bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of two catalytic mutations on full-length PRDM9 and its isolated PR/SET domain reveal a case of pseudo-modularity
Authors: Powers Natalie R. , Billings Timothy , Paigen Kenneth , Petkov Petko M. 
Published: August 2021

AbstractPRDM9 is a DNA-binding histone methyltransferase that designates and activates recombination hotspots in mammals by locally trimethylating lysines 4 and 36 of histone H3. In mice, we recently reported two independently produced point mutations at the same residue, glu360pro (Prdm9EP) and glu360lys (Prdm9EK), which severely reduce its H3K4 and H3K36 methyltransferase activitiesin vivo. Prdm9EPis slightly less hypomorphic thanPrdm9EK, but both mutations reduce both the number and amplitude of PRDM9-dependent H3K4me3 and H3K36me3 peaks in spermatocytes. While both mutations cause infertility with complete meiotic arrest in males,Prdm9EP, but notPrdm9EK, is compatible with some female fertility. When we tested the effects of these mutationsin vitro, bothPrdm9EPandPrdm9EKabolished H3K4 and H3K36 methyltransferase activity in full-length PRDM9. However, in the isolated PRDM9 PR/SET domain, these mutations selectively compromised H3K36 methyltransferase activity, while leaving H3K4 methyltransferase activity intact. The difference in these effects on the PR/SET domain versus the full-length protein show that PRDM9 is not an intrinsically modular enzyme; its catalytic domain is influenced by its tertiary structure and possibly by its interactions with DNA and other proteinsin vivo. These two informative mutations illuminate the enzymatic chemistry of PRDM9, and potentially of PR/SET domains in general, reveal the minimal threshold of PRDM9-dependent catalytic activity for female fertility, and potentially have some practical utility for genetic mapping and genomics.
Diffusely abnormal white matter converts to T2 lesion volume in the absence of acute inflammation
Authors: Dadar M. , Mahmoud S. , Narayanan S. , Collins DL. , Arnold DL. , Maranzano J. 
Published: August 2021

ABSTRACTDiffusely abnormal white matter (DAWM), characterised by biochemical changes of myelin in the absence of frank demyelination, has been associated with clinical progression in secondary progressive MS (SPMS). However, little is known about changes of DAWM over time and their relation to focal white matter lesions (FWML).The objectives of this work were: 1) To characterize the longitudinal evolution of FWML, DAWM, and DAWM that transforms into FWML, and 2) To determine whether gadolinium enhancement, known to be associated with the development of new FWML, is also related to DAWM voxels that transform into FWML.Our data included 4220 MRI scans of 689 SPMS participants, followed for 156 weeks and 2677 scans of 686 RRMS participants, followed for 96 weeks. FWML and DAWM were segmented using a previously validated, automatic thresholding technique based on normalized T2 intensity values. Using longitudinally registered images, DAWM voxels at each visit that transformed into FWML on the last MRI scan as well as their overlap with gadolinium enhancing lesion masks were identified.Our results showed that the average yearly rate of conversion of DAWM-to-FWML was 1.27cc for SPMS and 0.80cc for RRMS. FWML in SPMS participants significantly increased (t=3.9; p=0.0001) while DAWM significantly decreased (t=-4.3 p<0.0001) and the ratio FWML:DAWM increased (t=12.7; p<0.00001). RRMS participants also showed an increase in the FWML:DAWM Ratio (t=6.9; p<0.00001) but without a significant change of the individual volumes. Gadolinium enhancement was associated with 7.3% and 18.7% of focal New T2 lesion formation in the infrequent scans of the RRMS and SPMS cohorts, respectively. In comparison, only 0.1% and 0.0% of DAWM-to-FWML voxels overlapped with gadolinium enhancement.We conclude that DAWM transforms into FWML over time, in both RRMS and SPMS. DAWM appears to represent a form of pre-lesional pathology that contributes to T2 lesion volume increase over time, independent of new focal inflammation and gadolinium enhancement.
Genetic diversity of local and introduced cassava germplasm in Burundi using DArTseq molecular analyses
Authors: Pierre Niyonzima , Wamalwa Lydia Nanjala , Muiru William Maina , Simon Bigirimana , Kanju Edward , Ferguson Morag Elizabeth , Ndavi Malu Muia , Tumwegamire Silver 
Published: August 2021

AbstractIn Burundi, most of small-scale farmers still grow traditional cassava landraces that are adapted to local conditions and have been selected for consumer preferred attributes. They tend to be susceptible, in varying degrees, to devastating cassava viral diseases such as Cassava Brown Steak Disease (CBSD) and Cassava Mosaic Disease (CMD) with production annual losses of US$1 billion annually. For long term resistance to the disease, several breeding strategies have been proposed. A sound basis for a breeding program is to understand the genetic diversity of both landraces and elite introduced breeding cultivars. This will also assist in efforts to conserve landraces ahead of the broad distribution of improved varieties which have the possibility of replacing landraces. Our study aimed at determining the genetic diversity and relationships of local landraces and introduced elite germplasm using morphological and simple nucleotide polymorphism (SNP) markers as well as identifying a core set of germplasm from the local varieties to be used in the cassava breeding program. A total of 118 cultivars were characterized for morphological trait variation based on leaf, stem and root traits, and genetic variation using SNP markers. Results of morphological characterization based on Ward’s Method revealed three main clusters and five accessions sharing similar characteristics. Molecular characterization identified over 18,000 SNPs and six main clusters and three pairs of duplicates which should be pooled together as one cultivar to avoid redundancy. Results of population genetic analysis showed low genetic distance between populations and between local landraces and elite germplasm. Accessions that shared similar morphological traits were divergent at the molecular level indicating that clustering using morphological traits was inconsistent. Despite the variabilities found within the collection, it was observed that cassava germplasm in Burundi have a narrow genetic base.
Interaction between β-lactoglobulin and EGCG under high-pressure by molecular dynamics simulation
Authors: Huang Yechuan , Zhang Xicai , Suo Huayi 
Published: August 2021

ABSTRACTThe binding between β-lactoglobulin and epigallocatechin gallate (EGCG) under the pressure of 600 MPa was explored using molecular docking and molecular dynamics (MD) simulation. EGCG bound mainly in two regions with site 1 in internal cavity of the β-barrel and site 2 on the surface of protein. 150 ns MD was performed starting from the structure with the lowest binding energy at the two sites in molecular docking, respectively, it was found that the system fluctuated greatly when small molecule bound to site 2 at 0.1 MPa. The protein fluctuation and solvent accessible surface area became smaller under high-pressure. The binding of small molecules made the protein structure more stable with increasing of α-helix and β-sheet, while high-pressure destroyed α-helix of protein. The binding free energy of small molecules at site 1was higher than that at site 2 under 0.1 MPa, with higher van der Waals and hydrophobic interaction at site 1 while more hydrogen bonds at site 2. The binding free energy of both sites decreased under high-pressure, especially at site 1, causing binding free energy at site 1 was lower than that at site 2 under high-pressure.
Integrating genomics and multivariate evolutionary quantitative genetics: A case study of multivariate constraints on sexual selection inDrosophila serrata
Authors: Reddiex Adam J. , Chenoweth Stephen F. 
Published: August 2021

AbstractIn evolutionary quantitative genetics, the genetic variance-covariance matrix,G, and the vector of directional selection gradients,β, are key parameters for predicting multivariate selection responses and genetic constraints. Historically, investigations ofGandβhave not overlapped with those dissecting the genetic basis of quantitative traits. Thus, it remains unknown whether these parameters reflect pleiotropic effects at individual loci. Here, we integrate multivariate GWAS withGandβestimation in a well-studied system of multivariate constraint; sexual selection on male cuticular hydrocarbons (CHCs) inDrosophila serrata. In a panel of wild-derived resequenced lines, we augment genome-based REML, (GREML) to estimateGalongside multivariate SNP effects, detecting 532 significant associations from 1,652,276 SNPs. Constraint was evident, withβlying in a direction ofGwith low evolvability. Interestingly, minor frequency alleles typically increased male CHC-attractiveness suggesting opposing natural selection onβ. SNP effects were significantly misaligned with the major eigenvector ofG,gmax, but well aligned to the second and third eigenvectorsg2andg3. We discuss potential factors leading to these varied results including multivariate stabilising selection and mutational bias. Our framework may be useful as researchers increasingly access genomic methods to study multivariate selection responses in wild populations.
“At that moment, understanding the donation is crucial to make a decision”:A qualitative study exploring the process of postmortem brain tissue donation after suicide
Authors: Padoan Carolina Stopinski , Garcia Lucas França , Crespo Kleber Cardoso , Longaray Vanessa Kenne , Martini Murilo , Contessa Julia Carmargo , Kapczinski Flávio , de Oliveira Francine Hehn , Goldim José Roberto , da Silva Magalhães Pedro Vieira 
Published: August 2021

AbstractBackgroundThe direct examination of postmortem brain tissue can provide valuable help in refining knowledge on the pathophysiology and genetics of neuropsychiatric disorders. Obtaining postmortem consent for the donation of brain tissue after death by suicide can be difficult, as families may be overwhelmed by a violent and unexpected death. Examining the process of brain donation can inform on how the request can best be conducted, examining the existing barriers and enhancing communication, to the benefit of proxy donors.MethodsThis is a qualitative study, in which we employed in-depth interviews to investigate the donation process. Family members of decedents who were eligible for brain tissue donation were asked to consider the donation; irrespective of their decision, they were invited for an interview on the donation process at least 2 months after the suicide. Data collection and analyses were carried out according to a grounded theory framework, and collection, coding, and theorization occurred simultaneously.FindingsForty-one people participated in this study — 32 family members who had consented to donation and 9 who refused it. Five key themes emerged from our data analysis: the context of the families of potential donors, the invitation to talk to the research team, the experience with the request protocol, the participants’ assessment of the experience, and their participation in the study as an opportunity to heal. We arranged the main categories around 3 central stages of the experience described by participants: before the donation request, the request, and after the request.ConclusionsThe participants indicated that a brain donation request that is respectful and tactful can be made without adding to the family distress brought on by suicide and is viewed in a highly positive lens in the months following the event. Having an adequate understanding of tissue donation for research was crucial for satisfactory decision-making. Meeting with the donation team was considered a chance to talk to mental health professionals about suicide. Pondering brain donation was seen as an opportunity to transform the meaning of the death and invest it with a modicum of solace for being able to contribute to research.
Automated differentiation of malignant and benign primary solid liver lesions on MRI: an externally validated radiomics model
Authors: Starmans Martijn P.A. , Miclea Razvan L. , Vilgrain Valerie , Ronot Maxime , Purcell Yvonne , Verbeek Jef , Niessen Wiro J. , Ijzermans Jan N.M. , de Man Rob A. , Doukas Michail , Klein Stefan , Thomeer Maarten G. 
Published: August 2021

AbstractBackground & AimsDistinguishing malignant from benign primary solid liver lesions is highly important for treatment planning. However, diagnosis on radiological imaging is challenging. In this study, we developed a radiomics model based on magnetic resonance imaging (MRI) to distinguish the most common malignant and benign primary solid liver lesions, and externally validated the model in two centers.Approach & ResultsDatasets were retrospectively collected from three tertiary referral centers (A, B and C) including data from affiliated hospitals sent for revision. Patients with malignant (hepatocellular carcinoma and intrahepatic cholangiocarcinoma) and benign (hepatocellular adenoma and focal nodular hyperplasia) lesions were included. For each patient, only a T2-weighted MRI was included. A radiomics model was developed on dataset A using a combination of machine learning approaches, and internally evaluated on dataset A through cross-validation. Next, the model was externally validated on datasets B and C, and compared to scoring by two experienced abdominal radiologists on dataset C. In the resulting dataset, in total, 486 patients were included (A: 187, B: 98 and C: 201). Despite substantial MRI acquisition heterogeneity, the radiomics model developed on dataset A had a mean area under the receiver operating characteristic curve (AUC) of 0.78 in the internal validation on dataset A, and a similar AUC in the external validations (B: 0.74, C: 0.76). In dataset C, the two radiologists showed moderate agreement (Cohen’s κ: 0.61) and achieved AUCs of 0.86 and 0.82, respectively.ConclusionsOur radiomics model using T2-weighted MRI only can non-invasively distinguish malignant from benign primary solid liver lesions. External validation indicated that our model is generalizable despite substantial differences in the acquisition protocols.
Whole-brain connectivity during encoding: age-related differences and associations with cognitive and brain structural decline
Authors: Capogna Elettra , Sneve Markus H. , Raud Liisa , Folvik Line , Ness Hedda , Walhovd Kristine B. , Fjell Anders M. , Vidal-Piñeiro Didac 
Published: August 2021

AbstractThere is a limited understanding of age differences in functional connectivity during memory encoding. In the present study, a sample of cognitively healthy adult participants (n=488), a subsample of whom had longitudinal cognitive and brain structural data spanning 8 years back, underwent fMRI while performing an associative memory encoding task. We investigated 1) age changes in whole-brain connectivity during memory encoding; whether 2) encoding connectivity patterns overlap with the activity signatures of specific cognitive processes and whether 3) connectivity changes associated with memory encoding related to longitudinal brain structural and cognitive changes. Age was associated with decreased intranetwork connectivity and increased connectivity during encoding. Task-connectivity between mediotemporal and posterior parietal regions – which overlapped with areas involved in mental imagery – was related to better memory performance only in older age. The connectivity patterns supporting memory performance in older age reflected preservation of thickness of the medial temporal cortex. These investigations collectively indicate that functional patterns of connectivity should be interpreted in accordance with a maintenance rather than a compensation account.
Rapid and strain-specific resistance evolution ofStaphylococcus aureusagainst inhibitory molecules secreted byPseudomonas aeruginosa
Authors: Niggli Selina , Schwyter Lukas , Poveda Lucy , Grossmann Jonas , Kümmerli Rolf 
Published: August 2021

AbstractPseudomonas aeruginosaandStaphylococcus aureusfrequently occur together in polymicrobial infections, and there is evidence that their interactions negatively affect disease outcome in patients. At the molecular level, interactions between the two bacterial species are well-described, withP. aeruginosausually being the dominant species suppressingS. aureusthrough a variety of inhibitory molecules. However, in chronic infections the two species interact over prolonged periods of time, andS. aureusmight be able to evolve resistance against inhibitory molecules deployed byP. aeruginosa. Here, we used experimental evolution to test this hypothesis by exposing three differentS. aureusstrains (Cowan I, 6850, JE2) to the growth-inhibitory supernatant ofP. aeruginosaPAO1 over 30 days. Prior to evolution, we found thatS. aureusstrains were inhibited by secreted compounds regulatorily controlled by the PQS quorum-sensing system ofP. aeruginosa. Following evolution,S. aureusstrains were no longer inhibited: we observed that phenotypic adaptations were strain-specific and involved the up-regulation of virulence traits, such as staphyloxanthin production and the formation of small colony variants. At the genetic level, mutations in membrane transporters were the most frequent evolutionary targets. Our work indicates that adaptations ofS. aureusto co-infecting pathogens occurs rapidly and involves both virulence traits and membrane transporters involved in drug resistance. Thus, pathogen evolution could promote species co-existence, complicate treatment options and therefore worsen disease outcome.
Resisting stigma and evaluating realism in a direct-to-consumer advertisement for psychiatric drugs
Authors: Walker Tara 
Published: August 2021

Purpose
This study aims to examine how experience with mental illness influences perceptions of stigma and realism in a specific direct-to-consumer advertisement (DTCA) for bipolar depression.

Design/methodology/approach
An online survey had participants watch a 90 s advertisement for a prescription bipolar depression drug and then answer 24 questions about stigma, mental illness experience and the realism of the portrayals in the advertisement.

Findings
Findings show that people who identify as having experience with mental illness tend to see the ad as more stigmatizing and less realistic. Additionally, people who expressed more stigmatizing beliefs also tended to see more stigma present in the ad. Finally, the study reconfirms conclusions of previous research that people who have experience with mental health conditions possess fewer stigmatizing beliefs overall regarding mental illness.

Research limitations/implications
The sample population, while diverse in age and somewhat diverse in location, were highly educated, suggesting that they were not representative of the general population. Future studies may want to use more representative samples. A more nuanced approach to understanding experience is needed. While the sample in this study was purposively derived from communities with a higher rate of mental illness, a comprehensive experience scale to measure degrees of experience with mental illness would enhance understanding of this construct. Researchers may also want to look more deeply into the emotional responses of consumers who view these ads. To develop a greater understanding of the trajectory of DTCA, studies of online advertising for psychiatric drugs are needed.

Practical implications
The results of the study suggest that respondents with experience with mental illness may find ads that sell psychiatric medications unrealistic. This study presents the topic of realism in DTCA as an important construct for determining how consumers may perceive portrayals of disorders.

Social implications
The fact that people who have experience with mental illness found the Latuda ad to be generally unrealistic suggests that DTCA may be failing to represent mental illness in a way that demonstrates care for patients. Additionally, this research confirms that people who have had exposure to and experience with mental illness tend to hold less stigmatizing beliefs, (Link and Cullen, 1986; Corrigan et al., 2001; Angermeyer et al., 2004) a finding which supports the continuing project of increasing mental health literacy and awareness in the general population.

Originality/value
This study investigates the reactions of people who identify as having some experience with mental illness to see if they accept the portrayals of mental illness in DTCA or resist them by challenging their realism or identifying stigmatizing elements.
Socioeconomic wellbeing of women domestic workers in Pune: an exploratory study
Authors: Gupta Hima 
Published: August 2021

PurposeHousehold chores are one of the most essential aspects of each individual's daily routine. The author has observed people from middle and upper socioeconomic backgrounds, outsourcing women domestic workers to perform these household tasks. Even though these women domestic workers make up a significant portion of the total working class, they remain a socially and financially vulnerable section of society. The job of working in other people's private spaces comes with little or no regulation, social protection and no guarantee of decent work standards. The major aim of this study is to find out the social wellbeing of part-time domestic workers of Pune.Design/methodology/approachFor this purpose, the researchers have interviewed 167 women working in the Pune region of Maharashtra, India from the period of October 2020 to January 2021. Descriptive methods and factor analysis have been used to analyze the collected data, so that socioeconomic wellbeing correlated with the significant factors explored. Further, the factors identified that Exploratory Factor Analysis (EFAs) are further validated through reliability analysis (Cronbach’s alpha for economic wellbeing and social wellbeing index for social wellbeing).FindingsWith the help of this study, researchers have tried to explore the significant factors to the social and economic wellbeing of domestic workers. The qualitative facts collected during the interview time have substantiated the findings got in EFA.Originality/valueThe paper aims to provide ground-level insights to policymakers focusing on the domestic work sector, and the gaps identified in the research will help the policymakers to frame the guidelines for the betterment of these informal domestic workers.
Verifying rigor: analyzing qualitative research in international marketing
Authors: Singh Nitish , Benmamoun Mamoun , Meyr Elizabeth , Arikan Ramazan Hamza 
Published: August 2021

PurposeThere has been a growing call regarding broad criteria for assessing qualitative methods' reliability and validity in international marketing (IM) research. In response, this study synthesizes the past literature to present an overarching, yet adaptable, trustworthiness verification framework for assessing the rigor of various qualitative methods used in IM.Design/methodology/approachThe paper draws on qualitative research from various disciplines. It uses content analysis to examine how trustworthiness is conceptualized in qualitative studies in International Marketing Review (IMR) from 2005 to 2019.FindingsThe analysis reveals that strategies to ensure rigor and trustworthiness of qualitative research in IMR are partially applied. There remain gaps in implementing quality criteria across the trustworthiness dimensions of credibility, transferability, dependability, conformability and ethics.Research limitations/implicationsThis paper highlights the importance of incorporating strategies for assessing the quality of qualitative research in IM research. Since the analysis only focused on IMR, future research should explore and test the framework in other IM and business journals to reach a broader consensus in assessing qualitative studies' rigor.Originality/valueIM researchers have yet to develop a consensus regarding broad criteria for assessing qualitative methods' reliability and validity. This paper is an attempt to fill this gap.