Livestock abundance predicts vampire bat demography, immune profiles, and bacterial infection risk

Human activities create novel food resources that can alter wildlife–pathogen interactions. If resources amplify or dampen, pathogen transmission probably depends on both host ecology and pathogen biology, but studies that measure responses to provisioning across both scales are rare. We tested these relationships with a 4-year study of 369 common vampire bats across 10 sites in Peru and Belize that differ in the abundance of livestock, an important anthropogenic food source. We quantified innate and adaptive immunity from bats and assessed infection with two common bacteria. We predicted that abundant livestock could reduce starvation and foraging effort, allowing for greater investments in immunity. Bats from high-livestock sites had higher microbicidal activity and proportions of neutrophils but lower immunoglobulin G and proportions of lymphocytes, suggesting more investment in innate relative to adaptive immunity and either greater chronic stress or pathogen exposure. This relationship was most pronounced in reproductive bats, which were also more common in high-livestock sites, suggesting feedbacks between demographic correlates of provisioning and immunity. Infection with both Bartonella and haemoplasmas were correlated with similar immune profiles, and both pathogens tended to be less prevalent in high-livestock sites, although effects were weaker for haemoplasmas. These differing responses to provisioning might therefore reflect distinct transmission processes. Predicting how provisioning alters host–pathogen interactions requires considering how both within-host processes and transmission modes respond to resource shifts

Ecological and evolutionary drivers of hemoplasma infection and bacterial genotype sharing in a Neotropical bat community

Most emerging pathogens can infect multiple species, underlining the importance of understanding the ecological and evolutionary factors that allow some hosts to harbour greater infection prevalence and share pathogens with other species. However, our understanding of pathogen jumps is based primarily around viruses, despite bacteria accounting for the greatest proportion of zoonoses. Because bacterial pathogens in bats (order Chiroptera) can have conservation and human health consequences, studies that examine the ecological and evolutionary drivers of bacterial prevalence and barriers to pathogen sharing are crucially needed. Here were studied haemotropic Mycoplasma spp. (i.e., haemoplasmas) across a speciesâ€rich bat community in Belize over two years. Across 469 bats spanning 33 species, half of individuals and twoâ€thirds of species were haemoplasma positive. Infection prevalence was higher for males and for species with larger body mass and colony sizes. Haemoplasmas displayed high genetic diversity (21 novel genotypes) and strong host specificity. Evolutionary patterns supported codivergence of bats and bacterial genotypes alongside phylogenetically constrained host shifts. Bat species centrality to the network of shared haemoplasma genotypes was phylogenetically clustered and unrelated to prevalence, further suggesting rare—but detectable—bacterial sharing between species. Our study highlights the importance of using fine phylogenetic scales when assessing host specificity and suggests phylogenetic similarity may play a key role in host shifts not only for viruses but also for bacteria. Such work more broadly contributes to increasing efforts to understand crossâ€species transmission and the epidemiological consequences of bacterial pathogens

Widespread Contribution of Gdf7 Lineage to Cerebellar Cell Types and Implications for Hedgehog-Driven Medulloblastoma Formation

The roof plate is a specialized embryonic midline tissue of the central nervous system that functions as a signaling center regulating dorsal neural patterning. In the developing hindbrain, roof plate cells express Gdf7 and previous genetic fate mapping studies showed that these cells contribute mostly to non-neural choroid plexus epithelium. We demonstrate here that constitutive activation of the Sonic hedgehog signaling pathway in the Gdf7 lineage invariably leads to medulloblastoma. Lineage tracing analysis reveals that Gdf7-lineage cells not only are a source of choroid plexus epithelial cells, but are also present in the cerebellar rhombic lip and contribute to a subset of cerebellar granule neuron precursors, the presumed cell-of-origin for Sonic hedgehog-driven medulloblastoma. We further show that Gdf7-lineage cells also contribute to multiple neuronal and glial cell types in the cerebellum, including glutamatergic granule neurons, unipolar brush cells, Purkinje neurons, GABAergic interneurons, Bergmann glial cells, and white matter astrocytes. These findings establish hindbrain roof plate as a novel source of diverse neural cell types in the cerebellum that is also susceptible to oncogenic transformation by deregulated Sonic hedgehog signaling

Повышение эффективности термообработки растительных материалов в трубчатых реакторах

In agriculture products of pyrolysis of plant materials in the form of waste of the main production can be applied as a source of heat and electric power. Besides, their use prevents ecological pollution of the soil and the atmosphere. Pyrolysis plants can be used for work with tubular reactors anywhere. Due to them farmers can dry grain, using waste heat of diesel generators, heatgenerators, boiler plants and receiving thus gaseous products, liquid and firm fractions. A technology based on cyclic and continuous plant mass movement by a piston in a pipe from a loading site to a place of unloading of a firm phase consistently through cameras of drying, pyrolysis, condensation of gaseous products. Exhaust furnace gases with a temperature up to 600 degrees Celsius are given countercurrent material movement from a power equipment. The gaseous, liquid and firm products from the pyrolysis camera are used for heat and electric power generation. Calculation of parameters of subdrying and pyrolysis cameras is necessary for effective and steady operation of the tubular reactor. The authors determined the speed of raw materials movement, and also duration of drying and pyrolysis in working chambers. An analysis of a simplified mathematical model of process was confirmed with results of experiments. Models of heat treatment of wet plant materials in tubular reactors are worked out on a basis of equality of speeds of material movement in the reactor and distribution of a temperature front in material on radius. The authors defined estimated characteristic for determination of tubular reactor productivity and size of heat, required for drying and pyrolysis.В сельском хозяйстве продукты пиролиза растительных материалов в виде отходов основного производства можно применять в качестве источника тепла и электроэнергии. Кроме того, их использование предотвращает экологическое загрязнение почвы и атмосферы. Пиролизные установки с трубчатыми реакторами пригодны для работы в любом хозяйстве. С их помощью можно сушить зерно, используя бросовое тепло дизель-генераторов, теплогенераторов, котельных и получая при этом газообразные продукты, жидкую и твердую фракции. Показали, что в основе технологии лежит циклично-непрерывное перемещение растительной массы поршнем внутри трубы от участка загрузки до места выгрузки твердой фазы последовательно через камеры сушки, пиролиза, конденсации газообразных продуктов. Отметили, что противотоком перемещению материала от энергетического оборудования подают отработанные топочные газы с температурой до 600 градусов Цельсия. Из камеры пиролиза отводят газообразные, жидкие и твердые продукты, используемые для выработки теплоты и электроэнергии. Выявили, что для эффективной и устойчивой работы трубчатого реактора необходим расчет параметров камер подсушки и пиролиза. Определили скорость перемещения сырья, а также продолжительность сушки и пиролиза в рабочих камерах. Подтвердили экспериментально результаты анализа упрощенной математической модели процесса. Предложили модели термообработки влажных растительных материалов в трубчатых реакторах на основе равенства скоростей перемещения материала в реакторе и распространения температурного фронта в материале по радиусу. Привели расчетные характеристики для вычисления производительности трубчатого реактора и величины теплоты, потребной для сушки и пиролиза

Strong signature of natural selection within an FHIT intron implicated in prostate cancer risk

Previously, a candidate gene linkage approach on brother pairs affected with prostate cancer identified a locus of prostate cancer susceptibility at D3S1234 within the fragile histidine triad gene (FHIT), a tumor suppressor that induces apoptosis. Subsequent association tests on 16 SNPs spanning approximately 381 kb surrounding D3S1234 in Americans of European descent revealed significant evidence of association for a single SNP within intron 5 of FHIT. In the current study, resequencing and genotyping within a 28.5 kb region surrounding this SNP further delineated the association with prostate cancer risk to a 15 kb region. Multiple SNPs in sequences under evolutionary constraint within intron 5 of FHIT defined several related haplotypes with an increased risk of prostate cancer in European-Americans. Strong associations were detected for a risk haplotype defined by SNPs 138543, 142413, and 152494 in all cases (Pearson's χ2 = 12.34, df 1, P = 0.00045) and for the homozygous risk haplotype defined by SNPs 144716, 142413, and 148444 in cases that shared 2 alleles identical by descent with their affected brothers (Pearson's χ2 = 11.50, df 1, P = 0.00070). In addition to highly conserved sequences encompassing SNPs 148444 and 152413, population studies revealed strong signatures of natural selection for a 1 kb window covering the SNP 144716 in two human populations, the European American (π = 0.0072, Tajima's D= 3.31, 14 SNPs) and the Japanese (π = 0.0049, Fay & Wu's H = 8.05, 14 SNPs), as well as in chimpanzees (Fay & Wu's H = 8.62, 12 SNPs). These results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer. © 2008 Ding et al

Влияние на миокард предварительной иммунизации анатоксинами в постреанимационном периоде

Objective: to study the impact of preimmunization with tetanus, diphtheria, and staphylococcal anatoxins on postresuscitative myocardial pathology.Materials and methods. Chronic (5-week) experiments were made on 51 mongrel dogs immunized with tetanus, diphtheria, and staphylococcal anatoxins. Acute one-stage blood loss served as a model of dying. The dogs were resuscitated using autoblood by the complex procedure described by V. A. Negovsky et al. Monitoring (electrophysiological studies of the myocardium and thermodilution) was performed in the postresuscitative period. A morphological study and electron microscopy were made.Results. The authors revealed the stimulating effect of tetanus ana-toxin on the cardiovascular system, the best survival after resuscitation, with less pronounced myocardial dystrophic changes; depressed cardiac performance after immunization with diphtheria anatoxin, significant morphological changes lowering postresuscitative animal survival; deteriorated sinoatrial conduction, transient myocardial dystrophic and necrobiotic changets after immunization with staphylococcal anatoxin.Conclusion. Preimmunization with tetanus ana-toxin has a myocardial stimulating impact in the postresuscitative period, improves animal survival; immunization with diphtheria anatoxin deteriorates the recovery of cardiac performance, and negatively affects postresuscitative survival; immunization with staphylococcal anatoxin causes transient myocardial pathomorphological changes, without negatively affecting the survival rates after resuscitation. Цель. Изучить влияние предварительной иммунизации столбнячным, дифтерийным и стафилококковым анатоксинами на постреанимационную патологию миокарда.Материалы и методы. Хронические эксперименты (5 недель) проведены на 51 беспородных собаках, иммунизированных столбнячным, дифтерийным и стафилококковым анатоксинами. Моделью умирания служила острая одномоментная кровопотеря. Оживление собак проводилось аутогенной кровью по комплексной методике В. А. Неговского с соавт. В постреанимационном периоде проводили мониторинг (электрофизиологические методы исследования миокарда и термодилюция). Проводилось морфологическое исследование, электронная микроскопия.Результаты. Выявлено стимулирующее влияние столбнячного анатоксина на сердечно-сосудистую систему, наилучшая выживаемость после реанимации, при менее выраженных дистрофических изменениях миокарда; угнетение сердечной деятельности, при иммунизации дифтерийным анатоксином, выраженные морфологические изменения, снижающие выживаемость животных после реанимации; ухудшение синоатриальной проводимости, преходящие дистрофические и некробиотические изменения в миокарде, при иммунизации стафилококковым анатоксином.Заключение. Предварительная иммунизация столбнячным анатоксином оказывает стимулирующее действие на миокард в постреанимационном периоде, улучшает выживаемость животных, иммунизация дифтерийным анатоксином ухудшает восстановление сердечной деятельности и отрицательно влияет на выживаемость после реанимации, при иммунизации стафилококковым анатоксином, отмечены преходящие патоморфологические изменения в миокарде, не влияющие отрицательно на выживаемость после реанимации.

Active medulloblastoma enhancers reveal subgroup-specific cellular origins

Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Here, using H3K27ac and BRD4 chromatin immunoprecipitation followed by sequencing (ChIP-seq) coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-seq, that is responsible for subgroup divergence, and implicates candidate cells of origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins

Roof Plate-Derived Radial Glial-like Cells Support Developmental Growth of Rapidly Adapting Mechanoreceptor Ascending Axons

Spinal cord longitudinal axons comprise some of the longest axons in our body. However, mechanisms that drive this extra long-distance axonal growth are largely unclear. We found that ascending axons of rapidly adapting (RA) mechanoreceptors closely abut a previously undescribed population of roof plate-derived radial glial-like cells (RGLCs) in the spinal cord dorsal column, which form a network of processes enriched with growth-promoting factors. In dreher mutant mice that lack RGLCs, the lengths of ascending RA mechanoreceptor axon branches are specifically reduced, whereas their descending and collateral branches, and other dorsal column and sensory pathways, are largely unaffected. Because the number and intrinsic growth ability of RA mechanoreceptors are normal in dreher mice, our data suggest that RGLCs provide critical non-cell autonomous growth support for the ascending axons of RA mechanoreceptors. Together, our work identifies a developmental mechanism specifically required for long-range spinal cord longitudinal axons.This work was supported by the NIH (1R01NS083702 and R01NS094224 to W.L., R01NS080390 to K.J.M., R01 NS093009 to V.V.C., and F31-NS100325-01A1 and T32GM07517 to K.K.), and the Klingenstein-Simons Fellowship Awards in the Neurosciences to W.L.Peer reviewe

Genotypic resistance testing in HIV by arrayed primer extension

The analysis of mutations that are associated with the occurrence of drug resistance is important for monitoring the antiretroviral therapy of patients infected with human immunodeficiency virus (HIV). Here, we describe the establishment and successful application of Arrayed Primer Extension (APEX) for genotypic resistance testing in HIV as a rapid and economical alternative to standard sequencing. The assay is based on an array of oligonucleotide primers that are immobilised via their 5′-ends. Upon hybridisation of template DNA, a primer extension reaction is performed in the presence of the four dideoxynucleotides, each labelled with a distinct fluorophore. The inserted label immediately indicates the sequence at the respective position. Any mutation changes the colour pattern. We designed a microarray for the analysis of 26 and 33 codons in the HIV protease and reverse transcriptase, respectively, which are of special interest with respect to drug resistance. The enormous genome variability of HIV represents a big challenge for genotypic resistance tests, which include a hybridisation step, both in terms of specificity and probe numbers. The use of degenerated oligonucleotides resulted in a significant reduction in the number of primers needed. For validation, DNA of 94 and 48 patients that exhibited resistance to inhibitors of HIV protease and reverse transcriptase, respectively, were analysed. The validation included HIV subtype B, prevalent in industrialised countries, as well as non-subtype B samples that are more common elsewhere