Evolution of ASPM coding variation in apes and associations with brain structure in chimpanzees

Studying genetic mechanisms underlying primate brain morphology can provide insight into the evolution of human brain structure and cognition. In humans, loss‐of‐function mutations in the gene coding for ASPM (Abnormal Spindle Microtubule Assembly) have been associated with primary microcephaly, which is defined by a significantly reduced brain volume, intellectual disability and delayed development. However, less is known about the effects of common ASPM variation in humans and other primates. In this study, we characterized the degree of coding variation at ASPM in a large sample of chimpanzees (N = 241), and examined potential associations between genotype and various measures of brain morphology. We identified and genotyped five non‐synonymous polymorphisms in exons 3 (V588G), 18 (Q2772K, K2796E, C2811Y) and 27 (I3427V). Using T1‐weighted magnetic resonance imaging of brains, we measured total brain volume, cerebral gray and white matter volume, cerebral ventricular volume, and cortical surface area in the same chimpanzees. We found a potential association between ASPM V588G genotype and cerebral ventricular volume but not with the other measures. Additionally, we found that chimpanzee, bonobo, and human lineages each independently show a signature of accelerated ASPM protein evolution. Overall, our results suggest the potential effects of ASPM variation on cerebral cortical development, and emphasize the need for further functional studies. These results are the first evidence suggesting ASPM variation might play a role in shaping natural variation in brain structure in nonhuman primates.     

Quantitatively comparing morphological trends to environment in the fossil record (Cincinnatian series; Upper Ordovician)

Determining whether morphological trends in fossil species represent evolution within a lineage or lateral shifts in morphologically variable populations through time requires a thorough examination of the details of both morphology and paleoenvironment in time and space. The purpose of this study is to explore at high resolution the relationship between morphology of the trilobite Flexicalymene granulosa and paleoenvironmental conditions in Upper Ordovician deposits of southwestern Ohio and northern Kentucky. This is achieved by using geometric morphometrics to measure high-resolution morphological changes and by using gradient analysis to capture environmental gradients underlying faunal distribution patterns. Quantitatively comparing the outcomes of these two techniques provides an assessment of whether shape changes relates to environment. Results indicate that a significant amount of shape change, seen as an anteromedial movement of the eye region over time, corresponds to ordination scores. This suggests a relationship between certain aspects of morphology and environment. The combination of these quantitative techniques has provided the foundation for determining whether morphological trends within F. granulosa represent evolution or temporal shifts in geographic variation. Future work will involve examining this relationship in greater detail both geographically and stratigraphically.     

Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis

A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b), was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM) genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.     

Vanadium in Biological Action: Chemical,Pharmacological Aspects,and Metabolic Implications in Diabetes Mellitus

Vanadium compounds have been primarily investigated as potential therapeutic agents for the treatment of various major health issues, including cancer, atherosclerosis, and diabetes. The translation of vanadium-based compounds into clinical trials and ultimately into disease treatments remains hampered by the absence of a basic pharmacological and metabolic comprehension of such compounds. In this review, we examine the development of vanadium-containing compounds in biological systems regarding the role of the physiological environment, dosage, intracellular interactions, metabolic transformations, modulation of signaling pathways, toxicology, and transport and tissue distribution as well as therapeutic implications. From our point of view, the toxicological and pharmacological aspects in animal models and humans are not understood completely, and thus, we introduced them in a physiological environment and dosage context. Different transport proteins in blood plasma and mechanistic transport determinants are discussed. Furthermore, an overview of different vanadium species and the role of physiological factors (i.e., pH, redox conditions, concentration, and so on) are considered. Mechanistic specifications about different signaling pathways are discussed, particularly the phosphatases and kinases that are modulated dynamically by vanadium compounds because until now, the focus only has been on protein tyrosine phosphatase 1B as a vanadium target. Particular emphasis is laid on the therapeutic ability of vanadium-based compounds and their role for the treatment of diabetes mellitus, specifically on that of vanadate- and polioxovanadate-containing compounds. We aim at shedding light on the prevailing gaps between primary scientific data and information from animal models and human studies.

     

Distribution,degree of damage and risk of spread of Trioza erytreae (Hemiptera: Triozidae) in Kenya

The African citrus triozid (ACT), Trioza erytreae Del Guercio, is a destructive pest particularly on citrus, and vectors, “Candidatus” Liberibacter africanus (CLaf), which is the causal agent of the African citrus greening disease. Our study seeks to establish the distribution and host‐plant relationship of ACT across citrus production areas in Kenya. We also modelled the risk of spread using the maximum entropy modelling algorithm with known occurrence data. Our results infer that ACT is widely distributed and causes severe damage to four alternative host plants belonging to the family Rutaceae. The adults, immature stages (eggs and nymphs), galls and the percentage of infested leaves were significantly higher in shaded than unshaded trees. However, adult ACTs preferred Kenyan highlands to Victoria Lake and coastal regions. The average area under the curve of the model predictions was 0.97, indicating an optimal model performance. The environmental variables that most influenced the prediction were the precipitation of wettest quarter, precipitation of wettest month, mean diurnal range, temperature seasonality and mean temperature of the coldest quarter. The current prediction of ACT exceeded its existing range, especially in the Western, Nyanza, Central, Rift valley and Eastern regions of Kenya. The model predicted a contraction of suitable habitats for a potential spread in 2040 with an inland shift to higher altitudes in the cooler regions. The potential for further expansion to climatically suitable areas was more pronounced for the 2080 forecast. These findings provide relevant information to improve monitoring/surveillance and designing IPM strategies to limit its spread and damage.     

People’s desire to be in nature and how they experience it are partially heritable

Nature experiences have been linked to mental and physical health. Despite the importance of understanding what determines individual variation in nature experience, the role of genes has been overlooked. Here, using a twin design (TwinsUK, number of individuals = 2,306), we investigate the genetic and environmental contributions to a person’s nature orientation, opportunity (living in less urbanized areas), and different dimensions of nature experience (frequency and duration of public nature space visits and frequency and duration of garden visits). We estimate moderate heritability of nature orientation (46%) and nature experiences (48% for frequency of public nature space visits, 34% for frequency of garden visits, and 38% for duration of garden visits) and show their genetic components partially overlap. We also find that the environmental influences on nature experiences are moderated by the level of urbanization of the home district. Our study demonstrates genetic contributions to individuals’ nature experiences, opening a new dimension for the study of human–nature interactions.

Nature experiences have been linked to mental and physical health. This twin study reveals genetic influences on an individual’s orientation towards nature and nature experiences, opening a new dimension to understanding human-nature interactions.     

The double-stranded RNA-binding protein,Staufen1, is an IRES-transacting factor regulating HIV-1 cap-independent translation initiation

Translation initiation of the viral genomic mRNA (vRNA) of human immunodeficiency virus-type 1 (HIV-1) can be mediated by a cap- or an internal ribosome entry site (IRES)-dependent mechanism. A previous report shows that Staufen1, a cellular double-stranded (ds) RNA-binding protein (RBP), binds to the 5’untranslated region (5′UTR) of the HIV-1 vRNA and promotes its cap-dependent translation. In this study, we now evaluate the role of Staufen1 as an HIV-1 IRES-transacting factor (ITAF). We first confirm that Staufen1 associates with both the HIV-1 vRNA and the Gag protein during HIV-1 replication. We found that in HIV-1-expressing cells, siRNA-mediated depletion of Staufen1 reduces HIV-1 vRNA translation. Using dual-luciferase bicistronic mRNAs, we show that the siRNA-mediated depletion and cDNA-mediated overexpression of Staufen1 acutely regulates HIV-1 IRES activity. Furthermore, we show that Staufen1-vRNA interaction is required for the enhancement of HIV-1 IRES activity. Interestingly, we find that only Staufen1 harboring an intact dsRNA-binding domain 3 (dsRBD3) rescues HIV-1 IRES activity in Staufen1 CRISPR-Cas9 gene edited cells. Finally, we show that the expression of Staufen1-dsRBD3 alone enhances HIV-1 IRES activity. This study provides evidence of a novel role for Staufen1 as an ITAF promoting HIV-1 vRNA IRES activity.     

Remarkably Low KIR and HLA Diversity in Amerindians Reveals Signatures of Strong Purifying Selection Shaping the Centromeric KIR Region

The killer-cell immunoglobulin-like receptors (KIR) recognize human leukocyte antigen (HLA) molecules to regulate the cytotoxic and inflammatory responses of natural killer cells. KIR genes are encoded by a rapidly evolving gene family on chromosome 19 and present an unusual variation of presence and absence of genes and high allelic diversity. Although many studies have associated KIR polymorphism with susceptibility to several diseases over the last decades, the high-resolution allele-level haplotypes have only recently started to be described in populations. Here, we use a highly innovative custom next-generation sequencing method that provides a state-of-art characterization of KIR and HLA diversity in 706 individuals from eight unique South American populations: five Amerindian populations from Brazil (three Guarani and two Kaingang); one Amerindian population from Paraguay (Aché); and two urban populations from Southern Brazil (European and Japanese descendants from Curitiba). For the first time, we describe complete high-resolution KIR haplotypes in South American populations, exploring copy number, linkage disequilibrium, and KIR–HLA interactions. We show that all Amerindians analyzed to date exhibit the lowest numbers of KIR–HLA interactions among all described worldwide populations, and that 83–97% of their KIR–HLA interactions rely on a few HLA-C molecules. Using multiple approaches, we found signatures of strong purifying selection on the KIR centromeric region, which codes for the strongest NK cell educator receptors, possibly driven by the limited HLA diversity in these populations. Our study expands the current knowledge of KIR genetic diversity in populations to understand KIR–HLA coevolution and its impact on human health and survival.