bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRIB3-Regulated Akt Signal Pathway Affects Trophoblast Invasion in the Development of Preeclampsia
Authors: Sui Xin , Zhang Lei , Zhang Xu-Feng , Zhang Ya 
Published: September 2021

Objective The aim of the study is to explore the mechanism of tribbles pseudokinase 3 (TRIB3)-regulated Akt pathway in the development of preeclampsia (PE).
Study Design TRIB3 expression in the placenta of PE patient was determined by quantitative reverse transcriptase polymerase chain reaction and western blotting. Then HTR-8/SVneo or JEG-3 cells were transfected and divided into Mock, Control siRNA, TRIB3 siRNA-1, and TRIB3 siRNA-2 groups. Cell proliferation, invasion, and migration were determined by MTT assay, Transwell assay, and wound healing test, while the expression of TRIB3 and Akt pathway was measured by western blotting. PE rats were treated with TRIB3 siRNA, and blood pressure, 24-hour urinary protein, as well as serum levels of sFlt-1 and vascular endothelial growth factor (VEGF) were measured.
Results The placenta of PE patients presented with increased TRIB3 expression. In comparison with Mock group, the proliferation, invasion, and migration of HTR-8/SVneo and JEG-3 cells in TRIB3 siRNA-1 group and TRIB3 siRNA-2 group increased, with decreased TRIB3 expression but enhanced expression of p-Akt/Akt, MMP-2, and MMP-9. Rats in PE group showed increases in mean arterial pressure, SBP, 24-hour urinary protein, and serum sFlt-1 levels, but decreases in serum VEGF levels, fetal weight, and placental efficiency. Moreover, TRIB3 expression was upregulated, while p-Akt/Akt was downregulated in the placenta of rats in PE group. However, indicators above were significantly improved in rats treated with TRIB3 siRNA.
Conclusion TRIB3 was upregulated in the PE placenta, while silencing TRIB3 activated the Akt signaling pathway to promote the invasion and migration of trophoblast both in vitro and in vivo and ameliorated the development of PE symptoms in the PE rat model.
Key Points
Action spectroscopy of the isolated red Kaede fluorescent protein chromophore
Authors: Coughlan Neville J. A. , Stockett Mark H. , Kjær Christina , Ashworth Eleanor K. , Bulman Page Philip C. , Meech Stephen R. , Brøndsted Nielsen Steen , Blancafort Lluís , Hopkins W. Scott , Bull James N. 
Published: September 2021

Incorporation of fluorescent proteins into biochemical systems has revolutionized the field of bioimaging. In a bottom-up approach, understanding the photophysics of fluorescent proteins requires detailed investigations of the light-absorbing chromophore, which can be achieved by studying the chromophore in isolation. This paper reports a photodissociation action spectroscopy study on the deprotonated anion of the red Kaede fluorescent protein chromophore, demonstrating that at least three isomers–assigned to deprotomers–are generated in the gas phase. Deprotomer-selected action spectra are recorded over the S1 ← S0 band using an instrument with differential mobility spectrometry coupled with photodissociation spectroscopy. The spectrum for the principal phenoxide deprotomer spans the 480–660 nm range with a maximum response at ≈610 nm. The imidazolate deprotomer has a blue-shifted action spectrum with a maximum response at ≈545 nm. The action spectra are consistent with excited state coupled-cluster calculations of excitation wavelengths for the deprotomers. A third gas-phase species with a distinct action spectrum is tentatively assigned to an imidazole tautomer of the principal phenoxide deprotomer. This study highlights the need for isomer-selective methods when studying the photophysics of biochromophores possessing several deprotonation sites.
Modelling of beam energy absorbed locally in conduction mode laser metal fusion
Authors: Noori Rahim Abadi Seyyed Mohammad Ali , Mi Yongcui , Sikström Fredrik , Choquet Isabelle 
Published: September 2021

Abstract
Fluid dynamics models for laser material processing with metal fusion in conduction mode generally assume a constant absorptivity. This parameter is known to govern the process. However, it used to be pre-set by extrapolating absorptance measurements made at different conditions or adjusted to reproduce experimental bead shapes. In this study a new approach is developed. It consists in predicting the absorptance as a function of local surface conditions, including the surface temperature. The proposed absorptance model is applied to the metal alloy Ti-6Al-4V. It is found that the absorptance of this alloy changes with surface temperature over a wide range of beam incidence angles. Thermo-fluid simulations with tracking of the free-surface deformation are performed for conduction mode beam welding test cases with a Yb fibre laser and different travel speeds. It is found that the absorptivity coefficient commonly used for this process clearly underestimates the absorptance and the melt pool geometry predicted for the process conditions of this study. The computational results are also compared against experimental results and good quantitative agreement of the melt pool depth, width, length, free surface contour geometry, and the curvature of the end depression left after re-solidification at the laser switch-off location is obtained. The results show that the absorptance field predicted depends on the melt pool development stage, on the spatial location within the beam spot, and on the process conditions.
On backward attractors of interval maps*
Authors: Hantáková Jana , Roth Samuel 
Published: September 2021

Abstract
Special α-limit sets (sα-limit sets) combine together all accumulation points of all backward orbit branches of a point x under a noninvertible map. The most important question about them is whether or not they are closed. We challenge the notion of sα-limit sets as backward attractors for interval maps by showing that they need not be closed. This disproves a conjecture by Kolyada, Misiurewicz, and Snoha. We give a criterion in terms of Xiong’s attracting centre that completely characterizes which interval maps have all sα-limit sets closed, and we show that our criterion is satisfied in the piecewise monotone case. We apply Blokh’s models of solenoidal and basic ω-limit sets to solve four additional conjectures by Kolyada, Misiurewicz, and Snoha relating topological properties of sα-limit sets to the dynamics within them. For example, we show that the isolated points in a sα-limit set of an interval map are always periodic, the non-degenerate components are the union of one or two transitive cycles of intervals, and the rest of the sα-limit set is nowhere dense. Moreover, we show that sα-limit sets in the interval are always both F

σ
and G

δ
. Finally, since sα-limit sets need not be closed, we propose a new notion of β-limit sets to serve as backward attractors. The β-limit set of x is the smallest closed set to which all backward orbit branches of x converge, and it coincides with the closure of the sα-limit set. At the end of the paper we suggest several new problems about backward attractors.
Study on electronic properties and charge transfer doping of organic molecules adsorbed g-GaN monolayer
Authors: Shen Pengfei , Li Enling , Zhao Hongyuan , Cui Zhen , Shen Yang , Zhang Lin , Ma Deming 
Published: September 2021

Abstract
Two-dimensional GaN has attracted much attention owing to its excellent electronic and photoelectric properties. Tuning charge transfer and electronic characteristics of g-GaN are essential to its applications in electronic and optoelectronic devices. In this work, the electronic structures and charge transfer of organic molecules adsorbed g-GaN systems tetracyanoethylene (TCNE)/g-GaN, tetracyanoquinodimethane (TCNQ)/g-GaN, and tetrathiafulvalene (TTF)/g-GaN are explored based on first-principles. The results show that the TCNE and TCNQ molecules inject additional holes into g-GaN monolayer, and p-type doping is achieved in g-GaN monolayer. While a deep impurity level is introduced to TTF/g-GaN doping system, and the TTF injects minute quantities of additional electrons into g-GaN monolayer. The charge transfer and electronic characteristics of TCNE/g-GaN, TCNQ/g-GaN, and TTF/g-GaN doping systems are sensitive to applied vertical electric field. Our work has great potential for g-GaN application in nano electronic and photoelectric devices.
Initiation of buprenorphine for opioid use disorder in the hospital setting: Practice models, challenges, and legal considerations
Authors: Mospan Geoffrey A , Chaplin Michelle 
Published: September 2021

Abstract

Purpose
To provide health-system pharmacists with published examples of strategies utilized to offer buprenorphine to inpatients with opioid use disorder (OUD) along with information on challenges and legal considerations.

Summary
Hospitals and emergency departments (EDs) are a constant source of healthcare for patients with OUD. As a result, hospital practitioners can screen, diagnose, begin treatment, and facilitate transfer of care to the outpatient setting. Offering sublingual buprenorphine in the hospital can bridge the gap before outpatient care is established. Multiple studies have shown that initiating treatment in the ED or during inpatient hospitalization results in 47% to 74% of patients utilizing medication-assisted treatment at day 30 of follow-up, statistically superior to the rates achieved with brief interventions or referral alone. Moreover, initiating buprenorphine treatment in the ED has been shown to decrease healthcare costs. Despite the benefits of offering buprenorphine in the inpatient setting, several challenges must be solved by hospital administration, such as achieving clinician readiness to prescribe buprenorphine, developing relationships with outpatient providers of buprenorphine, and creating an efficient workflow. Treatment of OUD with buprenorphine is heavily regulated on the federal level. Pharmacists can participate in the development of these programs and ensure compliance with applicable laws.

Conclusion
As health systems continue to care for patients with OUD, starting buprenorphine in the inpatient setting can improve the transition to outpatient treatment. Several institutions have developed programs with positive results. With an understanding of the typical barriers and relevant laws when initiating buprenorphine in the hospital setting, health-system pharmacists can assist in the development and operation of these initiatives.
Mechanisms of reduced interspecific interference between territorial species
Authors: McEachin Shawn , Drury Jonathan P , Anderson Christopher N , Grether Gregory F 
Published: September 2021

AbstractInterspecific territoriality has complex ecological and evolutionary consequences. Species that interact aggressively often exhibit spatial or temporal shifts in activity that reduce the frequency of costly encounters. We analyzed data collected over a 13-year period on 50 populations of rubyspot damselflies (Hetaerina spp.) to examine how rates of interspecific fighting covary with fine-scale habitat partitioning and to test for agonistic character displacement in microhabitat preferences. In most sympatric species, interspecific fights occur less frequently than expected based on the species’ relative densities. Incorporating measurements of spatial segregation and species discrimination into the calculation of expected frequencies accounted for most of the reduction in interspecific fighting (subtle differences in microhabitat preferences could account for the rest). In 23 of 25 sympatric population pairs, we found multivariate differences between species in territory microhabitat (perch height, stream width, current speed, and canopy cover). As predicted by the agonistic character displacement hypothesis, sympatric species that respond more aggressively to each other in direct encounters differ more in microhabitat use and have higher levels of spatial segregation. Previous work established that species with the lowest levels of interspecific fighting have diverged in territory signals and competitor recognition through agonistic character displacement. In the other species pairs, interspecific aggression appears to be maintained as an adaptive response to reproductive interference, but interspecific fighting is still costly. We now have robust evidence that evolved shifts in microhabitat preferences also reduce the frequency of interspecific fighting.
Translational aspects of novel findings in genetics of male infertility—status quo 2021
Authors: Laan Maris , Kasak Laura , Punab Margus 
Published: September 2021

Abstract

Introduction
Male factor infertility concerns 7–10% of men and among these 40–60% remain unexplained.

Sources of data
This review is based on recent published literature regarding the genetic causes of male infertility.

Areas of agreement
Screening for karyotype abnormalities, biallelic pathogenic variants in the CFTR gene and Y-chromosomal microdeletions have been routine in andrology practice for &gt;20 years, explaining ~10% of infertility cases. Rare specific conditions, such as congenital hypogonadotropic hypogonadism, disorders of sex development and defects of sperm morphology and motility, are caused by pathogenic variants in recurrently affected genes, which facilitate high diagnostic yield (40–60%) of targeted gene panel-based testing.

Areas of controversy
Progress in mapping monogenic causes of quantitative spermatogenic failure, the major form of male infertility, has been slower. No ‘recurrently’ mutated key gene has been identified and worldwide, a few hundred patients in total have been assigned a possible monogenic cause.

Growing points
Given the high genetic heterogeneity, an optimal approach to screen for heterogenous genetic causes of spermatogenic failure is sequencing exomes or in perspective, genomes. Clinical guidelines developed by multidisciplinary experts are needed for smooth integration of expanded molecular diagnostics in the routine management of infertile men.

Areas timely for developing research
Di−/oligogenic causes, structural and common variants implicated in multifactorial inheritance may explain the ‘hidden’ genetic factors. It is also critical to understand how the recently identified diverse genetic factors of infertility link to general male health concerns across lifespan and how the clinical assessment could benefit from this knowledge.
Therapeutic reversal of Huntington’s disease by in vivo self-assembled siRNAs
Authors: Zhang Li , Wu Tengteng , Shan Yangyang , Li Ge , Ni Xue , Chen Xiaorui , Hu Xiuting , Lin Lishan , Li Yongchao , Guan Yalun , Gao Jinfeng , Chen Dingbang , Zhang Yu , Pei Zhong , Chen Xi 
Published: September 2021

Abstract
Huntington’s disease is an autosomal-dominant neurodegenerative disease caused by CAG expansion in exon 1 of the huntingtin (HTT) gene. Since mutant huntingtin (mHTT) protein is the root cause of Huntington’s disease, oligonucleotide-based therapeutic approaches using small interfering RNAs (siRNAs) and antisense oligonucleotides designed to specifically silence mHTT may be novel therapeutic strategies for Huntington’s disease. Unfortunately, the lack of an effective in vivo delivery system remains a major obstacle to realizing the full potential of oligonucleotide therapeutics, especially regarding the delivery of oligonucleotides to the cortex and striatum, the most severely affected brain regions in Huntington’s disease.
In this study, we present a synthetic biology strategy that integrates the naturally existing exosome-circulating system with artificial genetic circuits for self-assembly and delivery of mHTT-silencing siRNA to the cortex and striatum. We designed a cytomegalovirus promoter-directed genetic circuit encoding both a neuron-targeting rabies virus glycoprotein tag and an mHTT siRNA.
After being taken up by mouse livers after intravenous injection, this circuit was able to reprogramme hepatocytes to transcribe and self-assemble mHTT siRNA into rabies virus glycoprotein-tagged exosomes. The mHTT siRNA was further delivered through the exosome-circulating system and guided by a rabies virus glycoprotein tag to the cortex and striatum. Consequently, in three mouse models of Huntington’s disease treated with this circuit, the levels of mHTT protein and toxic aggregates were successfully reduced in the cortex and striatum, therefore ameliorating behavioural deficits and striatal and cortical neuropathologies.
Overall, our findings establish a convenient, effective and safe strategy for self-assembly of siRNAs in vivo that may provide a significant therapeutic benefit for Huntington’s disease.
Parkin interacting substrate phosphorylation by c-Abl drives dopaminergic neurodegeneration
Authors: Kim Hyojung , Shin Jeong-Yong , Jo Areum , Kim Ji Hun , Park Sangwook , Choi Jeong-Yun , Kang Ho Chul , Dawson Valina L , Dawson Ted M , Shin Joo-Ho , Lee Yunjong 
Published: September 2021

Abstract
Aberrant activation of the non-receptor kinase c-Abl is implicated in the development of pathogenic hallmarks of Parkinson’s disease, such as α-synuclein aggregation and progressive neuronal loss. c-Abl-mediated phosphorylation and inhibition of parkin ligase function lead to accumulation of parkin interacting substrate (PARIS) that mediates α-synuclein pathology-initiated dopaminergic neurodegeneration.
Here we show that, in addition to PARIS accumulation, c-Abl phosphorylation of PARIS is required for PARIS-induced cytotoxicity. c-Abl-mediated phosphorylation of PARIS at Y137 (within the Krüppel-associated box domain) drives its association with KAP1 and the repression of genes with diverse functions in pathways such as chromatin remodelling and p53-dependent cell death. One phosphorylation-dependent PARIS target, MDM4 (a p53 inhibitor that associates with MDM2; also known as MDMX), is transcriptionally repressed in a histone deacetylase-dependent manner via PARIS binding to insulin response sequence motifs within the MDM4 promoter. Virally induced PARIS transgenic mice develop c-Abl activity-dependent Parkinson’s disease features such as motor deficits, dopaminergic neuron loss and neuroinflammation. PARIS expression in the midbrain resulted in c-Abl activation, PARIS phosphorylation, MDM4 repression and p53 activation, all of which are blocked by the c-Abl inhibitor nilotinib. Importantly, we also observed aberrant c-Abl activation and PARIS phosphorylation along with PARIS accumulation in the midbrain of adult parkin knockout mice, implicating c-Abl in recessive Parkinson’s disease. Inhibition of c-Abl or PARIS phosphorylation by nilotinib or Y137F-PARIS expression in adult parkin knockout mice blocked MDM4 repression and p53 activation, preventing motor deficits and dopaminergic neurodegeneration. Finally, we found correlative increases in PARIS phosphorylation, MDM4 repression and p53 activation in post-mortem Parkinson’s disease brains, pointing to clinical relevance of the c-Abl-PARIS-MDM4-p53 pathway.
Taken together, our results describe a novel mechanism of epigenetic regulation of dopaminergic degeneration downstream of pathological c-Abl activation in Parkinson’s disease. Since c-Abl activation has been shown in sporadic Parkinson’s disease, PARIS phosphorylation might serve as both a useful biomarker and a potential therapeutic target to regulate neuronal loss in Parkinson’s disease.
Profile and management of hypertensive urgencies and emergencies in the emergency cardiology department of a tertiary hospital: a 12-month registry
Authors: Fragoulis Christos , Dimitriadis Kyriakos , Siafi Eirini , Iliakis Panagiotis , Kasiakogias Alexandros , Kalos Theodoros , Leontsinis Ioannis , Andrikou Ioannis , Konstantinidis Dimitrios , Nihoyannopoulos Petros , Tsivgoulis Georgios , Thomopoulos Costas , Tousoulis Dimitrios , Muiesan Maria L , Tsioufis Konstantinos P 
Published: September 2021

Abstract

Aims
Currently there are scarce epidemiological data regarding prevalence, clinical phenotype, and therapy of hypertensive urgencies (HU) and emergencies (HE). The aim of this article was to record the prevalence, clinical characteristics, and management of patients with HU and HE assessed in an emergency department (ED) of a tertiary hospital.

Methods and results
The population consisted of patients presenting with HE and HU in the ED (acute increase in systolic blood pressure (BP) ≥ 180 mmHg and/or diastolic BP ≥120 mmHg with and without acute target organ damage, respectively). Of the 38 589 patients assessed in the ED during a 12-month period, 353 (0.91%) had HU and HE. There were 256 (72.5%) cases presented as HU and 97 (27.5%) as HE. Primary causes for both HU and HE were stress/anxiety (44.9%), increased salt intake (33.9%), and non-adherence to medication (16.2%). Patients with HU reported mainly dizziness/headache (46.8%) and chest pain (27.4%), whereas those with HE presented dyspnoea (67%), chest pain (30.2%), dizziness/headache (10.3%), and neurological disorders (8.2%). In HE, the underlying associated conditions were pulmonary oedema (58%), acute coronary syndrome (22.6%), and neurological disorders/stroke (7.2%). All HE cases were hospitalized and received intensive healthcare, including dialysis.

Conclusion
This 1-year single-centre registry demonstrates a reasonable prevalence of HU and HE contributing to the high volume of visits to the ED. Stress, increased salt intake and non-adherence were main triggers of HE and HU. Dizziness and headache were the prevalent symptoms of HU patients while heart failure was the most common underlying disease in patients with HE.
Androgen-Binding Protein (Abp) Evolutionary History: Has Positive Selection Caused Fixation of Different Paralogs in Different Taxa of the Genus Mus?
Authors: Karn Robert C , Yazdanifar Golbahar , Pezer Željka , Boursot Pierre , Laukaitis Christina M 
Published: September 2021

Abstract
Comparison of the androgen-binding protein (Abp) gene regions of six Mus genomes provides insights into the evolutionary history of this large murid rodent gene family. We identified 206 unique Abp sequences and mapped their physical relationships. At least 48 are duplicated and thus present in more than two identical copies. All six taxa have substantially elevated LINE1 densities in Abp regions compared with flanking regions, similar to levels in mouse and rat genomes, although nonallelic homologous recombination seems to have only occurred in Mus musculus domesticus. Phylogenetic and structural relationships support the hypothesis that the extensive Abp expansion began in an ancestor of the genus Mus. We also found duplicated Abpa27’s in two taxa, suggesting that previously reported selection on a27 alleles may have actually detected selection on haplotypes wherein different paralogs were lost in each. Other studies reported that a27 gene and species trees were incongruent, likely because of homoplasy. However, L1MC3 phylogenies, supposed to be homoplasy-free compared with coding regions, support our paralog hypothesis because the L1MC3 phylogeny was congruent with the a27 topology. This paralog hypothesis provides an alternative explanation for the origin of the a27 gene that is suggested to be fixed in the three different subspecies of Mus musculus and to mediate sexual selection and incipient reinforcement between at least two of them. Finally, we ask why there are so many Abp genes, especially given the high frequency of pseudogenes and suggest that relaxed selection operates over a large part of the gene clusters.