walking in Drosophila. J Exp Biol [Epub ahead of print]. PubMed ID: 27688052 Summary: In insects, the coordinated motor output required for walking is based on the interaction between local pattern-generating networks providing basic rhythmicity and leg sensory signals which modulate this output on a cycle-to-cycle basis. How this interplay changes speed-dependently and thereby gives rise to the different coordination patterns observed at different speeds is understood insufficiently. This study used amputation to reduce sensory signals in single legs and decouple them mechanically during walking in Drosophila. This allows for the dissociation between locally-generated motor output in the stump and coordinating influences from intact legs. Leg stumps are still rhythmically active during walking. While the oscillatory frequency in intact legs is dependent on walking speed, stumps show a high and relatively constant oscillation frequency at all walking speeds. At low walking speeds strict cycle-to-cycle coupling between stumps and intact legs is not present. In contrast, at high walking speeds stump oscillations are strongly coupled to the movement of intact legs on a 1-to-1 basis. While during slow walking there is no preferred phase between stumps and intact legs, a preferred time interval between touch-down or lift-off events in intact legs and levation or depression of stumps is present. Based on these findings, the study hypothesizes that, as in other insects, walking speed in Drosophila is predominantly controlled by indirect mechanisms and that direct modulation of basic pattern-generating circuits plays a subsidiary role. Furthermore, inter-leg coordination strength seems to be speed-dependent and greater coordination is evident at higher walking speeds.

Mansourian, S., Corcoran, J., Enjin, A., Lofstedt, C., Dacke, M. and Stensmyr, M. C. (2016). Fecal-derived phenol induces egg-laying aversion in Drosophila. Curr Biol [Epub ahead of print]. PubMed ID: 27641770 Summary: Feces is an abundant, rich source of energy, utilized by a myriad of organisms, not least by members of the order Diptera, i.e., flies. How Drosophila melanogaster reacts to fecal matter remains unclear. This study examined oviposition behavior toward a range of fecal samples from mammals native to the putative Southeast African homeland of the fly. D. melanogaster displays a strong oviposition aversion toward feces from carnivorous mammals but indifference or even attraction toward herbivore dung. A set of four predictor volatiles were identified that can be used to differentiate fecal from non-fecal matter, as well as separate carnivore from herbivore feces. Of these volatiles, phenol-indicative of carnivore feces-confers egg-laying aversion and is detected by a single class of sensory neurons expressing Or46a. The Or46a-expressing neurons are necessary and sufficient for oviposition site aversion. It was further demonstrated that carnivore feces-unlike herbivore dung-contain a high rate of pathogenic bacteria taxa. These harmful bacteria produce phenol from L-tyrosine, an amino acid specifically enriched in high protein diets, such as consumed by carnivores. Finally, it was demonstrated that carnivore feces, as well as phenol, is also avoided by a ball-rolling species of dung beetle, suggesting that phenol is a widespread avoidance signal because of its association with pathogenic bacteria.

Du, E. J., Ahn, T. J., Wen, X., Seo, D. W., Na, D. L., Kwon, J. Y., Choi, M., Kim, H. W., Cho, H. and Kang, K. (2016). Nucleophile sensitivity of Drosophila TRPA1 underlies light-induced feeding deterrence. Elife 5. PubMed ID: 27656903 Summary: Solar irradiation including ultraviolet (UV) light causes tissue damage by generating reactive free radicals that can be electrophilic or nucleophilic due to unpaired electrons. Little is known about how free radicals induced by natural sunlight are rapidly detected and avoided by animals. This study found that Drosophila Transient Receptor Potential Ankyrin 1 (TRPA1), previously known only as an electrophile receptor, sensitively detects photochemically active sunlight through nucleophile sensitivity. Rapid light-dependent feeding deterrence in Drosophila was was found to be mediated only by the TRPA1(A) isoform, despite the TRPA1(A) and TRPA1(B) isoforms having similar electrophile sensitivities. Such isoform dependence re-emerges in the detection of structurally varied nucleophilic compounds and nucleophilicity-accompanying hydrogen peroxide (H2O2). Furthermore, these isoform-dependent mechanisms require a common set of TRPA1(A)-specific residues dispensable for electrophile detection. Collectively, TRPA1(A) rapidly responds to natural sunlight intensities through its nucleophile sensitivity as a receptor of photochemically generated radicals, leading to an acute light-induced behavioral shift in Drosophila.

Saturday, October 8th

Cattie, D.J., Richardson, C.E., Reddy, K.C., Ness-Cohn, E.M., Droste, R., Thompson, M.K., Gilbert, W.V. and Kim, D.H. (2016). Mutations in nonessential eIF3k and eIF3l genes confer lifespan extension and enhanced resistance to ER stress in Caenorhabditis elegans. PLoS Genet 12: e1006326. PubMed ID: 27690135 Evolutionary Homolog Study: The translation initiation factor eIF3 is a multi-subunit protein complex that coordinates the assembly of the 43S pre-initiation complex in eukaryotes. Prior studies have demonstrated that not all subunits of eIF3 are essential for the initiation of translation, suggesting that some subunits may serve regulatory roles. This study shows that loss-of-function mutations in the genes encoding the conserved eIF3k (see Drosophila CG10306) and eIF3l subunits of the translation initiation complex eIF3 result in a 40% extension in lifespan and enhanced resistance to endoplasmic reticulum (ER) stress in Caenorhabditis elegans. In contrast to previously described mutations in genes encoding translation initiation components that confer lifespan extension in C. elegans, loss-of-function mutations in eif-3.K or eif-3.L are viable, and mutants show normal rates of growth and development, and have wild-type levels of bulk protein synthesis. Lifespan extension resulting from EIF-3.K or EIF-3.L deficiency is suppressed by a mutation in the Forkhead family transcription factor DAF-16 (see Drosophila foxo). Mutations in eif-3.K or eif-3.L also confer enhanced resistance to ER stress, independent of IRE-1-XBP-1 (see Drosophila Ire1), ATF-6 (see Drosophila Atf6), and PEK-1 (see Drosophila PEK), and independent of DAF-16. These data suggest a pivotal functional role for conserved eIF3k and eIF3l accessory subunits of eIF3 in the regulation of cellular and organismal responses to ER stress and aging.

Matsukawa, K., Hashimoto, T., Matsumoto, T., Ihara, R., Chihara, T., Miura, M., Wakabayashi, T. and Iwatsubo, T. (2016). Familial ALS-linked mutations in Profilin 1 exacerbate TDP-43-induced degeneration in the retina of Drosophila melanogaster through an increase in the cytoplasmic localization of TDP-43. J Biol Chem [Epub ahead of print]. PubMed ID: 27634045 Summary: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive and selective loss of motor neurons. Causative genes for familial ALS (fALS) include mutations within profilin 1 (PFN1; see Drosophila Chickadee) have recently been identified in ALS18. Transgenic Drosophila melanogaster were generated overexpressing human PFN1 in the retinal photoreceptor neurons. Overexpression of wild-type or fALS mutant PFN1 caused no degenerative phenotypes in the retina. Double overexpression of fALS mutant PFN1 and human TDP-43 (see Drosophila TDP-43) markedly exacerbated the TDP-43-induced retinal degeneration, i.e., vacuolation and thinning of the retina, whereas co-expression of wild-type PFN1 did not aggravate the degenerative phenotype. Notably, co-expression of TDP-43 with fALS mutant PFN1 increased the cytoplasmic localization of TDP-43, the latter being remained in nuclei upon co-expression with wild-type PFN1, whereas co-expression of TDP-43 lacking the nuclear localization signal with fALS mutant PFN1 did not aggravate the retinal degeneration. Knockdown of endogenous Drosophila PFN1 did not alter the degenerative phenotypes of the retina in flies overexpressing wild-type TDP-43. These data suggest that ALS-linked PFN1 mutations exacerbate TDP-43-induced neurodegeneration in a gain-of-function manner, possibly by shifting the localization of TDP-43 from nuclei to cytoplasm.

M'Angale, P.G. and Staveley, B.E. (2016). Bcl-2 homologue Debcl enhances α-synuclein-induced phenotypes in Drosophila. PeerJ 4: e2461. PubMed ID: 27672511 Summary: The common hallmark for both sporadic and familial forms of Parkinson disease (PD) is mitochondrial dysfunction. Mammals have at least twenty proapoptotic and antiapoptotic Bcl-2 family members, in contrast, only two Bcl-2 family genes have been identified in Drosophila melanogaster, the proapoptotic mitochondrial localized Debcl and the antiapoptotic Buffy. The expression of the human transgene α-synuclein, a gene that is strongly associated with inherited forms of PD, in dopaminergic neurons (DA) of Drosophila, results in loss of neurons and locomotor dysfunction to model PD in flies. The altered expression of Debcl in the DA neurons and neuron-rich eye and along with the expression of α-synuclein offers an opportunity to highlight the role of Debcl in mitochondrial-dependent neuronal degeneration and death. The directed overexpression of Debcl using the Ddc-Gal4 transgene in the DA of Drosophila results in flies with severely decreased survival and a premature age-dependent loss in climbing ability. The inhibition of Debcl results in enhanced survival and improved climbing ability whereas the overexpression of Debcl in the α-synuclein-induced Drosophila model of PD results in more severe phenotypes. In addition, the co-expression of Debcl along with Buffy partially counteracts the Debcl-induced phenotypes, to improve the lifespan and the associated loss of locomotor ability observed. In complementary experiments, the overexpression of Debcl along with the expression of α-synuclein in the eye, enhances the eye ablation that results from the overexpression of Debcl. The co-expression of Buffy along with Debcl overexpression results in the rescue of the moderate developmental eye defects. The co-expression of Buffy along with inhibition of Debcl partially restores the eye to a roughened eye phenotype. Taken all together these results clarify on the role for Debcl in neurodegenerative disorders.

Griffin, R.M., Schielzeth, H. and Friberg, U. (2016). Autosomal and X linked additive genetic variation for lifespan and aging: Comparisons within and between the sexes in Drosophila melanogaster. G3 (Bethesda) [Epub ahead of print]. PubMed ID: 27678519 Summary: Theory makes several predictions concerning differences in genetic variation between the X chromosome and the autosomes due to male X hemizygosity. The X chromosome should i) typically show relatively less standing genetic variation than the autosomes, ii) exhibit more variation in males compared to females because of dosage compensation, and iii) potentially be enriched with sex-specific genetic variation. This study addressed each of these predictions for lifespan and aging in Drosophila melanogaster. To achieve unbiased estimates of X and autosomal additive genetic variance, 80 chromosome substitution lines were used; 40 for the X chromosome and 40 combining the two major autosomes, which were assayed for sex-specific and cross-sex genetic (co)variation. Significant X and autosomal additive genetic variance for both traits in both sexes (with reservation for X linked variation of aging in females) were found, but no conclusive evidence for depletion of X linked variation (measured through females) was found. Males display more X linked variation for lifespan than females, but it is unclear if this is due to dosage compensation since also autosomal variation is larger in males. Finally, the X chromosome is enriched for sex-specific genetic variation in lifespan. Results are overall less conclusive for aging. Collectively these data suggest the X chromosome has reduced capacity to respond to sexually concordant selection on lifespan from standing genetic variation, while its ability to respond to sexually antagonistic selection may be augmented.

Deshpande, M., Feiger, Z., Shilton, A. K., Luo, C. C., Silverman, E. and Rodal, A. A. (2016). Role of BMP receptor traffic in synaptic growth defects in an ALS model. Mol Biol Cell [Epub ahead of print]. PubMed ID: 27535427 Summary: TAR DNA-binding protein 43 (TDP-43) is genetically and functionally linked to Amyotrophic Lateral Sclerosis (ALS), and regulates transcription, splicing, and transport of thousands of RNA targets that function in diverse cellular pathways. In ALS, pathologically altered TDP-43 is thought to lead to disease by toxic gain-of-function effects on RNA metabolism, as well as by sequestering endogenous TDP-43 and causing its loss of function. However, it remains unclear which of the numerous cellular processes disrupted downstream of TDP-43 dysfunction lead to neurodegeneration. This study found that both loss- and gain-of-function of TDP-43 in Drosophila cause a reduction of synaptic-growth-promoting Bone Morphogenic Protein (BMP) signaling at the neuromuscular junction (NMJ). Further, a shift of BMP receptors from early to recycling endosomes was observed along with increased mobility of BMP receptor-containing compartments at the NMJ. Inhibition of the recycling endosome GTPase Rab11 partially rescued TDP-43-induced defects in BMP receptor dynamics and distribution, and suppressed BMP signaling, synaptic growth, and larval crawling defects. These results indicate that defects in receptor traffic lead to neuronal dysfunction downstream of TDP-43 misregulation, and that rerouting receptor traffic may be a viable strategy for rescuing neurological impairment.

Akbar, M. A., Mandraju, R., Tracy, C., Hu, W., Pasare, C. and Kramer, H. (2016). ARC syndrome-linked Vps33B protein is required for inflammatory endosomal maturation and signal termination. Immunity 45: 267-279. PubMed ID: 27496733 Summary: Toll-like receptors (TLRs) and other pattern-recognition receptors (PRRs) sense microbial ligands and initiate signaling to induce inflammatory responses. Although the quality of inflammatory responses is influenced by internalization of TLRs, the role of endosomal maturation in clearing receptors and terminating inflammatory responses is not well understood. This study reports that Drosophila and mammalian Vps33B proteins play critical roles in the maturation of phagosomes and endosomes following microbial recognition. Vps33B was necessary for clearance of endosomes containing internalized PRRs, failure of which resulted in enhanced signaling and expression of inflammatory mediators. Lack of Vps33B had no effect on trafficking of endosomes containing non-microbial cargo. These findings indicate that Vps33B function is critical for determining the fate of signaling endosomes formed following PRR activation. Exaggerated inflammatory responses dictated by persistence of receptors in aberrant endosomal compartments could therefore contribute to symptoms of Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, a disease linked to loss of Vps33B.

Fernandez-Funez, P., Sanchez-Garcia, J., de Mena, L., Zhang, Y., Levites, Y., Khare, S., Golde, T. E. and Rincon-Limas, D. E. (2016). Holdase activity of secreted Hsp70 masks amyloid-β42 neurotoxicity in Drosophila. Proc Natl Acad Sci U S A 113: E5212-5221. PubMed ID: 27531960 Summary: Alzheimer's disease (AD) is the most prevalent of a large group of related proteinopathies for which there is currently no cure. This study used Drosophila to explore a strategy to block Aβ42 neurotoxicity through engineering of the Heat shock protein 70 (Hsp70), a chaperone that has demonstrated neuroprotective activity against several intracellular amyloids. To target its protective activity against extracellular Aβ42, a signal peptide was added to Hsp70. This secreted form of Hsp70 (secHsp70) suppresses Aβ42 neurotoxicity in adult eyes, reduces cell death, protects the structural integrity of adult neurons, alleviates locomotor dysfunction, and extends lifespan. SecHsp70 binding to Aβ42 through its holdase domain is neuroprotective, but its ATPase activity is not required in the extracellular space. Thus, the holdase activity of secHsp70 masks Aβ42 neurotoxicity by promoting the accumulation of nontoxic aggregates. Combined with other approaches, this strategy may contribute to reduce the burden of AD and other extracellular proteinopathies.

De Rose, F., Corda, V., Solari, P., Sacchetti, P., Belcari, A., Poddighe, S., Kasture, S., Solla, P., Marrosu, F. and Liscia, A. (2016). Drosophila mutant model of Parkinson's disease revealed an unexpected olfactory performance: Morphofunctional evidences. Parkinsons Dis 2016: 3508073. PubMed ID: 27648340 Summary: Parkinson's disease (PD) is one of the most common neurodegenerative diseases characterized by the clinical triad: tremor, akinesia, and rigidity. Several studies have suggested that PD patients show disturbances in olfaction as one of the earliest, nonspecific nonmotor symptoms of disease onset. This study sought to use the fruit fly Drosophila melanogaster as a model organism to explore olfactory function in LRRK loss-of-function mutants, which was previously demonstrated to be a useful model for PD. Surprisingly, the results showed that the LRRK mutant, compared to the wild flies, presents a dramatic increase in the amplitude of the electroantennogram responses and this is coupled with a higher number of olfactory sensilla. In spite of the above reported results, the behavioural response to olfactory stimuli in mutant flies is impaired compared to that obtained in wild type flies. Thus, behaviour modifications and morphofunctional changes in the olfaction of LRRK loss-of-function mutants might be used as an index to explore the progression of parkinsonism in this specific model, also with the aim of studying and developing new treatments.

Friday, October 7th

Yang, D., Lian, T., Tu, J., Gaur, U., Mao, X., Fan, X., Li, D., Li, Y. and Yang, M. (2016). LncRNA mediated regulation of aging pathways in Drosophila melanogaster during dietary restriction. Aging (Albany NY) 8: 2182-2203. PubMed ID: 27687893 Summary: Dietary restriction (DR) extends lifespan in many species which is a well-known phenomenon. Long non-coding RNAs (lncRNAs) play an important role in regulation of cell senescence and important age-related signaling pathways. This study profiled the lncRNA and mRNA transcriptome of fruit flies at 7 day and 42 day during DR and fully-fed conditions, respectively. A large number of differentially expressed lncRNAs and their targets enriched in GO and KEGG analysis were found. Some new aging related signaling pathways during DR, such as hippo signaling pathway-fly, phototransduction-fly and protein processing in endoplasmic reticulum etc were also found. Novel lncRNAs XLOC_092363 and XLOC_166557 were found to be located in 10 kb upstream sequences of hairy and ems promoters, respectively. Furthermore, tissue specificity of some novel lncRNAs was analyzed at 7 day of DR in fly head, gut and fat body. Also the silencing of lncRNA XLOC_076307 resulted in altered expression level of its targets including Gadd45 (involved in FoxO signaling pathway). Together, these results implicate many lncRNAs closely associated with dietary restriction, which could provide a resource for lncRNA in aging and age-related disease field.

Sharma, S., Poetz, F., Bruer, M., Ly-Hartig, T. B., Schott, J., Seraphin, B. and Stoecklin, G. (2016). Acetylation-dependent control of global poly(A) RNA degradation by CBP/p300 and HDAC1/2. Mol Cell 63: 927-938. PubMed ID: 27635759 Summary: Acetylation of histones and transcription-related factors is known to exert epigenetic and transcriptional control of gene expression. This study reports that histone acetyltransferases (HATs) and histone deacetylases (HDACs) also regulate gene expression at the posttranscriptional level by controlling poly(A) RNA stability. Inhibition of HDAC1 and HDAC2 induces massive and widespread degradation of normally stable poly(A) RNA in mammalian and Drosophila cells. Acetylation-induced RNA decay depends on the HATs p300 and CBP, which acetylate the exoribonuclease CAF1a, a catalytic subunit of the CCR4-CAF1-NOT deadenlyase complex and thereby contribute to accelerating poly(A) RNA degradation. Taking adipocyte differentiation as a model, global stabilization of poly(A) RNA was observed during differentiation, concomitant with loss of CBP/p300 expression. This study uncovers reversible acetylation as a fundamental switch by which HATs and HDACs control the overall turnover of poly(A) RNA.

Ote, M., Ueyama, M. and Yamamoto, D. (2016). Wolbachia protein TomO targets nanos mRNA and restores germ stem cells in Drosophila Sex-lethal mutants. Curr Biol [Epub ahead of print]. PubMed ID: 27498563 Summary: Wolbachia, endosymbiotic bacteria prevalent in invertebrates, manipulate their hosts in a variety of ways: they induce cytoplasmic incompatibility, male lethality, male-to-female transformation, and parthenogenesis. However, little is known about the molecular basis for host manipulation by these bacteria. In Drosophila melanogaster, Wolbachia infection makes otherwise sterile Sex-lethal (Sxl) mutant females capable of producing mature eggs. Through a functional genomic screen for Wolbachia genes with growth-inhibitory effects when expressed in cultured Drosophila cells, this study identified the Wolbachia gene WD1278 encoding a novel protein called toxic manipulator of oogenesis (TomO), which phenocopies some of the Wolbachia effects in Sxl mutant D. melanogaster females. TomO enhances the maintenance of germ stem cells (GSCs) by elevating Nanos (Nos) expression via its interaction with nos mRNA, ultimately leading to the restoration of germ cell production in Sxl mutant females that are otherwise without GSCs.

Catrina, I.E., Bayer, L.V., Yanez, G., McLaughlin, J.M., Malaczek, K., Bagaeva, E., Marras, S.A. and Bratu, D.P. (2016). The temporally controlled expression of Drongo, the fruit fly homolog of AGFG1, is achieved in female germline cells via P-bodies and its localization requires functional Rab11. RNA Biol [Epub ahead of print]. PubMed ID: 27654348 Summary: To achieve proper RNA transport and localization, RNA viruses exploit cellular vesicular trafficking pathways. AGFG1, a host protein essential for HIV-1 and Influenza A replication, has been shown to mediate release of intron-containing viral RNAs from the perinuclear region. It is still unknown what its precise role in this release is, or whether AGFG1 also participates in cytoplasmic transport. This study reports the expression patterns during oogenesis for Drongo, the fruit fly homolog of AGFG1. It was found that temporally controlled Drongo expression is achieved by translational repression of drongo mRNA within P-bodies. A link was found between the recycling endosome pathway and Drongo, and proper Drongo localization at the oocyte's cortex during mid-oogenesis was found to require functional Rab11.

Thursday, October 6th

Sears, J. C. and Broihier, H. T. (2016). FoxO regulates microtubule dynamics and polarity to promote dendrite branching in Drosophila sensory neurons. Dev Biol [Epub ahead of print]. PubMed ID: 27546375 Summary: The size and shape of dendrite arbors are defining features of neurons and critical determinants of neuronal function. The molecular mechanisms establishing arborization patterns during development are not well understood, though properly regulated microtubule (MT) dynamics and polarity are essential. It has been found that FoxO regulates axonal MTs, raising the question of whether it also regulates dendritic MTs and morphology. This study demonstrates that FoxO promotes dendrite branching in all classes of Drosophila dendritic arborization (da) neurons. FoxO is required both for initiating growth of new branches and for maintaining existing branches. To elucidate FoxO function, MT organization was characterized in both foxO null and overexpressing neurons. FoxO was found to directs MT organization and dynamics in dendrites. Moreover, it is both necessary and sufficient for anterograde MT polymerization, which is known to promote dendrite branching. Lastly, FoxO promotes proper larval nociception, indicating a functional consequence of impaired da neuron morphology in foxO mutants. Together, these results indicate that FoxO regulates dendrite structure and function and suggest that FoxO-mediated pathways control MT dynamics and polarity.

Teckchandani, A. and Cooper, J. A. (2016). The ubiquitin-proteasome system regulates focal adhesions at the leading edge of migrating cells. Elife 5. PubMed ID: 27656905 Evolutionary Homolog Study Cell migration requires the cyclical assembly and disassembly of focal adhesions. Adhesion induces phosphorylation of focal adhesion proteins, including Cas (Crk-associated substrate/p130Cas/BCAR1; see Drosophila Cas). However, Cas phosphorylation stimulates adhesion turnover. This raises the question of how adhesion assembly occurs against opposition from phospho-Cas. This study shows that suppressor of cytokine signaling 6 (SOCS6; see Drosophila Socs36E) and Cullin 5 (see Drosophila Cullin 5), two components of the CRL5SOCS6 ubiquitin ligase, inhibit Cas-dependent focal adhesion turnover at the front but not rear of migrating epithelial cells. The front focal adhesions contain phospho-Cas which recruits SOCS6. If SOCS6 cannot access focal adhesions, or cullins or the proteasome are inhibited, adhesion disassembly is stimulated. This suggests that the localized targeting of phospho-Cas within adhesions by CRL5SOCS6 and concurrent cullin and proteasome activity provide a negative feedback loop, ensuring that adhesion assembly predominates over disassembly at the leading edge. By this mechanism, ubiquitination provides a new level of spatio-temporal control over cell migration.

Vieillard, J., Paschaki, M., Duteyrat, J. L., Augiere, C., Cortier, E., Lapart, J. A., Thomas, J. and Durand, B. (2016). Transition zone assembly and its contribution to axoneme formation in Drosophila male germ cells. J Cell Biol 214: 875-889. PubMed ID: 27646273 Summary: The ciliary transition zone (TZ) is a complex structure found at the cilia base. Defects in TZ assembly are associated with human ciliopathies. In most eukaryotes, three protein complexes (CEP290, NPHP, and MKS) cooperate to build the TZ. This study shows that in Drosophila melanogaster, mild TZ defects are observed in the absence of MKS components. In contrast, Cby and Azi1 cooperate to build the TZ by acting upstream of Cep290 and MKS components. Without Cby and Azi1, centrioles fail to form the TZ, precluding sensory cilia assembly, and no ciliary membrane cap associated with sperm ciliogenesis is made. This ciliary cap is critical to recruit the tubulin-depolymerizing kinesin Klp59D, required for regulation of axonemal growth. These results show that Drosophila TZ assembly in sensory neurons and male germ cells involves cooperative actions of Cby and Dila. They further reveal that temporal control of membrane cap assembly by TZ components and microtubule elongation by kinesin-13 is required for axoneme formation in male germ cells.

Aigouy, B. and Le Bivic, A. (2016). The PCP pathway regulates Baz planar distribution in epithelial cells. Sci Rep 6: 33420. PubMed ID: 27624969 Summary: The localisation of apico-basal polarity proteins along the Z-axis of epithelial cells is well understood while their distribution in the plane of the epithelium is poorly characterised. This study provides a systematic description of the planar localisation of apico-basal polarity proteins in the Drosophila ommatidial epithelium. The adherens junction proteins Shotgun and Armadillo, as well as the baso-lateral complexes, are bilateral, i.e. present on both sides of cell interfaces. In contrast, it is reported that other key adherens junction proteins, Bazooka and the myosin regulatory light chain (Spaghetti squash) are unilateral, i.e. present on one side of cell interfaces. Furthermore, planar cell polarity (PCP) and not the apical determinants Crumbs and Par-6 control Bazooka unilaterality in cone cells. Altogether, this work unravels an unexpected organisation and combination of apico-basal, cytoskeletal and planar polarity proteins that is different on either side of cell-cell interfaces and unique for the different contacts of the same cell.

Wednesday, October 5th

Busto, G. U., Guven-Ozkan, T., Chakraborty, M. and Davis, R. L. (2016). Developmental inhibition of miR-iab8-3p disrupts mushroom body neuron structure and adult learning ability. Dev Biol [Epub ahead of print]. PubMed ID: 27634569 Summary: MicroRNAs are small non-coding RNAs that inhibit protein expression post-transcriptionally. They have been implicated in many different physiological processes, but little is known about their individual involvement in learning and memory. Several miRNAs have been identified that either increased or decreased intermediate-term memory when inhibited in the central nervous system, including miR-iab8-3p. This paper reports a new developmental role for this miRNA. Blocking the expression of miR-iab8-3p during the development of the organism leads to hypertrophy of individual mushroom body neuron soma, a reduction in the field size occupied by axonal projections, and adult intellectual disability. Four potential mRNA targets of miR-iab8-3p were identified whose inhibition modulates intermediate-term memory including ceramide phosphoethanolamine synthase, which may account for the behavioral effects produced by miR-iab8-3p inhibition. These results offer important new information on a microRNA required for normal neurodevelopment and the capacity to learn and remember normally.

Zwarts, L., Goossens, T., Clements, J., Kang, Y. Y. and Callaerts, P. (2016). Axon branch-specific Semaphorin-1a signaling in Drosophila mushroom body development. Front Cell Neurosci 10: 210. PubMed ID: 27656129 Summary: Correct wiring of the mushroom body (MB) neuropil in the Drosophila brain involves appropriate positioning of different axonal lobes, as well as the sister branches that develop from individual axons. This positioning requires the integration of various guidance cues provided by different cell types, which help the axons find their final positions within the neuropil. Semaphorins are well-known for their conserved roles in neuronal development and axon guidance. This study investigated the role of Sema-1a in MB development more closely. Sema-1a is expressed in the MBs as well as surrounding structures, including the glial transient interhemispheric fibrous ring, throughout development. By loss- and gain-of-function experiments, it was shown that the MB axons display lobe and sister branch-specific Sema-1a signaling, which controls different aspects of axon outgrowth and guidance. Furthermore, these effects are modulated by the integration of MB intrinsic and extrinsic Sema-1a signaling pathways involving PlexA and PlexB. Finally, a role is also shown for neuronal- glial interaction in Sema-1a dependent β-lobe outgrowth.

Purice, M. D., Speese, S. D. and Logan, M. A. (2016). Delayed glial clearance of degenerating axons in aged Drosophila is due to reduced PI3K/Draper activity. Nat Commun 7: 12871. PubMed ID: 27647497 Summary: Advanced age is the greatest risk factor for neurodegenerative disorders, but the mechanisms that render the senescent brain vulnerable to disease are unclear. Glial immune responses provide neuroprotection in a variety of contexts. Thus, this study explored how glial responses to neurodegeneration are altered with age. Glia-axon phagocytic interactions were shown to change dramatically in the aged Drosophila brain. Aged glia clear degenerating axons slowly due to low phosphoinositide-3-kinase (PI3K) signalling and, subsequently, reduced expression of the conserved phagocytic receptor Draper/MEGF10. Importantly, boosting PI3K/Draper activity in aged glia significantly reverses slow phagocytic responses. Moreover, several hours post axotomy, early hallmarks of Wallerian degeneration (WD) are delayed in aged flies. It is proposed that slow clearance of degenerating axons is mechanistically twofold, resulting from deferred initiation of axonal WD and reduced PI3K/Draper-dependent glial phagocytic function. Interventions that boost glial engulfment activity, however, can substantially reverse delayed clearance of damaged neuronal debris.

Jeong, Y. T., Oh, S. M., Shim, J., Seo, J. T., Kwon, J. Y. and Moon, S. J. (2016). Mechanosensory neurons control sweet sensing in Drosophila. Nat Commun 7: 12872. PubMed ID: 27641708 Summary: Animals discriminate nutritious food from toxic substances using their sense of taste. Since taste perception requires taste receptor cells to come into contact with water-soluble chemicals, it is a form of contact chemosensation. Concurrent with that contact, mechanosensitive cells detect the texture of food and also contribute to the regulation of feeding. Little is known, however, about the extent to which chemosensitive and mechanosensitive circuits interact. This study shows Drosophila prefers soft food at the expense of sweetness and that this preference requires labellar mechanosensory neurons (MNs) and the mechanosensory channel Nanchung. Activation of these labellar MNs causes GABAergic inhibition of sweet-sensing gustatory receptor neurons, reducing the perceived intensity of a sweet stimulus. These findings expand understanding of the ways different sensory modalities cooperate to shape animal behaviour.

Tuesday, October 4th

Wood, J.G., Jones, B.C., Jiang, N., Chang, C., Hosier, S., Wickremesinghe, P., Garcia, M., Hartnett, D.A., Burhenn, L., Neretti, N. and Helfand, S.L. (2016). Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila. Proc Natl Acad Sci U S A [Epub ahead of print]. PubMed ID: 27621458 Summary: Transposable elements (TEs) are mobile genetic elements, highly enriched in heterochromatin, that constitute a large percentage of the DNA content of eukaryotic genomes. Aging in Drosophila melanogaster is characterized by loss of repressive heterochromatin structure and loss of silencing of reporter genes in constitutive heterochromatin regions. Using next-generation sequencing, this study found that transcripts of many genes native to heterochromatic regions and TEs increased with age in fly heads and fat bodies. A dietary restriction regimen, known to extend life span, represses the age-related increased expression of genes located in heterochromatin, as well as TEs. A corresponding age-associated increase in TE transposition in fly fat body cells was also observed that was delayed by dietary restriction. Furthermore, manipulating genes known to affect heterochromatin structure, including overexpression of Sir2, Su(var)3-9, and Dicer-2, as well as decreased expression of Adar, mitigate age-related increases in expression of TEs. Increasing expression of either Su(var)3-9 or Dicer-2 also leads to an increase in life span. Mutation of Dicer-2 leads to an increase in DNA double-strand breaks. Treatment with the reverse transcriptase inhibitor 3TC results in decreased TE transposition as well as increased life span in TE-sensitized Dicer-2 mutants. Together, these data support the retrotransposon theory of aging, which hypothesizes that epigenetically silenced TEs become deleteriously activated as cellular defense and surveillance mechanisms break down with age. Furthermore, interventions that maintain repressive heterochromatin and preserve TE silencing may prove key to preventing damage caused by TE activation and extending healthy life span.

Swain, A., Misulovin, Z., Pherson, M., Gause, M., Mihindukulasuriya, K., Rickels, R. A., Shilatifard, A. and Dorsett, D. (2016). Drosophila TDP-43 RNA-binding protein facilitates association of sister chromatid cohesion proteins with genes, enhancers and polycomb response elements. PLoS Genet 12: e1006331. PubMed ID: 27662615 Summary: The cohesin protein complex mediates sister chromatid cohesion and participates in transcriptional control of genes that regulate growth and development. Substantial reduction of cohesin activity alters transcription of many genes without disrupting chromosome segregation. Drosophila Nipped-B protein loads cohesin onto chromosomes, and together Nipped-B and cohesin occupy essentially all active transcriptional enhancers and a large fraction of active genes. It is unknown why some active genes bind high levels of cohesin and some do not. This study shows that the TBPH and Lark RNA-binding proteins influence association of Nipped-B and cohesin with genes and gene regulatory sequences. In vitro, TBPH and Lark proteins specifically bind RNAs produced by genes occupied by Nipped-B and cohesin. By genomic chromatin immunoprecipitation these RNA-binding proteins also bind to chromosomes at cohesin-binding genes, enhancers, and Polycomb response elements (PREs). RNAi depletion reveals that TBPH facilitates association of Nipped-B and cohesin with genes and regulatory sequences. Lark reduces binding of Nipped-B and cohesin at many promoters and aids their association with several large enhancers. Conversely, Nipped-B facilitates TBPH and Lark association with genes and regulatory sequences, and interacts with TBPH and Lark in affinity chromatography and immunoprecipitation experiments. Blocking transcription does not ablate binding of Nipped-B and the RNA-binding proteins to chromosomes, indicating transcription is not required to maintain binding once established. These findings demonstrate that RNA-binding proteins help govern association of sister chromatid cohesion proteins with genes and enhancers.

Loubiere, V., Delest, A., Thomas, A., Bonev, B., Schuettengruber, B., Sati, S., Martinez, A. M. and Cavalli, G. (2016). Coordinate redeployment of PRC1 proteins suppresses tumor formation during Drosophila development. Nat Genet [Epub ahead of print]. PubMed ID: 27643538 Summary: Polycomb group proteins form two main complexes, PRC2 and PRC1, which generally coregulate their target genes. This study shows that PRC1 components act as neoplastic tumor suppressors independently of PRC2 function. By mapping the distribution of PRC1 components and trimethylation of histone H3 at Lys27 (H3K27me3) across the genome, a large set of genes were identified that acquire PRC1 in the absence of H3K27me3 in Drosophila larval tissues. These genes massively outnumber canonical targets and are mainly involved in the regulation of cell proliferation, signaling and polarity. Alterations in PRC1 components specifically deregulate this set of genes, whereas canonical targets are derepressed in both PRC1 and PRC2 mutants. In human embryonic stem cells, PRC1 components colocalize with H3K27me3 as in Drosophila embryos, whereas in differentiated cell types they are selectively recruited to a large set of proliferation and signaling-associated genes that lack H3K27me3, suggesting that the redeployment of PRC1 components during development is evolutionarily conserved.

Ye, Y., Gu, L., Chen, X., Shi, J., Zhang, X. and Jiang, C. (2016). Chromatin remodeling during the in vivo glial differentiation in early Drosophila embryos. Sci Rep 6: 33422. PubMed ID: 27634414 Summary: Chromatin remodeling plays a critical role in gene regulation and impacts many biological processes. However, little is known about the relationship between chromatin remodeling dynamics and in vivo cell lineage commitment. This study revealed the patterns of histone modification change and nucleosome positioning dynamics and their epigenetic regulatory roles during the in vivo glial differentiation in early Drosophila embryos. The genome-wide average H3K9ac signals in promoter regions are decreased in the glial cells compared to the neural progenitor cells. However, H3K9ac signals are increased in a group of genes that are up-regulated in glial cells and involved in gliogenesis. There occurs extensive nucleosome remodeling including shift, loss, and gain. Nucleosome depletion regions (NDRs) form in both promoters and enhancers. As a result, the associated genes are up-regulated. Intriguingly, NDRs form in two fashions: nucleosome shift and eviction. Moreover, the mode of NDR formation is independent of the original chromatin state of enhancers in the neural progenitor cells.

Monday, October 3rd

Li, H., Hu, C., Bai, L., Li, H., Li, M., Zhao, X., Czajkowsky, D. M. and Shao, Z. (2016). Ultra-deep sequencing of ribosome-associated poly-adenylated RNA in early Drosophila embryos reveals hundreds of conserved translated sORFs. DNA Res [Epub ahead of print]. PubMed ID: 27559081 Summary: There is growing recognition that small open reading frames (sORFs) encoding peptides shorter than 100 amino acids are an important class of functional elements in the eukaryotic genome, with several already identified to play critical roles in growth, development, and disease. However, understanding of their biological importance has been hindered owing to the significant technical challenges limiting their annotation. This study combined ultra-deep sequencing of ribosome-associated poly-adenylated RNAs with rigorous conservation analysis to identify a comprehensive population of translated sORFs during early Drosophila embryogenesis. In total, 399 sORFs were identified, including those previously annotated but without evidence of translational capacity, those found within transcripts previously classified as non-coding, and those not previously known to be transcribed. Further, evidence was found for translation of many sORFs with different isoforms, suggesting their regulation is as complex as longer ORFs. Furthermore, many sORFs are found not associated with ribosomes in late-stage Drosophila S2 cells, suggesting that many of the translated sORFs may have stage-specific functions during embryogenesis. These results thus provide the first comprehensive annotation of the sORFs present during early Drosophila embryogenesis, a necessary basis for a detailed delineation of their function in embryogenesis and other biological processes.

Myat, M. M. and Patel, U. (2016). Receptor-type Guanylyl cyclase at 76C (Gyc76C) regulates de novo lumen formation during Drosophila tracheal development. PLoS One 11: e0161865. PubMed ID: 27642749 Summary: Lumen formation and maintenance are important for the development and function of essential organs such as the lung, kidney and vasculature. In the Drosophila embryonic trachea, lumena form de novo to connect the different tracheal branches into an interconnected network of tubes. This study identified a novel role for the receptor type guanylyl cyclase at 76C (Gyc76C) in de novo lumen formation in the Drosophila trachea. In embryos mutant for gyc76C or its downsteam effector protein kinase G (PKG) 1, tracheal lumena are disconnected. Dorsal trunk (DT) cells of gyc76C mutant embryos migrate to contact each other and complete the initial steps of lumen formation, such as the accumulation of E-cadherin (E-cad) and formation of an actin track at the site of lumen formation. However, the actin track and E-cad contact site of gyc76C mutant embryos did not mature to become a new lumen and DT lumena did not fuse. Also failure was observed of the luminal protein Vermiform to be secreted into the site of new lumen formation in gyc76C mutant trachea. These DT lumen formation defects were accompanied by altered localization of the Arf-like 3 GTPase (Arl3), a known regulator of vesicle-vesicle and vesicle-membrane fusion. In addition to the DT lumen defect, lumena of gyc76C mutant terminal cells were shorter compared to wild-type cells. These studies show that Gyc76C and downstream PKG-dependent signaling regulate de novo lumen formation in the tracheal DT and terminal cells, most likely by affecting Arl3-mediated luminal secretion.

Harumoto, T., Anbutsu, H., Lemaitre, B. and Fukatsu, T. (2016). Male-killing symbiont damages host's dosage-compensated sex chromosome to induce embryonic apoptosis. Nat Commun 7: 12781. PubMed ID: 27650264 Summary: Some symbiotic bacteria are capable of interfering with host reproduction in selfish ways. How such bacteria can manipulate host's sex-related mechanisms is of fundamental interest encompassing cell, developmental and evolutionary biology. This study uncovered the molecular and cellular mechanisms underlying Spiroplasma-induced embryonic male lethality in Drosophila melanogaster. Transcriptomic analysis reveals that many genes related to DNA damage and apoptosis are up-regulated specifically in infected male embryos. Detailed genetic and cytological analyses demonstrate that male-killing Spiroplasma causes DNA damage on the male X chromosome interacting with the male-specific lethal (MSL) complex. The damaged male X chromosome exhibits a chromatin bridge during mitosis, and bridge breakage triggers sex-specific abnormal apoptosis via p53-dependent pathways. Notably, the MSL complex is not only necessary but also sufficient for this cytotoxic process. These results highlight symbiont's sophisticated strategy to target host's sex chromosome and recruit host's molecular cascades toward massive apoptosis in a sex-specific manner.

Ordan, E. and Volk, T. (2016). Amontillado is required for Drosophila Slit processing and for tendon-mediated muscle patterning. Biol Open [Epub ahead of print]. PubMed ID: 27628033 Summary: Slit cleavage into an N-terminal and C-terminal polypeptides is essential for restricting the range of Slit activity. Although the Slit cleavage site has been characterized previously and is evolutionally conserved, the identity of the protease that cleaves Slit remains elusive. Previous analysis has indicated that Slit cleavage is essential to immobilize the active Slit-N at the tendon cell surfaces, mediating the arrest of muscle elongation. In an attempt to identify the protease required for Slit cleavage, this study performed an RNAi-based assay in the ectoderm and followed the process of elongation of the lateral transverse muscles toward tendon cells. The Drosophila homolog of Pheromone Convertase 2 (PC2) Amontillado (Amon) was identified as an essential protease for Slit cleavage. Further analysis indicated that Slit mobility on SDS polyacrylamide gel electrophoresis is slightly up-shifted in amon mutants, and its conventional cleavage into the Slit-N and Slit-C polypeptides is attenuated. Consistent with the requirement for Amon to promote Slit cleavage and membrane immobilization of Slit-N, the muscle phenotype of amon mutant embryos is rescued by co-expressing a membrane-bound form of full-length Slit lacking the cleavage site and knocked into the slit locus. The identification of a novel protease component essential for Slit processing may represent an additional regulatory step in the Slit signaling pathway.

Sunday, October 2nd

Marco Antonio, D. S. and Hartfelder, K. (2016).. Toward an understanding of divergent compound eye development in drones and workers of the honeybee (Apis mellifera L.): A correlative analysis of morphology and gene expression. J Exp Zool B Mol Dev Evol [Epub ahead of print]. PubMed ID: 27658924 Summary: Eye development in insects is best understood in Drosophila melanogaster, but little is known for other holometabolous insects. Combining a morphological with a gene expression analysis, this study investigated eye development in the honeybee, putting emphasis on the sex-specific differences in eye size. Optic lobe development starts from an optic lobe anlage in the larval brain, which sequentially gives rise to the lobula, medulla, and lamina. The lamina differentiates in the last larval instar, when it receives optic nerve projections from the developing retina. The expression analysis focused on seven genes important for Drosophila eye development: eyes absent, sine oculis, embryonic lethal abnormal vision, minibrain, small optic lobes, epidermal growth factor receptor, and roughest. All except small optic lobes were more highly expressed in third-instar drone larvae, but then, in the fourth and fifth instar, their expression was sex-specifically modulated, showing shifts in temporal dynamics. The clearest differences were seen for small optic lobes, which is highly expressed in the developing eye of workers, and minibrain and roughest, which showed a strong expression peak coinciding with retina differentiation. A microarray analysis for optic lobe/retina complexes revealed the differential expression of several metabolism-related genes, as well as of two micro-RNAs. While major morphological differences were not seen in the developing eye structures before the pupal stage, the expression differences observed for the seven candidate genes and in the transcriptional microarray profiles indicate that molecular signatures underlying sex-specific optic lobe and retina development become established throughout the larval stages.

Hickner, P. V., Rivaldi, C. L., Johnson, C. M., Siddappaji, M., Raster, G. J. and Syed, Z. (2016). The making of a pest: Insights from the evolution of chemosensory receptor families in a pestiferous and invasive fly, Drosophila suzukii. BMC Genomics 17: 648. PubMed ID: 27530109 Summary: Drosophila suzukii differs from other melanogaster group members in their proclivity for laying eggs in fresh fruit rather than in fermenting fruits. Earlier work has revealed how the olfactory landscape of D. suzukii is dominated by volatiles derived from its unique niche. This study annotated the Olfactory receptors and Gustatory Receptors in D. suzukii and two close relatives, D. biarmipes and D. takahashii, to identify candidate chemoreceptors associated with D. suzukii's unusual niche utilization. A total of 71 Or genes were annotated in D. suzukii, with nine of those being pseudogenes (12.7 %). Alternative splicing of two genes brings the total to 62 genes encoding 66 Ors. Duplications of Or23a and Or67a expanded D. suzukii's Or repertoire, while pseudogenization of Or74a, Or85a, and Or98b reduced the number of functional Ors to roughly the same as other annotated species in the melanogaster group. Seventy-one intact Gr genes and three pseudogenes were annotated in D. suzukii. Alternative splicing in three genes brings the total number of Grs to 81. Signatures of positive selection were identified in two Ors and three Grs at nodes leading to D. suzukii, while three copies in the largest expanded Or lineage, Or67a, also showed signs of positive selection at the external nodes. This analysis of D. suzukii's chemoreceptor repertoires in the context of nine melanogaster group drosophilids, including two of its closest relatives (D. biarmipes and D. takahashii), revealed several candidate receptors associated with the adaptation of D. suzukii to its unique ecological niche.

Huang, Y. and Agrawal, A. F. (2016). Experimental evolution of gene expression and plasticity in alternative selective regimes. PLoS Genet 12: e1006336. PubMed ID: 27661078 Summary: Little is known of how gene expression and its plasticity evolves as populations adapt to different environmental regimes. Expression is expected to evolve adaptively in all populations but only those populations experiencing environmental heterogeneity are expected to show adaptive evolution of plasticity. This study measured the transcriptome in a cadmium-enriched diet and a salt-enriched diet for experimental populations of Drosophila melanogaster that evolved for ~130 generations in one of four selective regimes: two constant regimes maintained in either cadmium or salt diets and two heterogeneous regimes that varied either temporally or spatially between the two diets. For populations evolving in constant regimes, a strong signature of counter-gradient evolution was found; the evolved expression differences between populations adapted to alternative diets is opposite to the plastic response of the ancestral population that is naive to both diets. Based on expression patterns in the ancestral populations, a set of genes was identified for which selection in heterogeneous regimes was predicted to result in increases in plasticity, and the expected pattern was found. In contrast, a set of genes where reduced plasticity was predicted did not follow expectation. Nonetheless, both gene sets showed a pattern consistent with adaptive expression evolution in heterogeneous regimes, highlighting the difference between observing 'optimal' plasticity and improvements in environment-specific expression. Looking across all genes, there is evidence in all regimes of differences in biased allele expression across environments ('allelic plasticity') and this is more common among genes with plasticity in total expression.

Tejeda, M. T., Arredondo, J., Liedo, P., Perez-Staples, D., Ramos-Morales, P. and Diaz-Fleischer, F. (2016). Reasons for success: rapid evolution for desiccation resistance and life-history changes in the polyphagous fly Anastrepha ludens. Evolution [Epub ahead of print]. PubMed ID: 27641541 Evolutionary Homolog Study Species that exhibit broad ranges of distribution may successfully navigate environmental changes by modifying some of their life history traits. Environmental humidity imposes a critical stress that organisms may overcome by increasing their resistance to desiccation. This study used experimental evolution to investigate adaptation to desiccation in the tephritid Anastrepha ludens, a species with high fecundity, late maturation and long lifespan. This study measured morphological, physiological, developmental as well as demographic changes involved in the adaptation to desiccation. Notwithstanding a low heritability (h2 = 0.237), desiccation resistance evolved extremely rapidly and few negative trade-offs were detected. Selected flies exhibited correlated increases in longevity, body size, the amount of body lipids and bulk water content, and in the duration of the pupal stage. Females further delayed sexual maturation, decreased daily fecundity but retained high lifetime reproductive potential. No differences in male mating competitiveness were found. Selected and control lines differed in longevity but not in total female fecundity, demonstrating that A. ludens flies have the capability for fast adaptation to desiccation without loosing their reproductive capability. Thus, it seems that a rapid evolutionary response to desiccation in this polyphagous insect works as a buffer for environmental variation and reduces the strength of selection on reproductive traits.

Cheng, C. and Kirkpatrick, M. (2016). Sex-specific selection and sex-biased gene expression in humans and flies. PLoS Genet 12: e1006170. PubMed ID: 27658217 Summary: Sexual dimorphism results from sex-biased gene expression, which evolves when selection acts differently on males and females. While there is an intimate connection between sex-biased gene expression and sex-specific selection, few empirical studies have studied this relationship directly. This study compare the two on a genome-wide scale in humans and flies. A distinctive "Twin Peaks" pattern in humans that relates the strength of sex-specific selection, quantified by genetic divergence was yound between male and female adults at autosomal loci, to the degree of sex-biased expression. Genes with intermediate degrees of sex-biased expression show evidence of ongoing sex-specific selection, while genes with either little or completely sex-biased expression do not. This pattern apparently results from differential viability selection in males and females acting in the current generation. The Twin Peaks pattern is also found in Drosophila using a different measure of sex-specific selection acting on fertility. A simple model was developed that successfully recapitulates the Twin Peaks. These results suggest that many genes with intermediate sex-biased expression experience ongoing sex-specific selection in humans and flies.

Sulak, M., Fong, L., Mika, K., Chigurupati, S., Yon, L., Mongan, N. P., Emes, R. D. and Lynch, V. J. (2016). TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants. Elife 5. PubMed ID: 27642012 Evolutionary Homolog Study A major constraint on the evolution of large body sizes in animals is an increased risk of developing cancer. There is no correlation, however, between body size and cancer risk. This lack of correlation is often referred to as 'Peto's Paradox'. This study showed that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 (see Drosophila p53) and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. Furthermore several of the TP53 retrogenes (TP53RTGs) were shown to be transcribed and likely translated. While TP53RTGs do not appear to directly function as transcription factors, they do contribute to the enhanced sensitivity of elephant cells to DNA damage and the induction of apoptosis by regulating activity of the TP53 signaling pathway. These results suggest that an increase in the copy number of TP53 may have played a direct role in the evolution of very large body sizes and the resolution of Peto's paradox in Proboscideans.

Saturday, October 1st

Williams, M. J., Perland, E., Eriksson, M. M., Carlsson, J., Erlandsson, D., Laan, L., Mahebali, T., Potter, E., Frediksson, R., Benedict, C. and Schioth, H. B. (2016). Recurrent sleep fragmentation induces insulin and neuroprotective mechanisms in middle-aged flies. Front Aging Neurosci 8: 180. PubMed ID: 27531979 Summary: Lack of quality sleep increases central nervous system oxidative stress and impairs removal of neurotoxic soluble metabolites from brain parenchyma. During aging poor sleep quality, caused by sleep fragmentation, increases central nervous system cellular stress. Currently, it is not known how organisms offset age-related cytotoxic metabolite increases in order to safeguard neuronal survival. Furthermore, it is not understood how age and sleep fragmentation interact to affect oxidative stress protection pathways. This study demonstrates that sleep fragmentation increases systems that protect against oxidative damage and neuroprotective endoplasmic reticulum molecular chaperones, as well as neuronal insulin and dopaminergic expression in middle-aged Drosophila males. Interestingly, even after sleep recovery the expression of these genes was still upregulated in middle-aged flies. Finally, sleep fragmentation generates higher levels of reactive oxygen species (ROS) in middle-aged flies and after sleep recovery these levels remain significantly higher than in young flies. The fact that neuroprotective pathways remain upregulated in middle-aged flies beyond sleep fragmentation suggests it might represent a strong stressor for the brain during later life.

Laranjeira, A., Schulz, J. and Dotti, C. G. (2016). Genes related to fatty acid beta-oxidation play a role in the functional decline of the Drosophila brain with age. PLoS One 11: e0161143. PubMed ID: 27518101 Summary: In living organisms, ageing is widely considered to be the result of a multifaceted process consisting of the progressive accumulation of damage over time, having implications both in terms of function and survival. The study of ageing presents several challenges, from the different mechanisms implicated to the great diversity of systems affected over time. The current study set out to identify genes involved in the functional decline of the brain with age and study its relevance in a tissue dependent manner using Drosophila melanogaster as a model system. The age-dependent upregulation is reported of genes involved in the metabolic process of fatty acid beta-oxidation in the nervous tissue of female wild-type flies. Downregulation of CG10814, dHNF4 and lipid mobilizing genes bmm and dAkh rescues the functional decline of the brain with age, both at the cellular and behaviour level, while over-expression worsens performance. The data proposes the occurrence of a metabolic alteration in the fly brain with age, whereby the process of beta-oxidation of fatty acids experiences a genetic gain-of-function. This event proved to be one of the main causes contributing to the functional decline of the brain with age.

Klepsatel, P., Galikova, M., Xu, Y. and Kuhnlein, R. P. (2016). Thermal stress depletes energy reserves in Drosophila. Sci Rep 6: 33667. PubMed ID: 27641694 Summary: Understanding how environmental temperature affects metabolic and physiological functions is of crucial importance to assess the impacts of climate change on organisms. This study used different laboratory strains and a wild-caught population of the fruit fly Drosophila melanogaster to examine the effect of temperature on the body energy reserves of an ectothermic organism. Permanent ambient temperature elevation or transient thermal stress was shown to cause significant depletion of body fat stores. Surprisingly, transient thermal stress induces a lasting "memory effect" on body fat storage, which also reduces survivorship of the flies upon food deprivation later after stress exposure. Functional analyses revealed that an intact heat-shock response is essential to protect flies from temperature-dependent body fat decline. Moreover, it was found that the temperature-dependent body fat reduction is caused at least in part by apoptosis of fat body cells, which might irreversibly compromise the fat storage capacity of the flies. Altogether, these results provide evidence that thermal stress has a significant negative impact on organismal energy reserves, which in turn might affect individual fitness.

Ahmadi, M. and Roy, R. (2016). AMPK acts as a molecular trigger to coordinate glutamatergic signals and adaptive behaviours during acute starvation. Elife 5. PubMed ID: 27642785 Evolutionary Homolog Study The stress associated with starvation is accompanied by compensatory behaviours that enhance foraging efficiency and increase the probability of encountering food. However, the molecular details of how hunger triggers changes in the activity of neural circuits to elicit these adaptive behavioural outcomes remains to be resolved. This study shows that AMP-activated protein kinase (AMPK; see Drosophila AMPKα) regulates neuronal activity to elicit appropriate behavioural outcomes in response to acute starvation, and this effect is mediated by the coordinated modulation of glutamatergic inputs. AMPK targets both the AMPA-type glutamate receptor GLR-1 (see Drosophila Glu-RIIA) and the metabotropic glutamate receptor MGL-1 (see Drosophila mGluR) in one of the primary circuits that governs behavioural response to food availability in C. elegans. Overall, this study suggests that AMPK acts as a molecular trigger in the specific starvation-sensitive neurons to modulate glutamatergic inputs and to elicit adaptive behavioural outputs in response to acute starvation.

Vaccaro, A., Birman, S. and Klarsfeld, A. (2016). Chronic jet lag impairs startle-induced locomotion in Drosophila. Exp Gerontol 85: 24-27. PubMed ID: 27639775 Summary: Endogenous circadian clocks with ~24-h periodicity are found in most organisms from cyanobacteria to humans. Daylight synchronizes these clocks to solar time. In humans, shift-work and jet lag perturb clock synchronization, and such perturbations, when repeated or chronic, are strongly suspected to be detrimental to healthspan. This study investigated locomotor aging and longevity in Drosophila melanogaster with genetically or environmentally disrupted clocks. Two mutations in period (per, a gene essential for circadian rhythmicity in Drosophila) were compared, after introducing them in a common reference genetic background: the arrhythmic per01, and perT which displays robust short 16-h rhythms. Compared to the wild type, both per mutants showed reduced longevity and decreased startle-induced locomotion in aging flies, while spontaneous locomotor activity was not impaired. The per01 phenotypes were generally less severe than those of perT, suggesting that chronic jet lag is more detrimental to aging than arrhythmicity in Drosophila. Interestingly, the adjustment of environmental light-dark cycles to the endogenous rhythms of the perT mutant fully suppressed the acceleration in the age-related decline of startle-induced locomotion, while it accelerated this decline in wild-type flies. Overall, these results show that chronic jet lag accelerates a specific form of locomotor aging in Drosophila, and that this effect can be alleviated by environmental changes that ameliorate circadian rhythm synchronization.

Yerushalmi, G. Y., Misyura, L., Donini, A. and MacMillan, H. A. (2016). Chronic dietary salt stress mitigates hyperkalemia and facilitates chill coma recovery in Drosophila melanogaster. J Insect Physiol 95: 89-97. PubMed ID: 27642001 Summary: Chill susceptible insects like Drosophila lose the ability to regulate water and ion homeostasis at low temperatures. This loss of hemolymph ion and water balance drives a hyperkalemic state that depolarizes cells, causing cellular injury and death. The ability to maintain ion homeostasis at low temperatures and/or recover ion homeostasis upon rewarming is closely related to insect cold tolerance. It was thus hypothesized that changes to organismal ion balance, which can be achieved in Drosophila through dietary salt loading, could alter whole animal cold tolerance phenotypes. Drosophila melanogaster was put in the presence of diets highly enriched in NaCl, KCl, xylitol (an osmotic control) or sucrose (a dietary supplement known to impact cold tolerance) for 24h, and it was confirmed that they consumed the novel food. Independently of their osmotic effects, NaCl, KCl, and sucrose supplementation all improved the ability of flies to maintain K+ balance in the cold, which allowed for faster recovery from chill coma after 6h at 0° C. These supplements, however, also slightly increased the critical thermal minimum and had little impact on survival rates following chronic cold stress (24h at 0° C), suggesting that the effect of diet on cold tolerance depends on the measure of cold tolerance assessed. In contrast to prolonged salt stress, brief feeding (1.5h) on diets high in salt slowed coma recovery, suggesting that the long-term effects of NaCl and KCl on chilling tolerance result from phenotypic plasticity, induced in response to a salty diet, rather than simply the presence of the diet in the gut lumen.

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