Miracle-dz/UniFAR-FTUs huggingface dataset:
Lin28a ameliorates glucotoxicity-induced β-cell dysfunction and apoptosis

An excessive and prolonged increase in glucose levels causes β-cell dysregulation, which is accompanied by impaired insulin synthesis and secretion, a condition known as glucotoxicity. Although it is known that both Lin28a and Lin28b regulate glucose metabolism, other molecular mechanisms that may protect against glucotoxicity are poorly understood. We investigated whether Lin28a overexpression can improve glucotoxicity-induced β-cell dysregulation in INS-1 and primary rat islet cells. INS-1, a rat insulinoma cell line was cultured and primary rat islet cells were isolated from SD-rats. To define the effect of Lin28a in chronic high glucose-induced β-cell dysregulation, we performed several in vitro and ex-vivo experiments. Chronic exposure to high glucose led to a downregulation of Lin28a mRNA and protein expression, followed by a decrease in insulin mRNA expression and secretion in β-cells. The mRNA and protein expression levels of PDX-1 and BETA2, were reduced; The levels of apoptotic factors, including c-caspase3 and the Bax/Bcl-2 ratio, were increased due to glucotoxicity. Adenovirus-mediated Lin28a overexpression in β-cells reversed the glucotoxicity-induced reduction of insulin secretion and insulin mRNA expression via regulation of β-cell-enriched transcription factors such as PDX-1 and BETA2. Adenovirus-mediated overexpression of Lin28a downregulated the glucotoxicity-induced upregulation of c-caspase3 levels and the Bax/Bcl-2 ratio, while inhibition of endogenous Lin28a by small interfering RNA resulted in their up-regulation. Lin28a counteracted glucotoxicity-induced downregulation of p-Akt and p-mTOR. Our results suggest that Lin28a protects pancreatic β-cells from glucotoxicity through inhibition of apoptotic factors via the PI3 kinase/Akt/mTOR pathway.
Effect of Iron Stress, Light Stress, and Nitrogen Source on Physiological Aspects of Marine Red Tide Alga

Abstract Effect of iron (Fe) stress, light stress, and nitrogen (N) source on physiological aspects of the marine red tide alga Heterosigma akashiwo was investigated in batch cultures. Cellular chlorophyll and carotenoid contents increased under low light stress and decreased under iron stress. A specific pigment was induced under light stress. Nitrate reductase and nitrite reductase activities of nitrate-grown cells decreased under iron and light stress, while those of ammonium-grown cells were negligible. The cell density and the growth rate decreased under Fe stress, and this decrease can be aggravated by light stress. Compared with ammonium-grown cells, nitrate-grown cells showed an increase in the cell density and the growth rate. Intracellular C:N ratios indicated that the Fe-stress effect on nitrate or ammonium did not specifically involve in the nitrate assimilatory pathway, and light stress would aggravate the Fe-stress effect.
Extended plasma half-life of albumin-binding domain fused human IgA upon pH-dependent albumin engagement of human FcRn in vitro and in vivo

ABSTRACT Albumin has a serum half-life of 3 weeks in humans. This feature can be used to improve the pharmacokinetics of shorter-lived biologics. For instance, an albumin-binding domain (ABD) can be used to recruit albumin. A prerequisite for such design is that the ABD-albumin interaction does not interfere with pH-dependent binding of albumin to the human neonatal Fc receptor (FcRn), as FcRn acts as the principal regulator of the half-life of albumin. Thus, there is a need to know how ABDs act in the context of fusion partners and human FcRn. Here, we studied the binding and transport properties of human immunoglobulin A1 (IgA1), fused to a Streptococcus protein G-derived engineered ABD, in in vitro and in vivo systems harboring human FcRn. IgA has great potential as a therapeutic protein, but its short half-life is a major drawback. We demonstrate that ABD-fused IgA1 binds human FcRn pH-dependently and is rescued from cellular degradation in a receptor-specific manner in the presence of albumin. This occurs when ABD is fused to either the light or the heavy chain. In human FcRn transgenic mice, IgA1-ABD in complex with human albumin, gave 4-6-fold extended half-life compared to unmodified IgA1, where the light chain fusion showed the longest half-life. When the heavy chain-fused protein was pre-incubated with an engineered human albumin with improved FcRn binding, cellular rescue and half-life was further enhanced. Our study reveals how an ABD, which does not interfere with albumin binding to human FcRn, may be used to extend the half-life of IgA. Abbreviations: ABD - Albumin binding domain, ADA – anti-drug-antibodies, ADCC - Antibody-dependent cellular cytotoxicity, ELISA - Enzyme-linked Immunosorbent assay, FcαRI - Fcα receptor, FcγR - Fcγ receptor, FcRn - The neonatal Fc receptor, GST - Glutathione S-transferase, HC - Heavy chain, HERA - Human endothelial cell-based recycling assay, Her2 - Human epidermal growth factor 2, HMEC - Human microvascular endothelial cells, IgG - Immunoglobulin G, IgA - Immunoglobulin A, LC - Light chain, QMP - E505Q/T527M/K573P, WT - Wild type
Clinical and genetic characterization of PYROXD1‐related myopathy patients from Turkey

Congenital myopathies (CMs) are a heterogeneous group of inherited muscle disorders characterized by muscle weakness at birth, while limb‐girdle muscular dystrophies (LGMD) have a later onset and slower disease progression. Thus, detailed clinical phenotyping of genetically defined disease entities are required for the full understanding of genotype–phenotype correlations. A recently defined myopathic genetic disease entity is caused by bi‐allelic variants in a gene coding for pyridine nucleotide‐disulfide oxidoreductase domain 1 (PYROXD1) with unknown substrates. Here, we present three patients from two consanguineous Turkish families with mild LGMD, facial weakness, normal CK levels, and slow progress. Genomic analyses revealed a homozygous known pathogenic missense variant (c.464A>G, p.Asn155Ser) in family 1 with two affected females. In the affected male of family 2, we found this variant in a compound heterozygous state together with a novel frameshift variant (c.329_332delTCTG, p.Leu112Valfs*8), which is the second frameshift variant known so far in PYROXD1. We have been able to define a large homozygous region in family 1 sharing a common haplotype with family 2 in the critical region. Our data suggest that c.464A>G is a Turkish founder mutation. To gain deeper insights, we performed a systematic review of all published PYROXD1‐related myopathy cases. Our analysis showed that the c.464A > G variant was found in 87% (20/23) of the patients and that it may cause either a childhood‐ or adult‐onset phenotype, irrespective of its presence in a homozygous or compound heterozygous state. Interestingly, only four patients had elevated CK levels (up to 1000 U/L), and cardiac involvement was found in few compound heterozygous cases.
Concentric Sub‐micrometer‐Sized Cables Composed of Ni Nanowires and Sub‐micrometer‐Sized Fullerene Tubes

Highly ordered arrays of submicrometer‐sized coaxial cables composed of submicrometer‐sized C60 and C70 tubes filled with Ni nanowires are successfully prepared by combining a sol–gel method with an electrodeposition process. The wall thickness of the submicrometer‐sized tubes can be adjusted by the concentration of fullerenes and the immersion time. The thermal stability of the submicrometer‐sized C60 tubes is studied by Raman spectroscopy and it is found that these structures can be easily decomposed to form carbon nanotubes at relatively low temperatures (above 573 K) in an alumina template. These novel coaxial cable structures have been characterized by transmission electron microscopy (TEM), high‐resolution TEM (HRTEM), scanning electron microscopy (SEM), field‐emission SEM (FESEM), Raman spectroscopy, elemental mapping, energy dispersive X‐ray (EDX) spectroscopy, X‐ray diffraction (XRD), vibrating sample magnetometer (VSM) experiments, and superconducting quantum interference device (SQUID) measurements. Magnetic measurements show that these submicrometer‐sized cables exhibit enhanced ferromagnetic behavior as compared to bulk nickel. Moreover, submicrometer‐sized C70/Ni cables show uniaxial magnetic anisotropy with the easy magnetic axis being parallel to the long axis of the Ni nanowires. C70/Ni cables also exhibit a new magnetic transition at ca. 10 K in the magnetization–temperature (M–T) curve, which is not observed for the analogous C60/Ni structures. The origin of this transition is not yet clear, but might be related to interactions between the Ni nanowires and C70 molecules. There is no preferred magnetization axis in submicrometer‐sized C60/Ni cables, which implies that the Ni nanocrystals have different packing modes in the two composites. These different crystalline packing modes lead to different magnetic anisotropy in the two composites, although the Ni nanocrystals have the same face‐centered cubic (fcc) structure in both cases.
Comparison between Human Scent Compounds Collected on Cotton and Cotton Blend Materials for SPME-GC/MS Analysis

Human scent evidence has been used for centuries in various European countries and is now becoming more prevalent in the United States. Human scent evidence is collected either directly or indirectly and then used for scent discrimination with specially trained canines. The direct method allows the canine to smell an article of evidence, whereas the indirect method involves pre-scenting the canine with a sorbent material onto which traces of human scent have been previously collected. Even though there is no standardized collection material for human scent samples across various law enforcement agencies cotton based materials are commonly used. The purpose of this study was to investigate the ability of different types of sorbent materials, mainly cotton and cotton blend materials, to trap and release a combination of volatile organic compounds (VOCs) previously reported as human scent compounds. Volatile Organic Compounds in the headspace of the samples were extracted and identifi ed using solid-phase micro-extraction gas chromatography / mass spectrometry (SPME-GC/MS). The results showed that cotton blend materials released signifi cantly greater amounts of polar compounds when compared to the pure cotton materials. It appears that the chemical composition of the materials rather than the surface morphology plays the greater role in governing the trapping and releasing capabilities of the materials for human scent collection.
Communicating COVID-19 health information to culturally and linguistically diverse communities: insights from a participatory research collaboration.

OBJECTIVE To consider the challenges of communicating COVID-19 directives to culturally and linguistically diverse (CALD) communities in Australia, and present evidence-based solutions to influence policy and practice on promoting relevant health behaviours; to advance participatory research methodologies for health behaviour change. Type of program or service: We present a case study of a participatory research collaboration between CALD community leaders and health behaviour change scientists during the COVID-19 crisis. The goal was to better understand the role of community leaders in shaping health behaviours in their communities and how that role might be leveraged for better health outcomes. METHODS This article is the culmination of a series of dialogues between CALD community and advocacy leaders, and health behaviour change scientists in July 2020. The academic authors recruited 12 prominent CALD community leaders, conducted five semi-structured dialogues with small groups, and worked with all participants to develop insights that were applicable to the many different CALD communities represented in the research collaboration. RESULTS Three key findings emerged: 1) partnerships between CALD leaders, communities and government are critical for effective health communication; 2) shifting behaviour requires moving beyond disseminating information to designing tailored solutions; and 3) the diverse needs and circumstances of people and communities must be at the centre of health communication and behaviour change strategies. LESSONS LEARNT The collaborative process we undertook in this study enabled us to identify key challenges experienced and solutions offered by CALD leaders in communicating health information throughout the COVID-19 pandemic. Partnering with communities that are subject to health messaging can reduce inequalities in healthcare communication by enabling the development of strategies that help align human behaviour with the recommendations of health experts. This - along with sustained partnership and collaboration with CALD communities, understanding the cultural context, and the appropriate tailoring and delivery of communications - will ensure health-related messages are not lost in translation. The lessons provided in this paper are applicable not only to the current pandemic but also to post-pandemic social and economic recovery.
Preconcentration and Determination of 2,6-Dichlorobenzamide in Water by Stir Bar Extraction and High-Performance Liquid Chromatography–Tandem Mass Spectrometry

Polyacrylate stir bar sorptive extraction (SBSE) of 2,6-dichlorobenzamide followed by liquid desorption and analysis by liquid chromatography–tandem mass spectrometry using electrospray ionization is presented. The parameters influencing the methods were optimized and included a stirring speed of 500 revolutions per minute, an extraction time of two hours, a sample volume of 15 milliliters, 30 percent NaCl, and liquid desorption using acetonitrile under ultrasonication for fifteen minutes. A reverse phase C18 column was used with isocratic elution (50 percent acetonitrile and 50 percent 5 millimoles per liter aqueous ammonium acetate buffer at pH 2.4), a flow rate of 0.4 milliliter per minute, and an injection volume of 10 microliters. Quantitative analysis was carried out by multiple reaction monitoring using positive polarity. The developed method required low sample volume (15 milliliters) and provided satisfactory figures of merit with a limit of detection of 0.002 microgram per liter, a limit of quantification of 0.006 microgram per liter, and good precision (inter-day relative standard deviation below 10 percent). The polyacrylate Twister was employed for up to twenty-five extraction and liquid desorption cycles. The applicability of the method was assessed by analyzing ground water collected at five sites in North Italy. The concentrations of 2,6-dichlorobenzamide were between 0.070 and 0.282 microgram per liter. Preliminary results on the use of polar stir bars for the determination of other polar pesticides in water are also provided.
Dynamic Changes in Electrocardiogram Parameters After Epicardial Substrate Catheter Ablation of Brugada Syndrome.

BACKGROUND Catheter ablation (CA) is effective for recurrent episodes of ventricular fibrillation (VF) in Brugada syndrome (BrS). VF development in BrS is associated with several electrocardiogram (ECG) abnormalities. This study investigated changes in ECG parameters in high-risk BrS patients who underwent epicardial CA.Methods and Results:In all, 27 BrS patients were implanted with an implantable cardioverter-defibrillator (ICD). Patients were divided into 2 groups: (1) an ablation group (n=11) that underwent epicardial CA because of VF recurrence; and (2) a primary prevention (PP) group (n=16) with ICD implantation only. ECG parameters were evaluated before and 12 months after CA and compared with ECG parameters in the PP group. The T wave peak-to-end interval was significantly longer and the number of abnormal spikes in leads V1-V3 at the second, third, and fourth intercostal spaces was greater in the ablation than PP group. After ablation, ST levels and the sum of abnormal spikes in leads V1-V3 were significantly decreased. The mean (±SD) number of ICD shocks decreased markedly during a mean follow-up period of 42.0 months (from 3.8±3.7 to 0.2±0.4/year). Four patients had an ICD shock following the ablation procedure. Greater reductions in ST-segment elevation and abnormal spikes were observed in the group without than with VF recurrence. CONCLUSIONS Improvements in surface ECG parameters appear to be associated with successful ablation in high-risk BrS patients.
SCALED PRODUCTION OF RAFT CTA - A STAR PERFORMER

Synthesis of the Chain Transfer Agent. The starting point for the synthesis of the RAFT TTC-ester was a published procedure 1 involving multiple steps to obtain the RAFT TTC-acid. Following isolation of the RAFT TTC-acid, acid catalyzed esterification with butanol yielded the desired RAFT TTC-ester. In this procedure, the use of a phase transfer catalyst is necessary to give reasonable reaction rates and the key intermediates form as precipitates, which results in difficult mixing upon scale-up and leads to high levels of side products. To improve the process and purity for large scale preparation, laboratory development work was undertaken with the goal of developing a “one step” process where all the reaction intermediates remain soluble in the reaction medium. This “one step” process involves combining the dodecylmercaptan, acetone (solvent and reagent), carbon disulfide, and chloroform in a single reaction vessel and no phase transfer catalyst is required. The potassium hydroxide solution is then fed into the reaction vessel over time while providing efficient cooling in order to control the exotherm and to keep the bulk reaction temperature below a set point. The reactions described in Scheme 1 occur without formation of precipitates and therefore in-process mixing is efficient. The intermediate product is then acidified using hydrochloric acid to give the desired RAFT TTC-acid in high yield and high purity (>90%). A series of water washes and phase separations are required to isolate the product solution. The volatiles are then removed under reduced pressure to give the crude acid intermediate. The subsequent acid catalyzed esterification with butanol yields the RAFT TTC-ester. Results and Discussion From a processing standpoint the most challenging part of the procedure was heat removal, which was necessary due to the vigorous reaction exotherm during the potassium hydroxide (KOH) addition. As shown in Figure 2, there was also a latent exotherm following the completed KOH addition (100%), which accounts for 40% of the total energy removed during the process. The total heat of reaction was ~2,400 BTU/lb dodecylmercaptan.
Why do people oppose mask wearing? A comprehensive analysis of U.S. tweets during the COVID-19 pandemic

Abstract Objective Facial masks are an essential personal protective measure to fight the COVID-19 (coronavirus disease) pandemic. However, the mask adoption rate in the United States is still less than optimal. This study aims to understand the beliefs held by individuals who oppose the use of facial masks, and the evidence that they use to support these beliefs, to inform the development of targeted public health communication strategies. Materials and Methods We analyzed a total of 771 268 U.S.-based tweets between January to October 2020. We developed machine learning classifiers to identify and categorize relevant tweets, followed by a qualitative content analysis of a subset of the tweets to understand the rationale of those opposed mask wearing. Results We identified 267 152 tweets that contained personal opinions about wearing facial masks to prevent the spread of COVID-19. While the majority of the tweets supported mask wearing, the proportion of anti-mask tweets stayed constant at about a 10% level throughout the study period. Common reasons for opposition included physical discomfort and negative effects, lack of effectiveness, and being unnecessary or inappropriate for certain people or under certain circumstances. The opposing tweets were significantly less likely to cite external sources of information such as public health agencies’ websites to support the arguments. Conclusions Combining machine learning and qualitative content analysis is an effective strategy for identifying public attitudes toward mask wearing and the reasons for opposition. The results may inform better communication strategies to improve the public perception of wearing masks and, in particular, to specifically address common anti-mask beliefs.
Conical intersections in solution: non-equilibrium versus equilibrium solvation

In this contribution we discuss some dynamical properties of a recently proposed protonated Schiff base model to study the solvation effect on conical intersection (CI) dynamics [I. Burghardt, L. S. Cederbaum, and J. T. Hynes, Faraday Discuss. 127, 395 (2004)]. We consider two dynamical solvation regimes: equilibrium and non-equilibrium. In the first regime, the solvent instantaneously equilibrates to the evolving solute charge distribution, an assumption of many schemes for quantum chemical calculations in solution. In the second regime, appropriate for describing the actual dynamics, account is taken of the (inertial) dynamics of the solvent electrical polarization field. In this regime, both the excited electronic state dynamics and the non-adiabatic transitions in the CI region leading from the excited state to the ground electronic state, calculated via a surface hopping method, are found to differ significantly from those which follow from an equilibrium solvation characterization. Nonetheless, an equilibrium solvation description is useful in locating the seam of CIs which results from the chromophore–solvent interaction.
Aging changes in bladder HCN are associated with increasing heterogeneity of adrenergic/mucosal influence on detrusor control in the mouse.

A geroscience-informed approach to the increasing prevalence of bladder control problems in older adults requires understanding the impact of aging on dynamic mechanisms that ensure resilience in response to stressors challenging asymptomatic voluntary control over urine storage and voiding. Bladder control is predicated on sensory neural information about bladder volume. Modulation of volume-induced bladder wall tensions by autonomic and mucosal factors controls neural sensitivity to bladder volume. We hypothesized that HCN (hyperpolarization-activated cyclic nucleotide-gated) channels integrate these factors and thereby mediate adrenergic detrusor tension control. Furthermore, loss of HCN expression compromises that integration, and could result in loss of precision of detrusor control. Using a lifespan mouse model, RT-qPCR and pharmacologic studies in pre-tensioned intact and mucosa-denuded bladder strips were made. The dominant hcn1 expression declines with maturation and aging, however aging is also associated with increased variance around mean values. In strips from mature animals, isoproterenol had less effect in denuded muscle strips than in intact strips, and HCN blockade diminished isoproterenol responsiveness. With aging, variances about mean response values significantly increased, paralleling hcn1 expression. Our findings support a role for HCN in providing neuroendocrine/paracrine integration and suggest an association of increased heterogeneity of HCN expression in aging with reductions in response precision to neuroendocrine control. The functional implication is an increased risk of dysfunction of brainstem/bladder regulation of neuronal sensitivity to bladder volume. This supports the clinical model of the aging bladder phenotype as an expression of loss of resilience, and not as emerging bladder pathology with aging.