Self-Assemblage and Quorum in the Earthworm Eisenia fetida (Oligochaete, Lumbricidae)

Despite their ubiquity and ecological significance in temperate ecosystems, the behavioural ecology of earthworms is not well described. This study examines the mechanisms that govern aggregation behaviour specially the tendency of individuals to leave or join groups in the compost earthworm Eisenia fetida, a species with considerable economic importance, especially in waste management applications. Through behavioural assays combined with mathematical modelling, we provide the first evidence of self-assembled social structures in earthworms and describe key mechanisms involved in cluster formation. We found that the probability of an individual joining a group increased with group size, while the probability of leaving decreased. Moreover, attraction to groups located at a distance was observed, suggesting a role for volatile cues in cluster formation. The size of earthworm clusters appears to be a key factor determining the stability of the group. These findings enhance our understanding of intra-specific interactions in earthworms and have potential implications for extraction and collection of earthworms in vermicomposting processes

Damaged Intestinal Epithelial Integrity Linked to Microbial Translocation in Pathogenic Simian Immunodeficiency Virus Infections

The chronic phase of HIV infection is marked by pathological activation of the immune system, the extent of which better predicts disease progression than either plasma viral load or CD4+ T cell count. Recently, translocation of microbial products from the gastrointestinal tract has been proposed as an underlying cause of this immune activation, based on indirect evidence including the detection of microbial products and specific immune responses in the plasma of chronically HIV-infected humans or SIV-infected Asian macaques. We analyzed tissues from SIV-infected rhesus macaques (RMs) to provide direct in situ evidence for translocation of microbial constituents from the lumen of the intestine into the lamina propria and to draining and peripheral lymph nodes and liver, accompanied by local immune responses in affected tissues. In chronically SIV-infected RMs this translocation is associated with breakdown of the integrity of the epithelial barrier of the gastrointestinal (GI) tract and apparent inability of lamina propria macrophages to effectively phagocytose translocated microbial constituents. By contrast, in the chronic phase of SIV infection in sooty mangabeys, we found no evidence of epithelial barrier breakdown, no increased microbial translocation and no pathological immune activation. Because immune activation is characteristic of the chronic phase of progressive HIV/SIV infections, these findings suggest that increased microbial translocation from the GI tract, in excess of capacity to clear the translocated microbial constituents, helps drive pathological immune activation. Novel therapeutic approaches to inhibit microbial translocation and/or attenuate chronic immune activation in HIV-infected individuals may complement treatments aimed at direct suppression of viral replication

Productive Hepatitis C Virus Infection of Stem Cell-Derived Hepatocytes Reveals a Critical Transition to Viral Permissiveness during Differentiation

Primary human hepatocytes isolated from patient biopsies represent the most physiologically relevant cell culture model for hepatitis C virus (HCV) infection, but these primary cells are not readily accessible, display individual variability, and are largely refractory to genetic manipulation. Hepatocyte-like cells differentiated from pluripotent stem cells provide an attractive alternative as they not only overcome these shortcomings but can also provide an unlimited source of noncancer cells for both research and cell therapy. Despite its promise, the permissiveness to HCV infection of differentiated human hepatocyte-like cells (DHHs) has not been explored. Here we report a novel infection model based on DHHs derived from human embryonic (hESCs) and induced pluripotent stem cells (iPSCs). DHHs generated in chemically defined media under feeder-free conditions were subjected to infection by both HCV derived in cell culture (HCVcc) and patient-derived virus (HCVser). Pluripotent stem cells and definitive endoderm were not permissive for HCV infection whereas hepatic progenitor cells were persistently infected and secreted infectious particles into culture medium. Permissiveness to infection was correlated with induction of the liver-specific microRNA-122 and modulation of cellular factors that affect HCV replication. RNA interference directed toward essential cellular cofactors in stem cells resulted in HCV-resistant hepatocyte-like cells after differentiation. The ability to infect cultured cells directly with HCV patient serum, to study defined stages of viral permissiveness, and to produce genetically modified cells with desired phenotypes all have broad significance for host-pathogen interactions and cell therapy

A Horizon Scan to Support Chemical Pollution–Related Policymaking for Sustainable and Climate‐Resilient Economies

While chemicals are vital to modern society through materials, agriculture, textiles, new technology, medicines, and consumer goods, their use is not without risks. Unfortunately, our resources seem inadequate to address the breadth of chemical challenges to the environment and human health. Therefore, it is important we use our intelligence and knowledge wisely to prepare for what lies ahead. The present study used a Delphi‐style approach to horizon‐scan future chemical threats that need to be considered in the setting of chemicals and environmental policy, which involved a multidisciplinary, multisectoral, and multinational panel of 25 scientists and practitioners (mainly from the United Kingdom, Europe, and other industrialized nations) in a three‐stage process. Fifteen issues were shortlisted (from a nominated list of 48), considered by the panel to hold global relevance. The issues span from the need for new chemical manufacturing (including transitioning to non‐fossil‐fuel feedstocks); challenges from novel materials, food imports, landfills, and tire wear; and opportunities from artificial intelligence, greater data transparency, and the weight‐of‐evidence approach. The 15 issues can be divided into three classes: new perspectives on historic but insufficiently appreciated chemicals/issues, new or relatively new products and their associated industries, and thinking through approaches we can use to meet these challenges. Chemicals are one threat among many that influence the environment and human health, and interlinkages with wider issues such as climate change and how we mitigate these were clear in this exercise. The horizon scan highlights the value of thinking broadly and consulting widely, considering systems approaches to ensure that interventions appreciate synergies and avoid harmful trade‐offs in other areas. We recommend further collaboration between researchers, industry, regulators, and policymakers to perform horizon scanning to inform policymaking, to develop our ability to meet these challenges, and especially to extend the approach to consider also concerns from countries with developing economies

Association between HIV infection and mitochondrial DNA copy number in peripheral blood: A population-based, prospective cohort study

Background. Low mitochondrial DNA (mtDNA) copy number (CN) is a predictor of adverse aging outcomes, and its status may be altered in human immunodefciency virus (HIV)-infected persons. Tis study evaluated the cross-sectional and longitudinal change of mtDNA CN by HIV markers. Methods. mtDNA CN was measured in the ALIVE (AIDS Linked to the Intravenous Experience) cohort of persons with a history of injecting drugs. Multivariable linear regression models controlling for demographic characteristics, behavior, and hepatitis C virus (HCV) seropositivity assessed the relationship of mtDNA CN to HIV markers (CD4+ T-cell counts, viral load, antiretroviral therapy [ART] use). Linear mixed models tested the association between HIV markers and age-related mtDNA CN trajectories. Results. Among 741 individuals at baseline, 436 (59%) were infected with HIV. HIV-infected individuals who had lower CD4+ T-cell counts (P =.01), had higher viral loads (P \u3c.01), and were not receiving ART (P \u3c.01) had signifcantly lower mtDNA CNs than uninfected persons; there was no difference between participants who were uninfected and HIV-infected individuals who had well-controlled HIV levels. In longitudinal follow-up of 507 participants, from age 50 years onward, mtDNA CN declined signifcantly faster among HIV-infected individuals than among HIV-uninfected persons (-0.03 units of change/year vs 0.006 units of change/year; P =.04), even among infected individuals with well-controlled HIV. Conclusion. Before 50 years of age, mtDNA CN is similar between HIV-infected individuals with well-controlled HIV and uninfected persons, but from age 50 onward, mtDNA CN declines signifcantly faster among all infected individuals than among HIV-uninfected persons

Interpreting Neutron Reflectivity Profiles of Diblock Copolymer Nanocomposite Thin Films Using Hybrid Particle-Field Simulations

Mixtures of block copolymers and nanoparticles (block copolymer nanocomposites) are known to microphase separate into a plethora of microstructures, depending on the composition, length scale, and nature of interactions among its different constituents. Confining these nanocomposites in thin films yields an even larger array of structures, which are not normally observed in the bulk. In contrast to the bulk, exploring various microstructures in thin films by the experimental route remains a challenging task. In this work, we present a modeling scheme using the hybrid particle-field simulation approach based on a coarse-grained model for representing polymer chains by continuous curves and coupling fictitious dynamics of nanoparticles to the thermodynamic forces. The simulation approach is general enough to predict microphase separation in thin films of <i>any block copolymer nanocomposite</i> with the specific details encoded in the interaction parameters. The approach is benchmarked by comparisons with the depth profiles obtained from the neutron reflectivity experiments for symmetric poly­(deuterated styrene-<i>b</i>-<i>n</i>-butyl methacrylate) copolymers blended with spherical magnetite nanoparticles covered by hydrogenated poly­(styrene) corona. We show that the hybrid particle-field approach is an accurate way to model and extract quantitative information about the physical parameters in the block copolymer nanocomposites. This work benchmarks the application of the hybrid particle-field model to derive the interaction parameters for exploring different microstructures in thin films containing block copolymer nanocomposites

Paucity of CD4(+)CCR5(+) T cells is a typical feature of natural SIV hosts

In contrast to lentiviral infections of humans and macaques, simian immunodeficiency virus (SIV) infection of natural hosts is nonpathogenic despite high levels of viral replication. However, the mechanisms underlying this absence of disease are unknown. Here we report that natural hosts for SIV infection express remarkably low levels of CCR5 on CD4(+) T cells isolated from blood, lymph nodes, and mucosal tissues. Given that this immunologic feature is found in 5 different species of natural SIV hosts (sooty mangabeys, African green monkeys, mandrills, sun-tailed monkeys, and chimpanzees) but is absent in 5 nonnatural/recent hosts (humans, rhesus, pigtail, cynomolgus macaques, and baboons), it may represent a key feature of the coevolution between the virus and its natural hosts that led to a nonpathogenic infection. Beneficial effects of low CCR5 expression on CD4(+) T cells may include the reduction of target cells for viral replication and a decreased homing of activated CD4(+) T cells to inflamed tissue

CD127 and CD25 Expression Defines CD4 +

Decreased CD4(+) T cell counts are the best marker of disease progression during HIV infection. However, CD4(+) T cells are heterogeneous in phenotype and function, and it is unknown how preferential depletion of specific CD4(+) T cell subsets influences disease severity. CD4(+) T cells can be classified into three subsets by the expression of receptors for two T cell-tropic cytokines, IL-2 (CD25) and IL-7 (CD127). The CD127(+)CD25(low/−) subset includes IL-2-producing naive and central memory T cells; the CD127(−)CD25(−) subset includes mainly effector T cells expressing perforin and IFN-γ; and the CD127(low)CD25(high) subset includes FoxP3-expressing regulatory T cells. Herein we investigated how the proportions of these T cell subsets are changed during HIV infection. When compared with healthy controls, HIV-infected patients show a relative increase in CD4(+)CD127(−)CD25(−) T cells that is related to an absolute decline of CD4(+)CD127(+)CD25(low/−) T cells. Interestingly, this expansion of CD4(+)CD127(−) T cells was not observed in naturally SIV-infected sooty mangabeys. The relative expansion of CD4(+)CD127(−)CD25(−) T cells correlated directly with the levels of total CD4(+) T cell depletion and immune activation. CD4(+)CD127(−)CD25(−) T cells were not selectively resistant to HIV infection as levels of cell-associated virus were similar in all non-naive CD4(+) T cell subsets. These data indicate that, during HIV infection, specific changes in the fraction of CD4(+) T cells expressing CD25 and/or CD127 are associated with disease progression. Further studies will determine whether monitoring the three subsets of CD4(+) T cells defined based on the expression of CD25 and CD127 should be used in the clinical management of HIV-infected individuals