RFX6 Maintains Gene Expression and Function of Adult Human Islet α-Cells.

Mutations in the gene encoding the transcription factor regulatory factor X-box binding 6 (RFX6) are associated with human diabetes. Within pancreatic islets, RFX6 expression is most abundant in islet α-cells, and α-cell RFX6 expression is altered in diabetes. However, the roles of RFX6 in regulating gene expression, glucagon output, and other crucial human adult α-cell functions are not yet understood.

HNF1α maintains pancreatic α and β cell functions in primary human islets.

HNF1A haploinsufficiency underlies the most common form of human monogenic diabetes (HNF1A-maturity onset diabetes of the young [HNF1A-MODY]), and hypomorphic HNF1A variants confer type 2 diabetes risk. But a lack of experimental systems for interrogating mature human islets has limited our understanding of how the transcription factor HNF1α regulates adult islet function. Here, we combined conditional genetic targeting in human islet cells, RNA-Seq, chromatin mapping with cleavage under targets and release using nuclease (CUT&RUN), and transplantation-based assays to determine HNF1α-regulated mechanisms in adult human pancreatic α and β cells.

Curative islet and hematopoietic cell transplantation in diabetic mice without toxic bone marrow conditioning.

Mixed hematopoietic chimerism can promote immune tolerance of donor-matched transplanted tissues, like pancreatic islets. However, adoption of this strategy is limited by the toxicity of standard treatments that enable donor hematopoietic cell engraftment. Here, we address these concerns with a non-myeloablative conditioning regimen that enables hematopoietic chimerism and allograft tolerance across fully mismatched major histocompatibility complex (MHC) barriers.

Intoxication and pitch control in tonal and non-tonal language speakers.

Alcohol intoxication is known to affect pitch variability in non-tonal languages. In this study, intoxication's effects on pitch were examined in tonal and non-tonal language speakers, in both their native language (L1; German, Korean, Mandarin) and nonnative language (L2; English). Intoxication significantly increased pitch variability in the German group (in L1 and L2), but not in the Korean or Mandarin groups (in L1 or L2), although there were individual differences.

Islet cell replacement and transplantation immunology in a mouse strain with inducible diabetes.

Improved models of experimental diabetes are needed to develop cell therapies for diabetes. Here, we introduce the B6 RIP-DTR mouse, a model of experimental diabetes in fully immunocompetent animals. These inbred mice harbor the H2 major histocompatibility complex (MHC), selectively express high affinity human diphtheria toxin receptor (DTR) in islet β-cells, and are homozygous for the Ptprc (CD45.

The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans.

Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression.

ZIP Code-Level Estimation of Air Quality and Health Risk Due to Particulate Matter Pollution in New York City.

Exposure to PM is associated with hundreds of premature mortalities every year in New York City (NYC). Current air quality and health impact assessment tools provide county-wide estimates but are inadequate for assessing health benefits at neighborhood scales, especially for evaluating policy options related to energy efficiency or climate goals. We developed a new ZIP Code-Level Air Pollution Policy Assessment (ZAPPA) tool for NYC by integrating two reduced form models─Community Air Quality Tools (C-TOOLS) and the Co-Benefits Risk Assessment Health Impacts Screening and Mapping Tool (COBRA)─that propagate emissions changes to estimate air pollution exposures and health benefits.

Cultural factors weaken but do not reverse left-to-right spatial biases in numerosity processing: Data from Arabic and English monoliterates and Arabic-English biliterates.

Directional response biases due to a conceptual link between space and number, such as a left-to-right hand bias for increasing numerical magnitude, are known as the SNARC (Spatial-Numerical Association of Response Codes) effect. We investigated how the SNARC effect for numerosities would be influenced by reading-writing direction, task instructions, and ambient visual environment in four literate populations exemplifying opposite reading-writing cultures-namely, Arabic (right-to-left script) and English (left-to-right script). Monoliterates and biliterates in Jordan and the U.

SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment.

Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β cells can be infected by SARS-CoV-2 and cause β cell depletion.

Standing by: The spatial organization of coercive institutions in China.

How do authoritarian states organize their coercive institutions over space? We argue that autocrats maximize the utility of their limited coercive resources by clustering them with perceived threats in society, i.e., segments of the population that are ideologically distant and have mobilizational potential.

Collaboration between Law Enforcement Agencies in Combating Cybercrime: Implications of a Taiwanese Case Study about ATM Hacking.

An increasing number of cybercrimes has presented new global challenges to law enforcement agencies that traditionally operate within designated geographical jurisdictions and patrol territories. The borderless nature of cyberspace has brought substantial opportunities-both legal and illegal-to its users, and many local law enforcement agencies have encountered motivated offenders taking advantage of the globally connected Internet and causing damage locally and transnationally. This study examines a high-profile case of European criminals who hacked into a Taiwanese financial institution-First Commercial Bank (FCB)-and programmed its ATMs to "spit out" cash netting the thieves $2.

In vivo studies of glucagon secretion by human islets transplanted in mice.

Little is known about regulated glucagon secretion by human islet α-cells compared to insulin secretion from β-cells, despite conclusive evidence of dysfunction in both cell types in diabetes mellitus. Distinct insulins in humans and mice permit in vivo studies of human β-cell regulation after human islet transplantation in immunocompromised mice, whereas identical glucagon sequences prevent analogous in vivo measures of glucagon output from human α-cells. Here, we use CRISPR-Cas9 editing to remove glucagon codons 2-29 in immunocompromised NSG mice, preserving the production of other proglucagon-derived hormones.

Molecular and genetic regulation of pig pancreatic islet cell development.

Reliance on rodents for understanding pancreatic genetics, development and islet function could limit progress in developing interventions for human diseases such as diabetes mellitus. Similarities of pancreas morphology and function suggest that porcine and human pancreas developmental biology may have useful homologies. However, little is known about pig pancreas development.

Architecture of the Short External Rotator Muscles of the Hip.

Background: Muscle architecture, or the arrangement of sarcomeres and fibers within muscles, defines functional capacity. There are limited data that provide an understanding of hip short external rotator muscle architecture. The purpose of this study was thus to characterize the architecture of these small hip muscles.

Perception of nonnative tonal contrasts by Mandarin-English and English-Mandarin sequential bilinguals.

This study examined the role of acquisition order and crosslinguistic similarity in influencing transfer at the initial stage of perceptually acquiring a tonal third language (L3). Perception of tones in Yoruba and Thai was tested in adult sequential bilinguals representing three different first (L1) and second language (L2) backgrounds: L1 Mandarin-L2 English (MEBs), L1 English-L2 Mandarin (EMBs), and L1 English-L2 intonational/non-tonal (EIBs). MEBs outperformed EMBs and EIBs in discriminating L3 tonal contrasts in both languages, while EMBs showed a small advantage over EIBs on Yoruba.

Comparison of lateral lumbar interbody fusion (LLIF) with open versus percutaneous screw fixation for adult degenerative scoliosis.

Study Design: Retrospective Review.

Objectives: Compare clinical outcomes and radiographic correction of adult degenerative scoliosis (ADS) patients treated with lateral lumbar interbody fusion (LLIF), combined either with percutaneous (no laminectomy) versus open laminectomy/pedicle screw instrumentation.

Methods: Twenty-two ADS patients undergoing combined LLIF and posterior instrumentation were divided into two groups: thirteen patients underwent LLIF with laminectomy and posterior pedicle instrumentation (Group-1, six revision); nine patients underwent LLIF with percutaneous pedicle instrumentation (no decompression) (Group-2).

Early TLR4 Blockade Attenuates Sterile Inflammation-mediated Stress in Islets During Isolation and Promotes Successful Transplant Outcomes.

Background: During the isolation process, pancreatic islets are exposed to an environment of sterile inflammation resulting in an upregulated inflammatory state before transplantation. Toll-like receptor 4 (TLR4) has been identified as a major mediator of sterile inflammation. Therefore, we sought to determine whether early TLR4 blockade would be effective in reducing the inflammatory burden in islets pretransplant.

A Modern Comparison of Urodynamic Findings in Diabetic Versus Nondiabetic Women.

Objectives: Few contemporary studies exist regarding urodynamic (UDS) findings in patients with diabetes mellitus (DM), and data are conflicting. Our aim was to compare UDS findings in women with and without DM.

Methods: Data from female patients in a prospectively maintained UDS database (2010-2014) were reviewed.

Ex-vivo generation of drug-eluting islets improves transplant outcomes by inhibiting TLR4-Mediated NFkB upregulation.

The systemic administration of immunosuppressive and anti-inflammatory drugs is routinely employed in organ transplantation to minimize graft rejection and improve graft survival. Localized drug delivery has the potential to improve transplant outcomes by providing sustained exposure to efficacious drug concentrations while avoiding systemic immunosuppression and off-target effects. Here, we describe the synthesis of a novel prodrug and its direct covalent conjugation to pancreatic islets via a cleavable linker.

Islet damage during isolation as assessed by miRNAs and the correlation of miRNA levels with posttransplantation outcome in islet autotransplantation.

High-quality pancreatic islets are essential for better posttransplantation endocrine function in total pancreatectomy with islet autotransplantation (TPIAT), yet stress during the isolation process affects quality and yield. We analyzed islet-enriched microRNAs (miRNAs) -375 and -200c released during isolation to assess damage and correlated the data with posttransplantation endocrine function. The absolute concentration of miR-375, miR-200c, and C-peptide was measured in various islet isolation steps, including digestion, dilution, recombination, purification, and bagging, in 12 cases of TPIAT.

Pancreatic β-Cell-Derived IP-10/CXCL10 Isletokine Mediates Early Loss of Graft Function in Islet Cell Transplantation.

Pancreatic islets produce and secrete cytokines and chemokines in response to inflammatory and metabolic stress. The physiological role of these "isletokines" in health and disease is largely unknown. We observed that islets release multiple inflammatory mediators in patients undergoing islet transplants within hours of infusion.

Current issues in allogeneic islet transplantation.

Purpose Of Review: Transplantation of allogenic pancreatic islets is a minimally invasive treatment option to control severe hypoglycemia and dependence on exogenous insulin among type 1 diabetes (T1D) patients. This overview summarizes the current issues and progress in islet transplantation outcomes and research.

Recent Findings: Several clinical trials from North America and other countries have documented the safety and efficacy of clinical islet transplantation for T1D patients with impaired hypoglycemia awareness.

MiR-375 and miR-200c as predictive biomarkers of islet isolation and transplantation in total pancreatectomy with islet autotransplantation.

Background: Total pancreatectomy with islet autotransplantation (TPIAT) is a promising treatment for refractory chronic pancreatitis. Predictable biomarkers for the endocrine function after transplantation would be helpful in selecting patients for TPIAT. This study aims to identify novel biomarkers for predicting the outcome of islet isolation and transplantation in TPIAT patients.

Venous hypertensive myelopathy associated with cervical spondylosis.

Background Context: Venous hypertensive myelopathy (VHM) results from spinal vascular malformations of arteriovenous shunting that increases spinal venous pressure, leading to congestive edema and neurologic dysfunction. There has been no report of VHM associated with cervical spondylotic myelopathy (CSM).

Purpose: The aim of this study was to report an extremely rare case of VHM likely due to CSM.