222 research outputs found
Livestock abundance predicts vampire bat demography, immune profiles, and bacterial infection risk
Human activities create novel food resources that can alter wildlifeβpathogen 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 hostβpathogen 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 speciesΓ’β¬rich bat community in Belize over two years. Across 469 bats spanning 33 species, half of individuals and twoΓ’β¬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 rareΓ’β¬βbut detectableΓ’β¬βbacterial 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 crossΓ’β¬species transmission and the epidemiological consequences of bacterial pathogens
ΠΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠ΅ΡΠΌΠΎΠΎΠ±ΡΠ°Π±ΠΎΡΠΊΠΈ ΡΠ°ΡΡΠΈΡΠ΅Π»ΡΠ½ΡΡ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»ΠΎΠ² Π² ΡΡΡΠ±ΡΠ°ΡΡΡ ΡΠ΅Π°ΠΊΡΠΎΡΠ°Ρ
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.Π ΡΠ΅Π»ΡΡΠΊΠΎΠΌ Ρ
ΠΎΠ·ΡΠΉΡΡΠ²Π΅ ΠΏΡΠΎΠ΄ΡΠΊΡΡ ΠΏΠΈΡΠΎΠ»ΠΈΠ·Π° ΡΠ°ΡΡΠΈΡΠ΅Π»ΡΠ½ΡΡ
ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»ΠΎΠ² Π² Π²ΠΈΠ΄Π΅ ΠΎΡΡ
ΠΎΠ΄ΠΎΠ² ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΡΡΠ²Π° ΠΌΠΎΠΆΠ½ΠΎ ΠΏΡΠΈΠΌΠ΅Π½ΡΡΡ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΈΡΡΠΎΡΠ½ΠΈΠΊΠ° ΡΠ΅ΠΏΠ»Π° ΠΈ ΡΠ»Π΅ΠΊΡΡΠΎΡΠ½Π΅ΡΠ³ΠΈΠΈ. ΠΡΠΎΠΌΠ΅ ΡΠΎΠ³ΠΎ, ΠΈΡ
ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΡΠ΅Π΄ΠΎΡΠ²ΡΠ°ΡΠ°Π΅Ρ ΡΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π·Π°Π³ΡΡΠ·Π½Π΅Π½ΠΈΠ΅ ΠΏΠΎΡΠ²Ρ ΠΈ Π°ΡΠΌΠΎΡΡΠ΅ΡΡ. ΠΠΈΡΠΎΠ»ΠΈΠ·Π½ΡΠ΅ ΡΡΡΠ°Π½ΠΎΠ²ΠΊΠΈ Ρ ΡΡΡΠ±ΡΠ°ΡΡΠΌΠΈ ΡΠ΅Π°ΠΊΡΠΎΡΠ°ΠΌΠΈ ΠΏΡΠΈΠ³ΠΎΠ΄Π½Ρ Π΄Π»Ρ ΡΠ°Π±ΠΎΡΡ Π² Π»ΡΠ±ΠΎΠΌ Ρ
ΠΎΠ·ΡΠΉΡΡΠ²Π΅. Π‘ ΠΈΡ
ΠΏΠΎΠΌΠΎΡΡΡ ΠΌΠΎΠΆΠ½ΠΎ ΡΡΡΠΈΡΡ Π·Π΅ΡΠ½ΠΎ, ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΡ Π±ΡΠΎΡΠΎΠ²ΠΎΠ΅ ΡΠ΅ΠΏΠ»ΠΎ Π΄ΠΈΠ·Π΅Π»Ρ-Π³Π΅Π½Π΅ΡΠ°ΡΠΎΡΠΎΠ², ΡΠ΅ΠΏΠ»ΠΎΠ³Π΅Π½Π΅ΡΠ°ΡΠΎΡΠΎΠ², ΠΊΠΎΡΠ΅Π»ΡΠ½ΡΡ
ΠΈ ΠΏΠΎΠ»ΡΡΠ°Ρ ΠΏΡΠΈ ΡΡΠΎΠΌ Π³Π°Π·ΠΎΠΎΠ±ΡΠ°Π·Π½ΡΠ΅ ΠΏΡΠΎΠ΄ΡΠΊΡΡ, ΠΆΠΈΠ΄ΠΊΡΡ ΠΈ ΡΠ²Π΅ΡΠ΄ΡΡ ΡΡΠ°ΠΊΡΠΈΠΈ. ΠΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ Π² ΠΎΡΠ½ΠΎΠ²Π΅ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ Π»Π΅ΠΆΠΈΡ ΡΠΈΠΊΠ»ΠΈΡΠ½ΠΎ-Π½Π΅ΠΏΡΠ΅ΡΡΠ²Π½ΠΎΠ΅ ΠΏΠ΅ΡΠ΅ΠΌΠ΅ΡΠ΅Π½ΠΈΠ΅ ΡΠ°ΡΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ ΠΌΠ°ΡΡΡ ΠΏΠΎΡΡΠ½Π΅ΠΌ Π²Π½ΡΡΡΠΈ ΡΡΡΠ±Ρ ΠΎΡ ΡΡΠ°ΡΡΠΊΠ° Π·Π°Π³ΡΡΠ·ΠΊΠΈ Π΄ΠΎ ΠΌΠ΅ΡΡΠ° Π²ΡΠ³ΡΡΠ·ΠΊΠΈ ΡΠ²Π΅ΡΠ΄ΠΎΠΉ ΡΠ°Π·Ρ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎ ΡΠ΅ΡΠ΅Π· ΠΊΠ°ΠΌΠ΅ΡΡ ΡΡΡΠΊΠΈ, ΠΏΠΈΡΠΎΠ»ΠΈΠ·Π°, ΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΠΈΠΈ Π³Π°Π·ΠΎΠΎΠ±ΡΠ°Π·Π½ΡΡ
ΠΏΡΠΎΠ΄ΡΠΊΡΠΎΠ². ΠΡΠΌΠ΅ΡΠΈΠ»ΠΈ, ΡΡΠΎ ΠΏΡΠΎΡΠΈΠ²ΠΎΡΠΎΠΊΠΎΠΌ ΠΏΠ΅ΡΠ΅ΠΌΠ΅ΡΠ΅Π½ΠΈΡ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π° ΠΎΡ ΡΠ½Π΅ΡΠ³Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΎΠ±ΠΎΡΡΠ΄ΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎΠ΄Π°ΡΡ ΠΎΡΡΠ°Π±ΠΎΡΠ°Π½Π½ΡΠ΅ ΡΠΎΠΏΠΎΡΠ½ΡΠ΅ Π³Π°Π·Ρ Ρ ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠΎΠΉ Π΄ΠΎ 600 Π³ΡΠ°Π΄ΡΡΠΎΠ² Π¦Π΅Π»ΡΡΠΈΡ. ΠΠ· ΠΊΠ°ΠΌΠ΅ΡΡ ΠΏΠΈΡΠΎΠ»ΠΈΠ·Π° ΠΎΡΠ²ΠΎΠ΄ΡΡ Π³Π°Π·ΠΎΠΎΠ±ΡΠ°Π·Π½ΡΠ΅, ΠΆΠΈΠ΄ΠΊΠΈΠ΅ ΠΈ ΡΠ²Π΅ΡΠ΄ΡΠ΅ ΠΏΡΠΎΠ΄ΡΠΊΡΡ, ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΠ΅ Π΄Π»Ρ Π²ΡΡΠ°Π±ΠΎΡΠΊΠΈ ΡΠ΅ΠΏΠ»ΠΎΡΡ ΠΈ ΡΠ»Π΅ΠΊΡΡΠΎΡΠ½Π΅ΡΠ³ΠΈΠΈ. ΠΡΡΠ²ΠΈΠ»ΠΈ, ΡΡΠΎ Π΄Π»Ρ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠΉ ΠΈ ΡΡΡΠΎΠΉΡΠΈΠ²ΠΎΠΉ ΡΠ°Π±ΠΎΡΡ ΡΡΡΠ±ΡΠ°ΡΠΎΠ³ΠΎ ΡΠ΅Π°ΠΊΡΠΎΡΠ° Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌ ΡΠ°ΡΡΠ΅Ρ ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΠΎΠ² ΠΊΠ°ΠΌΠ΅Ρ ΠΏΠΎΠ΄ΡΡΡΠΊΠΈ ΠΈ ΠΏΠΈΡΠΎΠ»ΠΈΠ·Π°. ΠΠΏΡΠ΅Π΄Π΅Π»ΠΈΠ»ΠΈ ΡΠΊΠΎΡΠΎΡΡΡ ΠΏΠ΅ΡΠ΅ΠΌΠ΅ΡΠ΅Π½ΠΈΡ ΡΡΡΡΡ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΡΡΡΠΊΠΈ ΠΈ ΠΏΠΈΡΠΎΠ»ΠΈΠ·Π° Π² ΡΠ°Π±ΠΎΡΠΈΡ
ΠΊΠ°ΠΌΠ΅ΡΠ°Ρ
. ΠΠΎΠ΄ΡΠ²Π΅ΡΠ΄ΠΈΠ»ΠΈ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ Π°Π½Π°Π»ΠΈΠ·Π° ΡΠΏΡΠΎΡΠ΅Π½Π½ΠΎΠΉ ΠΌΠ°ΡΠ΅ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΏΡΠΎΡΠ΅ΡΡΠ°. ΠΡΠ΅Π΄Π»ΠΎΠΆΠΈΠ»ΠΈ ΠΌΠΎΠ΄Π΅Π»ΠΈ ΡΠ΅ΡΠΌΠΎΠΎΠ±ΡΠ°Π±ΠΎΡΠΊΠΈ Π²Π»Π°ΠΆΠ½ΡΡ
ΡΠ°ΡΡΠΈΡΠ΅Π»ΡΠ½ΡΡ
ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»ΠΎΠ² Π² ΡΡΡΠ±ΡΠ°ΡΡΡ
ΡΠ΅Π°ΠΊΡΠΎΡΠ°Ρ
Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΡΠ°Π²Π΅Π½ΡΡΠ²Π° ΡΠΊΠΎΡΠΎΡΡΠ΅ΠΉ ΠΏΠ΅ΡΠ΅ΠΌΠ΅ΡΠ΅Π½ΠΈΡ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π° Π² ΡΠ΅Π°ΠΊΡΠΎΡΠ΅ ΠΈ ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½ΠΈΡ ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ½ΠΎΠ³ΠΎ ΡΡΠΎΠ½ΡΠ° Π² ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π΅ ΠΏΠΎ ΡΠ°Π΄ΠΈΡΡΡ. ΠΡΠΈΠ²Π΅Π»ΠΈ ΡΠ°ΡΡΠ΅ΡΠ½ΡΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ Π΄Π»Ρ Π²ΡΡΠΈΡΠ»Π΅Π½ΠΈΡ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΡΡΡΠ±ΡΠ°ΡΠΎΠ³ΠΎ ΡΠ΅Π°ΠΊΡΠΎΡΠ° ΠΈ Π²Π΅Π»ΠΈΡΠΈΠ½Ρ ΡΠ΅ΠΏΠ»ΠΎΡΡ, ΠΏΠΎΡΡΠ΅Π±Π½ΠΎΠΉ Π΄Π»Ρ ΡΡΡΠΊΠΈ ΠΈ ΠΏΠΈΡΠΎΠ»ΠΈΠ·Π°
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
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 Ο2 = 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 Ο2 = 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 (Ο = 0.0072, Tajima's D= 3.31, 14 SNPs) and the Japanese (Ο = 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. Β© 2008 Ding et al
ΠΠ»ΠΈΡΠ½ΠΈΠ΅ Π½Π° ΠΌΠΈΠΎΠΊΠ°ΡΠ΄ ΠΏΡΠ΅Π΄Π²Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ ΠΈΠΌΠΌΡΠ½ΠΈΠ·Π°ΡΠΈΠΈ Π°Π½Π°ΡΠΎΠΊΡΠΈΠ½Π°ΠΌΠΈ Π² ΠΏΠΎΡΡΡΠ΅Π°Π½ΠΈΠΌΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΌ ΠΏΠ΅ΡΠΈΠΎΠ΄Π΅
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.Β Π¦Π΅Π»Ρ. ΠΠ·ΡΡΠΈΡΡ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΠΏΡΠ΅Π΄Π²Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ ΠΈΠΌΠΌΡΠ½ΠΈΠ·Π°ΡΠΈΠΈ ΡΡΠΎΠ»Π±Π½ΡΡΠ½ΡΠΌ, Π΄ΠΈΡΡΠ΅ΡΠΈΠΉΠ½ΡΠΌ ΠΈ ΡΡΠ°ΡΠΈΠ»ΠΎΠΊΠΎΠΊΠΊΠΎΠ²ΡΠΌ Π°Π½Π°ΡΠΎΠΊΡΠΈΠ½Π°ΠΌΠΈ Π½Π° ΠΏΠΎΡΡΡΠ΅Π°Π½ΠΈΠΌΠ°ΡΠΈΠΎΠ½Π½ΡΡ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π°.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. Π₯ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΡ (5 Π½Π΅Π΄Π΅Π»Ρ) ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Ρ Π½Π° 51 Π±Π΅ΡΠΏΠΎΡΠΎΠ΄Π½ΡΡ
ΡΠΎΠ±Π°ΠΊΠ°Ρ
, ΠΈΠΌΠΌΡΠ½ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΡΠΎΠ»Π±Π½ΡΡΠ½ΡΠΌ, Π΄ΠΈΡΡΠ΅ΡΠΈΠΉΠ½ΡΠΌ ΠΈ ΡΡΠ°ΡΠΈΠ»ΠΎΠΊΠΎΠΊΠΊΠΎΠ²ΡΠΌ Π°Π½Π°ΡΠΎΠΊΡΠΈΠ½Π°ΠΌΠΈ. ΠΠΎΠ΄Π΅Π»ΡΡ ΡΠΌΠΈΡΠ°Π½ΠΈΡ ΡΠ»ΡΠΆΠΈΠ»Π° ΠΎΡΡΡΠ°Ρ ΠΎΠ΄Π½ΠΎΠΌΠΎΠΌΠ΅Π½ΡΠ½Π°Ρ ΠΊΡΠΎΠ²ΠΎΠΏΠΎΡΠ΅ΡΡ. ΠΠΆΠΈΠ²Π»Π΅Π½ΠΈΠ΅ ΡΠΎΠ±Π°ΠΊ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΎΡΡ Π°ΡΡΠΎΠ³Π΅Π½Π½ΠΎΠΉ ΠΊΡΠΎΠ²ΡΡ ΠΏΠΎ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½ΠΎΠΉ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠ΅ Π. Π. ΠΠ΅Π³ΠΎΠ²ΡΠΊΠΎΠ³ΠΎ Ρ ΡΠΎΠ°Π²Ρ. Π ΠΏΠΎΡΡΡΠ΅Π°Π½ΠΈΠΌΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΌ ΠΏΠ΅ΡΠΈΠΎΠ΄Π΅ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ ΠΌΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³ (ΡΠ»Π΅ΠΊΡΡΠΎΡΠΈΠ·ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π° ΠΈ ΡΠ΅ΡΠΌΠΎΠ΄ΠΈΠ»ΡΡΠΈΡ). ΠΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΎΡΡ ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅, ΡΠ»Π΅ΠΊΡΡΠΎΠ½Π½Π°Ρ ΠΌΠΈΠΊΡΠΎΡΠΊΠΎΠΏΠΈΡ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΡΡΠ²Π»Π΅Π½ΠΎ ΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠ΅Π΅ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΡΡΠΎΠ»Π±Π½ΡΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°ΡΠΎΠΊΡΠΈΠ½Π° Π½Π° ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎ-ΡΠΎΡΡΠ΄ΠΈΡΡΡΡ ΡΠΈΡΡΠ΅ΠΌΡ, Π½Π°ΠΈΠ»ΡΡΡΠ°Ρ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΡ ΠΏΠΎΡΠ»Π΅ ΡΠ΅Π°Π½ΠΈΠΌΠ°ΡΠΈΠΈ, ΠΏΡΠΈ ΠΌΠ΅Π½Π΅Π΅ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΡ
Π΄ΠΈΡΡΡΠΎΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡΡ
ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π°; ΡΠ³Π½Π΅ΡΠ΅Π½ΠΈΠ΅ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎΠΉ Π΄Π΅ΡΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ, ΠΏΡΠΈ ΠΈΠΌΠΌΡΠ½ΠΈΠ·Π°ΡΠΈΠΈ Π΄ΠΈΡΡΠ΅ΡΠΈΠΉΠ½ΡΠΌ Π°Π½Π°ΡΠΎΠΊΡΠΈΠ½ΠΎΠΌ, Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠ΅ ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ, ΡΠ½ΠΈΠΆΠ°ΡΡΠΈΠ΅ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΡ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
ΠΏΠΎΡΠ»Π΅ ΡΠ΅Π°Π½ΠΈΠΌΠ°ΡΠΈΠΈ; ΡΡ
ΡΠ΄ΡΠ΅Π½ΠΈΠ΅ ΡΠΈΠ½ΠΎΠ°ΡΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠΌΠΎΡΡΠΈ, ΠΏΡΠ΅Ρ
ΠΎΠ΄ΡΡΠΈΠ΅ Π΄ΠΈΡΡΡΠΎΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈ Π½Π΅ΠΊΡΠΎΠ±ΠΈΠΎΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ Π² ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π΅, ΠΏΡΠΈ ΠΈΠΌΠΌΡΠ½ΠΈΠ·Π°ΡΠΈΠΈ ΡΡΠ°ΡΠΈΠ»ΠΎΠΊΠΎΠΊΠΊΠΎΠ²ΡΠΌ Π°Π½Π°ΡΠΎΠΊΡΠΈΠ½ΠΎΠΌ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΡΠ΅Π΄Π²Π°ΡΠΈΡΠ΅Π»ΡΠ½Π°Ρ ΠΈΠΌΠΌΡΠ½ΠΈΠ·Π°ΡΠΈΡ ΡΡΠΎΠ»Π±Π½ΡΡΠ½ΡΠΌ Π°Π½Π°ΡΠΎΠΊΡΠΈΠ½ΠΎΠΌ ΠΎΠΊΠ°Π·ΡΠ²Π°Π΅Ρ ΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠ΅Π΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Π½Π° ΠΌΠΈΠΎΠΊΠ°ΡΠ΄ Π² ΠΏΠΎΡΡΡΠ΅Π°Π½ΠΈΠΌΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΌ ΠΏΠ΅ΡΠΈΠΎΠ΄Π΅, ΡΠ»ΡΡΡΠ°Π΅Ρ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΡ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
, ΠΈΠΌΠΌΡΠ½ΠΈΠ·Π°ΡΠΈΡ Π΄ΠΈΡΡΠ΅ΡΠΈΠΉΠ½ΡΠΌ Π°Π½Π°ΡΠΎΠΊΡΠΈΠ½ΠΎΠΌ ΡΡ
ΡΠ΄ΡΠ°Π΅Ρ Π²ΠΎΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΈΠ΅ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎΠΉ Π΄Π΅ΡΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΈ ΠΎΡΡΠΈΡΠ°ΡΠ΅Π»ΡΠ½ΠΎ Π²Π»ΠΈΡΠ΅Ρ Π½Π° Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΡ ΠΏΠΎΡΠ»Π΅ ΡΠ΅Π°Π½ΠΈΠΌΠ°ΡΠΈΠΈ, ΠΏΡΠΈ ΠΈΠΌΠΌΡΠ½ΠΈΠ·Π°ΡΠΈΠΈ ΡΡΠ°ΡΠΈΠ»ΠΎΠΊΠΎΠΊΠΊΠΎΠ²ΡΠΌ Π°Π½Π°ΡΠΎΠΊΡΠΈΠ½ΠΎΠΌ, ΠΎΡΠΌΠ΅ΡΠ΅Π½Ρ ΠΏΡΠ΅Ρ
ΠΎΠ΄ΡΡΠΈΠ΅ ΠΏΠ°ΡΠΎΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ Π² ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π΅, Π½Π΅ Π²Π»ΠΈΡΡΡΠΈΠ΅ ΠΎΡΡΠΈΡΠ°ΡΠ΅Π»ΡΠ½ΠΎ Π½Π° Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΡ ΠΏΠΎΡΠ»Π΅ ΡΠ΅Π°Π½ΠΈΠΌΠ°ΡΠΈΠΈ.
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 5β²-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
- β¦