Adipose Vascular Endothelial Growth Factor Regulates Metabolic Homeostasis through Angiogenesis

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Highlights? Two-way modulations of adipose VEGF were generated with aP2-Cre transgene ? Adipose VEGF KO reduces vasculature, increases hypoxia and inflammation in fat ? Adipose VEGF KO accelerates the development of metabolic disease in high-fat diet ? Induced adipose VEGF has opposite effect on fat and restores metabolic homeostasis     

Comparative Genomics of Wolbachia and the Bacterial Species Concept

The importance of host-specialization to speciation processes in obligate host-associated bacteria is well known, as is also the ability of recombination to generate cohesion in bacterial populations. However, whether divergent strains of highly recombining intracellular bacteria, such as Wolbachia, can maintain their genetic distinctness when infecting the same host is not known. We first developed a protocol for the genome sequencing of uncultivable endosymbionts. Using this method, we have sequenced the complete genomes of the Wolbachia strains wHa and wNo, which occur as natural double infections in Drosophila simulans populations on the Seychelles and in New Caledonia. Taxonomically, wHa belong to supergroup A and wNo to supergroup B. A comparative genomics study including additional strains supported the supergroup classification scheme and revealed 24 and 33 group-specific genes, putatively involved in host-adaptation processes. Recombination frequencies were high for strains of the same supergroup despite different host-preference patterns, leading to genomic cohesion. The inferred recombination fragments for strains of different supergroups were of short sizes, and the genomes of the co-infecting Wolbachia strains wHa and wNo were not more similar to each other and did not share more genes than other A- and B-group strains that infect different hosts. We conclude that Wolbachia strains of supergroup A and B represent genetically distinct clades, and that strains of different supergroups can co-exist in the same arthropod host without converging into the same species. This suggests that the supergroups are irreversibly separated and that barriers other than host-specialization are able to maintain distinct clades in recombining endosymbiont populations. Acquiring a good knowledge of the barriers to genetic exchange in Wolbachia will advance our understanding of how endosymbiont communities are constructed from vertically and horizontally transmitted genes.     

A Gene Transfer Agent and a Dynamic Repertoire of Secretion Systems Hold the Keys to the Explosive Radiation of the Emerging Pathogen Bartonella

Gene transfer agents (GTAs) randomly transfer short fragments of a bacterial genome. A novel putative GTA was recently discovered in the mouse-infecting bacterium Bartonella grahamii. Although GTAs are widespread in phylogenetically diverse bacteria, their role in evolution is largely unknown. Here, we present a comparative analysis of 16 Bartonella genomes ranging from 1.4 to 2.6 Mb in size, including six novel genomes from Bartonella isolated from a cow, two moose, two dogs, and a kangaroo. A phylogenetic tree inferred from 428 orthologous core genes indicates that the deadly human pathogen B. bacilliformis is related to the ruminant-adapted clade, rather than being the earliest diverging species in the genus as previously thought. A gene flux analysis identified 12 genes for a GTA and a phage-derived origin of replication as the most conserved innovations. These are located in a region of a few hundred kb that also contains 8 insertions of gene clusters for type III, IV, and V secretion systems, and genes for putatively secreted molecules such as cholera-like toxins. The phylogenies indicate a recent transfer of seven genes in the virB gene cluster for a type IV secretion system from a cat-adapted B. henselae to a dog-adapted B. vinsonii strain. We show that the B. henselae GTA is functional and can transfer genes in vitro. We suggest that the maintenance of the GTA is driven by selection to increase the likelihood of horizontal gene transfer and argue that this process is beneficial at the population level, by facilitating adaptive evolution of the host-adaptation systems and thereby expansion of the host range size. The process counters gene loss and forces all cells to contribute to the production of the GTA and the secreted molecules. The results advance our understanding of the role that GTAs play for the evolution of bacterial genomes.     

Psychosocial Working Conditions and Cognitive Complaints among Swedish Employees

Background

Cognitive complaints involving problems with concentration, memory, decision-making and thinking are relatively common in the work force. The sensitivity of both subjective and objective cognitive functioning to common psychiatric conditions, stress levels and to cognitive load makes it plausible that psychosocial working conditions play a role in cognitive complaints. Thus, this study aimed to test the associations between psychosocial work factors and cognitive complaints in nationally representative samples of the Swedish work force. Cross-sectional (n = 9751) and prospective (n = 3644; two time points two years apart) sequential multiple regression analyses were run, adjusting for general confounders, depressive- and sleeping problems. Additional prospective analyses were run adjusting for baseline cognitive complaints.

Cross-sectional results

High quantitative demands, information and communication technology (ICT) demands, underqualification and conflicts were positively associated with cognitive complaints, while social support, good resources at work and overqualification were negatively associated with cognitive complaints in all models. Skill discretion and decision authority were weakly associated with cognitive complaints. Conflicts were more strongly associated with cognitive complaints in women than in men, after adjustment for general confounders.

Prospective results

Quantitative job demands, ICT demands and underqualification were positively associated with future cognitive complaints in all models, including when adjusted for baseline cognitive complaints. Decision authority was weakly positively associated with future cognitive complaints, only after adjustment for depressive- and sleeping problems respectively. Social support was negatively associated with future cognitive complaints after adjustment for general confounders and baseline cognitive complaints. Skill discretion and resources were negatively associated with future cognitive complaints after adjustment for general confounders. The associations between quantitative demands and future cognitive complaints were stronger in women.

Discussion/Conclusions

The findings indicate that psychosocial working conditions should be taken into account when considering cognitive complaints among employees.     

Comprehensive Histone Phosphorylation Analysis and Identification of Pf14-3-3 Protein as a Histone H3 Phosphorylation Reader in Malaria Parasites

The important role of histone posttranslational modifications, particularly methylation and acetylation, in Plasmodium falciparum gene regulation has been established. However, the role of histone phosphorylation remains understudied. Here, we investigate histone phosphorylation utilizing liquid chromatography and tandem mass spectrometry to analyze histones extracted from asexual blood stages using two improved protocols to enhance preservation of PTMs. Enrichment for phosphopeptides lead to the detection of 14 histone phospho-modifications in P. falciparum. The majority of phosphorylation sites were observed at the N-terminal regions of various histones and were frequently observed adjacent to acetylated lysines. We also report the identification of one novel member of the P. falciparum histone phosphosite binding protein repertoire, Pf14-3-3I. Recombinant Pf14-3-3I protein bound to purified parasite histones. In silico structural analysis of Pf14-3-3 proteins revealed that residues responsible for binding to histone H3 S10ph and/or S28ph are conserved at the primary and the tertiary structure levels. Using a battery of H3 specific phosphopeptides, we demonstrate that Pf14-3-3I preferentially binds to H3S28ph over H3S10ph, independent of modification of neighbouring residues like H3S10phK14ac and H3S28phS32ph. Our data provide key insight into histone phosphorylation sites. The identification of a second member of the histone modification reading machinery suggests a widespread use of histone phosphorylation in the control of various nuclear processes in malaria parasites.     

Decreased Proportion of Cytomegalovirus Specific CD8 T-Cells but No Signs of General Immunosenescence in Alzheimer’s Disease

Cytomegalovirus (CMV) has been suggested as a contributing force behind the impaired immune responsiveness in the elderly, with decreased numbers of naïve T-cells and an increased proportion of effector T-cells. Immunological impairment is also implicated as a part of the pathogenesis in Alzheimer’s disease (AD). The aim of this study was to investigate whether AD patients present with a different CMV-specific CD8 immune profile compared to non-demented controls. Blood samples from 50 AD patients and 50 age-matched controls were analysed for HLA-type, CMV serostatus and systemic inflammatory biomarkers. Using multi-colour flow cytometry, lymphocytes from peripheral blood mononuclear cells were analysed for CMV-specific CD8 immunity with MHC-I tetramers A01, A02, A24, B07, B08 and B35 and further classified using CD27, CD28, CD45RA and CCR7 antibodies. Among CMV seropositive subjects, patients with AD had significantly lower proportions of CMV-specific CD8 T-cells compared to controls, 1.16 % vs. 4.13 % (p=0.0057). Regardless of dementia status, CMV seropositive subjects presented with a lower proportion of naïve CD8 cells and a higher proportion of effector CD8 cells compared to seronegative subjects. Interestingly, patients with AD showed a decreased proportion of CMV-specific CD8 cells but no difference in general CD8 differentiation.     

Vertical stratification of a temperate forest caterpillar community in eastern North America

Vertical niche partitioning might be one of the main driving forces explaining the high diversity of forest ecosystems. However, the forest’s vertical dimension has received limited investigation, especially in temperate forests. Thus, our knowledge about how communities are vertically structured remains limited for temperate forest ecosystems. In this study, we investigated the vertical structuring of an arboreal caterpillar community in a temperate deciduous forest of eastern North America. Within a 0.2-ha forest stand, all deciduous trees ≥ 5 cm diameter at breast height (DBH) were felled and systematically searched for caterpillars. Sampled caterpillars were assigned to a specific stratum (i.e. understory, midstory, or canopy) depending on their vertical position and classified into feeding guild as either exposed feeders or shelter builders (i.e. leaf rollers, leaf tiers, webbers). In total, 3892 caterpillars representing 215 species of butterflies and moths were collected and identified. While stratum had no effect on caterpillar density, feeding guild composition changed significantly with shelter-building caterpillars becoming the dominant guild in the canopy. Species richness and diversity were found to be highest in the understory and midstory and declined strongly in the canopy. Family and species composition changed significantly among the strata; understory and canopy showed the lowest similarity. Food web analyses further revealed an increasing network specialization towards the canopy, caused by an increase in specialization of the caterpillar community. In summary, our study revealed a pronounced stratification of a temperate forest caterpillar community, unveiling a distinctly different assemblage of caterpillars dwelling in the canopy stratum.     

Urinary Excretion of Silicon in Men,Non-pregnant Women,and Pregnant Women: a Cross-sectional Study

Biological Trace Element Research - Silicon is a trace element found mainly in plant-based food and proposed to be beneficial for bone health. Urinary excretion of Si has been shown to be a...     

Feeding of Arapaima sp.: integrating stomach contents and local ecological knowledge

The giant arapaima (Arapaima sp.) has been described as a fish of change in Amazonia because of its important role in the conservation of floodplains, food security and income generation for rural communities. Nonetheless, despite the cultural, ecological and economic importance of arapaima, data on diet are scarce. Aiming to expand knowledge about arapaima diet in western Amazonia, scientific knowledge was integrated with the knowledge of local dwellers. During the low-water period (September 2018) and the falling-water period (June 2019), arapaima stomachs were collected from 11 floodplain lakes in the middle Juruá River. All fishes were measured [TL (total length)] and sexed. Food items from each stomach were categorized as fishes, invertebrates, plants and bone remains and weighed. Also, in the latter period, experienced local fishers were interviewed about arapaima feeding. This integrated approach revealed that young arapaima eat fish and invertebrates but adult arapaima eat fish of a wide range of species, which were mainly of low and intermediate trophic positions. This study reports the first case of cannibalism for arapaima and also shows that during the low-water period, many individuals had empty stomachs or only some small fish-bone remains and/or plant material. Arapaima sex and TL had no influence on the absence of prey in stomach contents. Overall, it can be concluded that local people had consistent ethnobiological knowledge of arapaima feeding ecology that could be useful within management projects in the region.     

Mechanical cues in cellular signalling and communication

Multicellular organisms comprise an organized array of individual cells surrounded by a meshwork of biomolecules and fluids. Cells have evolved various ways to communicate with each other, so that they can exchange information and thus fulfil their specified and unique functions. At the same time, cells are also physical entities that are subjected to a variety of local and global mechanical cues arising in the microenvironment. Cells are equipped with several different mechanisms to sense the physical properties of the microenvironment and the mechanical forces arising within it. These mechanical cues can elicit a variety of responses that have been shown to play a crucial role in vivo. In this review, we discuss the current views and understanding of cell mechanics and demonstrate the emerging evidence of the interplay between physiological mechanical cues and cell-cell communication pathways.