The Hirschsprung disease (HSCR) is an inherited disease that is controlled by multiple genes and has a complicated genetic mechanism. HSCR patients suffer from various extents of constipation due to ...dysplasia of the enteric nervous system (ENS), which can be so severe as to cause complete intestinal obstruction. Many genes have been identified as playing causative roles in ENS dysplasia and HSCR, among them the endothelin receptor type B gene (Ednrb) has been identified to play an important role. Mutation of Ednrb causes a series of symptoms that include deafness, pigmentary abnormalities, and aganglionosis. In our previous studies of three rat models carrying the same spotting lethal (sl) mutation on Ednrb, the haplotype of a region on chromosome (Chr) 2 was found to be responsible for the differing severities of the HSCR-like symptoms. To confirm that the haplotype of the responsible region on Chr 2 modifies the severity of aganglionosis caused by Ednrb mutation and to recreate a rat model with severe symptoms, we selected the GK inbred strain, whose haplotype in the responsible region on Chr 2 resembles that of the rat strain in which severe symptoms accompany the Ednrbsl mutation. An Ednrb mutation was introduced into the GK rat by crossing with F344-Ednrbsl and by genome editing. The null mutation of Ednrb was found to cause embryonic death in F2 progeny possessing the GK haplotype in the responsible region on Chr 2. The results of this study are unexpected, and they provide new clues and animal models that promise to contribute to studies on the genetic regulatory network in the development of ENS and on embryogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
No statutory mental health services exist for justice-involved individuals in Pakistan. The lack of expertise in forensic psychiatry serves to deny individuals with mental illness the ...critical support needed for mental healthcare and adequate court dispositions with serious unintended consequences including capital punishment for those who could otherwise be deemed treatment and not punishment worthy. A landmark judgement by the Supreme Court of Pakistan in February 2021 criticized the lack of forensic psychiatry expertise in Pakistan and directing the development of forensic mental health services and forensic psychiatry training in Pakistan.
Objectives
The key objectives are: 1. Understanding the timeline of how justice invloved individuals are manged by psychiatric services 2. The importance of the Supreme Court of Pakistan Judgement in affecting change 3. Highlights on how Queen’s University will enhance forensic psychiatry in Pakistan
Methods
A literature review and personal networking facilitated the collection of important data in how justice invloved individuals are supported in Pakistan. The author has published and presented to Pakistani psychiatrists and the Pakistani judiciary on this topic. Queen’s University is aiming to implement a 3-year plan to develop an online curriculum and certificate course to help train the trainers.
Results
In the Pakistan’s most populous province, Punjab, prevalence rates for psychotic illnesses (3.7%), major depression (10%), and personality disorders (65%) among men with higher rates for psychotic disorders (4.0%) and major depression (12%) among women.
Conclusions
In conclusion there is a dire need to develop forensic psychiatry in Pakistan and other low/middle income countries.
Disclosure
No significant relationships.
Atherosclerosis, the main contributor to coronary heart disease, is characterised by an accumulation of lipids such as cholesterol in the arterial wall. Reverse cholesterol transport (RCT) reduces ...cholesterol via its conversion into bile acids (BAs). During RCT in non-hepatic peripheral tissues, cholesterol is transferred to high-density lipoprotein (HDL) particles and returned to the liver for conversion into BAs predominantly via the rate-limiting enzyme, cholesterol 7 α-hydroxylase (CYP7A1). Numerous reports have described that polyphenol induced increases in BA excretion and corresponding reductions in total and LDL cholesterol in animal and in-vitro studies, but the process whereby this occurs has not been extensively reviewed. There are three main mechanisms by which BA excretion can be augmented: (1) increased expression of CYP7A1; (2) reduced expression of intestinal BA transporters; and (3) changes in the gut microbiota. Here we summarise the BA metabolic pathways focusing on CYP7A1, how its gene is regulated via transcription factors, diurnal rhythms, and microRNAs. Importantly, we will address the following questions: (1) Can polyphenols enhance BA secretion by modulating the CYP7A1 biosynthetic pathway? (2) Can polyphenols alter the BA pool via changes in the gut microbiota? (3) Which polyphenols are the most promising candidates for future research? We conclude that while in rodents some polyphenols induce CYP7A1 expression predominantly by the LXRα pathway, in human cells, this may occur through FXR, NF-KB, and ERK signalling. Additionally, gut microbiota is important for the de-conjugation and excretion of BAs. Puerarin, resveratrol, and quercetin are promising candidates for further research in this area.
The integration of molecular approaches in medicine allows for a more precise understanding of the mechanisms underlying infectious diseases, paving the way for targeted therapies, personalized ...medicine, and the development of new diagnostic tools ...
As global warming and climate variability bring about more frequent and intense rainstorms and accelerate sea level rise, our social and built environments are at heightened risk of flood-induced ...damages and costs. All levels of governance stand to benefit from deepened understanding of possible outcomes resulting from decentralized human behavior in the realm of water resources engineering and management, particularly in coastal areas. Game theory allows scientists to predict preferred strategies and interactions of rational self-interested actors in coalitional games, wherein players increase their individual payoffs through formation of strategic subsets. When applied to infrastructure planning, this practice can be used to identify which coalitions should form to benefit their overall hydrologic system. This research aims to inform green infrastructure decisions in Charleston, South Carolina’s Market Street watershed using a coalitional game theory solution concept, the Shapley value, in combination with rainfall-runoff simulation in storm water management model (SWMM). Results offer insights into stormwater services and flood managers concerning suggested areas of focus for green infrastructure spending and advocacy to reduce flooding and resulting property damage.
Abstract
Accurate annotation of genes and transposable elements (TEs) is vital for understanding genomes, but current annotation pipelines often misannotate TEs as genes. This study reveals how the ...general transcription factor II-I repeat domain-containing protein 2 (GTF2IRD2) erroneously annotated DNA transposons in non-mammalian species, as it contains a 3′ fused hAT transposase domain. We also demonstrate the generality of this problem by identifying misannotated TEs as genes in other vertebrate genomes. Such misannotations can lead to errors in phylogenetic analyses and wasted time for investigators. The study proposes adding a final TE-check to gene annotation pipelines to mitigate this problem.
•Tractable formulations for cardinality constrained risk parity are developed.•Valid inequalities are presented that tighten the formulations.•Computational experiments show the effectiveness in ...terms of speed and out of sample performance.
The risk parity optimization problem produces portfolios where each asset contributes an equal amount to the overall portfolio risk. While most work has investigated the problem using all assets, minimal work has investigated the cardinality constrained variant, which reduces the associated portfolio overhead. In this work, we present the first formulations that can be solved to global optimality by off-the-shelf solvers. Specifically, we propose two new quadratically constrained quadratic integer programs, a non-convex and a convex one, that can be solved to global optimality without the need of specialized algorithms, heuristics or approximations. We strengthen our formulations by adding tighter variable bounds and valid constraints. Computational experiments on real-world financial data indicate the effectiveness of our formulations at producing portfolios with equal risk contributions of chosen cardinality size. Specifically, the convex formulation is shown to be very efficient in terms of both speed and accuracy, while producing portfolios with great out-of-sample performance.
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•This work provides an up-to date review on methods for isolation and characterization of microcrystalline cellulose (MCC).•Interest for MCC is exponentially increasing.•New sources, ...new isolation processes, new treatments induce new types of MCC materials for industrialization.•Opportunities of MCC-based composite polymers for the future are presented and discussed.
Considering its widespread usage in various fields, such as food, pharmaceutical, medical, cosmetic and polymer composites industries, microcrystalline cellulose (MCC) is becoming impellent due to increasing demand of alternatives to non-renewable and scarce fossil materials. Although it still suffers from some drawbacks, MCC has recently gained more interest owing to its renewability, non-toxicity, economic value, biodegradability, high mechanical properties, high surface area and biocompatibility. New sources, new isolation processes, and new treatments are currently under development to satisfy the increasing demand of producing new types of MCC-based materials on an industrial scale. Therefore, this review assembles the current knowledge on the isolation of MCC from different sources using various procedures, its characterization, and its application in bio-composites. Challenges and future opportunities of MCC-based composites are discussed as well as obstacles remaining for their extensive uses.
This article presents a compact wideband multi‐input multi‐output (MIMO) antenna with a high port‐to‐port isolation, having a height h = 3.5 mm for 4G, 5G, and Internet of things (IoT) applications. ...Two identical planar inverted‐F antennas (PIFA) are used in this antenna system. For achieving wideband characteristics, closed‐ended and open‐ended rectangular slots are etched out on top plate of each PIFA, whereas a slot is etched in ground plane under the top plate of each PIFA. For achieving high isolation, a rectangular slot is etched out in the center of ground plane between two PIFAs. For further reduction in mutual coupling, a small rectangular strip is connected between the top plates of two PIFAs that introduce an antiresonance for enhancing isolation between two PIFA elements. The minimum isolation obtained between the ports of the two PIFAs is about −20 dB. The minimum impedance bandwidth obtained by the two PIFAs is from 2 to around 3.6 GHz, thus become a wide band antenna covering WLAN band (2.45GHz), 4G‐LTE bands, WiMAX bands (IMT‐2.1 GHz, IMT‐2.3 GHz, and IMT‐E 2.6 GHz), and a sub‐6 GHz 5G band (3.4‐3.6 GHz). The simulated results are compared with the measured ones that are generally found in good agreement. Being low profile and compact, this antenna can be used for advanced 5G communication systems and IoT devices.
The herpes simplex virus (HSV) is a double-stranded DNA human virus that causes persistent infections with recurrent outbreaks. HSV exists in two forms: HSV-1, responsible for oral herpes, and HSV-2, ...primarily causing genital herpes. Both types can lead to significant complications, including neurological issues. Conventional treatment, involving acyclovir and its derivatives, faces challenges due to drug resistance. This underscores the imperative for continual research and development of new drugs, with a particular emphasis on exploring the potential of natural antivirals. Flavonoids have demonstrated promise in combating various viruses, including those within the herpesvirus family. This review, delving into recent studies, reveals the intricate mechanisms by which flavonoids decode their antiviral capabilities against HSV. By disrupting key stages of the viral life cycle, such as attachment to host cells, entry, DNA replication, latency, and reactivation, flavonoids emerge as formidable contenders in the ongoing battle against HSV infections.
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