Membrane transporters modulating the toxicity of arsenic, cadmium, and mercury in human cells.

Non-essential metals are extremely toxic to living organisms, posing significant health risks, particularly in developing nations where they are a major contributor to illness and death. Although their toxicity is widely acknowledged, the mechanisms by which they are regulated within human cells remain incompletely understood. Specifically, the role of membrane transporters in mediating heavy metal toxicity is not well comprehended.

Spindle Cell Neoplasm With a Novel MN1::TAF3 Fusion: A Rare Case in a Toddler.

Spindle cell tumors in the pediatric population are uncommonly reported. This case discusses an 18-month-old who presented initially with unilateral ptosis and was found to have an orbital spindle cell tumor. Pathology evaluation of the tissue was extensive with nonspecific morphologic and immunohistochemical features.

A conformation-locking inhibitor of SLC15A4 with TASL proteostatic anti-inflammatory activity.

Dysregulation of pathogen-recognition pathways of the innate immune system is associated with multiple autoimmune disorders. Due to the intricacies of the molecular network involved, the identification of pathway- and disease-specific therapeutics has been challenging. Using a phenotypic assay monitoring the degradation of the immune adapter TASL, we identify feeblin, a chemical entity which inhibits the nucleic acid-sensing TLR7/8 pathway activating IRF5 by disrupting the SLC15A4-TASL adapter module.

Absence of mitochondrial SLC25A51 enhances PARP1-dependent DNA repair by increasing nuclear NAD+ levels.

Though the effect of the recently identified mitochondrial NAD+ transporter SLC25A51 on glucose metabolism has been described, its contribution to other NAD+-dependent processes throughout the cell such as ADP-ribosylation remains elusive. Here, we report that absence of SLC25A51 leads to increased NAD+ concentration not only in the cytoplasm and but also in the nucleus. The increase is not associated with upregulation of the salvage pathway, implying an accumulation of constitutively synthesized NAD+ in the cytoplasm and nucleus.

The influence of patient-centered teaching on medical students' stigmatization of the mentally ill.

Aim: Stigmatization by healthcare workers poses a challenge to providing care to the mentally ill. Bedside teaching during undergraduate medical education offers students an opportunity to directly interact with patients with a range of psychiatric disorders and thereby gather reflective experience. The present study investigates if this .

Clinical utility of whole-genome DNA methylation profiling as a primary molecular diagnostic assay for central nervous system tumors-A prospective study and guidelines for clinical testing.

Background: Central nervous system (CNS) cancer is the 10th leading cause of cancer-associated deaths for adults, but the leading cause in pediatric patients and young adults. The variety and complexity of histologic subtypes can lead to diagnostic errors. DNA methylation is an epigenetic modification that provides a tumor type-specific signature that can be used for diagnosis.

Comprehensive Review of Anal Cytology.

Background: The incidence of anal cancer has increased over at least the past decade, with estimates of a continued increase in the coming years. Women are more commonly affected than men in the general population; separate high-risk populations have also been identified. While the pathophysiology of anal cancer is thought to be similar to its cervical counterpart, well-defined and standardized screening guidelines have not been established as is seen in cervical cancer prevention.

The fractal brain: scale-invariance in structure and dynamics.

The past 40 years have witnessed extensive research on fractal structure and scale-free dynamics in the brain. Although considerable progress has been made, a comprehensive picture has yet to emerge, and needs further linking to a mechanistic account of brain function. Here, we review these concepts, connecting observations across different levels of organization, from both a structural and functional perspective.

A hybrid biological neural network model for solving problems in cognitive planning.

A variety of behaviors, like spatial navigation or bodily motion, can be formulated as graph traversal problems through cognitive maps. We present a neural network model which can solve such tasks and is compatible with a broad range of empirical findings about the mammalian neocortex and hippocampus. The neurons and synaptic connections in the model represent structures that can result from self-organization into a cognitive map via Hebbian learning, i.

Pediatric Donor Cell Acute Lymphoblastic Leukemia Following Bone Marrow Transplant for GATA2 Mutation.

Donor cell leukemia is a rare complication following hematopoietic stem cell transplant (HSCT). There are currently few reports in children and only rare, reported cases of donor-derived myelodysplastic syndrome/acute myeloid leukemia in patients with an underlying germline GATA2 mutation. Most reported cases are myeloid in origin and occur following related HSCT.

It Takes a Village: Providing International Pediatric Pathology Services in a Resource-Limited Setting.

Objectives: Partnerships between low- to middle-income countries (LMICs) and high-income countries (HICs) is one strategy to mitigate observed health disparities. Cambodia's Angkor Hospital for Children (AHC), an LMIC institution, faces shortages in health care resources, including pathology services. A partnership was created with Children's Wisconsin (CW), an HIC hospital, including provision of pathology services.

Investigation of Mitochondrial ADP-Ribosylation Via Immunofluorescence.

ADP-ribosylation is a posttranslational protein modification, involved in various cellular processes, ranging from DNA-damage repair to apoptosis. While its function has been studied amply with respect to genotoxic stress-associated nuclear ADP-ribosylation, the functional relevance of mitochondrial ADP-ribosylation remains so far poorly studied. This is mainly attributed to the absence of powerful techniques able to detect the modification.

MyoD induces ARTD1 and nucleoplasmic poly-ADP-ribosylation during fibroblast to myoblast transdifferentiation.

While protein ADP-ribosylation was reported to regulate differentiation and dedifferentiation, it has so far not been studied during transdifferentiation. Here, we found that MyoD-induced transdifferentiation of fibroblasts to myoblasts promotes the expression of the ADP-ribosyltransferase . Comprehensive analysis of the genome architecture by Hi-C and RNA-seq analysis during transdifferentiation indicated that ARTD1 locally contributed to A/B compartmentalization and coregulated a subset of MyoD target genes that were however not sufficient to alter transdifferentiation.

The Magnet Is Sometimes "Off"-Practical Strategies for Optimizing Challenging Musculoskeletal MR Imaging.

To describe practical solutions to the unique technical challenges of musculoskeletal magnetic resonance imaging, including off-isocenter imaging, artifacts from motion and metal prostheses, small field-of-view imaging, and non-conventional scan angles and slice positioning. Unique challenges of musculoskeletal magnetic resonance imaging require a collaborative approach involving radiologists, physicists, and technologists utilizing optimized magnetic resonance protocols, specialized coils, and unique patient positioning, in order to reliably diagnose critical musculoskeletal MR image findings.

Uncovering the Invisible: Mono-ADP-ribosylation Moved into the Spotlight.

Adenosine diphosphate (ADP)-ribosylation is a nicotinamide adenine dinucleotide (NAD)-dependent post-translational modification that is found on proteins as well as on nucleic acids. While ARTD1/PARP1-mediated poly-ADP-ribosylation has extensively been studied in the past 60 years, comparably little is known about the physiological function of mono-ADP-ribosylation and the enzymes involved in its turnover. Promising technological advances have enabled the development of innovative tools to detect NAD and NAD/NADH (H for hydrogen) ratios as well as ADP-ribosylation.

Correlation of anal cytology with follow-up histology and Human Papillomavirus genotyping: A 10-year experience from an academic medical center.

Background: Anal cytology (AC) is accepted as a practical screening modality for anal cancer. However, studies suggest that AC and anal biopsy dysplasia correlation is less robust than in cervicovaginal specimens. The current study goals were to look at our institutional experience in a subset of ACs and correlate with surgical pathology (SP), as well as evaluate their Human Papillomavirus (HPV) status.

A Type I-F Anti-CRISPR Protein Inhibits the CRISPR-Cas Surveillance Complex by ADP-Ribosylation.

CRISPR-Cas systems are bacterial anti-viral systems, and phages use anti-CRISPR proteins (Acrs) to inactivate these systems. Here, we report a novel mechanism by which AcrIF11 inhibits the type I-F CRISPR system. Our structural and biochemical studies demonstrate that AcrIF11 functions as a novel mono-ADP-ribosyltransferase (mART) to modify N250 of the Cas8f subunit, a residue required for recognition of the protospacer-adjacent motif, within the crRNA-guided surveillance (Csy) complex from Pseudomonas aeruginosa.

Intraductal papillary squamous neoplasm of the pancreas: Cyto-histologic correlation of a novel entity.

We correlate the cytologic and histologic features of a squamous-lined pancreatic cystic lesion with a complex papillary architecture and an associated KRAS mutation, which to our knowledge has not been previously described. A 69 year-old woman presented with intermittent left upper quadrant pain. CT imaging revealed a 1 cm solid lesion in the pancreatic tail with peripheral calcification.

Iatrogenic humeral anatomic neck fracture after intraosseous vascular access.

Intraosseous infusion has become a key tool in the resuscitation of critically ill or injured patients, both in pre-hospital settings and in emergency departments. Intraosseous access is obtained through the percutaneous placement of a needle into the medullary space of a bone, thereby allowing access into the systemic venous circulation via the medullary space, which is essential to treat patients in shock, cardiac arrest, airway compromise, or major trauma. This becomes critically important when obtaining conventional intravenous access is difficult or impossible.

Practical Comparison of the BioFire FilmArray Pneumonia Panel to Routine Diagnostic Methods and Potential Impact on Antimicrobial Stewardship in Adult Hospitalized Patients with Lower Respiratory Tract Infections.

Lower respiratory tract infections, including hospital-acquired and ventilator-associated pneumonia, are common in hospitalized patient populations. Standard methods frequently fail to identify the infectious etiology due to the polymicrobial nature of respiratory specimens and the necessity of ordering specific tests to identify viral agents. The potential severity of these infections combined with a failure to clearly identify the causative pathogen results in administration of empirical antibiotic agents based on clinical presentation and other risk factors.

Multicenter Evaluation of the BioFire FilmArray Pneumonia/Pneumonia Plus Panel for Detection and Quantification of Agents of Lower Respiratory Tract Infection.

The ability to provide timely identification of the causative agents of lower respiratory tract infections can promote better patient outcomes and support antimicrobial stewardship efforts. Current diagnostic testing options include culture, molecular testing, and antigen detection. These methods may require collection of various specimens, involve extensive sample treatment, and can suffer from low sensitivity and long turnaround times.

Erratum: Hopp, A.K., et al Regulation of Glucose Metabolism by NAD and ADP-Ribosylation. 2019, , 890.

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