Environmental controls on bacteriohopanepolyol profiles of benthic microbial mats from Lake Fryxell,Antarctica

Bacteriohopanepolyols (BHPs) are pentacyclic triterpenoid lipids that contribute to the structural integrity and physiology of some bacteria. Because some BHPs originate from specific classes of bacteria, BHPs have potential as taxonomically and environmentally diagnostic biomarkers. For example, a stereoisomer of bacteriohopanetetrol (informally BHT II) has been associated with anaerobic ammonium oxidation (anammox) bacteria and suboxic to anoxic marine environments where anammox is active. As a result, the detection of BHT II in the sedimentary record and fluctuations in the relative abundance of BHT II may inform reconstructions of nitrogen cycling and ocean redox changes through the geological record. However, there are uncertainties concerning the sources of BHT II and whether or not BHT II is produced in abundance in non‐marine environments, both of which are pertinent to interpretations of BHT II signatures in sediments. To address these questions, we investigate the BHP composition of benthic microbial mats from Lake Fryxell, Antarctica. Lake Fryxell is a perennially ice‐covered lake with a sharp oxycline in a density‐stabilized water column. We describe the diversity and abundance of BHPs in benthic microbial mats across a transect from oxic to anoxic conditions. Generally, BHP abundances and diversity vary with the morphologies of microbial mats, which were previously shown to reflect local environmental conditions, such as irradiance and oxygen and sulfide concentrations. BHT II was identified in mats that exist within oxic to anoxic portions of the lake. However, anammox bacteria have yet to be identified in Lake Fryxell. We examine our results in the context of BHPs as biomarkers in modern and ancient environments.     

Direct Nanoscale Characterization of Deep Levels in AgCuInGaSe2 Using Electron Energy‐Loss Spectroscopy in the Scanning Transmission Electron Microscope

A new experimental framework for the characterization of defects in semiconductors is demonstrated. Through the direct, energy‐resolved correlation of three analytical techniques spanning six orders of magnitude in spatial resolution, a critical mid‐bandgap electronic trap level (E_V + 0.56 eV) within Ag_0.2Cu_0.8In_1?xGa_xSe₂ is traced to its nanoscale physical location and chemical source. This is achieved through a stepwise, site‐specific correlated characterization workflow consisting of device‐scale (≈1 mm²) deep level transient spectroscopy (DLTS) to survey the traps present, scanning probe–based DLTS (scanning‐DLTS) for mesoscale‐resolved (hundreds of nanometers) mapping of the target trap state's spatial distribution, and scanning transmission electron microscope based electron energy‐loss spectroscopy (STEM‐EELS) and X‐ray energy‐dispersive spectroscopy for nanoscale energy‐, structure, and chemical‐resolved investigation of the defect source. This first demonstration of the direct observation of sub‐bandgap defect levels via STEM‐EELS, combined with the DLTS methods, provides strong evidence that the long‐suspected Cu_In/Ga substitutional defects are indeed the most likely source of the E_V + 0.56 eV trap state and serves as a key example of this approach for the fundamental identification of defects within semiconductors, in general.     

In vitro behavior and UV response of melanocytes derived from carriers of CDKN2A mutations and MC1R variants

Coinheritance of germline mutation in cyclin‐dependent kinase inhibitor 2A (CDKN2A) and loss‐of‐function (LOF) melanocortin 1 receptor (MC1R) variants is clinically associated with exaggerated risk for melanoma. To understand the combined impact of these mutations, we established and tested primary human melanocyte cultures from different CDKN2A mutation carriers, expressing either wild‐type MC1R or MC1RLOF variant(s). These cultures expressed the CDKN2A product p16 (INK4A) and functional MC1R. Except for 32ins24 mutant melanocytes, the remaining cultures showed no detectable aberrations in proliferation or capacity for replicative senescence. Additionally, the latter cultures responded normally to ultraviolet radiation (UV) by cell cycle arrest, JNK, p38, and p53 activation, hydrogen peroxide generation, and repair of DNA photoproducts. We propose that malignant transformation of melanocytes expressing CDKN2A mutation and MC1RLOF allele(s) requires acquisition of somatic mutations facilitated by MC1R genotype or aberrant microenvironment due to CDKN2A mutation in keratinocytes and fibroblasts.     

Ocean acidification refugia in variable environments

Climate change refugia in the terrestrial biosphere are areas where species are protected from global environmental change and arise from natural heterogeneity in landscapes and climate. Within the marine realm, ocean acidification, or the global decline in seawater pH, remains a pervasive threat to organisms and ecosystems. Natural variability in seawater carbon dioxide (CO₂) chemistry, however, presents an opportunity to identify ocean acidification refugia (OAR) for marine species. Here, we review the literature to examine the impacts of variable CO₂ chemistry on biological responses to ocean acidification and develop a framework of definitions and criteria that connects current OAR research to management goals. Under the concept of managing vulnerability, the most likely mechanisms by which OAR can mitigate ocean acidification impacts are by reducing exposure to harmful conditions or enhancing adaptive capacity. While local management options, such as OAR, show some promise, they present unique challenges, and reducing global anthropogenic CO₂ emissions must remain a priority.     

PyMINEr Finds Gene and Autocrine-Paracrine Networks from Human Islet scRNA-Seq

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Functional UQCRC1 polymorphisms affect promoter activity and body lipid accumulation

Obesity and type 2 diabetes constitute leading public health problems worldwide. Studies have shown that insulin resistance affiliated with these conditions is associated with skeletal muscle lipid accumulation, while the latter is associated with mitochondrial dysfunctions. However, the initiation and regulation of mitochondrial biogenesis rely heavily on approximately 1000 nuclear-encoded mitochondrial regulatory proteins. In this study, we targeted the ubiquinol-cytochrome c reductase core protein I gene, a nuclear-encoded component of mitochondrial complex III, for its association with subcutaneous fat depth (SFD) and skeletal muscle lipid accumulation (SMLA) using cattle as a model. Four promoter polymorphisms were identified and genotyped on approximately 250 Wagyu x Limousin F2 progeny. Statistical analysis revealed that two completely linked polymorphic sites, g.13487C>T and g.13709G>C (r2 = 1), were significantly associated with both SFD (p < 0.01) and SMLA (p < 0.0001). The difference between TTCC and CCGG haplotypes was 0.178 cm for SFD and 0.624 scores for SMLA. Interestingly, the former haplotype produced higher promoter activities than the latter by 43% to 49% in three cell lines (p < 0.05). In addition to Rett syndrome and breast/ovarian cancer observed in other studies, we report evidence for the first time, to our knowledge, that overexpression of ubiquinol-cytochrome c reductase core protein I might affect mitochondrial morphology and/or physiology and lead to development of obesity and related conditions.     

The calcium-sensing receptor and its interacting proteins

Seven membrane-spanning, or G protein-coupled receptors were originally thought to act through het-erotrimeric G proteins that in turn activate intracellular enzymes or ion channels, creating relatively simple, linear signalling pathways. Although this basic model remains true in that this family does act via a relatively small number of G proteins, these signalling systems are considerably more complex because the receptors interact with or are located near additional proteins that are often unique to a receptor or subset of receptors. These additional proteins give receptors their unique signalling personalities. The extracellular Ca-sensing receptor (CaR) signals via Galpha(i), Galpha(q) and Galpha(12/13), but its effects in vivo demonstrate that the signalling pathways controlled by these subunits are not sufficient to explain all its biologic effects. Additional structural or signalling proteins that interact with the CaR may explain its behaviour more fully. Although the CaR is less well studied in this respect than other receptors, several CaR-interacting proteins such as filamin, a potential scaffolding protein, receptor activity modifying proteins (RAMPs) and potassium channels may contribute to the unique characteristics of the CaR. The CaR also appears to interact with additional proteins common to other G protein-coupled receptors such as arrestins, G protein receptor kinases, protein kinase C, caveolin and proteins in the ubiquitination pathway. These proteins probably represent a few initial members of CaR-based signalling complex. These and other proteins may not all be associated with the CaR in all tissues, but they form the basis for understanding the complete nature of CaR signalling.     

Picomolar inhibitors as transition-state probes of 5'-methylthioadenosine nucleosidases.

Transition states can be predicted from an enzyme's affinity to related transition-state analogues. 5'-Methylthioadenosine nucleosidases (MTANs) are involved in bacterial quorum sensing pathways and thus are targets for antibacterial drug design. The transition-state characteristics of six MTANs are compared by analyzing dissociation constants (K(d)) with a small array of representative transition-state analogues. These inhibitors mimic early or late dissociative transition states with K(d) values in the picomolar range. Our results indicate that the K(d) ratio for mimics of early and late transition states are useful in distinguishing between these states. By this criterion, the transition states of Neisseria meningitides and Helicobacter pylori MTANs are early dissociative, whereas Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae MTANs have late dissociative characters. This conclusion is confirmed independently by the characteristic [1'- (3)H] and [1'- (14)C] kinetic isotope effects (KIEs) of these enzymes. Large [1'- (3)H] and unity [1'- (14)C] KIEs are observed for late dissociative transition states, whereas early dissociative states showed close-to-unity [1'- (3)H] and significant [1'- (14)C] KIEs. K d values of various MTANs for individual transition-state analogues provide tentative information about transition-state structures due to varying catalytic efficiencies of enzymes. Comparing K d ratios for mimics of early and late transition states removes limitations inherent to the enzyme and provides a better predictive tool in discriminating between possible transition-state structures.     

Predator densities and white-tailed deer fawn survival

Predation is the dominant source of mortality for white-tailed deer (Odocoileus virginianus) <6 months old throughout North America. Yet, few white-tailed deer fawn survival studies have occurred in areas with 4 predator species or have considered concurrent densities of deer and predator species. We monitored survival and cause-specific mortality from birth to 6 months for 100 neonatal fawns during 2013–2015 in the Upper Peninsula of Michigan, USA, while simultaneously estimating population densities of deer, American black bear (Ursus americanus), coyote (Canis latrans), bobcat (Lynx rufus), and gray wolf (Canis lupus). We estimated fawn predation risk in response to sex, birth mass, and date of birth. Six-month fawn survival pooled among years was 36%, and fawn mortality risk was not related to birth mass, date of birth, or sex. Estimated mean annual deer and predator densities were 334 fawns/100 km², 25.9 black bear/100 km², 23.8 coyotes/100 km², 3.8 bobcat/100 km², and 2.8 wolves/100 km². Despite lower estimated per-individual kill rates, coyotes and black bears were the leading sources of fawn mortality because they had greater densities relative to bobcats and wolves. Our results indicate that the presence of more predator species in a system is not entirely additive in its effect on fawn survival. © The Wildlife Society, 2019