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Kaplan Buck opublikował 1 rok, 8 miesięcy temu
Most α-Gal-sensitized individuals develop IgE specific against this glycan, but only a small fraction develop the AGS. This review summarizes our current understanding of ATR and its impact on the continuum α-Gal sensitization, allergy, and the AGS. We propose that the α-Gal-specific IgE response in humans is an evolutionary adaptation associated with ATR and allergic klendusity with the trade-off of developing AGS.Empathy for pain involves sensory and visceromotor brain regions relevant also in the first-person pain experience. Focusing on brain activations associated to vicarious experiences of pain triggered by artistic or non-artistic images, the present study aims to investigate common and distinct brain activation patterns associated to these two vicarious experiences of pain and to assess whether empathy for pain brain regions contribute to the formation of an aesthetic judgment in non-art expert observers. Artistic and non-artistic facial expressions (painful and neutral) were shown to participants inside the scanner and then aesthetically rated in a subsequent behavioural session. Results showed that empathy for pain brain regions (i.e., bilateral insular cortex, posterior sector of the anterior cingulate cortex and the anterior portion of the middle cingulate cortex) and bilateral inferior frontal gyrus are commonly activated by artistic and non-artistic painful facial expressions. For the artistic representation of pain, the activity recorded in these regions directly correlated with participants’ aesthetic judgment. Results also showed the distinct activation of a large cluster located in the PCC/precuneus for non-artistic stimuli. This study suggests that non-beauty specific mechanisms such as empathy for pain are crucial components of the aesthetic experience of artworks.Tails are versatile structures with diverse forms and functions across vertebrates. They are involved in almost all behaviors critical to survival including locomotion, feeding, and predator avoidance. Although the tail’s role in locomotion and stability has been widely studied, its role in prey capture is relatively unknown. Lizards are an ideal system to examine the tail’s impact on prey capture as most are capable of autotomizing, or dropping, their tail in response to predation and intraspecific competition. Tail autotomy can lower reproduction, decrease locomotor performance, impart instability during jumping, and decrease social status. Desert banded geckos (Coleonyx variegatus) frequently capture evasive prey in nature and appear to use their tail during strikes. However, it is unclear if these tail movements are important for the strike itself, or if they simply draw attention to that part of the body. We used high-speed 3D videography to quantify prey capture performance and kinematics of C. variegatredation across a wide variety of species and ecological niches.Inadequate diagnostics compromise cancer care across lower- and middle-income countries (LMICs). We hypothesized that an inexpensive gene expression assay using paraffin-embedded biopsy specimens from LMICs could distinguish lymphoma subtypes without pathologist input. We reviewed all biopsy specimens obtained at the Instituto de Cancerología y Hospital Dr. Bernardo Del Valle in Guatemala City between 2006 and 2018 for suspicion of lymphoma. Diagnoses were established based on the World Health Organization classification and then binned into 9 categories nonmalignant, aggressive B-cell, diffuse large B-cell, follicular, Hodgkin, mantle cell, marginal zone, natural killer/T-cell, or mature T-cell lymphoma. We established a chemical ligation probe-based assay (CLPA) that quantifies expression of 37 genes by capillary electrophoresis with reagent/consumable cost of approximately $10/sample. To assign bins based on gene expression, 13 models were evaluated as candidate base learners, and class probabilities from each model were then used as predictors in an extreme gradient boosting super learner. Cases with call probabilities less then 60% were classified as indeterminate. Four (2%) of 194 biopsy specimens in storage less then 3 years experienced assay failure. Diagnostic samples were divided into 70% (n = 397) training and 30% (n = 163) validation cohorts. Overall accuracy for the validation cohort was 86% (95% confidence interval [CI] 80%-91%). After excluding 28 (17%) indeterminate calls, accuracy increased to 94% (95% CI 89%-97%). Concordance was 97% for a set of high-probability calls (n = 37) assayed by CLPA in both the United States and Guatemala. Accuracy for a cohort of relapsed/refractory biopsy specimens (n = 39) was 79% and 88%, respectively, after excluding indeterminate cases. Machine-learning analysis of gene expression accurately classifies paraffin-embedded lymphoma biopsy specimens and could transform diagnosis in LMICs.Adaptive radiations are characterized by the diversification and ecological differentiation of species, and replicated cases of this process provide natural experiments for understanding the repeatability and pace of molecular evolution. During adaptive radiation, genes related to ecological specialization may be subject to recurrent positive directional selection. However, it is not clear to what extent patterns of lineage-specific ecological specialization (including phenotypic convergence) are correlated with shared signatures of molecular evolution. To test this, we sequenced whole exomes from a phylogenetically dispersed sample of 38 murine rodent species, a group characterized by multiple, nested adaptive radiations comprising extensive ecological and phenotypic diversity. We found that genes associated with immunity, reproduction, diet, digestion, and taste have been subject to pervasive positive selection during the diversification of murine rodents. We also found a significant correlation between genome-wide positive selection and dietary specialization, with a higher proportion of positively selected codon sites in derived dietary forms (i.e., carnivores and herbivores) than in ancestral forms (i.e., omnivores). Despite striking convergent evolution of skull morphology and dentition in two distantly related worm-eating specialists, we did not detect more genes with shared signatures of positive or relaxed selection than in a nonconvergent species comparison. Although a small number of the genes we detected can be incidentally linked to craniofacial morphology or diet, protein-coding regions are unlikely to be the primary genetic basis of this complex convergent phenotype. Our results suggest a link between positive selection and derived ecological phenotypes, and highlight specific genes and general functional categories that may have played an integral role in the extensive and rapid diversification of murine rodents.Gammaproteobacteria from the family Endozoicomonadaceae have emerged as widespread associates of dense marine animal communities. Their abundance in coral reefs involves symbiotic relationships and possibly host nutrition. We explored functions encoded in the genome of an uncultured Endozoicomonadaceae 'Candidatus Acestibacter aggregatus’ that lives inside gill cells of large Acesta excavata clams in deep-water coral reefs off mid-Norway. The dominance and deep branching lineage of this symbiont was confirmed using 16S rRNA gene sequencing and phylogenomic analysis from shotgun sequencing data. The 4.5 Mb genome binned in this study has a low GC content of 35% and is enriched in transposon and chaperone gene annotations indicating ongoing adaptation. Genes encoding functions potentially involved with the symbiosis include ankyrins, repeat in toxins, secretion and nutritional systems. Complete pathways were identified for the synthesis of eleven amino acids and six B-vitamins. A minimal chitinolytic machinery was indicated from a glycosyl hydrolase GH18 and a lytic polysaccharide monooxygenase LPMO10. Expression of the latter was confirmed using proteomics. Signal peptides for secretion were identified for six polysaccharide degrading enzymes, ten proteases and three lipases. Our results suggest a nutritional symbiosis fuelled by enzymatic products from extracellular degradation processes.
Inflammatory bowel diseases (IBD) are rising in prevalence and are associated with high health care costs. We estimated trends in U.S. health care spending in patients with IBD between 1996 and 2016.
We used data on national health care spending developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project. We estimated corresponding U.S. age-specific prevalence of IBD from the Global Burden of Diseases Study. From these 2 sources, we estimated prevalence-adjusted, temporal trends in U.S. health care spending in patients with IBD, stratified by age groups (<20 years, 20-44 years, 45-64 years, ≥65 years) and by type of care (ambulatory, inpatient, emergency department [ED], pharmaceutical prescriptions, and nursing care), using joinpoint regression, expressed as an annual percentage change (APC) with 95% confidence intervals.
Overall, annual U.S. health care spending on IBD increased from $6.4 billion (95% confidence interval, 5.7-7.4) in 1996 to $25.4 billion (95% confidence interval, 22.4-28.7) in 2016, corresponding to a per patient increase in annual spending from $5714 to $14,033. Substantial increases in per patient spending on IBD were observed in patients aged ≥45 years. Between 2011 and 2016, inpatient and ED care accounted for 55.8% of total spending and pharmaceuticals accounted for 19.9%, with variation across age groups (inpatient/ED vs pharmaceuticals ages ≥65 years, 57.6% vs 11.2%; ages 45-64 years, 49.5% vs 26.9%; ages 20-44 years, 59.2% vs 23.6%).
Even after adjusting for rising prevalence, U.S. health care spending on IBD continues to progressively increase, primarily in middle-aged and older adults, with unplanned health care utilization accounting for the majority of costs.
Even after adjusting for rising prevalence, U.S. health care spending on IBD continues to progressively increase, primarily in middle-aged and older adults, with unplanned health care utilization accounting for the majority of costs.Regulation of autophagy in neurons remains unclear. In this issue, Kulkarni et al. (2021. J. Cell Biol.https//doi.org/10.1083/jcb.202002084) show with elegant live imaging that in dendrites, but not in axons, autophagosome motility and function is regulated by synaptic activity.Induction of long-term potentiation (LTP) in excitatory neurons triggers a large transient increase in the volume of dendritic spines followed by decays to sustained size expansion, a process termed structural LTP (sLTP) that contributes to the cellular basis of learning and memory. Although mechanisms regulating the early and sustained phases of sLTP have been studied intensively, how the acute spine enlargement immediately after LTP stimulation is achieved remains elusive. Here, we report that endophilin A1 orchestrates membrane dynamics with actin polymerization to initiate spine enlargement in NMDAR-mediated LTP. Upon LTP induction, Ca2+/calmodulin enhances binding of endophilin A1 to both membrane and p140Cap, a cytoskeletal regulator. Consequently, endophilin A1 rapidly localizes to the plasma membrane and recruits p140Cap to promote local actin polymerization, leading to spine head expansion. Moreover, its molecular functions in activity-induced rapid spine growth are required for LTP and long-term memory.


