Ice discharge from Greenland's marine-terminating glaciers contributes to half of all mass loss from the ice sheet, with numerous mechanisms proposed to explain their retreat. Here, we examine K.I.V ...Steenstrups Nordre Bræ ('Steenstrup') in Southeast Greenland, which, between 2018 and 2021, retreated ~7 km, thinned ~20%, doubled in discharge, and accelerated ~300%. This rate of change is unprecedented amongst Greenland's glaciers and now places Steenstrup in the top 10% of glaciers by contribution to ice-sheet-wide discharge. In contrast to expected behaviour from a shallow, grounded tidewater glacier, Steenstrup was insensitive to high surface temperatures that destabilised many regional glaciers in 2016, appearing instead to respond to a >2 °C anomaly in deeper Atlantic water (AW) in 2018. By 2021, a rigid proglacial mélange had developed alongside notable seasonal variability. Steenstrup's behaviour highlights that even long-term stable glaciers with high sills are vulnerable to sudden and rapid retreat from warm AW intrusion.
Venezuelan equine encephalitis virus (VEEV) poses a major public health risk due to its amenability for use as a bioterrorism agent and its severe health consequences in humans. ML336 is a recently ...developed chemical inhibitor of VEEV, shown to effectively reduce VEEV infection in vitro and in vivo. However, its limited solubility and stability could hinder its clinical translation. To overcome these limitations, lipid-coated mesoporous silica nanoparticles (LC-MSNs) were employed. The large surface area of the MSN core promotes hydrophobic drug loading while the liposome coating retains the drug and enables enhanced circulation time and biocompatibility, providing an ideal ML336 delivery platform. LC-MSNs loaded 20 ± 3.4 μg ML336/mg LC-MSN and released 6.6 ± 1.3 μg/mg ML336 over 24 hours. ML336-loaded LC-MSNs significantly inhibited VEEV in vitro in a dose-dependent manner as compared to unloaded LC-MSNs controls. Moreover, cell-based studies suggested that additional release of ML336 occurs after endocytosis. In vivo safety studies were conducted in mice, and LC-MSNs were not toxic when dosed at 0.11 g LC-MSNs/kg/day for four days. ML336-loaded LC-MSNs showed significant reduction of brain viral titer in VEEV infected mice compared to PBS controls. Overall, these results highlight the utility of LC-MSNs as drug delivery vehicles to treat VEEV.
The COVID-19 pandemic brings unforeseen challenges in medical education. The current study aims to: 1) describe third-year medical students’ experiences with the novel Shelf-Exam-Type Question ...Didactics (SET QD) before (in-person) and during (virtual) COVID-19.
In this qualitative study using grounded theory, we conducted purposive sampling and used 23 in-depth semi-structured interviews. Audio recordings were transcribed verbatim and the Atlas.Ti software was used to manage the thematic analysis.
There are three themes and eight subthemes that emerged: 1) The SET QD Framework (sub-themes: questions as learning opportunities; interleaving; notable clinical scenarios; team learning; accountability). 2) Experienced Educator (subtheme: transformational teaching). 3) Virtual Accessibility (sub-themes: alleviating time constraints, and mitigating life-stressors).
Medical students regarded SET QD as impactful for shelf exam preparation, clinical preparation, and long-term retention of the material. This novel virtual didactic method may be used in non-surgical clerkships as well.
•SET QD helps prepare medical students for surgery clerkship learning objectives.•SET QD is a novel active-learning and learner-centered virtual didactic model.•SET QD may be beneficial for clinical didactics in non-surgical clerkships.
We prove a Künneth theorem for the Vietoris–Rips homology and cohomology of a semi-uniform space. We then interpret this result for graphs, where we show that the Künneth theorem holds for graphs ...with respect to the strong graph product. We finish by computing the Vietoris–Rips cohomology of the torus endowed with diferent semi-uniform structures.
Nipah virus (NiV) is an emergent paramyxovirus that causes fatal encephalitis in up to 70 per cent of infected patients, and there is evidence of human-to-human transmission. Endothelial syncytia, ...comprised of multinucleated giant-endothelial cells, are frequently found in NiV infections, and are mediated by the fusion (F) and attachment (G) envelope glycoproteins. Identification of the receptor for this virus will shed light on the pathobiology of NiV infection, and spur the rational development of effective therapeutics. Here we report that ephrinB2, the membrane-bound ligand for the EphB class of receptor tyrosine kinases (RTKs), specifically binds to the attachment (G) glycoprotein of NiV. Soluble Fc-fusion proteins of ephrinB2, but not ephrinB1, effectively block NiV fusion and entry into permissive cell types. Moreover, transfection of ephrinB2 into non-permissive cells renders them permissive for NiV fusion and entry. EphrinB2 is expressed on endothelial cells and neurons, which is consistent with the known cellular tropism for NiV. Significantly, we find that NiV-envelope-mediated infection of microvascular endothelial cells and primary cortical rat neurons is inhibited by soluble ephrinB2, but not by the related ephrinB1 protein. Cumulatively, our data show that ephrinB2 is a functional receptor for NiV.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Since 2013, we have offered a robust “Introduction to Surgery” elective (ITS) for preclinical medical students. The present study investigates whether participants of the ITS elective were ...more likely to match into surgical residencies than non-ITS participants.
Methods
This is a retrospective case-control study of medical students from two medical schools in Southern California who participated in the ITS elective and those who did not. Descriptive results and univariate analysis using STATA were utilized to analyze the de-identified data who matched between 2016 and 2021 were included.
Results
Overall, 87 (8.9%) of the 982 matched students participated in the ITS elective, with an increase in participation from 1.2% in 2016 to 13.9% in 2021 (P < .001). Among ITS participants, 49.4% matched into a surgical specialty compared to only 22.9% for non-ITS students (P < .001). There was no difference between ITS and non-ITS students with regards to procedural specialty match (14.9% vs 12.6%, P = .537).
Conclusion
ITS participants were more than twice as likely to match into a surgical specialty than non-participants. Future qualitative research will help discern the relative impact of the ITS course versus a student’s baseline predisposition to surgery.
miR825-5p down-regulates immunity against Pseudomonas syringae and mediates cleavage of the sequence encoding the conserved motif within the MIST1 Toll/interleukin-1 (TIR) domain, triggering ...production of phased siRNAs that cleave additional TIR-carrying genes.
Abstract
Plants encode numerous intracellular receptors known as nucleotide-binding leucine-rich repeat receptors (NLRs) that recognize pathogen-derived effectors or their activity to activate defenses. miRNAs regulate NLR genes in many species, often triggering the production of phased siRNAs (phasiRNAs). Most such examples involve genes encoding NLRs carrying coiled-coil domains, although a few include genes encoding NLRs carrying a Toll/interleukin-1 domain (TNL). Here, we characterize the role of miR825-5p in Arabidopsis, using a combination of bioinformatics, transgenic plants with altered miRNA levels and/or reporters, small RNAs, and virulence assays. We demonstrate that miR825-5p down-regulates the TNL MIST1 by targeting for endonucleolytic cleavage the sequence coding for TIR2, a highly conserved amino acid motif, linked to a catalytic residue essential for immune function. miR825-5p acts as a negative regulator of basal resistance against Pseudomonas syringae. miR825-5p triggers the production from MIST1 of a large number of phasiRNAs that can mediate cleavage of both MIST1 and additional TNL gene transcripts, potentially acting as a regulatory hub. miR825-5p is expressed in unchallenged leaves and transcriptionally down-regulated in response to pathogen-associated molecular patterns (PAMPs). Our results show that miR825-5p, which is required for full expression of PAMP-triggered immunity, establishes a link between PAMP perception and expression of uncharacterized TNL genes.
Neurons maintain axonal homeostasis via employing a unique organization of the microtubule (MT) cytoskeleton, which supports axonal morphology and provides tracks for intracellular transport. ...Abnormal MT-based trafficking hallmarks the pathology of neurodegenerative diseases, but the exact mechanism regulating MT dynamics in axons remains enigmatic. Here we report on a regulation of MT dynamics by AuTophaGy(ATG)-related proteins, which previously have been linked to the autophagy pathway. We find that ATG proteins required for LC3 lipid conjugation are dispensable for survival of excitatory neurons and instead regulate MT stability via controlling the abundance of the MT-binding protein CLASP2. This function of ATGs is independent of their role in autophagy and requires the active zone protein ELKS1. Our results highlight a non-canonical role of ATG proteins in neurons and suggest that pharmacological activation of autophagy may not only promote the degradation of cytoplasmic material, but also impair axonal integrity via altering MT stability.
Broad emission lines in quasars enable us to “resolve” structure and kinematics of the broad-line emitting region (BLR) thought to involve an accretion disk feeding a supermassive black hole. ...Interpretation of broad line measures within the 4DE1 formalism simplifies the apparent confusion among such data by contrasting and unifying properties of so-called high and low accreting Population A and B sources. Hβ serves as an estimator of black hole mass, Eddington ratio and source rest frame; the latter being a valuable input for Civλ1549 studies which allow us to isolate the blueshifted wind component. Optical and HST-UV spectra yield Hβ and Civλ1549 spectra for low-luminosity sources while VLT-ISAAC and FORS and TNG-LRS provide spectra for high-luminosity sources. New high-S/N data for Civ in high-luminosity quasars are presented here for comparison with the other previously published data. Comparison of Hβ and Civλ1549 profile widths/shifts indicates that much of the emission from the two lines arise in regions with different structure and kinematics. Covering a wide range of luminosity and redshift shows evidence for a correlation between Civλ1549 blueshift and source Eddington ratio, with a weaker trend with source luminosity (similar amplitude outflows are seen over four of the five dex luminosity ranges in our combined samples). At low luminosity (z ≲ 0.7) only Population A sources show evidence for a significant outflow while at high luminosity the outflow signature begins to appear in Population B quasars as well.
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