Explore the vast range of titles available.

Ionotropic glutamate receptor (iGIuR) family members are integrated into supramolecular complexes that modulate their location and function at excitatory synapses. However, a lack of structural information beyond isolated receptors or fragments thereof currently limits the mechanistic understanding of physiological iGIuR signaling. Here, we report structural and functional analyses of the prototypical molecular bridge linking postsynaptic iGIuR δ2 (GIuD2) and presynaptic β-neurexin 1 (β-NRX1) via CbIn1, a C1q-like synaptic organizer. We show how CbIn1 hexamers \"anchor\" GIuD2 amino-terminal domain dimers to monomeric β-NRX1. This arrangement promotes synaptogenesis and is essential for D-serine–dependent GIuD2 signaling in vivo, which underlies long-term depression of cerebellar parallel fiber–Purkinje cell (PF-PC) synapses and motor coordination in developing mice. These results lead to a model where protein and small-molecule ligands synergistically control synaptic iGIuR function.

Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form. This physical transformation of neurons is facilitated by the engulfment and degradation of axonal branches and synapses by surrounding glial cells, including microglia and astrocytes. However, the small size of phagocytic organelles and the complex, highly ramified morphology of glia have made it difficult to define the contribution of these and other glial cell types to this crucial process. Here, we used large-scale, serial section transmission electron microscopy (TEM) with computational volume segmentation to reconstruct the complete 3D morphologies of distinct glial types in the mouse visual cortex, providing unprecedented resolution of their morphology and composition. Unexpectedly, we discovered that the fine processes of oligodendrocyte precursor cells (OPCs), a population of abundant, highly dynamic glial progenitors, frequently surrounded small branches of axons. Numerous phagosomes and phagolysosomes (PLs) containing fragments of axons and vesicular structures were present inside their processes, suggesting that OPCs engage in axon pruning. Single-nucleus RNA sequencing from the developing mouse cortex revealed that OPCs express key phagocytic genes at this stage, as well as neuronal transcripts, consistent with active axon engulfment. Although microglia are thought to be responsible for the majority of synaptic pruning and structural refinement, PLs were ten times more abundant in OPCs than in microglia at this stage, and these structures were markedly less abundant in newly generated oligodendrocytes, suggesting that OPCs contribute substantially to the refinement of neuronal circuits during cortical development.

Histoplasmosis is a systemic fungal disease caused by the pathogen Histoplasma spp. that results in significant morbidity and mortality in persons with HIV/AIDS and can also affect immunocompetent individuals. Although some PCR and antigen-detection assays have been developed, conventional diagnosis has largely relied on culture, which can take weeks. Our aim was to provide a proof of principle for rationally designing and standardizing PCR assays based on Histoplasma-specific genomic sequences. Via automated comparisons of aligned genome contigs/scaffolds and gene (sub)sequences, we identified protein-coding genes that are present in existing sequences of Histoplasma strains but not in other genera. Two of the genes, PPK and CFP4, were used for designing primer sets for conventional and real-time PCR assays. Both resulted in a 100% analytical specificity in vitro and detected 62/62 H. capsulatum isolates using purified DNA. We also obtained positive detections of 2/2 confirmed H. capsulatum clinical FFPE (formalin-fixed paraffin-embedded) samples using both primer sets. Positive control plasmid 10-fold serial dilutions confirmed the analytical sensitivity of the assays. The findings suggest that these novel primer sets should allow for detection sensitivity and reduce false positive results/cross-reactions. New assays for detecting pathogenic fungi, constructed along these lines, could be simple and affordable to implement.

Background The study purpose is to compare outcomes associated with completion of genetic testing between telemedicine and in-person gastrointestinal cancer risk assessment appointments during the COVID-19 pandemic. Methods Data was collected on patients with scheduled appointments between July 2020 and June 2021 in a gastrointestinal cancer risk evaluation program (GI-CREP) that utilized both telemedicine and in-person visits throughout the COVID-19 pandemic, and a survey was administered. Results A total of 293 patients had a GI-CREP appointment scheduled and completion rates of in-person versus telemedicine appointments were similar. Individuals diagnosed with cancer and those with Medicaid insurance had lower rates of appointment completion. Although telehealth was the preferred visit modality, there were no differences in recommending genetic testing nor in the consent rate for genetic testing between in-person and telemedicine visits. However, of patients who consented for genetic testing, more than three times more patients seen via telemedicine did not complete genetic testing compared to those seen in-person (18.3% versus 5.2%, p = 0.008). Furthermore, telemedicine visits had a longer turnaround time for genetic test reporting (32 days versus 13 days, p < 0.001). Conclusions Compared to in-person GI-CREP appointments, telemedicine was associated with lower rates of genetic testing completion, and longer turnaround time for results.

Background Severe chest wall injuries are potentially life-threatening injuries which require a standardized multidisciplinary management strategy for prevention of posttraumatic complications and adverse outcome. Case presentation We report the successful management of a 55-year old man who sustained a complete “bony disruption” of the thoracic cage secondary to an “all-terrain vehicle” roll-over accident. The injury pattern consisted of a bilateral “flail chest” with serial segmental rib fractures, bilateral hemo-pneumothoraces and pulmonary contusions, bilateral midshaft clavicle fractures, a displaced transverse sternum fracture with significant diastasis, and an unstable T9 hyperextension injury. After initial life-saving procedures, the chest wall injuries were sequentially stabilized by surgical fixation of bilateral clavicle fractures, locked plating of the displaced sternal fracture, and a two-level anterior spine fixation of the T9 hyperextension injury. The patient had an excellent radiological and physiological outcome at 6 months post injury. Conclusion Severe chest wall trauma with a complete “bony disruption” of the thoracic cage represents a rare, but detrimental injury pattern. Multidisciplinary management with a staged timing for addressing each of the critical injuries, represents the ideal approach for an excellent long-term outcome.

Date Presented 4/16/2015 Combining task-specific training with afferent stimulation delivered via glove electrode in individuals with chronic stroke may result in changes at the arm sensation and function. Improvements were maintained at 3-mo follow-up.

Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form1. This transformation is facilitated by the engulfment and degradation of excess axonal branches and inappropriate synapses by surrounding glial cells, including microglia and astrocytes2,3. However, the small size of phagocytic organelles and the complex, highly ramified morphology of glia has made it difficult to determine the contribution of these and other glial cell types to this process. Here, we used large scale, serial electron microscopy (ssEM) with computational volume segmentation to reconstruct the complete 3D morphologies of distinct glial types in the mouse visual cortex. Unexpectedly, we discovered that the fine processes of oligodendrocyte precursor cells (OPCs), a population of abundant, highly dynamic glial progenitors4, frequently surrounded terminal axon branches and included numerous phagolysosomes (PLs) containing fragments of axons and presynaptic terminals. Single- nucleus RNA sequencing indicated that cortical OPCs express key phagocytic genes, as well as neuronal transcripts, consistent with active axonal engulfment. PLs were ten times more abundant in OPCs than in microglia in P36 mice, and declined with age and lineage progression, suggesting that OPCs contribute very substantially to refinement of neuronal circuits during later phases of cortical development.

QMCPACK is an open source quantum Monte Carlo package for ab-initio electronic structure calculations. It supports calculations of metallic and insulating solids, molecules, atoms, and some model Hamiltonians. Implemented real space quantum Monte Carlo algorithms include variational, diffusion, and reptation Monte Carlo. QMCPACK uses Slater-Jastrow type trial wave functions in conjunction with a sophisticated optimizer capable of optimizing tens of thousands of parameters. The orbital space auxiliary field quantum Monte Carlo method is also implemented, enabling cross validation between different highly accurate methods. The code is specifically optimized for calculations with large numbers of electrons on the latest high performance computing architectures, including multicore central processing unit (CPU) and graphical processing unit (GPU) systems. We detail the program's capabilities, outline its structure, and give examples of its use in current research calculations. The package is available at http://www.qmcpack.org .

It is interesting that the Atlanta Braves will reward Steve Avery for his sub-par year with a 1996 salary that will exceed the lifetime earnings of Babe Ruth, Joe DiMaggio, Lou Gehrig and Mickey Mantle combined. I'm not suggesting that the Yankees got a better deal, but among these guys, a total of 8,804 regular-season major-league games were played for less money than Avery will make this year, and the Braves might get nine complete games out of him. At this rate, they will be offering multiyear, seven-figure contracts to the ball boys in another 10 years. Hey, I can do that job. The article \"How the South sees Buchanan,\" referring to Pat Buchanan's rhetoric as \"anti-immigration and pro-Confederate,\" is appallingly misleading. Buchanan proposes stopping illegal immigration and placing some controls on legal immigration for a few years until the illegals are detected and either deported or assimilated. He praises immigrants who assimilate into our culture. Buchanan has never uttered a pro-Confederate statement. The article said Buchanan \"has questioned efforts to deport alleged Nazi war criminals,\" which on the surface is true. It is misleading without also mentioning that the one alleged Nazi war criminal defended by Buchanan was cleared of all charges by an Israeli court, and a terrible miscarriage of justice was prevented, mostly because of Buchanan's courage to face the politically correct press that is still trying to find something wrong with this act of political bravery.