Breaking barriers? Ethnicity and socioeconomic background impact on early career progression in the fields of ecology and evolution

The academic disciplines of Science, Technology, Engineering and Mathematics (STEM) have long suffered from a lack of diversity. While in recent years there has been some progress in addressing the underrepresentation of women in STEM subjects, other characteristics that have the potential to impact on equality of opportunity have received less attention. In this study, we surveyed 188 early career scientists (ECRs), defined as within 10 years of completing their PhD, in the fields of ecology, evolutionary biology, behaviour, and related disciplines. We examined associations between ethnicity, age, sexual orientation, sex, socioeconomic background, and disability, with measures of career progression, namely publication record, number of applications made before obtaining a postdoc, type of contract, and number of grant applications made. We also queried respondents on perceived barriers to progression and potential ways of overcoming them. Our key finding was that socioeconomic background and ethnicity were associated with measures of career progression. While there was no difference in the number of reported first‐authored papers on PhD completion, ethnic minority respondents reported fewer other‐authored papers. In addition, ECRs from a lower socioeconomic background were more likely to report being in teaching and research positions, rather than research‐only positions, the latter being perceived as more prestigious by some institutions. We discuss our findings in the context of possible inequality of opportunity. We hope that this study will stimulate wider discussion and help to inform strategies to address the underrepresentation of minority groups in the fields of ecology and evolution, and STEM subjects more widely.     

Modulation of Lipid Kinase PI4KIIα Activity and Lipid Raft Association of Presenilin 1 Underlies γ-Secretase Inhibition by Ginsenoside (20S)-Rg3

Amyloid β-peptide (Aβ) pathology is an invariant feature of Alzheimer disease, preceding any detectable clinical symptoms by more than a decade. To this end, we seek to identify agents that can reduce Aβ levels in the brain via novel mechanisms. We found that (20S)-Rg3, a triterpene natural compound known as ginsenoside, reduced Aβ levels in cultured primary neurons and in the brains of a mouse model of Alzheimer disease. The (20S)-Rg3 treatment induced a decrease in the association of presenilin 1 (PS1) fragments with lipid rafts where catalytic components of the γ-secretase complex are enriched. The Aβ-lowering activity of (20S)-Rg3 directly correlated with increased activity of phosphatidylinositol 4-kinase IIα (PI4KIIα), a lipid kinase that mediates the rate-limiting step in phosphatidylinositol 4,5-bisphosphate synthesis. PI4KIIα overexpression recapitulated the effects of (20S)-Rg3, whereas reduced expression of PI4KIIα abolished the Aβ-reducing activity of (20S)-Rg3 in neurons. Our results substantiate an important role for PI4KIIα and phosphoinositide modulation in γ-secretase activity and Aβ biogenesis.     

Biophysical characterization of a designed TMV coat protein mutant, R46G, that elicits a moderate hypersensitivity response in Nicotiana sylvestris

The hypersensitivity resistance response directed by the N' gene in Nicotiana sylvestris is elicited by the tobacco mosaic virus (TMV) coat protein R46G, but not by the U1 wild-type TMV coat protein. In this study, the structural and hydrodynamic properties of R46G and wild-type coat proteins were compared for variations that may explain N' gene elicitation. Circular dichroism spectroscopy reveals no significant secondary or tertiary structural differences between the elicitor and nonelicitor coat proteins. Analytical ultracentrifugation studies, however, do show different concentration dependencies of the weight average sedimentation coefficients at 4 degrees C. Viral reconstitution kinetics at 20 degrees C were used to determine viral assembly rates and as an initial assay of the rate of 20S formation, the obligate species for viral reconstitution. These kinetic results reveal a decreased lag time for reconstitution performed with R46G that initially lack the 20S aggregate. However, experiments performed with 20S initially present reveal no detectable differences indicating that the mechanism of viral assembly is similar for the two coat protein species. Therefore, an increased rate of 20S formation from R46G subunits may explain the differences in the viral reconstitution lag times. The inferred increase in the rate of 20S formation is verified by direct measurement of the 20S boundary as a function of time at 20 degrees C using velocity sedimentation analysis. These results are consistent with the interpretation that there may be an altered size distribution and/or lifetime of the small coat protein aggregates in elicitors that allows N. sylvestris to recognize the invading virus.     

Altered transarcolemmal Ca transport modifies the myofibrillar ultrastructure and protein metabolism in cultured adult ventricular cardiomyocytes

The present study was designed to investigate how prolonged (24-72 h) exposure to modifiers of Ca transarcolemmal transport affects the myofibrillar structure, protein turnover and content of myofibrillar proteins in adult guinea pig cardiomyocytes maintained beating synchronously in long-term cultures. First we established the functional responses (the contractile activity and [Ca]_i transients) of the cultured myocytes to acute exposures to several drugs used in this study. The ultrastructural characteristics of these cultures under the various treatments were determined using immunohistochemistry and confocal scanning laser microscopy, and their biochemical properties were evaluated using analysis of total cellular protein content, myofibrillar protein content and SDS-PAGE electrophoretic examination. We compared the effects of 24, 36 and 72 h-long exposures to the various specific Ca-flux modifiers. Increased Ca influx via Ca_L-channel agonist (Bay K 8644) or via the reversed- mode of the Na/Ca exchanger (veratrine) did not alter the myofibrillar structure or the specific protein profiles or proteosynthesis. However, when cytosolic Ca was increased by three different types of inhibitors of Ca extrusion from the cells via Na/Ca exchange, (Na-free solution, 5 mM NiCl₂ and 10^-6 M ouabain), very significant changes in all investigated parameters occurred almost immediately. Twenty-four h-long exposure to Na-free did not affect significantly the total cellular protein (TCP), but the protein synthesis was decreased by 87% and the total myofibrillar protein (TMP) content was decreased by 38%. The myofibrils were heavily fragmented. Similarly, 24 h-long exposure to 5 mM NiCl₂ did not affect the TCP, but it reduced protein synthesis by about 90% and decreased the total myofibrillar protein content by 30%. These effects were even more pronounced at 72 h of exposure and they were accompanied with a complete disassembly of myofilaments. Exposure to 10^-6 M ouabain over 72 h resulted in > 80% inhibition of protein synthesis, a 45% decrease in TCP content and a 53% in TMP content. In contrast, 10^-7 M ouabain did not produce any such changes. The changes produced by the Na/Ca-exchange inhibitors were accompanied by only minor changes in DNA content, indicating that the myocytes remained viable. Moreover, these effects were not due to the associated contractile arrest, since exposure to Ca_L-channel antagonists (5-20 M nifedipine or 10 M verapamil) produced only very minor changes in the myofibrillar structure and in protein profiles.Our data demonstrate that short-term (up to 72 h) increased Ca influx or contractile arrest of well-interconnected, spontaneously beating adult cardiomyocytes does not affect their ultrastructural characteristics or their myofibrillar protein turnover greatly, while any situations leading to Ca accumulation (via inhibition of Na/Ca exchange) affect cardiomyocyte function and ultrastructure almost immediately. These data are in sharp contrast to those previously reported from immature, neonatal myocytes.     

Recommendation of short tandem repeat profiling for authenticating human cell lines, stem cells, and tissues

Cell misidentification and cross-contamination have plagued biomedical research for as long as cells have been employed as research tools. Examples of misidentified cell lines continue to surface to this day. Efforts to eradicate the problem by raising awareness of the issue and by asking scientists voluntarily to take appropriate actions have not been successful. Unambiguous cell authentication is an essential step in the scientific process and should be an inherent consideration during peer review of papers submitted for publication or during review of grants submitted for funding. In order to facilitate proper identity testing, accurate, reliable, inexpensive, and standardized methods for authentication of cells and cell lines must be made available. To this end, an international team of scientists is, at this time, preparing a consensus standard on the authentication of human cells using short tandem repeat (STR) profiling. This standard, which will be submitted for review and approval as an American National Standard by the American National Standards Institute, will provide investigators guidance on the use of STR profiling for authenticating human cell lines. Such guidance will include methodological detail on the preparation of the DNA sample, the appropriate numbers and types of loci to be evaluated, and the interpretation and quality control of the results. Associated with the standard itself will be the establishment and maintenance of a public STR profile database under the auspices of the National Center for Biotechnology Information. The consensus standard is anticipated to be adopted by granting agencies and scientific journals as appropriate methodology for authenticating human cell lines, stem cells, and tissues.     

The relationship of the oral microbiotia to periodontal health and disease

The oral microbial community represents the best-characterized consortium associated with the human host. There are strong correlations between the qualitative composition of the oral microbiota and clinically healthy or diseased states. However, additional studies are needed to elucidate the mechanisms that define these microbial/host relationships.     

Rotavirus replication: plus-sense templates for double-stranded RNA synthesis are made in viroplasms

Rotavirus plus-strand RNAs not only direct protein synthesis but also serve as templates for the synthesis of the segmented double-stranded RNA (dsRNA) genome. In this study, we identified short-interfering RNAs (siRNAs) for viral genes 5, 8, and 9 that suppressed the expression of NSP1, a nonessential protein; NSP2, a component of viral replication factories (viroplasms); and VP7, an outer capsid protein, respectively. The loss of NSP2 expression inhibited viroplasm formation, genome replication, virion assembly, and synthesis of the other viral proteins. In contrast, the loss of VP7 expression had no effect on genome replication; instead, it inhibited only outer-capsid morphogenesis. Similarly, neither genome replication nor any other event of the viral life cycle was affected by the loss of NSP1. The data indicate that plus-strand RNAs templating dsRNA synthesis within viroplasms are not susceptible to siRNA-induced RNase degradation. In contrast, plus-strand RNAs templating protein synthesis in the cytosol are susceptible to degradation and thus are not the likely source of plus-strand RNAs for dsRNA synthesis in viroplasms. Indeed, immunofluorescence analysis of bromouridine (BrU)-labeled RNA made in infected cells provided evidence that plus-strand RNAs are synthesized within viroplasms. Furthermore, transfection of BrU-labeled viral plus-strand RNA into infected cells suggested that plus-strand RNAs introduced into the cytosol do not localize to viroplasms. From these results, we propose that plus-strand RNAs synthesized within viroplasms are the primary source of templates for genome replication and that trafficking pathways do not exist within the cytosol that transport plus-strand RNAs to viroplasms. The lack of such pathways confounds the development of reverse genetics systems for rotavirus.     

Extending the chronology of deposits at Blombos Cave, South Africa, back to 140 ka using optical dating of single and multiple grains of quartz

Optically stimulated luminescence (OSL) measurements are reported for both single aliquots (of two different sizes) and single grains of quartz from deposits within Blombos Cave. Ages have been obtained for six sediments from the Middle Stone Age (MSA) occupation levels and for two sterile sands, one underlying the archaeological sediment and one overlying the Later Stone Age occupation levels. The ages for the archaeological sediments were obtained from single-grain measurements that enabled unrepresentative grains to be rejected. The MSA occupation levels have ages that, within error limits, are in stratigraphic order and fall between the OSL age for the oldest dune sand (143.2+/-5.5 ka) and a previously published OSL age for the sterile sand ( approximately 70 ka) that separates the Middle and Later Stone Age deposits. The earliest MSA archaeological phase, M3, from where fragments of ochre were found as well as human teeth, is dated to 98.9+/-4.5 ka, coinciding with the sea-level high of oxygen isotope substage 5c. The cave then appears to be unoccupied until oxygen isotope substage 5a on the basis of four OSL ages for archaeological phase M2, ranging from 84.6+/-5.8 to 76.8+/-3.1 ka; these levels contained large hearths and bone tools. An age of 72.7+/-3.1 ka was obtained for the final MSA archaeological phase, M1, from which deliberately engraved ochre and shell beads were recovered along with bifacial stone points. We conclude that the periods of occupation were determined by changes in sea level, with abundant sources of seafood available in times of high sea level and with the cave being closed by the accumulation of large dunes during periods of low sea level, such as during oxygen isotope stages 4 and 6.     

New ages for Middle and Later Stone Age deposits at Mumba rockshelter, Tanzania: optically stimulated luminescence dating of quartz and feldspar grains

The archaeological deposits at Mumba rockshelter, northern Tanzania, have been excavated for more than 70 years, starting with Margit and Ludwig Köhl-Larsen in the 1930s. The assemblages of Middle Stone Age (MSA) and Later Stone Age (LSA) artefacts collected from this site constitute the type sequences for these cultural phases in East Africa. Despite its archaeological importance, however, the chronology of the site is poorly constrained, despite the application since the 1980s of several dating methods (radiocarbon, uranium-series and amino acid racemisation) to a variety of materials recovered from the deposits. Here, we review these previous chronologies for Mumba and report new ages obtained from optically stimulated luminescence (OSL) and infrared stimulated luminescence (IRSL) measurements on single grains of quartz and multi-grain aliquots of potassium (K) feldspar from the MSA and LSA deposits. Measurements of single grains of quartz allowed the rejection of unrepresentative grains and the application of appropriate statistical models to obtain the most reliable age estimates, while measurements of K-feldspars allowed the chronology to be extended to older deposits. The seven quartz ages and four K-feldspar ages provide improved temporal constraints on the archaeological sequence at Mumba. The deposits associated with the latest Kisele Industry (Bed VI-A) and the earliest Mumba Industry (Bed V) are dated to 63.4 ± 5.7 and 56.9 ± 4.8 ka (thousands of years ago), respectively, thus constraining the time of transition between these two archaeological phases to ∼60 ka. An age of 49.1 ± 4.3 ka has been obtained for the latest deposits associated with the Mumba Industry, which show no evidence for post-depositional mixing and contain ostrich eggshell (OES) beads and abundant microlithics. The Nasera Industry deposits (Bed III) contain large quantities of OES beads and date to 36.8 ± 3.4 ka. We compare the luminescence ages with the previous chronologies for Mumba, and briefly discuss how the revised chronology fits in the context of existing archaeological records and palaeoclimatic reconstructions for East Africa.     

Perception of male-male competition influences Drosophila copulation behaviour even in species where females rarely remate

Males in many taxa are known to exhibit behavioural plasticity in response to the perceived intensity of sperm competition, reflected in Drosophila melanogaster by increased copulation duration following prior exposure to a rival. We tested the prediction that males do not adjust their copulation effort in response to the presence of a competitor in Drosophila species where there is little or no sperm competition. Contrary to expectations, male plasticity in copulation duration was found in both Drosophila subobscura and Drosophila acanthoptera, species in which females rarely remate. These results are discussed in relation to the adaptive basis of plasticity in these species.