Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling

Cells rely on the coordinated regulation of lipid phosphoinositides and Rab GTPases to define membrane compartment fates along distinct trafficking routes. The family of disease-related myotubularin (MTM) phosphoinositide phosphatases includes catalytically inactive members, or pseudophosphatases, with poorly understood functions. We found that Drosophila MTM pseudophosphatase Sbf coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. Sbf dynamically interacts with class II phosphatidylinositol 3-kinase and stably recruits Mtm to promote turnover of a PI(3)P subpool essential for endosomal trafficking. Sbf also functions as a guanine nucleotide exchange factor that promotes Rab21 GTPase activation associated with PI(3)P endosomes. Of importance, Sbf, Mtm, and Rab21 function together, along with Rab11-mediated endosomal trafficking, to control macrophage protrusion formation. This identifies Sbf as a critical coordinator of PI(3)P and Rab21 regulation, which specifies an endosomal pathway and cortical control.     

Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity,Leading to the Under Replication of DNA

Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA) deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation: the intracellular accumulation of dCTP inhibits PARP-1 activity. CDA deficiency results in incomplete DNA replication when cells enter mitosis, leading to the formation of ultrafine anaphase bridges between sister-chromatids at “difficult-to-replicate” sites such as centromeres and fragile sites. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. The stimulation of PARP-1 activity in CDA-deficient cells restores replication and, thus, chromosome segregation. Moreover, increasing intracellular dCTP levels generates under-replication-induced sister-chromatid bridges as efficiently as PARP-1 knockdown. These results have direct implications for Bloom syndrome (BS), a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3’-5’ DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of ultrafine anaphase bridges due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our study describes previously unknown pathological consequences of the distortion of dNTP pools and reveals an unexpected role for PARP-1 in preventing DNA under-replication and chromosome segregation defects.     

The ecological importance of unregulated tributaries to macroinvertebrate diversity and community composition in a regulated river

Hydrobiologia - In regulated rivers, dams alter longitudinal gradients in flow regimes, geomorphology, water quality and temperature with associated impacts on aquatic biota. Unregulated...     

The importance of scale in comparative microbiome research: New insights from the gut and glands of captive and wild lemurs

Research on animal microbiomes is increasingly aimed at determining the evolutionary and ecological factors that govern host–microbiome dynamics, which are invariably intertwined and potentially synergistic. We present three empirical studies related to this topic, each of which relies on the diversity of Malagasy lemurs (representing a total of 19 species) and the comparative approach applied across scales of analysis. In Study 1, we compare gut microbial membership across 14 species in the wild to test the relative importance of host phylogeny and feeding strategy in mediating microbiome structure. Whereas host phylogeny strongly predicted community composition, the same feeding strategies shared by distant relatives did not produce convergent microbial consortia, but rather shaped microbiomes in host lineage‐specific ways, particularly in folivores. In Study 2, we compare 14 species of wild and captive folivores, frugivores, and omnivores, to highlight the importance of captive populations for advancing gut microbiome research. We show that the perturbational effect of captivity is mediated by host feeding strategy and can be mitigated, in part, by modified animal management. In Study 3, we examine various scent‐gland microbiomes across three species in the wild or captivity and show them to vary by host species, sex, body site, and a proxy of social status. These rare data provide support for the bacterial fermentation hypothesis in olfactory signal production and implicate steroid hormones as mediators of microbial community structure. We conclude by discussing the role of scale in comparative microbial studies, the links between feeding strategy and host–microbiome coadaptation, the underappreciated benefits of captive populations for advancing conservation research, and the need to consider the entirety of an animal's microbiota. Ultimately, these studies will help move the field from exploratory to hypothesis‐driven research.     

Avian biodiversity across Auckland’s volcanic cone reserves

Auckland, a city with a population of approximately 1.7 million, is located directly on the Auckland Volcanic Field, a late Quaternary-era monogenetic field. There are at least 53 volcanoes across the field, many of which are of geological, cultural and ecological significance, such as for being reserves for native species; however, few assessments of the richness of avian biodiversity across the volcanoes have been made. To address this data shortfall, we conducted avian biodiversity surveys using stationary point counts within nine of Auckland's volcanic cone reserves. Thirty-eight species were detected across the sites, of which 18 were native. Our estimates of relative species abundances and detection probabilities revealed that the most common native birds within these reserves were silvereyes, tui and southern black-backed gulls, while common mynas, house sparrows, Eurasian blackbirds and eastern rosellas were the most common introduced species. In addition to tui and silvereyes, the presence of other natives critical to the functioning of native ecosystems, such as New Zealand fantails, grey warblers and New Zealand pigeon, suggest that the volcanoes possess a diverse native avifauna supported by native flora that warrant continued and intensified restoration efforts. We discuss several feasible strategies for improving faunal and floral biodiversity across the volcanic cone reserves. Continued avian biodiversity surveys are also of critical importance as they will enable us to further evaluate and prioritise restoration projects within Auckland's multitude of diverse volcanic cone reserves.     

Global offtake of wild animals from wetlands: critical issues for fish and birds

Hydrobiologia - The global offtake of wild animals is valued at US$400 billion annually and supports the livelihoods of 15% of the global population. Wetlands are amongst the most important...     

SREBP1 is required for the induction by glucose of pancreatic beta-cell genes involved in glucose sensing

Previous studies have reported both positive and negative effects of culture of islets at high glucose concentrations on regulated insulin secretion. Here, we have reexamined this question in mouse islets and determined the role of changes in lipid synthesis in the effects of glucose. Glucose-stimulated insulin secretion (GSIS) and gene expression were examined in islets from C57BL/6 mice or littermates deleted for sterol-regulatory element binding protein-1 (SREBP1) after 4 days of culture at high glucose concentrations. Culture of control islets at 30 versus 8 mmol/l glucose led to enhanced secretion at both basal (3 mmol/l) and stimulatory (17 mmol/l) glucose concentrations and to enhanced triacylglycerol accumulation. These changes were associated with increases in the expression of genes involved in glucose sensing (glucose transporter 2, glucokinase, sulfonylurea receptor 1, inwardly rectifying K(+) channel 6.2), differentiation (pancreatic duodenal homeobox 1), and lipogenesis (Srebp1, fatty acid synthase, acetyl-coenzyme A carboxylase 1, stearoyl-coenzyme A desaturase 1). When cultured at either 8 or 30 mmol/l glucose, SREBP1-deficient (SREBP1(-/-)) islets displayed reduced GSIS and triacylglycerol content compared with normal islets. Correspondingly, glucose induction of the above genes in control islets was no longer observed in SREBP1(-/-) mouse islets. We conclude that enhanced lipid synthesis mediated by SREBP1c-dependent genes is required for the adaptive changes in islet gene expression and insulin secretion at high glucose concentrations.     

Human-mediated introgression of exotic chukar (Alectoris chukar, Galliformes) genes from East Asia into native Mediterranean partridges

Mediterranean red-legged (Alectoris rufa) and rock (Alectoris graeca) partridge populations are affected by genetic pollution. The chukar partridge (Alectoris chukar), a species only partly native to Europe, is the most frequently introgressive taxon detected in the genome of hybrid partridges. Both theoretical (evolutionary) and practical (resources management) matters spur to get insight into the geographic origin of the A. chukar hybridizing swarm. The phenotypic A. rufa populations colonizing the easternmost part of the distribution range of this species, the islands of Elba (Italy) and Corsica (France), were investigated. The analysis of both mitochondrial (mtDNA: Cytochrome-b gene plus Control Region: 2,250 characters) and nuclear (Short Tandem Repeats, STR; Random Amplified Polymorphic DNA, RAPD) genomes of 25 wild (Elba) and 20 captive (Corsica) partridges, disclosed spread introgression of chukar origin also in these populations. All mtDNA haplotypes of Elba and Corsica partridges along with those we obtained from other A. rufa (total, n = 111: Italy, Spain, France) and A. graeca (n = 6, Italy), were compared with the mtDNA haplotypes of chukars (n = 205) sampled in 20 countries. It was found that the A. chukar genes detected in red-legged (n = 43) and rock partridges (n = 4) of Spain, France and Italy as well as in either introduced (Italy) or native (Greece, Turkey) chukars (n = 35) were all from East Asia. Hence, a well-defined geographic origin of the exotic chukar genes polluting the genome of native Mediterranean A. rufa and A. graeca (inter-specific level) as well as A. chukar (intra-specific level), was demonstrated.