Scrambled Eggs: Apoptotic cell clearance by non-professional phagocytes in the Drosophila ovary

This manuscript was supported by NIH grant R01 GM060574 to KM. (R01 GM060574 - NIH)https://www.frontiersin.org/articles/10.3389/fimmu.2017.01642/fullPublished versio

Effector Caspase Dcp-1 and IAP Protein Bruce Regulate Starvation-Induced Autophagy during Drosophila Melanogaster Oogenesis

A complex relationship exists between autophagy and apoptosis, but the regulatory mechanisms underlying their interactions are largely unknown. We conducted a systematic study of Drosophila melanogaster cell death–related genes to determine their requirement in the regulation of starvation-induced autophagy. We discovered that six cell death genes—death caspase-1 (Dcp-1), hid, Bruce, Buffy, debcl, and p53—as well as Ras–Raf–mitogen activated protein kinase signaling pathway components had a role in autophagy regulation in D. melanogaster cultured cells. During D. melanogaster oogenesis, we found that autophagy is induced at two nutrient status checkpoints: germarium and mid-oogenesis. At these two stages, the effector caspase Dcp-1 and the inhibitor of apoptosis protein Bruce function to regulate both autophagy and starvation-induced cell death. Mutations in Atg1 and Atg7 resulted in reduced DNA fragmentation in degenerating midstage egg chambers but did not appear to affect nuclear condensation, which indicates that autophagy contributes in part to cell death in the ovary. Our study provides new insights into the molecular mechanisms that coordinately regulate autophagic and apoptotic events in vivo.Canadian Institutes of Health (MOP-78882); National Institutes of Health (R01 GM60574); Summer Undergraduate Research Fellowship program at Boston University; National Science Foundation (0450339

Defective phagocytic corpse processing results in neurodegeneration and can be rescued by TORC1 activation

This work was supported by NIH Grants R01 GM094452 (K.M.) and F31 GM099425 (J.I.E.), BU Alzheimer's Disease Core Center NIH Grant P30 AG13846, Boston University Undergraduate Research Opportunities Program grants (J.A.T., V.S.), and NIH Grant R01 AG044113 to M.B.F. We thank the Bloomington Stock Center, TRiP at Harvard Medical School, the Kyoto Drosophila Genetic Resource Center, Estee Kurant, Eric Baehrecke, Marc Freeman, and Mary Logan for fly strains. We thank Todd Blute for assistance with electron microscopy and the Developmental Studies Hybridoma Bank for antibodies. (R01 GM094452 - NIH; F31 GM099425 - NIH; R01 AG044113 - NIH; P30 AG13846 - BU Alzheimer's Disease Core Center NIH Grant; Boston University Undergraduate Research Opportunities Program)https://www.jneurosci.org/content/36/11/3170.longPublished versionPublished versio

Modulation Of Hsp25 And Tnf-alpha During The Early Stages Of Functional Overload Of A Rat Slow And Fast Muscle

Early events in response to abrupt increases in activation and loading with muscle functional overload (FO) are associated with increased damage and inflammation. Heat shock protein 25 (HSP25) may protect against these stressors. and its expression can be regulated by muscle loading and activation. The purpose of this study was to investigate the responses of HSP25. phosphorylated HSP25 (pHSP25), and tumor necrosis factor-alpha (TNF-alpha) during FO of the slow soleus and fast plantaris. We compared the HSP25 mRNA, HSP25 protein, pHSP25, and TNF-alpha responses in the soleus and plantaris after 0.5, 1, 2, 3, and 7 days of FO. HSP25 and pHSP25 were quantified in soluble and insoluble fractions. HSP25 mRNA increased immediately in both muscles and decreased with continued FO. However, HSP25 mRNA levels were consistently higher in the Muscles of FO than control rats. In the soluble fraction. HSP25 increased in the plantaris after 2-7 days of FO with the greatest response at 3 and 7 days. The pHSP25 response to FO was greater in the plantaris than soleus at all points in the soluble fraction and at 0.5 days in the insoluble fraction. TNF-alpha levels in the plantaris, but not soleus, were higher than control at 0.5-2 days of FO. This may have contributed to the greater FO response in pHSP25 in the plantaris than soleus as TNF-alpha increased pHSP25 in C2C12 myotubes. These results suggest that the initial responses of pHSP25 and TNF-alpha to mechanical stress and inflammation associated with FO are greater in a fast than slow extensor muscle

Randomised trials conducted using cohorts : a scoping review

Acknowledgements We thank Margaret Sampson, MLIS, PhD, AHIP (Children’s Hospital of Eastern Ontario, Ottawa, Canada) for developing the search strategies on behalf of the CONSORT team. We thank Dr Philippa Fibert, St Mary’s University, Twickenham, London for her help in screening publications for inclusion.Peer reviewe

Genome-wide variation and transcriptional changes in diverse developmental processes underlie the rapid evolution of seasonal adaptation

Many organisms enter a dormant state in their life cycle to deal with predictable changes in environments over the course of a year. The timing of dormancy is therefore a key seasonal adaptation, and it evolves rapidly with changing environments. We tested the hypothesis that differences in the timing of seasonal activity are driven by differences in the rate of development during diapause in Rhagoletis pomonella, a fly specialized to feed on fruits of seasonally limited host plants. Transcriptomes from the central nervous system across a time series during diapause show consistent and progressive changes in transcripts participating in diverse developmental processes, despite a lack of gross morphological change. Moreover, population genomic analyses suggested that many genes of small effect enriched in developmental functional categories underlie variation in dormancy timing and overlap with gene sets associated with development rate in Drosophila melanogaster. Our transcriptional data also suggested that a recent evolutionary shift from a seasonally late to a seasonally early host plant drove more rapid development during diapause in the early fly population. Moreover, genetic variants that diverged during the evolutionary shift were also enriched in putative cis regulatory regions of genes differentially expressed during diapause development. Overall, our data suggest polygenic variation in the rate of developmental progression during diapause contributes to the evolution of seasonality in R. pomonella. We further discuss patterns that suggest hourglass-like developmental divergence early and late in diapause development and an important role for hub genes in the evolution of transcriptional divergence

An RNAi screen of the kinome in epithelial follicle cells of the Drosophila melanogaster ovary reveals genes required for proper germline death and clearance

Programmed cell death and cell corpse clearance are an essential part of organismal health and development. Cell corpses are often cleared away by professional phagocytes such as macrophages. However, in certain tissues, neighboring cells known as nonprofessional phagocytes can also carry out clearance functions. Here, we use the Drosophila melanogaster ovary to identify novel genes required for clearance by nonprofessional phagocytes. In the Drosophila ovary, germline cells can die at multiple time points. As death proceeds, the epithelial follicle cells act as phagocytes to facilitate the clearance of these cells. We performed an unbiased kinase screen to identify novel proteins and pathways involved in cell clearance during two death events. Of 224 genes examined, 18 demonstrated severe phenotypes during developmental death and clearance while 12 demonstrated severe phenotypes during starvation-induced cell death and clearance, representing a number of pathways not previously implicated in phagocytosis. Interestingly, it was found that several genes not only affected the clearance process in the phagocytes, but also non-autonomously affected the process by which germline cells died. This kinase screen has revealed new avenues for further exploration and investigation.R01 GM060574 - NIGMS NIH HHS; R35 GM127338 - NIGMS NIH HHS; 5R35GM127338-05 REVISED - NIH/National Institute of General Medical Scienceshttps://academic.oup.com/g3journal/article/11/2/jkaa066/6080751?login=truePublished versio

Reporting transparency and completeness in trials : Paper 3 – trials conducted using administrative databases do not adequately report elements related to use of databases

Acknowledgments The development of CONSORT-ROUTINE and the present review were funded by grants from the Canadian Institutes of Health Research (PI Thombs, #PJT-156172; PIs Thombs and Kwakkenbos, #PCS-161863) and from the United Kingdom National Institute of Health Research (NIHR) Clinical Trials Unit Support Funding (PI Juszczak, Co-PI Gale, supported salary of SM). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Dr. Langan was supported by a Wellcome Senior Clinical Fellowship in Science (205039/Z/16/Z). Dr. Moher is supported by a University Research Chair (uOttawa). Dr. Gale was supported by the United Kingdom Medical Research Council through a Clinician Scientist Fellowship. Dr. Thombs was supported by a Tier 1 Canada Research Chair.Peer reviewedPublisher PD

The linear polarisation of southern bright stars measured at the parts-per-million level

We report observations of the linear polarisation of a sample of 50 nearby southern bright stars measured to a median sensitivity of ~4.4 x 10^{-6}. We find larger polarisations and more highly polarised stars than in the previous PlanetPol survey of northern bright stars. This is attributed to a dustier interstellar medium in the mid-plane of the Galaxy, together with a population containing more B-type stars leading to more intrinsically polarised stars, as well as using a wavelength more sensitive to intrinsic polarisation in late-type giants. Significant polarisation had been identified for only six stars in the survey group previously, whereas we are now able to deduce intrinsic polarigenic mechanisms for more than twenty. The four most highly polarised stars in the sample are the four classical Be stars (alpha Eri, alpha Col, eta Cen and alpha Ara). For the three of these objects resolved by interferometry, the position angles are consistent with the orientation of the circumstellar disc determined. We find significant intrinsic polarisation in most B stars in the sample; amongst these are a number of close binaries and an unusual binary debris disk system. However these circumstances do not account for the high polarisations of all the B stars in the sample and other polarigenic mechanisms are explored. Intrinsic polarisation is also apparent in several late type giants which can be attributed to either close, hot circumstellar dust or bright spots in the photosphere of these stars. Aside from a handful of notable debris disk systems, the majority of A to K type stars show polarisation levels consistent with interstellar polarisation.Peer reviewe