Recombinant adeno-associated viruses (rAAVs) are efficient gene delivery vectors via intravenous delivery; however, natural serotypes display a finite set of tropisms. To expand their utility, we ...evolved AAV capsids to efficiently transduce specific cell types in adult mouse brains. Building upon our Cre-recombination-based AAV targeted evolution (CREATE) platform, we developed Multiplexed-CREATE (M-CREATE) to identify variants of interest in a given selection landscape through multiple positive and negative selection criteria. M-CREATE incorporates next-generation sequencing, synthetic library generation and a dedicated analysis pipeline. We have identified capsid variants that can transduce the central nervous system broadly, exhibit bias toward vascular cells and astrocytes, target neurons with greater specificity or cross the blood-brain barrier across diverse murine strains. Collectively, the M-CREATE methodology accelerates the discovery of capsids for use in neuroscience and gene-therapy applications.
We perform direct numerical simulations of an unstably stratified turbulent channel flow to address the effects of buoyancy on the boundary layer dynamics and mean field quantities. We systematically ...span a range of parameters in the space of friction Reynolds number (
$\mathit{Re}_{{\it\tau}}$
) and Rayleigh number (
$\mathit{Ra}$
). Our focus is on deviations from the logarithmic law of the wall due to buoyant motion. The effects of convection in the relevant ranges are discussed, providing measurements of mean profiles of velocity, temperature and Reynolds stresses as well as of the friction coefficient. A phenomenological model is proposed and shown to capture the observed deviations of the velocity profile in the log-law region from the non-convective case.
Background
To minimize blood loss during hepatic surgery, various methods are used to reduce pressure and flow within the hepato‐splanchnic circulation. In this study, the effect of low‐ to moderate ...doses of vasopressin, a potent splanchnic vasoconstrictor, on changes in portal and hepatic venous pressures and splanchnic and hepato‐splanchnic blood flows were assessed in elective liver resection surgery.
Methods
Twelve patients were studied. Cardiac output (CO), stroke volume (SV), mean arterial (MAP), central venous (CVP), portal venous (PVP) and hepatic venous pressures (HVP) were measured, intraoperatively, at baseline and during vasopressin infusion at two infusion rates (2.4 and 4.8 U/h). From arterial and venous blood gases, the portal (splanchnic) and hepato‐splanchnic blood flow changes were calculated, using Fick′s equation.
Results
CO, SV, MAP and CVP increased slightly, but significantly, while systemic vascular resistance and heart rate remained unchanged at the highest infusion rate of vasopressin. PVP was not affected by vasopressin, while HVP increased slightly. Vasopressin infusion at 2.4 and 4.8 U/h reduced portal blood flow (−26% and −37%, respectively) and to a lesser extent hepato‐splanchnic blood flow (−9% and −14%, respectively). The arterial‐portal vein lactate gradient was not significantly affected by vasopressin. Postoperative serum creatinine was not affected by vasopressin.
Conclusion
Short‐term low to moderate infusion rates of vasopressin induced a splanchnic vasoconstriction without metabolic signs of splanchnic hypoperfusion or subsequent renal impairment. Vasopressin caused a centralization of blood volume and increased cardiac output. Vasopressin does not lower portal or hepatic venous pressures in this clinical setting.
Abstract
Histone lysine methylations have primarily been linked to selective recruitment of reader or effector proteins that subsequently modify chromatin regions and mediate genome functions. Here, ...we describe a divergent role for histone H4 lysine 20 mono-methylation (H4K20me1) and demonstrate that it directly facilitates chromatin openness and accessibility by disrupting chromatin folding. Thus, accumulation of H4K20me1 demarcates highly accessible chromatin at genes, and this is maintained throughout the cell cycle. In vitro, H4K20me1-containing nucleosomal arrays with nucleosome repeat lengths (NRL) of 187 and 197 are less compact than unmethylated (H4K20me0) or trimethylated (H4K20me3) arrays. Concordantly, and in contrast to trimethylated and unmethylated tails, solid-state NMR data shows that H4K20 mono-methylation changes the H4 conformational state and leads to more dynamic histone H4-tails. Notably, the increased chromatin accessibility mediated by H4K20me1 facilitates gene expression, particularly of housekeeping genes. Altogether, we show how the methylation state of a single histone H4 residue operates as a focal point in chromatin structure control. While H4K20me1 directly promotes chromatin openness at highly transcribed genes, it also serves as a stepping-stone for H4K20me3-dependent chromatin compaction.
Abstract
Background/Introduction
Contemporary data that describe underlying causes of acute heart failure (AHF) epidemiology in a nation-wide unselected real-life cohort is lacking. Advances in ...diagnostics, including imaging and genetics, have facilitated the identification of the underlying cause of heart failure (HF). This is the first Icelandic nation-wide study on HF epidemiology of patients hospitalised for AHF.
Purpose
Investigate the underlying causes of AHF in Iceland and the patients‘ prognosis according to phenotypes.
Methods
This study used data from the Icelandic Heart Failure Registry (IHFR) and included all hospital admissions for AHF at Landspitali University Hospital from January 2020 to June 2022 (n = 1723). Differences in survival between HF phenotypes were analysed using a multivariate log-rank test, both after diagnosis and after the first discharge.
Results
The study found that 39.8% of the cases had heart failure with reduced ejection fraction (HFrEF), 17.4% had HF with mildly reduced ejection fraction (HFmrEF), 40.3% had HF with preserved ejection fraction (HFpEF), 0.9% had HF with improved ejection fraction (HFimpEF), and 1.5% had unknown ejection fraction (EF). The average length of hospital admission varied by phenotype, ranging from 8.1 to 15.9 days. Women accounted for 41.15% of all admissions, with the most common phenotype amongst women being HFpEF (57.8%) and the least common being HFrEF (25.1%). The mean age at admission was 75.8 years. Roughly 79% of the whole cohort had NYHA class III-IV at admission; 33% of HFrEF, 13% of HFmrEF and 32% of HFpEF admissions. The most common underlying cause of AHF was coronary artery disease (CAD, 30.9%) followed by atrial fibrillation (15.0%), hypertension (9.8%), diastolic dysfunction (9.4%) and valvular heart disease (9.2%). Other more rare causes were dilated cardiomyopathy (4.4%), amyloidosis (3.2%), broken heart disease (1.5%), myocarditis (0.4%), postpartum cardiomyopathy (0.2%) and Fabry disease (0.1%). During the study period, 422 mortalities were recorded, with 106 in-hospital deaths. After excluding in-hospital mortalities, no significant difference in survival between phenotypes was observed after the first discharge. However, a significant difference in survival was observed with respect to the date of diagnosis (p = 0.0191).
Conclusion
This study provides new insights into the underlying causes of AHF and patients' prognosis according to phenotypes in Iceland. Our results demonstrate that the most common underlying cause of AHF was CAD, followed by atrial fibrillation and hypertension and that the cohort was highly symptomatic, with a large proportion of patients having NYHA class III-IV at admission. Our findings also highlight significant differences in the prevalence of HF phenotypes between genders, with women more commonly presenting with HFpEF and less commonly with HFrEF.
The size selectivity of four codends were compared in the Gulf of St. Lawrence, Canada, redfish fishery (Sebastes mentella), including the regulated diamond mesh codend with a mesh opening of 90 mm ...(T0) and three experimental codends of different mesh openings (90, 100, 110 mm) in which the netting is turned 90° to the direction of tow (T90). Results for the regulated codend showed that there was little size selection, catching greater than 97% of redfish over all of the length classes observed. Considering the fished population, the smallest T90 codend would catch 30% fewer redfish under the minimum landing size (MLS) of 22 cm compared with the T0 codend, but would also lose 16% of catch above 22 cm. The T90 codend with 100 mm mesh opening had the same size selectivity as the smallest T90 codend. The 110 mm T90 codend would catch 50% less redfish below MLS but lose 40% of redfish above MLS. Overall, results show that T90 codends improve size selectivity in which large proportions of undersized fish are successfully released.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In brined shrimp (ca. 3% NaCl), the effects of three different lactic acid bacteria bacteriocins (crude 6.54 X 10(10)U of bacteriocin activity (BU)/g and purified 8.13 X 10(23) BU/g nisin Z, carnocin ...UI49 232 X lO(4) BU/g, and crude bavaricin A 2.78 BU/g) on bacterial growth and shelf life were compared with those of a benzoate-sorbate solution (0.1% each wt/wt) and a control with no preservatives. The shelf life of shrimp subjected to the control treatment was found to be 10 days. Carnocin UI49 did not extend the shelf life, while crude bavaricin A (a cell-free supernatant of Lactobacillus bavaricus MI 401) resulted in a shelf life of 16 days, as opposed to 31 days with nisin Z for both its crude and purified forms. The benzoate-sorbate solution preserved the brined shrimp for the whole storage period (59 days). In the control, carnocin UI49, and crude bavaricin A treatments, a gram-positive flora dominated towards the end of the storage period while in the nisin Z treatment a gram-negative flora was more pronounced
Listeria spp. and Listeria monocytogenes contamination was evaluated in cooked peeled shrimp (final or semifinal product, 82 samples) and the shrimp-processing environment (two plants, 613 samples) ...in eight surveys conducted from 1998 through 2001. Listeria was detected in 12.5% (78) of the 695 samples (11.2% of the samples were positive for L. monocytogenes), but none of the samples of final product contained Listeria. One hundred seventy-two L. monocytogenes isolates were characterized by pulsed-field gel electrophoresis. Cleavage with macrorestriction enzymes AscI and ApaI yielded 14 different pulsotypes in the plants; two types were dominant, one in each plant. Sixty-three of the 106 isolates in plant A and 43 of the 66 isolates in plant B were of the dominant types. Certain strains, mainly of serotypes 1/2c and 4b and pulsotypes 1A and 2H, were persistent for long periods in both plants. Adaptation of good hygienic practices in the processing plants, including strict rules concerning traffic of staff and equipment, and existing hygienic requirements appeared to be effective in preventing contamination between areas within plants and in the final product. The persistence of Listeria strains in these two processing plants indicates the importance of detecting the places in the processing environment (e.g., transporters, equipment, floors, and drains) where L. monocytogenes can survive so that cleaning and disinfection efforts can be directed to such niches.
Listeria spp. and
Listeria monocytogenes contamination of cold-smoked salmon (
n=125) and its processing environment (
n=522) were evaluated during surveys conducted in 1997–1998 and 2001 as well as ...in samples of final products analysed in 2001. The overall frequencies of
Listeria spp. and
L. monocytogenes in samples from all sources were 15.1% and 11.3%, respectively, but the incidence of
L. monocytogenes in cold-smoked salmon final products was only 4%. A total of 201
L. monocytogenes isolates were characterised by Pulsed-Field Gel Electrophoresis (PFGE) in order to trace
L. monocytogenes contamination in the processing plants. The combination of
AscI and
ApaI macrorestriction patterns yielded 24 different pulsotypes in 6 plants. One pulsotype observed by
AscI restriction digestion comprised 148 of the 167 typed isolates from two processing plants. Two other pulsotypes predominated in samples from raw material, processing environments and final products. The results indicate that raw material, floors, and drains are potential sources of the
L. monocytogenes found on cold-smoked salmon products. This highlights the need to readdress the design and cleaning of processing plants and equipment, and staff behavior. Hindering the introduction into and spread of the organism through the processing environment is necessary to avoid jeopardizing safety of the final product.
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