bluuebunny/crossref_metadata_2025 huggingface dataset:
2-Oxo-imidazole dipeptides in meat
Authors: Komae Somei , Kasamatsu Shingo , Ihara Hideshi
Published: August 2022

2-Oxo-imidazole dipeptides (2-oxo-IDPs) are highly functional, but it is unclear whether 2-oxo-IDPs exist in meat. Here, we measured 2-oxo-IDPs levels in meat and observed that they varied according to animal species and body parts. In addition, 2-oxo-IDPs in chicken breast extract increased after aeration in the presence of CuSO4/ascorbate, suggesting the potential of elevated 2-oxo-IDPs in effective usage of meat.
Fenretinide combines perturbation of signaling kinases, cell–extracellular matrix interactions and matrix metalloproteinase activation to inhibit invasion in oral squamous cell carcinoma cells
Authors: Wang Daren , Pei Ping , Shea Fortune F , Bissonnette Caroline , Nieto Kari , Din Corrine , Liu Yayuan , Schwendeman Steven P , Lin Yan X , Spinney Richard , Mallery Susan R
Published: August 2022

Basement membrane invasion defines malignant transformation of surface premalignancy. Treatment of oral squamous cell carcinoma (OSCC) cells with the synthetic vitamin A derivative, fenretinide (4HPR), induces numerous cancer-preventive effects including suppression of basement membrane invasion, elimination of anchorage-independent growth, disruption of actin cytoskeletal components and inhibition of the invasion-enabling focal adhesive kinase. The purpose of this study was to elucidate 4HPR’s effects on additional invasion-relevant mechanisms including matrix metalloproteinase (MMP) activation and function, cell–extracellular matrix (ECM) attachments and interaction with a kinase that is essential for the epithelial–myoepithelial transformation i.e. c-Jun NH2-terminal kinase (JNK). Our data revealed that 4HPR binds with high affinity to the ATP-binding site of all three JNK isoforms with concurrent suppression of kinase function. Additional studies showed 4HPR treatment inhibited both OSCC cell–ECM adhesion and MMP activation and function. JNK downregulation and induced expression studies confirmed that the JNK3 isoform conveyed that largest impact on OSCC migration and invasion. Biodegradable polymeric implants formulated to preserve 4HPR’s function and bioavailability were employed to assess 4HPR’s chemopreventive impact on an OSCC tumor induction model. These studies revealed 4HPR local delivery significantly inhibited OSCC tumor size, mitotic indices and expression of the endothelial marker, erythroblast transformation-specific-related gene with concurrent increases in tumor apoptosis (cleaved caspase-3). Collectively, these data show that 4HPR suppresses invasion at multiple sites including ‘outside-in’ signaling, cell–ECM interactions and suppression of MMPs. These functions are also essential for physiologic function. Regulation is therefore essential and reinforces the pharmacologic advantage of local delivery chemopreventive formulations. .
Global media ethics, the good life, and justice
Authors: Hove Thomas
Published: August 2022

One of the challenges for global media ethics is to define a theoretical perspective from which to adjudicate cross-cultural value conflicts. Early work in this field attempted to identify a universal norm from which the specific, applied norms of media professions and practices could be derived. However, postcolonial and pluralist critiques have revealed potential problems with this approach. To avoid such problems, neo-Aristotelian critiques have proposed focusing less on defining universal norms of obligated action and more on acknowledging local variations in conceptions of the good life. These critiques rightly stress the goal of understanding the diversity of ethical values both within and across cultures. However, when the goal of media ethics is to provide guidance for cooperative resolutions of value conflicts, the generalizability of norms remains an important issue. This article reframes this debate more as a division of labor than as a rivalry in approaches.
SC2sepsis: sepsis single-cell whole gene expression database
Authors: Li Yinjiaozhi , Tan Ruoming , Chen Yang , Liu Zhaojun , Chen Erzhen , Pan Tingting , Qu Hongping
Published: August 2022

Sepsis, one of the major challenges in the intensive care unit, is characterized by complex host immune status. Improved understandings of the phenotypic changes of immune cells during sepsis and the driving molecular mechanisms are critical to the elucidation of sepsis pathogenesis. Single-cell RNA sequencing (scRNA-seq), which interprets transcriptome at a single-cell resolution, serves as a useful tool to uncover disease-related gene expression signatures of different cell populations in various diseases. It has also been applied to studies on sepsis immunopathological mechanisms. Due to the fact that most sepsis-related studies utilizing scRNA-seq have very small sample sizes and there is a lack of an scRNA-seq database for sepsis, we developed Sepsis Single-cell Whole Gene Expression Database Website (SC2sepsis) (http://www.rjh-sc2sepsis.com/), integrating scRNA-seq datasets of human peripheral blood mononuclear cells from 45 septic patients and 26 healthy controls, with a total amount of 232 226 cells. SC2sepsis is a comprehensive resource database with two major features: (i) retrieval of 1988 differentially expressed genes between pathological and healthy conditions and (ii) automatic cell-type annotation, which is expected to facilitate researchers to gain more insights into the immune dysregulation of sepsis.

Database URL

http://www.rjh-sc2sepsis.com/
Cardiac mechanics in response to proteasome inhibition: a prospective study
Authors: Makris Nikolaos , Georgiopoulos Georgios , Laina Aggeliki , Tselegkidi Maria-Eirini , Fotiou Despoina , Kanellias Nikolaos , Eleftherakis-Papaiakovou Evaggelos , Migkou Magda , Papanagnou Eleni-Dimitra , Katogiannis Konstantinos , Petropoulos Ioannis , Anninos Hector , Bampatsias Dimitrios , Maneta Eleni , Samouilidou Elisabeth , Nikas Dimitris , Ciliberti Giorgia , Stellos Konstantinos , Terpos Evaggelos , Gavriatopoulou Maria , Trougakos Ioannis P , Ikonomidis Ignatios , Dimopoulos Meletios-Athanasios , Kastritis Efstathios , Stamatelopoulos Kimon
Published: August 2022

Aim

Ubiquitin-Proteasome System (UPS) is of paramount importance regarding the function of the myocardial cell. Consistently, inhibition of this system has been found to affect myocardium in experimental models; yet, the clinical impact of UPS inhibition on cardiac function has not been comprehensively examined. Our aim was to gain insight into the effect of proteasome inhibition on myocardial mechanics in humans.

Methods and results

We prospectively evaluated 48 patients with multiple myeloma and an indication to receive carfilzomib, an irreversible proteasome inhibitor. All patients were initially evaluated and underwent echocardiography with speckle tracking analysis. Carfilzomib was administered according to Kd treatment protocol. Follow-up echocardiography was performed at the 3rd and 6th month. Proteasome activity (PrA) was measured in peripheral blood mononuclear cells.

At 3 months after treatment, we observed early left ventricular (LV) segmental dysfunction and deterioration of left atrial (LA) remodelling, which was sustained and more pronounced than that observed in a cardiotoxicity control group. At 6 months, LV and right ventricular functions were additionally attenuated (P < 0.05 for all). These changes were independent of blood pressure, endothelial function, inflammation, and cardiac injury levels. Changes in PrA were associated with changes in global longitudinal strain (GLS), segmental LV strain, and LA markers (P < 0.05 for all). Finally, baseline GLS < −18% or LA strain rate > 1.71 were associated with null hypertension events.

Conclusion

Inhibition of the UPS induced global deterioration of cardiac function.
Current and future use of neuromodulation in heart failure
Authors: Duncker David , Bauersachs Johann
Published: August 2022

Autonomic imbalance is a common finding in heart failure (HF) with reduced ejection fraction (HFrEF). Addressing different targets within the autonomic nervous systems has been evaluated in patients with HF, including renal sympathetic denervation, vagal nerve stimulation, and baroreceptor activation therapy (BAT). Although all are pathophysiologically plausible and promising, only BAT shows sufficient evidence for implementation into clinical practice in randomized controlled trials. Baroreceptor activation therapy can be used in patients with symptomatic HFrEF despite optimal guideline-directed medication and device therapy. This article reviews the current and future use of neuromodulation in HF and provides an overview on current guideline recommendations and clinical practice.
ZW sex-chromosome evolution and contagious parthenogenesis in Artemia brine shrimp
Authors: Elkrewi Marwan , Khauratovich Uladzislava , Toups Melissa A , Bett Vincent Kiplangat , Mrnjavac Andrea , Macon Ariana , Fraisse Christelle , Sax Luca , Huylmans Ann Kathrin , Hontoria Francisco , Vicoso Beatriz
Published: August 2022

Eurasian brine shrimp (genus Artemia) have closely related sexual and asexual lineages of parthenogenetic females, which produce rare males at low frequencies. Although they are known to have ZW chromosomes, these are not well characterized, and it is unclear whether they are shared across the clade. Furthermore, the underlying genetic architecture of the transmission of asexuality, which can occur when rare males mate with closely related sexual females, is not well understood. We produced a chromosome-level assembly for the sexual Eurasian species Artemia sinica and characterized in detail the pair of sex chromosomes of this species. We combined this new assembly with short-read genomic data for the sexual species Artemia sp. Kazakhstan and several asexual lineages of Artemia parthenogenetica, allowing us to perform an in-depth characterization of sex-chromosome evolution across the genus. We identified a small differentiated region of the ZW pair that is shared by all sexual and asexual lineages, supporting the shared ancestry of the sex chromosomes. We also inferred that recombination suppression has spread to larger sections of the chromosome independently in the American and Eurasian lineages. Finally, we took advantage of a rare male, which we backcrossed to sexual females, to explore the genetic basis of asexuality. Our results suggest that parthenogenesis is likely partly controlled by a locus on the Z chromosome, highlighting the interplay between sex determination and asexuality.
Suppressor mutations that make the essential transcription factor Spn1/Iws1 dispensable inSaccharomyces cerevisiae
Authors: López-Rivera Francheska , Chuang James , Spatt Dan , Gopalakrishnan Rajaraman , Winston Fred
Published: August 2022

Spn1/Iws1 is an essential eukaryotic transcription elongation factor that is conserved from yeast to humans as an integral member of the RNA polymerase II elongation complex. Several studies have shown that Spn1 functions as a histone chaperone to control transcription, RNA splicing, genome stability, and histone modifications. However, the precise role of Spn1 is not understood, and there is little understanding of why it is essential for viability. To address these issues, we have isolated 8 suppressor mutations that bypass the essential requirement for Spn1 in Saccharomyces cerevisiae. Unexpectedly, the suppressors identify several functionally distinct complexes and activities, including the histone chaperone FACT, the histone methyltransferase Set2, the Rpd3S histone deacetylase complex, the histone acetyltransferase Rtt109, the nucleosome remodeler Chd1, and a member of the SAGA coactivator complex, Sgf73. The identification of these distinct groups suggests that there are multiple ways in which Spn1 bypass can occur, including changes in histone acetylation and alterations in other histone chaperones. Thus, Spn1 may function to overcome repressive chromatin by multiple mechanisms during transcription. Our results suggest that bypassing a subset of these functions allows viability in the absence of Spn1.
Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial
Authors: Kumar Premranjan , Liu Chun , Suliburk James , Hsu Jean W , Muthupillai Raja , Jahoor Farook , Minard Charles G , Taffet George E , Sekhar Rajagopal V
Published: August 2022

Background

Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

Methods

Twenty-four OA and 12 young adults (YA) were studied. OA was randomized to receive either GlyNAC (N = 12) or isonitrogenous alanine placebo (N = 12) for 16-weeks; YA (N = 12) received GlyNAC for 2-weeks. Participants were studied before, after 2-weeks, and after 16-weeks of supplementation to assess GSH concentrations, OxS, MFO, molecular regulators of energy metabolism, inflammation, endothelial function, IR, aging hallmarks, gait speed, muscle strength, 6-minute walk test, body composition, and blood pressure.

Results

Compared to YA, OA had GSH deficiency, OxS, mitochondrial dysfunction (with defective molecular regulation), inflammation, endothelial dysfunction, IR, multiple aging hallmarks, impaired physical function, increased waist circumference, and systolic blood pressure. GlyNAC (and not placebo) supplementation in OA improved/corrected these defects.

Conclusion

GlyNAC supplementation in OA for 16-weeks was safe and well-tolerated. By combining the benefits of glycine, NAC and GSH, GlyNAC is an effective nutritional supplement that improves and reverses multiple age-associated abnormalities to promote health in aging humans.

Clinical Trials Registration Number: NCT01870193
Till Death Do Us Part?: Exploring the Social Convoys of Conjugally Bereaved Women
Authors: Hackett Sara E , de Medeiros Kate
Published: August 2022

Objectives

The hierarchical mapping technique (HMT) is used to study social convoys, peoples’ support systems. Recent research integrating the HMT and the continuing bonds framework suggests that deceased persons may be influential convoy members. Extending this idea, the current study aimed to gain insight regarding how older conjugally bereaved women view the role of a deceased romantic partner in their convoy.

Methods

The study utilized a qualitative descriptive approach. Twenty heterosexual women (mean age = 78 years, range = 65–93 years), recruited via social media and snowball sampling, participated in one 90-min interview. Each discussed their bereavement journey and completed an HMT diagram to comment on how, if at all, their deceased romantic partner was part of their social convoy and their place within it.

Results

Fifteen of the 20 women placed the deceased in the innermost circle of the diagram, with them yet separate from other convoy members. Thematic analysis of transcripts revealed 5 major themes: “We’re part of each other,” “I think he supports me,” “He would want me to be happy,” “I just feel so grateful,” and “I think about him every day but I don’t talk about him every day.”

Discussion

Perceptions that deceased romantic partners continue to play a key role in conjugally bereaved older women’s lives offer researchers the unique opportunity to examine how loss is carried into old age. Furthermore, this study may assist with the development of interventions that destigmatize continuing bond expressions for conjugally bereaved heterosexual women.
Mitigating the effect of errors in source parameters on seismic (waveform) tomography
Authors: Blom Nienke , Hardalupas Phil-Simon , Rawlinson Nicholas
Published: August 2022

We investigate the effect of errors in earthquake source parameters on the tomographic inverse problem and propose mitigation strategies for avoiding artefacts caused by such errors. In global catalogues, mislocation errors can amount to tens of kilometres both horizontally and vertically, while fault plane uncertainties can be of the order of tens of degrees. We conduct a perturbation study investigating both errors in the source location and in the moment tensor. Spatial perturbations of 5 km and fault plane perturbations of 5° result in measured time-shifts of the order of 0.5 to several seconds, which in five iterations lead to artefacts with amplitudes of the order of 0.5–1 per cent spanning up to several hundreds of kilometres. Larger perturbations (e.g. 20 km) lead to artefacts similar in amplitude (∼5 per cent) to the features judged to be interpretable in tomographic models. This can be further exacerbated by the cumulative effect of systematic errors. Mitigation strategies consist of removing a region around the source from the gradient and discarding traces where amplitudes are comparatively small. The most problematic type of error is a horizontal mislocation, because its imprint is not removed by such measures—discarding a ‘suspicious’ event may be the only option if no trustworthy ground truth is available. Although this study focuses on (adjoint) waveform tomography, a large part of the results are equally valid for any other type of imaging method that is based on time- and/or phase-shift measurements. The concerns and mitigation strategies presented here therefore have broader applicability.
Examining semantic (dis)similarity in news through news organizations’ ideological similarity, similarity in truthfulness, and public engagement on social media: a network approach
Authors: Li Yue , Bond Robert M
Published: August 2022

The rise of homogenization and polarization in the news may inhibit individuals’ understanding of an issue and the functioning of a democratic society. This study applies a network approach to understanding patterns of semantic similarity and divergence across news coverage. Specifically, we focus on how (a) inter-organizational networks based on media ideology, (b) inter-organizational networks based on news truthfulness, and (c) public engagement that news articles received on social media may affect semantic similarity in the news. We use large-scale user logs data on social media platforms (i.e., Facebook and Twitter) and news text data from more than 100 news organizations over 10 months to examine the three potential processes. Our results show that the similarity between news organizations in terms of media ideology and news truthfulness is positively associated with semantic similarity, whereas the public engagement that news articles received on social media is negatively associated with semantic similarity. Our study contributes to theory development in mass communication by shifting to a network paradigm that connects news organizations, news content, and news audiences. We demonstrate how scholars across communication disciplines may collaborate to integrate distinct theories, connect multiple levels, and link otherwise separate dimensions. Methodologically, we demonstrate how synchronizing network science with natural language processing and combining social media log data with text data can help to answer research questions that communication scholars are interested in. The findings’ implications for news polarization are discussed.
Association of Impulsivity With Food, Nutrients, and Fitness in a Longitudinal Birth Cohort Study
Authors: Matrov Denis , Kurrikoff Triin , Villa Inga , Sakala Katre , Pulver Aleksander , Veidebaum Toomas , Shimmo Ruth , Harro Jaanus
Published: August 2022

Background

Impulsivity is a psychiatric vulnerability factor strongly associated with substance abuse but also with unhealthy diet. Whether these associations extend to specific nutrients is largely unknown. Therefore, we investigated the longitudinal association between diet, cardiorespiratory fitness, and 2 impulsivity dimensions in a representative sample of south Estonian adolescents and young adults. Impulsivity and dietary intake were measured 3 times in 2 birth cohorts at regular intervals in individuals aged 15 to 33 years.

Methods

The sample included 2 birth cohorts of the longitudinal Estonian Children Personality Behaviour and Health Study. The analytic sample size consisted of 2883 observations (56.4% females). The primary outcomes were adaptive and maladaptive impulsivity scores measured by an original 24-item Likert-type questionnaire. Impulsivity scores were predicted from the food diaries data converted into nutrient categories. A linear mixed-effects approach was used to model the time dependence between observations.

Results

Lower maladaptive impulsivity was associated with higher cardiorespiratory fitness (β = −.07; 95% CI = −0.12; −0.03). Higher maladaptive impulsivity was associated with lower dietary intake of zinc (β = −.10; −0.15; −0.06) and vegetables (β = −.04; −0.07; −0.01) and higher intake of sodium (β = .06; 0.02; 0.10). Vitamin B6 was positively associated with adaptive impulsivity (β = .04; 0.01; 0.07). Additionally, some of the adjusted models showed significant but weak associations with selenium, alcohol, fish, and cereal products.

Conclusions

Food choice may affect the neurochemistry and therefore regulate the manifestations of impulsivity. We identified associations between several (micro)nutrients and maladaptive impulsivity.
Association Between Human Immunodeficiency Virus Viremia and Compromised Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant
Authors: Hwa Shi-Hsia , Snyman Jumari , Bernstein Mallory , Ganga Yashica , Cele Sandile , Muema Daniel , Tan Chee Wah , Khan Khadija , Karim Farina , Hanekom Willem , Bernstein Leslie , Kaufmann Stefan H E , Wang Lin-Fa , Ndung’u Thumbi , Sigal Alex ,   the COMMIT-KZN Team, Steyn Adrie , Leslie Alasdair , Ramjit Dirhona , Wong Emily , Harling Guy , Kloverpris Henrik , Marakalala Jackson , Seeley Janet , Giandhari Jennifer , Dullabh Kaylesh , Nyamande Kennedy , Herbst Kobus , Naidoo Kogie , Mazibuko Matilda , Archary Moherndran , Moshabela Mosa , Padayatchi Nesri , Klein Nigel , Mbatha Nikiwe , Ngcobo Nokuthula , Gumede Nokwanda , Ngcobo Nokwanda , Goulder Philip , Jeena Prakash , Madansein Rajhmun , Gupta Ravindra K , Harrichandparsad Rohen , Singh Samita , Khoza Thandeka , Smit Theresa , Planck Max , Patel Vinod , Ndhlovu Zaza
Published: August 2022

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may be associated with worse clinical outcomes in people with human immunodeficiency virus (HIV) (PWH). We report anti–SARS-CoV-2 antibody responses in patients hospitalized with coronavirus disease 2019 in Durban, South Africa, during the second SARS-CoV-2 infection wave dominated by the Beta (B.1.351) variant.

Methods

Thirty-four participants with confirmed SARS-CoV-2 infection were followed up with weekly blood sampling to examine antibody levels and neutralization potency against SARS-CoV-2 variants. Participants included 18 PWH, of whom 11 were HIV viremic.

Results

SARS-CoV-2–specific antibody concentrations were generally lower in viremic PWH than in virologically suppressed PWH and HIV-negative participants, and neutralization of the Beta variant was 4.9-fold lower in viremic PWH. Most HIV-negative participants and antiretroviral therapy–suppressed PWH also neutralized the Delta (B.1.617.2) variant, whereas the majority of viremic PWH did not. CD4 cell counts <500/μL were associated with lower frequencies of immunoglobulin G and A seroconversion. In addition, there was a high correlation between a surrogate virus neutralization test and live virus neutralization against ancestral SARS-CoV-2 virus in both PWH and HIV-negative individuals, but correlation decreased for the Beta variant neutralization in PWH.

Conclusions

HIV viremia was associated with reduced Beta variant neutralization. This highlights the importance of HIV suppression in maintaining an effective SARS-CoV-2 neutralization response.
Inflammation and Metabolism of Influenza-Stimulated Peripheral Blood Mononuclear Cells From Adults With Obesity Following Bariatric Surgery
Authors: Green William D , Alwarawrah Yazan , Al-Shaer Abrar E , Shi Qing , Armstrong Michael , Manke Jonathan , Reisdorph Nichole , Farrell Timothy M , Hursting Steven D , MacIver Nancie J , Beck Melinda A , Shaikh Saame Raza
Published: August 2022

Background

Obesity dysregulates immunity to influenza infection. Therefore, there is a critical need to investigate how obesity impairs immunity and to establish therapeutic approaches that mitigate the impact of increased adiposity. One mechanism by which obesity may alter immune responses is through changes in cellular metabolism.

Methods

We studied inflammation and cellular metabolism of peripheral blood mononuclear cells (PBMCs) isolated from individuals with obesity relative to lean controls. We also investigated if impairments to PBMC metabolism were reversible upon short-term weight loss following bariatric surgery.

Results

Obesity was associated with systemic inflammation and poor inflammation resolution. Unstimulated PBMCs from participants with obesity had lower oxidative metabolism and adenosine triphosphate (ATP) production compared to PBMCs from lean controls. PBMC secretome analyses showed that ex vivo stimulation with A/Cal/7/2009 H1N1 influenza led to a notable increase in IL-6 with obesity. Short-term weight loss via bariatric surgery improved biomarkers of systemic metabolism but did not improve markers of inflammation resolution, PBMC metabolism, or the PBMC secretome.

Conclusions

These results show that obesity drives a signature of impaired PBMC metabolism, which may be due to persistent inflammation. PBMC metabolism was not reversed after short-term weight loss despite improvements in measures of systemic metabolism.
Effects of the news finds me perception on algorithmic news attitudes and social media political homophily
Authors: Gil de Zúñiga Homero , Cheng Zicheng , González-González Pablo
Published: August 2022

Prior literature on political filter bubbles suggests an overall positive association between social media use and political networks diversification. Sometimes, this might not be the case. This study argues that the News Finds Me perception (NFM) or the belief that “one” can be well-informed about public affairs without actively seeking information as news will find “me” through “my” networks, tend to nurture a positive attitude toward algorithmic news gatekeeping. Likewise, NFM’s news over-reliance on one’s social network support the development of homogeneous information and discussion political networks in social media (political homophily). Results based on a variety of ordinary least squares regression models (cross-sectional, lagged, and autoregressive) from a U.S. representative panel survey, as we all as autoregressive structural equation model tests, indicate that this is indeed the case. This study serves to specifically clarify when and how social media and the NFM facilitate politically homogeneous filter bubbles.
Trajectories of Maternal and Paternal Psychological Distress After Fetal Diagnosis of Moderate–Severe Congenital Heart Disease
Authors: Mangin-Heimos Kathryn S , Strube Michael , Taylor Kaylin , Galbraith Kymberli , O’Brien Erin , Rogers Cynthia , Lee Caroline K , Ortinau Cynthia
Published: August 2022

Objective

The aim of this study was to compare trajectories of maternal and paternal psychological distress after prenatal diagnosis of fetal moderate–severe congenital heart disease (CHD), from pregnancy through early-mid infancy.

Methods

Pregnant women who received a prenatal diagnosis of fetal moderate–severe CHD, and their partners, were enrolled in a prospective, longitudinal study. Symptoms of psychological distress were measured twice during pregnancy and twice after birth, using the Depression Anxiety Stress Scales (DASS-42). Patterns and predictors of psychological distress were examined using generalized hierarchical linear modeling.

Results

Psychological distress was present in 42% (18/43) of mothers and 22% (8/36) of fathers at least once during the study. The rates of distress did not differ between mothers and fathers. There was also no change in probability of distress over time or difference in distress trajectories between mothers and fathers. However, individual trajectories demonstrated considerable variability in symptoms for both mothers and fathers. Predictors of psychological distress included low social support for mothers and a history of mental health conditions for fathers.

Conclusions

Parents who receive a prenatal diagnosis of fetal CHD commonly report symptoms of psychological distress from the time of diagnosis through early-mid infancy and display highly variable trajectories. These data suggest that early and repeated psychological screening is important once a fetal CHD diagnosis is made and that providing mental health and social support to parents may be an important component of their ongoing care.
Spin-driven jet feedback in idealized simulations of galaxy groups and clusters
Authors: Huško Filip , Lacey Cedric G , Schaye Joop , Schaller Matthieu , Nobels Folkert S J
Published: August 2022

We implement a black hole spin evolution and jet feedback model into SWIFT, a smoothed particle hydrodynamics code. The jet power is determined self-consistently assuming that the black hole accretion rate is equal to the Bondi rate (i.e. the accretion efficiency is 100 per cent), and using a realistic, spin-dependent efficiency. The jets are launched along the spin axis of the black hole, resulting in natural reorientation and precession. We apply the model to idealized simulations of galaxy groups and clusters, finding that jet feedback successfully quenches gas cooling and star formation in all systems. Our group-size halo (M200 = 1013 M⊙) is quenched by a strong jet episode triggered by a cooling flow, and it is kept quenched by a low-power jet fed from hot halo accretion. In more massive systems (M200 ≳ 1014 M⊙), hot halo accretion is insufficient to quench the galaxies, or to keep them quenched after the first cooling episode. These galaxies experience multiple episodes of gas cooling, star formation, and jet feedback. In the most massive galaxy cluster that we simulate (M200 = 1015 M⊙), we find peak cold gas masses of 1010 M⊙ and peak star formation rates of a few times 100 $\mathrm{M}_\odot \,\, \mathrm{yr}^{-1}$. These values are achieved during strong cooling flows, which also trigger the strongest jets with peak powers of 1047$\mathrm{erg}\, \mathrm{s}^{-1}$. These jets subsequently shut off the cooling flows and any associated star formation. Jet-inflated bubbles draw out low-entropy gas that subsequently forms dense cooling filaments in their wakes, as seen in observations.
Resistance Evolution against Host-directed Antiviral Agents: Buffalopox Virus Switches to Use p38-ϒ under Long-term Selective Pressure of an Inhibitor Targeting p38-α
Authors: Chander Yogesh , Kumar Ram , Verma Assim , Khandelwal Nitin , Nagori Himanshu , Singh Namita , Sharma Shalini , Pal Yash , Puvar Apurvasinh , Pandit Rameshchandra , Shukla Nitin , Chavada Priyank , Tripathi Bhupendra N , Barua Sanjay , Kumar Naveen
Published: August 2022

Host-dependency factors have increasingly been targeted to minimize antiviral drug resistance. In this study, we have demonstrated that inhibition of p38 mitogen-activated protein kinase (a cellular protein) suppresses buffalopox virus (BPXV) protein synthesis by targeting p38-MNK1-eIF4E signaling pathway. In order to provide insights into the evolution of drug resistance, we selected resistant mutants by long-term sequential passages (P; n = 60) in the presence of p38 inhibitor (SB239063). The P60-SB239063 virus exhibited significant resistance to SB239063 as compared to the P60-Control virus. To provide mechanistic insights on the acquisition of resistance by BPXV-P60-SB239063, we generated p38-α and p38-ϒ (isoforms of p38) knockout Vero cells by CRISPR/Cas9-mediated genome editing. It was demonstrated that unlike the wild type (WT) virus which is dependent on p38-α isoform, the resistant virus (BPXV-P60-SB239063) switches over to use p38-ϒ so as to efficiently replicate in the target cells. This is a rare evidence wherein a virus was shown to bypass the dependency on a critical cellular factor under selective pressure of a drug.
BH3 mimetics targeting BCL-XL impact the senescent compartment of pilocytic astrocytoma
Authors: Selt Florian , Sigaud Romain , Valinciute Gintvile , Sievers Philipp , Zaman Julia , Alcon Clara , Schmid Simone , Peterziel Heike , Tsai Jessica W , Guiho Romain , Martínez-Barbera Juan Pedro , Pusch Stefan , Deng Jing , Zhai Yifan , van Tilburg Cornelis M , Schuhman Martin U , El Damaty Ahmed , Bandopadhayay Pratiti , Herold-Mende Christel , von Deimling Andreas , Pfister Stefan M , Montero Joan , Capper David , Oehme Ina , Sahm Felix , Jones David T W , Witt Olaf , Milde Till
Published: August 2022

Background

Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and a mitogen-activated protein kinase (MAPK)-driven disease. Oncogenic MAPK-signaling drives the majority of cells into oncogene-induced senescence (OIS). While OIS induces resistance to antiproliferative therapies, it represents a potential vulnerability exploitable by senolytic agents.

Methods

We established new patient-derived PA cell lines that preserve molecular features of the primary tumors and can be studied in OIS and proliferation depending on expression or repression of the SV40 large T antigen. We determined expression of anti-apoptotic BCL-2 members in these models and primary PA. Dependence of senescent PA cells on anti-apoptotic BCL-2 members was investigated using a comprehensive set of BH3 mimetics.

Results

Senescent PA cells upregulate BCL-XL upon senescence induction and show dependency on BCL-XL for survival. BH3 mimetics with high affinity for BCL-XL (BCL-XLi) reduce metabolic activity and induce mitochondrial apoptosis in senescent PA cells at nano-molar concentrations. In contrast, BH3 mimetics without BCL-XLi activity, conventional chemotherapy, and MEK inhibitors show no effect.

Conclusions

Our data demonstrate that BCL-XL is critical for survival of senescent PA tumor cells and provides proof-of-principle for the use of clinically available BCL-XL-dependent senolytics.
Generation of chromosome 1p/19q co-deletion by CRISPR/Cas9-guided genomic editing
Authors: Li Chao , Liu Zhong , Zhang Xiaoxia , Wang Huafeng , Friedman Gregory K , Ding Qiang , Zhao Xinyang , Li Hu , Kim Kitai , Yu Xi , Burt Nabors L , Han Xiaosi , Zhao Rui
Published: August 2022

Background

Chromosomal translocation has been detected in many human cancers including gliomas and is considered a driving force in tumorigenesis. Co-deletion of chromosome arms 1p and 19q is a hallmark for oligodendrogliomas. On the molecular level, 1p/19q co-deletion results from t(1;19)(q10;p10), which leads to the concomitant formation of a hybrid chromosome containing the 1q and 19p arms. A method to generate 1p/19q co-deletion is lacking, which hinders the investigation of how 1p/19q co-deletion contributes to gliomagenesis.

Methods

We hypothesized that chromosomal translocation, such as t(1;19)(q10;p10) resulting in the 1p/19q co-deletion, may be induced by simultaneously introducing DNA double-strand breaks (DSBs) into chromosomes 1p and 19q using CRISPR/Cas9. We developed a CRISPR/Cas9-based strategy to induce t(1;19)(q10;p10) and droplet digital PCR (ddPCR) assays to detect the hybrid 1q/19p and 1p/19q chromosomes.

Results

After translocation induction, we detected both 1p/19q and 1q/19p hybrid chromosomes by PCR amplification of the junction regions in HEK 293T, and U-251 and LN-229 glioblastoma cells. Sequencing analyses of the PCR products confirmed DNA sequences matching both chromosomes 1 and 19. Furthermore, the 1p/19q hybrid chromosome was rapidly lost in all tested cell lines. The 1q/19p hybrid chromosome also become undetectable over time likely due to cell survival disadvantage.

Conclusion

We demonstrated that t(1;19)(q10;p10) may be induced by CRISPR/Cas9-mediated genomic editing. This method represents an important step toward engineering the 1p/19q co-deletion to model oligodendrogliomas. This method may also be generalizable to engineering other cancer-relevant translocations, which may facilitate the understanding of translocation roles in cancer progression.
Glycosylphosphatidylinositol anchor lipid remodeling directs proteins to the plasma membrane and governs cell wall mechanics
Authors: Xu Zuopeng , Gao Yihong , Gao Chengxu , Mei Jiasong , Wang Shaogan , Ma Jiaxin , Yang Hanlei , Cao Shaoxue , Wang Yan , Zhang Fengxia , Liu Xiangling , Liu Qiaoquan , Zhou Yihua , Zhang Baocai
Published: August 2022

Glycosylphosphatidylinositol (GPI) anchoring is a common protein modification that targets proteins to the plasma membrane (PM). Knowledge about the GPI lipid tail, which guides the secretion of GPI-anchored proteins (GPI-APs), is limited in plants. Here, we report that rice (Oryza sativa) BRITTLE CULM16 (BC16), a membrane-bound O-acyltransferase (MBOAT) remodels GPI lipid tails and governs cell wall biomechanics. The bc16 mutant exhibits fragile internodes, resulting from reduced cell wall thickness and cellulose content. BC16 is the only MBOAT in rice and is located in the endoplasmic reticulum and Golgi apparatus. Yeast gup1Δ mutant restoring assay and GPI lipid composition analysis demonstrated BC16 as a GPI lipid remodelase. Loss of BC16 alters GPI lipid structure and disturbs the targeting of BC1, a GPI-AP for cellulose biosynthesis, to the PM lipid nanodomains. Atomic force microscopy revealed compromised deposition of cellulosic nanofibers in bc16, leading to an increased Young’s modulus and abnormal mechanical properties. Therefore, BC16-mediated lipid remodeling directs the GPI-APs, such as BC1, to the cell surface to fulfill multiple functions, including cellulose organization. Our work unravels a mechanism by which GPI lipids are remodeled in plants and provides insights into the control of cell wall biomechanics, offering a tool for breeding elite crops with improved support strength.
Comparing Canadian paediatric rheumatology practice to the 2019 ACR Juvenile Idiopathic Arthritis guidelines: results from the CAPRI Registry
Authors: Park Jonathan , Batthish Michelle , Berard Roberta A , Chédeville Gaëlle , Proulx-Gauthier Jean-Philippe , Rumsey Dax G , Tucker Lori B , Wong Stephanie , Guzman Jaime ,   for the CAPRI Registry Investigators, Cabral David , Chédeville Gaëlle , Duffy Ciarán , Gerhold Kerstin , Guzman Jaime , Hiraki Linda , Huber Adam , Schmeling Heinrike , Shiff Natalie , Tucker Lori , Basodan Daniah , Batthish Michelle , Berard Roberta A , Bolaria Roxana , Bruns Alessandra , Cabral David , Campillo Sarah , Cellucci Tania , Chan Mercedes , Chédeville Gaëlle , Chhabra Amieleena , Dancey Paul , Demirkaya Erkan , Dhalla Muhammed , Duffy Ciaran , Duffy Karen Watanabe , Gerschman Tommy , Guzman Jaime , Heale Liane , Houghton Kristin , Human Andrea , Jurencak Roman , LeBlanc Claire , Lim Lilian , Miettunen Paivi , Morishita Kim , Ng Honyan , Proulx-Gauthier Jean-Philippe , Roth Johannes , Rozenblyum Evelyn , Rumsey Dax G , Schmeling Heinrike , Scuccimarri Rosie , Soon Gordon , Tucker Lori B
Published: August 2022

Objective

To identify differences between baseline Canadian JIA practices and the 2019 ACR guidelines for JIA.

Methods

Canadian paediatric rheumatologists were surveyed for their opinions on reasonable a priori target adherence rates for JIA guideline recommendations. Prospectively collected data for 266 newly diagnosed children from 2017 to 2019 were analysed to calculate observed adherence rates. Kaplan–Meier survival curves were used to estimate the cumulative incidence of starting synthetic or biologic DMARDs (sDMARD or bDMARD, respectively) for different patient groups.

Results

A total of 25/61 (41%) eligible physicians answered the survey. Most survey respondents (64%) felt that adherence targets should vary depending on the strength of the recommendation and quality of evidence, from a mean of 84% for strong recommendations with high-quality evidence to 29% for conditional recommendations with very low-quality evidence. Data showed 13/19 (68%) recommendations would have met proposed targets and 10/19 (53%) had ≥80% observed adherence. Exceptions were the use of subcutaneous vs oral MTX (53%) and infrequent treatment escalation from NSAIDs to bDMARDs in patients with sacroiliitis (31%) or enthesitis (0%). By 12 weeks, 95% of patients with polyarthritis received sDMARDs, 38% of patients with systemic JIA received bDMARDs and 22% of patients with sacroiliitis received bDMARDs.

Conclusion

Canadian paediatric rheumatology practices were in line with many 2019 JIA guideline recommendations before their publication, except for frequent use of oral MTX and infrequent direct escalation from NSAIDs to bDMARDs in sacroiliitis and enthesitis.
Politics at the Gun Counter: Examining Partisanship and Masculinity among Conservative Gun Sellers during the 2020 Gun Purchasing Surge
Authors: An Minyoung , Carlson Jennifer
Published: August 2022

How does gender shape how conservatives “do partisanship”? This paper draws on interviews with a group of conservative Americans—gun sellers—during a year of record gun sales amid a global pandemic, civil unrest, and democratic instability. In 2020, gun sellers navigated an increasingly diverse clientele, including what they understood as an increase in liberal, progressive, and leftist gun buyers. This unique influx bucked decades-long trends of partisan sorting in America and compelled gun sellers to “do partisanship” as they fielded the new gun buyers in their stores. Integrating the literatures on the gender gap in partisanship with scholarship on hegemonic masculinity, this paper examines how gun sellers mobilized masculinity as a means of expressing and engaging in partisanship. Our analysis details how interviewees (1) embrace a brand of hegemonic masculinity that champions self-preservation and preparedness, (2) define themselves against liberal politics and policies they deem emasculating, and (3) draw partisan boundaries around gun ownership that reinforce conservatives as responsible gun owners while denigrating liberals as emotional, impressionable, and incompetent. We argue that partisanship can be understood as a gendered practice that provides insight into how conservatives make political meaning in their everyday lives.
Sall4 Guides p53-Mediated Enhancer Interference upon DNA Damage in Mouse Embryonic Stem Cells
Authors: Wang Lei , Tan Xiaojun , Chen Lu , Xu Sisi , Huang Weiping , Chen Nan , Wu Yizhou , Wang Chunyan , Zhou Daqiang , Li Mangmang
Published: August 2022

p53 plays a pivotal role in maintaining the genomic stability of mouse embryonic stem cells (mESCs) through transcriptionally activating and repressing target genes. However, how p53 recognizes its repressed targets remains largely unknown. Herein, we demonstrate that Sall4 negatively regulates DNA damage induced apoptosis (DIA) of mESCs through mediating p53 recruitment to enhancers of ESC-associated genes repressed by p53 from promoters of p53-activated genes. Upon DNA damage, Sall4 is transcriptionally repressed by p53 and plays an anti-apoptotic role without altering p53 activation. Moreover, Sall4 is identified as a novel p53-interacting partner. Consistently, Sall4 exerts its anti-apoptotic function in a p53-dependent manner. Intriguingly, Sall4 depletion not only promotes the transcriptional activation of several p53-regulated pro-apoptotic genes but also compromises p53-mediated repression of ESC master transcription factors in response to DNA damage. Mechanistically, Sall4 balances p53-binding affinity between p53-activated and -repressed genes through tethering p53 to ESC enhancers. In light of our study, Sall4 may contribute to tumorigenesis by antagonizing p53-mediated apoptosis.
Frequency of maternal supplementation of energy and protein during late gestation modulates preweaning growth of their beef offspring
Authors: Izquierdo Vinicius , Vedovatto Marcelo , Palmer Elizabeth A , Oliveira Rhaiza A , Silva Hiran M , Vendramini João M B , Moriel Philipe
Published: August 2022

This study evaluated the effects of decreasing the frequency of dried distillers grains (DDG) supplementation during third trimester of gestation on cow physiology and offspring preweaning growth. At 201 ± 7 d prepartum (day 0 of the study), 120 Brangus crossbred cows were stratified by body weight (BW = 543 ± 53 kg) and body condition score (BCS = 5.47 ± 0.73), and then assigned randomly to 1 of 20 bahiagrass (Paspalum notatum) pastures (six cows and 4.7 ha/pasture). Treatments were randomly assigned to pastures (five pastures/treatment) and consisted of cows offered no DDG supplementation (NOSUP) or precalving supplementation of DDG dry matter at 1 kg/cow daily (7×), 2.33 kg/cow every Monday, Wednesday, and Friday (3×), or 7 kg/cow every Monday (1×) from day 0 to 77. All cows assigned to DDG supplementation received the same total amount of DDG dry matter (77 kg/cow) from day 0 to 77. All cow-calf pairs were managed similarly from day 77 until calf weaning (day 342). Supplementation frequency did not impact (P ≥ 0.16) any forage or cow reproduction data. Cow BCS on days 77, 140, and 342 did not differ among 1×, 3×, and 7× cows (P ≥ 0.29) but all supplemented cows, regardless of supplementation frequency, had greater BCS on days 77, 140, and 342 compared to NOSUP cows (P ≤ 0.04). Cows offered 1× supplementation had greater plasma concentrations of IGF-1 on days 35 and 140 compared to NOSUP, 3× and 7× cows (P ≤ 0.04), whereas 3× and 7× cows had greater plasma concentrations of IGF-1 on day 35 compared to NOSUP cows (P ≤ 0.005). Average plasma concentrations of glucose did not differ among 1×, 3×, and 7× cows (P ≥ 0.44), but all supplemented cows had greater plasma concentrations of glucose compared to NOSUP cows (P ≤ 0.05). Birth BW of the first offspring did not differ between 3× and 7× calves (P = 0.54) but both groups were heavier at birth compared to NOSUP calves (P ≤ 0.05). On day 342, calves born from 7× cows were the heaviest (P ≤ 0.05), whereas calves born from 1× and 3× cows had similar BW (P = 0.97) but both groups were heavier compared to calves born from NOSUP cows (P ≤ 0.05). In summary, decreasing the frequency of DDG supplementation, from daily to one or three times weekly, during third trimester of gestation of beef cows did not impact cow BCS but altered maternal plasma concentrations of IGF-1 and glucose, leading to reduced offspring preweaning growth.
ODR arbitration for secured transactions in Colombia
Authors: Lozada Nicolás , Talero Diana
Published: August 2022

The overall view of the registration and enforcement of secured transactions in Colombia has evolved since the national government adopted the electronic arbitration model rules. This kind of arbitration has facilitated the enforcement of secured transactions without resorting to ordinary courts, saving costs and time in enforcement proceedings. This article explains the step-by-step process that the Colombian government had to go through to create and implement an online dispute resolution system dedicated to secured transactions. The article gives an account of the international standards and models that provide the general guide to create a secured transactions system, along with explaining the Colombian regulatory framework that allowed the creation of the secured transactions system, and ending with the enforcement strategies of online arbitration in Colombian secured transactions.