bluuebunny/crossref_metadata_2025 huggingface dataset:
An herbal drug combination identified by knowledge graph alleviates the clinical symptoms of plasma cell mastitis patients: a nonrandomized controlled trial
Authors: Liu Caigang , Yu Hong , Chen Guanglei , Yang Qichao , Niu Nan , Han Ling , Zhao Dongyu , Wang Manji , Liu Yuanyuan , Yang Yongliang
Published: December 2022

Background

Plasma cell mastitis (PCM) is a nonbacterial breast inflammation with severe and intense clinical manifestation yet treatment methods for PCM are still rather limited. Although the mechanism of PCM remains unclear, mounting evidences suggest that the dysregulation of immune system is closely associated with the pathogenesis of PCM. Drug combinations or combination therapy could exert improved efficacy and reduced toxicity through hitting multiple discrete cellular targets.

Methods

We have developed a knowledge graph architecture towards immunotherapy and systematic immunity that consists of herbal drug-target interactions with a novel scoring system to select drug combinations based on target-hitting rates and phenotype relativeness. To this end, we employed this knowledge graph to identify an herbal drug combination for PCM and we subsequently evaluated the efficacy of the herbal drug combination in clinical trial

Results

Our clinical data suggests that the herbal drug combination could significantly reduce the serum level of various inflammatory cytokines, downregulate serum IgA and IgG level, reduce the recurrence rate and reverse the clinical symptoms of PCM patients with improvements of general health status.

Conclusions

In summary, we reported that an herbal drug combination identified by knowledge graph can alleviate the clinical symptoms of plasma cell mastitis patients. We demonstrated that the herbal drug combination holds great promise as an effective remedy for PCM, acting through the regulation of immunoinflammatory pathways and improvement of systematic immune level. In particular, the herbal drug combination could significantly reduce the recurrence rate of PCM, a major obstacle for PCM treatment. Our data suggests that the herbal drug combination is expected to feature prominently in future PCM treatment.

Funding

C. Liu’s lab was supported by grants from the Public Health Science and Technology Project of Shenyang (Grant: 22-321-32-18); Y. Yang’s laboratory was supported by the National Natural Science Foundation of China (Grant: 81874301), the Fundamental Research Funds for Central University (Grant: DUT22YG122) and the Key Research project of ‘be Recruited and be in Command’ in Liaoning Province (Personal Target Discovery for Metabolic Diseases).

Clinical trial number

ClinicalTrials.gov:NCT05530226
Novel 10-channel phased-array coil design for carotid wall MRI at 3T
Authors: de Buck Matthijs H.S. , Jezzard Peter , Frost Robert , Randell Chris , Hurst Katherine , Choudhury Robin P. , Robson Matthew D. , Biasiolli Luca
Published: December 2022

Background

Accurate assessment of plaque accumulation near the carotid bifurcation is important for the effective prevention and treatment of stroke. However, vessel and plaque delineation using MRI can be limited by low contrast-to-noise ratio (CNR) and long acquisition times. In this work, a novel 10-channel phased-array receive coil design for bilateral imaging of the carotid bifurcation using 3T MRI is proposed.

Methods

The novel 10-channel receive coil was compared to a commercial 4-channel receive coil configuration using data acquired from phantoms and healthy volunteers (N = 9). The relative performance of the coils was assessed, by comparing signal-to-noise ratio (SNR), g-factor noise amplification, and the CNR between vessel wall and lumen using black-blood sequences. Patient data were acquired from 12 atherosclerotic carotid artery disease patients.

Results

The 10-channel coil consistently provided substantially increased SNR in phantoms (+88 ± 2%) and improved CNR in healthy carotid arteries (+62 ± 11%), or reduced g-factor noise amplification. Patient data showed excellent delineation of atherosclerotic plaque along the length of the carotid bifurcation using the 10-channel coil.

Conclusions

The proposed 10-channel coil design allows for improved visualization of the carotid arteries and the carotid bifurcation and increased parallel imaging acceleration factors.
Assessment of quality of life of breast cancer patients attending a tertiary hospital in Bangladesh
Authors: Islam Kazi Faria , Awal Abdul , Ummey Shaon Farzana Tamanna , Hossain Md. Badrul , Samson Aliayah , Momo James Senjeh , Hasan Mehedi , Hanif Abu. A. M. , Mahmud Ilias , Mridha Malay Kanti
Published: December 2022

Objective

Breast cancer is the most commonly diagnosed malignancy and a leading cause of death among women. This cross-sectional study assessed the quality of life (QOL) of breast cancer patients attending a tertiary hospital in Dhaka, Bangladesh.

Method

Data were obtained from 359 female breast cancer patients at a tertiary hospital between November 23 and December 9, 2019, using a digital platform (Kobo Toolbox). A Bangla translation of the QOL questionnaire (EORTC-QLQ-C30) was used to assess QOL. The survey comprised three scales: global health, functional, and symptoms scale. For the functional and global health scales, we adopted a cut-off level of ≥66% score for good QOL and ≤33% for poor QOL, which was reversed for the symptoms scale. Using STATA 13.0, we performed descriptive and logistic regression analyses.

Result

Among the 359 patients, 86.35% were housewives, and 50.42% of them came from the Dhaka division. In contrast to the 38.44% and 42.90 % of respondents who scored highly in the social and cognitive categories of the functional scale, respectively, only 8.92% of patients had a high global health status score. Financial difficulties (28.97%) and fatigue (17.82%) were reported as the most distressing factors followed by loss of appetite (14.76%) and insomnia (13.65%). The logistic regression models revealed that women ≥40 years had higher odds of exhibiting the poor quality of health concerning physical function (AOR 3.59, p=0.005), role function (AOR 3.89, p=0.002), and emotional function (AOR, 2.87, p=0.009) as compared to women<40 years.

Conclusion

Our study emphasizes the necessity of integrating psychosocial components for both patients and informal caregivers in the cancer treatment service. Additionally, it is critical to design and implement multi-sectoral policies and integrative techniques to alleviate the most distressing issues for breast cancer patients, as demonstrated in our study: financial hardships, exhaustion, and pain.
GDockScore: a graph-based protein-protein docking scoring function
Authors: McFee Matthew , Kim Philip M.
Published: December 2022

Protein complexes play vital roles in a variety of biological processes such as mediating biochemical reactions, the immune response, and cell signalling, with three-dimensional structure specifying function. Computational docking methods provide a means to determine the interface between two complexed polypeptide chains without using time-consuming experimental techniques. The docking process requires the optimal solution to be selected with a scoring function. Here we propose a novel graph-based deep learning model that utilizes mathematical graph representations of proteins to learn a scoring function (GDockScore). GDockScore was pre-trained on docking outputs generated with the Protein Data Bank (PDB) biounits and the RosettaDock protocol, and then fine-tuned on HADDOCK decoys generated on the ZDOCK Protein Docking Benchmark. GDockScore performs similarly to the Rosetta scoring function on docking decoys generated using the RosettaDock protocol. Furthermore, state-of-the-art is achieved on the CAPRI score set, a challenging dataset for developing docking scoring functions. The model implementation is available athttps://gitlab.com/mcfeemat/gdockscore.
Syngeneic model of carcinogen-induced tumor mimics basal/squamous, stromal-rich, and neuroendocrine molecular and immunological features of muscle-invasive bladder cancer
Authors: Shah Shruti D , Gillard Bryan M , Wrobel Michelle M , Karasik Ellen , Moser Michael T , Mastri Michalis , Sule Norbert , Brackett Craig M , Huss Wendy J , Foster Barbara A
Published: December 2022

Background

Bladder cancer is a heterogenous disease and the emerging knowledge on molecular classification of bladder tumors could have impact to drive treatment decisions based on molecular subtype. Pre-clinical models representing each subtype are needed to test novel therapies. Carcinogen-induced bladder cancer models represent heterogeneous, immune-competent, pre-clinical testing options with many features found in the human disease.

Methods

Invasive bladder tumors were induced in C57BL/6 mice when continuously exposed to N-butyl-N-(4-hydroxbutyl nitrosamine) (BBN) in the drinking water. Tumors were excised and serially passed by subcutaneous implantation into sex-matched syngeneic C57BL/6 hosts. Eight tumor lines were developed and named BBN-induced Urothelium Roswell Park (BURP) tumor lines. The BURP lines were characterized by applying consensus molecular classification to RNA expression, histopathology, and immune profiles by CIBERSORT. Two lines were further characterized for cisplatin response.

Results

Eight BURP tumor lines were established with 3 male and 3 female BURP tumor lines, having the basal/squamous (BaSq) molecular phenotype and morphology. BURP-16SR was established from a male mouse and has a stromal-rich (SR) molecular phenotype and a sarcomatoid carcinoma morphology. BURP-19NE was established from a male mouse and has a neuroendocrine (NE)-like molecular phenotype and poorly differentiated morphology. The established BURP tumor lines have unique immune profiles with fewer immune infiltrates compared to their originating BBN-induced tumors. The immune profiles of the BURP tumor lines capture some of the features observed in the molecular classifications of human bladder cancer. BURP-16SR growth was inhibited by cisplatin treatment, while BURP-24BaSq did not respond to cisplatin.

Conclusions

The BURP tumor lines represent several molecular classifications, including basal/squamous, stroma-rich, and NE-like. The stroma-rich (BURP-16SR) and NE-like (BURP-19NE) represent unique immunocompetent models that can be used to test novel treatments in these less common bladder cancer subtypes. Six basal/squamous tumor lines were established from both male and female mice. Overall, the BURP tumor lines have less heterogeneity than the carcinogen-induced tumors and can be used to evaluate treatment response without the confounding mixed response often observed in heterogeneous tumors. Additionally, basal/squamous tumor lines were established and maintained in both male and female mice, thereby allowing these tumor lines to be used to compare differential treatment responses between sexes.
Ascending and Descending Aortic ECM Hydrogels for Modeling Aortic Wall Biology
Authors: Lee Yoojin C. , Richards Tara D. , Fantini Dalia A. , Kaczorowski David J. , Brown Bryan N. , Phillippi Julie A.
Published: December 2022

Althoughin vitromodeling systems are becoming increasingly advanced, the complex pathophysiology of aortic diseases remains a challenge to mimic and adequately replicate. Biomechanical weakening of the vessel wall, medial degeneration and remodeling are all hallmarks of aneurysmal diseases via incompletely understood mechanisms. Understanding what factors disrupt the multi-layer biology of large blood vessels during the progression of aneurysmal disease can aid in the unmet clinical need to slow or halt disease progression. In particular, the microvascular network of the vasa vasorum provides the primary blood supply to the outer aortic wall and is a key component of inter-layer vascular health. Different origins of the vasa vasorum correspond to the anatomically specific functions of the aortic regions, which can further pertain to the differing origins of vascular wall cells and putative differences in the composition of extracellular matrix (ECM). Biologic scaffolds produced from ECM are useful biomaterials to understand biological processes and address wound healing, stem cell differentiation, and angiogenesis for bothin vitroandin vivodisease models. In the present study, we investigated putative differences in composition and structure between ascending and descending aorta-derived ECM to better understand intra- and inter-layer cell-matrix interactions relevant to vasa vasorum function in the aorta. Ascending and descending aortic ECM (AECM) hydrogels were shown to retain bioactivity and influence contractility of human vasa vasorum-associated pericytes. A comprehensive understanding of the effect of layer-specific ECM on cells in different aortic regions could help uncover novel disease mechanisms.
Molecular basis of interactions between CaMKII and α-actinin-2 that underlie dendritic spine enlargement
Authors: Curtis Ashton J. , Zhu Jian , Penny Christopher J. , Gold Matthew G.
Published: December 2022

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is essential for long-term potentiation (LTP) of excitatory synapses that is linked to learning and memory. In this study, we focused on understanding how interactions between CaMKIIα and the actin crosslinking protein α-actinin-2 underlie long-lasting changes in dendritic spine architecture. We found that association of the two proteins was unexpectedly elevated following stimulation of NMDA receptors to trigger structural LTP in primary hippocampal neurons. Furthermore, disruption of interactions between the two proteins prevented the accumulation of enlarged mushroom-type dendritic spines following NMDA receptor activation. α-actinin-2 binds to the regulatory segment of CaMKII. Calorimetry experiments, and a crystal structure of α-actinin-2 EF hands 3 and 4 in complex with the CaMKII regulatory segment, indicate that the regulatory segment of autoinhibited CaMKII is not fully accessible to α-actinin-2. Pull-down experiments show that occupation of the CaMKII substrate binding groove by GluN2B markedly increases α-actinin-2 access to the CaMKII regulatory segment. Overall, our study provides new mechanistic insight into the molecular basis of structural LTP and reveals an added layer of sophistication to the function of CaMKII.
A NOVEL METHOD FOR BLOOD DETECTION USING FLUORESCENT DYE
Authors: Vajpayee Kamayani , Desai Preet , Dash Hirak Ranjan , Shukla Ritesh Kumar
Published: December 2022

Detection of the body fluid present at a crime scene is essential for any forensic investigation. Amongst all the body fluids (sweat, semen, vaginal fluid, saliva, etc.,) blood is the most frequently encountered evidence at the crime scene. Currently, reagents like benzidine, orthotoluidine, tetramethylbenzidine, phenolphthalein, leucomalachite green, luminol, and fluorescein are used to screen the presence of blood on different surfaces (porous/nonporous). Majority of these tests are based on colorimetric changes owing to the nature of hemoglobin to catalyze the oxidation of chromogenic compounds. Apart from aiding the investigation, these reagents show toxic behavior (DNA damage, carcinogenic, etc.) and false-positive results. Hence, to circumvent this issue, the present study attempts to develop a state-of-art methodology for preliminary blood detection and screening using fluorescein-derived 2’,7’-dichlorofluorescein di-acetate (DCFDA) dye. It is hereby proposed that the fluorescein-based dye can successfully detect blood and bloodstains aged up to 20 days. Moreover, supplemental experiments have suggested that the dye doesn’t interfere with DNA integritycausing any damage to DNA. Parallelly, no false-positive reactions have been observed as tested against similar-looking substances.
White Matter microstructure effect in ADHD: a two-sample mendelian randomization study
Authors: Tavares Maria Eduarda de Araujo , Carpena Marina Xavier , Vitola Eduardo Schneider , Bandeira Cibele Edom , Cupertino Renata Basso , Colbeich Eduarda , da Cunha Pamela Ferreira , Rovaris Diego Luiz , Grevet Eugenio Horacio , da Silva Bruna Santos , Bau Claiton Henrique Dotto
Published: December 2022

Introduction

Genome Wide Association Studies (GWAS) revealed the highly polygenic architecture of Attention-Deficit/Hyperactivity Disorder (ADHD) and highlighted the contribution of common variants related to brain development and function. In parallel, several imaging studies attempted to discover disorder-related brain structures, with some significant findings concerning white matter. Two-sample mendelian randomization (2SMR) is a powerful tool to evaluate causality between two phenotypes using summary statistics data. We aimed to investigate a possible causal relationship between white matter genetically predicted variation and ADHD diagnosis through 2SMR.

Methods

A unidirectional two-sample MR analysis was performed based on summary statistics of GWAS between 22 different white matter (WM) mean fractional anisotropy measures and ADHD. We used 4 different MR approaches, considering IVW random effects as the main analysis, followed by several sensitivity analyses. Linkage Disequilibrium Score Regression (LDSC) was evaluated in the same set of samples to corroborate the direction of associations.

Results and Discussion

Our most consistent finding across MR and LDSC approach, following the sensitivity analyses, indicate that the decreased WM microstructure integrity of the fornix stria terminalis (FXSTivwbeta:-0.266 SE:0.083 pFDR:0.021) genetic liability has a causal influence on ADHD diagnosis. The FXST is formed by connection fibers inside the limbic system, which is crucial to emotional processing, learning, and memory, functions usually impaired in ADHD. Therefore, this study increases knowledge concerning ADHD neurobiology and provides novel evidence of the causal effect of WM integrity in the limbic system, which could contribute to the advances in additional diagnostic tools as well as pharmacological brain structure targets.
Early and late onset preeclampsia associated with different placental pathology and clinical risk characteristics
Authors: Zhang Peilin , Shama Naureen
Published: December 2022

Background

Preeclampsia is classified as early onset and late onset types with different clinical manifestation and pathogenesis. Placental pathology of preeclampsia has been largely based on description of the early onset type, and the morphologic features of placenta from late onset preeclampsia were similar to those of non-preeclamptic placentas.

Objective

To identify clinically relevant maternal and neonatal risk characteristics and placental pathology for early onset and late onset preeclampsia.

Study design

We have collected all placental pathology information as well as maternal and neonatal birth information from March 2020 to December 2021 including preeclampsia and non-preeclampsia patients. We compared preterm and term preeclampsia in regards to maternal and neonatal complication and placental pathology by using logistic regression models to determine the important clinical risk factors associated with preeclampsia and placental pathology.

Results

A total 3724 placentas including 614 placentas from preeclamptic and 3110 non-preeclamptic patients were studied. Preterm preeclampsia (<37 weeks) was similar to early onset preeclampsia (<34 weeks) in maternal and neonatal complications as well as placental pathology, and these features were statistically different from those from term preeclampsia. More male fetuses were associated with early onset preeclampsia and female fetuses associated with late onset term preeclampsia when compared to non-preeclamptic patients. Maternal race/ethnicity and marital status were associated with preeclampsia but this association was no longer significant after logistic regression analysis. Preterm preeclampsia was statistically associated with gestational diabetes, placental infarcts, intrauterine fetal growth restriction and fetal vascular malperfusion, whereas term preeclampsia was associated with decidual vasculopathy and maternal obesity.

Conclusions

Early onset preeclampsia is a different clinical syndrome from the late onset type with clinical implication of pathogenesis and management.
Condom use and HIV testing among adults in Switzerland: repeated national cross-sectional surveys 2007, 2012, and 2017
Authors: Buitrago-Garcia Diana , Salanti Georgia , Low Nicola
Published: December 2022

Background

Monitoring of HIV and sexually transmitted infection (STI) prevention is important for guiding national sexual health programmes for both the general population and key populations. The objectives of this study were to examine patterns of condom use at last intercourse and lifetime HIV testing from 2007 to 2017 in Switzerland, and to explore factors associated with these behaviours in men and women with opposite-sex partners and with same sex partners.

Methods

We analysed data from the 2007, 2012 and 2017 Swiss Health Survey. At each time point, outcome and population group, we conducted a descriptive analysis of weighted data and conducted multivariable logistic regression to obtain adjusted odds ratios (aOR) with 95% confidence intervals (CI) and compared outcomes between the timepoints.

Results

In total, 43,949 people were interviewed: 21,274 men and 22,675 women, who reported having sex only with partners of the opposite sex, 633 men who reported sex with a male partner and 699 women who reported sex with a female partner. Among the three surveys the prevalence of condom use varied from 24 to 26% of men and 18 to 21% in women with only opposite-sex partners (aOR men, 0.93, 95% CI 0.82, 1.06; women 0.98, 95% CI 0.86 to 1.11). In men with any same sex partner the prevalence of condom use increased from 43% in 2007 to 54% in 2017 (aOR 1.80, 95% CI 0.97, 3.34). In multivariable analysis, the factor most strongly associated with condom use was sex with an occasional partner at last intercourse. HIV testing ever increased across all three survey years in all groups: 2017 vs. 2007, aOR men with only opposite-sex partners 1.57 (95% CI 1.42, 1.74), women with only opposite-sex partners 1.54 (1.39, 1.71), men with any same sex partner 1.85 (0.96, 3.55), women with any same sex partner 1.31 (0.74, 2.30).

Conclusions

Monitoring of condom use, and HIV testing should continue and contribute to the development of the national sexual health programme. Stronger promotion of condoms for people with opposite-sex partners might be needed, since overall condom use at last intercourse has not changed since 2007.
Assessment of Environmental Factors Associated with Antibiotic Resistance Genes (ARGs) in the Yangtze Delta, China
Authors: Miao Jiazheng , Ling Yikai , Chen Xiaoyuan , Wu Siyuan , Umar Sajid , Xu Shixin , Anderson Benjamin D.
Published: December 2022

The emergence of antimicrobial resistance (AMR) is an urgent and complex public health challenge worldwide. As a sub-problem of AMR, antibacterial resistance (ABR) is of particular concern due to inadequacy of alternative medication. Earlier studies have shown that ABR is not only impacted by antibiotics, but also affected by the interactions between bacteria and their environments. Therefore, to combat ABR in a specific region, local environmental conditions must be investigated to comprehensively understand which environmental factors might contribute to ABR and propose more tailored solutions. This study surveyed environmental contributors of antibiotic resistance genes (ARGs), the parameter for measuring ABR, in the Yangtze Delta. A high abundance of ARGs was detected, despite low antibiotic and heavy metal concentrations. Phosphorus, chromium, manganese, calcium, and strontium were identified as potential key contributors of ARGs. Suppression of ARGs could be realized through decreasing the concentration of phosphorus in surface water. Group 2A light metals (e.g., magnesium and calcium) could be developed as eco-friendly reagents for controlling antibiotic resistance in the future.
IKBKB reduces huntingtin aggregation by phosphorylating Serine 13 via a non-canonical IKK pathway
Authors: Cariulo Cristina , Martufi Paola , Verani Margherita , Toledo-Sherman Leticia , Lee Ramee , Dominguez Celia , Petricca Lara , Caricasole Andrea
Published: December 2022

N-terminal phosphorylation at residues T3 and S13 is believed to have important beneficial implications for the biological and pathological properties of mutant huntingtin, where IKBKB was identified as a candidate regulator of huntingtin N-terminal phosphorylation. The paucity of mechanistic information on IKK pathways, together with the lack of sensitive methods to quantify endogenous huntingtin phosphorylation, prevented detailed study of the role of IKBKB in Huntington’s disease. Using novel ultrasensitive assays, we demonstrate that IKBKB can regulate endogenous S13 huntingtin phosphorylation in a manner dependent on its kinase activity and known regulators. We found that the ability of IKBKB to phosphorylate endogenous huntingtin S13 is mediated through a non-canonical IRF3-mediated IKK-pathway, distinct from the established involvement of IKBKB in mutant huntingtin’s pathological mechanisms mediated via the canonical pathway. Furthermore, increased huntingtin S13 phosphorylation by IKBKB resulted in decreased aggregation of mutant huntingtin in cells, again dependent on its kinase activity. These findings point to a non-canonical IKK-pathway linking S13 huntingtin phosphorylation to the pathological properties of mutant huntingtin aggregation, thought to be significant to Huntington’s disease.
Cis-regulatory evolution of the potassium channel genekcnj13during pigment pattern diversification inDaniofish
Authors: Podobnik Marco , Singh Ajeet P. , Fu Zhenqiang , Dooley Christopher M. , Frohnhöfer Hans Georg , Firlej Magdalena , Elhabashy Hadeer , Weyand Simone , Weir John R. , Lu Jianguo , Nüsslein-Volhard Christiane , Irion Uwe
Published: December 2022

Teleost fish of the genusDanioare excellent models to study the genetic and cellular bases of pigment pattern variation in vertebrates. The two sister speciesDanio rerioandDanio aesculapiishow divergent patterns of horizontal stripes and vertical bars that are partly caused by the evolution of the potassium channel genekcnj13. InD. rerio, kcnj13is required in melanophores for interactions with xanthophores and iridophores, which cause location-specific pigment cell shapes and thereby influence colour pattern and contrast. Here, we show that cis-regulatory rather than protein coding changes underliekcnj13evolution between the two species.D. aesculapiiexpress lowerkcnj13levels and exhibit low-contrast patterns similar toD. reriomutants. Our results suggest that homotypic and heterotypic interactions between the pigment cells and their shapes diverged between species by quantitative changes inkcnj13expression during pigment pattern diversification.
Hepatitis E virus genome replication is independent of cyclophilins A and B
Authors: Buchanan Frazer J.T. , Chen Shucheng , Harris Mark , Herod Morgan R.
Published: December 2022

Hepatitis E virus (HEV) is an emerging pathogen responsible for more than 20 million cases of acute hepatitis globally per annum. Healthy individuals typically have a self-limiting infection, however, mortality rates in some populations such as pregnant women can reach 30%. A detailed understanding of the virus lifecycle is lacking, mainly due to limitations in experimental systems. In this regard, the cyclophilins are an important family of proteins that have peptidyl-prolyl isomerase activity and play roles in the replication of a number of positive-sense RNA viruses, including hepatotropic viruses such as hepatitis C virus (HCV). Cyclophilin A (CypA) and cyclophilin B (CypB) are the two most abundant human cyclophilins in hepatocytes and are therefore potential targets for pan-viral therapeutics. Here, we investigated the importance of CypA and CypB for HEV genome replication using a sub-genomic replicon system. This system removes the requirements for viral entry and packaging and therefore allows for the sensitive measurement of viral genome replication in isolation. Using pharmacological inhibition by cyclosporine A (CsA), known to suppress HCV replication, and silencing by shRNA we find that CypA and CypB are not essential for replication of genotype 1 or 3 HEV replication. However, we find that silencing of CypB reduces replication of genotype 1 HEV in some cells, but not genotype 3. These data suggests HEV is atypical in its requirements for cyclophilin for viral genome replication and that this phenomenon could be genotype specific.
MADS31 supports female germline development by repressing the post-fertilization program in cereal ovules
Authors: Yang Xiujuan , Li Gang , Shi Jin , Wilkinson Laura G. , Aubert Matthew K. , Houston Kelly , Shirley Neil J. , Colombo Lucia , Tucker Matthew R.
Published: December 2022

The female germline of flowering plants develops within a niche of somatic ovule cells, also referred to as the nucellus. How niche cells maintain their own somatic developmental program, yet support the development of adjoining germline cells, remains largely unknown. Here we report that MADS31, a conserved MADS-box transcription factor from the B-sister subclass, is a potent regulator of niche cell identity in barley. MADS31 is preferentially expressed in nucellar cells directly adjoining the germline, and loss-of-functionmads31mutants exhibit deformed and disorganized nucellar cells, leading to impaired germline development and partial female sterility. Molecular assays indicate that MADS31 encodes a potent transcriptional repressor, repressing genes in the ovule that are normally active in the seed. One prominent target of MADS31 isNRPD4b, a seed-expressed component of RNA polymerase IV/V that is involved in gene silencing via RNA directed DNA methylation.NRPD4bis directly repressed by MADS31in vivoand is de-repressed inmads31ovules, while overexpression ofNRPD4brecapitulates themads31ovule phenotype. This coincides with specific changes in histone methylation and is consistent withNRPD4bbeing directly repressed by MADS31 to maintain ovule niche functionality. Our findings reveal a new mechanism by which somatic ovule tissues maintain their own identity before transitioning to the post-fertilization program.
Metagenomic insights for antimicrobial resistance surveillance in soils with different land uses in Brazil
Authors: Ordine João Vitor Wagner , de Souza Gabrielle Messias , Tamasco Gustavo , Virgilio Stela , Fernandes Ana Flávia Tonelli , Silva-Rocha Rafael , Guazzaroni María-Eugenia
Published: December 2022

Anthropization in terrestrial environments commonly leads to land use transformation, changing soil properties and their microbial communities. This, combined with the exacerbated use of antibiotics in human and animal health promotes the expansion of the soil resistome. Considering the urgent need for surveillance of antimicrobial resistance (AMR), we aimed to evaluate how different land practices (urban, farming and forest) can affect the soil resistome and the dynamics of their bacterial communities. We collected eight soil samples from different locations in the countryside of São Paulo (Brazil), assessed the community profiles based on 16S rRNA sequencing and analyzed the soil metagenomes based on shotgun sequencing. Our results highlight differences in the communities’ structure and their dynamics which were correlated with land practices. Additionally, differences were observed in the abundance and diversity of antibiotic resistance genes (ARGs) and virulence factors (VFs) across studied soils, where a higher presence and homogeneity ofvanRO, mtrAandrbpAgenes were detected in livestock soils. We observed thatStaphylococcusandBacillusare positively correlated with each other and are markers for agricultural communities. Moreover, the abundance and diversity of ARGs and VFs observed in farming soils raises concerns regarding the potential spread of these genes in the environment. Together, our findings reinforce the importance and urgency of AMR surveillance in the environment, especially in soils undergoing deep land use transformations due to anthropic activity.
Long-term effects of THC exposure on reward learning and motivated behavior in adolescent and adult male rats
Authors: Halbout Briac , Hutson Collin , Hua Leann , Inshishian Victoria , Mahler Stephen V. , Ostlund Sean B.
Published: December 2022

Rationale

The endocannabinoid system makes critical contributions to reward processing, motivation, and behavioral control. Repeated exposure to THC or other cannabinoid drugs can cause persistent adaptions in the endocannabinoid system and associated neural circuitry. It remains unclear how such treatments affect the way rewards are processed and pursued.

Objective and methods

We examined if repeated THC exposure (5 mg/kg/day for 14 days) during adolescence or adulthood led to long-term changes in rats’ capacity to flexibly encode and use action-outcome associations for goal-directed decision making. Effects on hedonic feeding and progressive ratio responding were also assessed.

Results

THC exposure had no effect on rats’ ability to flexibly select actions following reward devaluation. However, instrumental contingency degradation learning, which involves avoiding an action that is unnecessary for reward delivery, was augmented in rats with a history of adult but not adolescent THC exposure. THC-exposed rats also displayed more vigorous instrumental behavior in this study, suggesting a motivational enhancement. A separate experiment found that while THC exposure had no effect on hedonic feeding behavior, it increased rats’ willingness to work for food on a progressive ratio schedule, an effect that was more pronounced when THC was administered to adults. Adolescent and adult THC exposure had opposing effects on the CB1-receptor dependence of progressive ratio performance, decreasing and increasing sensitivity to rimonabant-induced behavioral suppression, respectively.

Conclusions

Our findings reveal that exposure to a translationally relevant THC exposure regimen induces long-lasting, age-dependent alterations in cognitive and motivational processes that regulate the pursuit of rewards.
Microdissection and culturing of adult lateral entorhinal cortex layer II neurons from APP/PS1 Alzheimer model mice
Authors: Hanssen Katrine Sjaastad , Witter Menno P. , Sandvig Axel , Sandvig Ioanna , Kobro-Flatmoen Asgeir
Published: December 2022

Background

Primary neuronal cultures enable cell-biological studies of Alzheimer’s disease (AD), albeit typically non-neuron-specific. The first cortical neurons affected in AD reside in layer II of the lateralmost part of the entorhinal cortex, and they undergo early accumulation of intracellular amyloid-β, form subsequent tau pathology, and start degenerating pre-symptomatically. These vulnerable entorhinal neurons uniquely express the glycoprotein reelin and provide selective inputs to the hippocampal memory system. Gaining a more direct access to study these neurons is therefore highly relevant.

New method

We demonstrate a methodological approach for microdissection and long-term culturing of adult lateral entorhinal layer II-neurons from AD-model mice.

Results

We maintain adult microdissected lateralmost entorhinal layer II-neurons beyond two months in culture. We show that they express neuronal markers, and that they are electrophysiologically active by 15 daysin vitroand continuing beyond 2 months.

Comparison with existing methods

Primary neurons are typically harvested from embryonic or early postnatal brains because such neurons are easier to culture compared to adult neurons. Methods to culture adult primary neurons have been reported, however, to our knowledge, culturing of adult entorhinal subregion-specific primary neurons from AD-model animals has not been reported.

Conclusions

Our methodological approach offers a window to study initial pathological changes in the AD disease-cascade. This includes the study of proteinopathy, single-neuron changes, and network-level dysfunction.

Highlights

We microdissect and culture neurons from layer II of the lateralmost part of the entorhinal cortex from adult AD model mice and littermate controls

These entorhinal neurons self-organize into networks, express reelin, NeuN and intracellular amyloid-β.

The neurons are electrophysiologically active by day 15 in culture and remain viable beyond two months.
Interaction with single-stranded DNA-binding protein modulatesEscherichia coliRadD DNA repair activities
Authors: Garcia Miguel A. Osorio , Wood Elizabeth A. , Keck James L. , Cox Michael M.
Published: December 2022

The bacterial RadD enzyme is important for multiple genome maintenance pathways, including RecA DNA strand exchange and RecA-independent suppression of DNA crossover template switching. However, much remains unknown about the precise roles of RadD. One potential clue into RadD mechanisms is its direct interaction with the single-stranded DNA binding protein (SSB), which coats single-stranded DNA exposed during genome maintenance reactions in cells. Interaction with SSB stimulates the ATPase activity of RadD. To probe the mechanism and importance of RadD/SSB complex formation, we identified a pocket on RadD that is essential for binding SSB. In a mechanism shared with many other SSB-interacting proteins, RadD uses a hydrophobic pocket framed by basic residues to bind the C-terminal end of SSB. RadD variants that substitute acidic residues for basic residues in the SSB binding site impair RadD/SSB complex formation and eliminate SSB stimulation of RadD ATPase activityin vitro. MutantE. colistrains carrying charge reversalradDchanges display increased sensitivity to DNA damaging agents synergistically with deletions ofradAandrecG, although the phenotypes of the SSB-bindingradDmutants are not as severe a fullradDdeletion. This suggests that RadD has multiple functions in the cell, with a subset requiring the interaction with SSB.
Distinct adaptations of endocrine and cognitive functions may contribute to high variability in long-term weight loss outcome after bariatric surgery
Authors: Lammert Mathis , Medawar Evelyn , Hartmann Hendrik , Grasser Linda , Dietrich Arne , Fenske Wiebke , Horstmann Annette
Published: December 2022

Background

Bariatric surgery has been widely recognized as the most efficient long-term treatment method in severe obesity, yet therapy success shows considerable interindividual variability. Postoperative metabolic adaptations, including improved gut hormone secretion (GLP-1, PYY and ghrelin), and restored executive function may play an explanatory role in weight loss, yet causes for poor success in individual patients remain unknown. This study investigates gut-hormonal and cognitive characteristics in extreme weight loss responders to bariatric surgery.

Methods

Patients (n=47) with high or low excessive weight loss (EWL) at least 2 years after Roux-en-Y-gastric bypass or sleeve gastrectomy were allocated into good responders (GR, EWL 82.4 ± 11.6%) and poor responders (PR, EWL 24.0 ±SD12.8%) to study differences in postprandial secretion of GLP-1, PYY, ghrelin and in working memory (WM).

Results

Mean BMI was 47.1 ± 6.2 kg/m2in poor responders (n=21) and 28.9 ± 3.1 kg/m2in good responders (n=26,p< 0.001). Fasted GLP-1 and PYY were comparable for GR and PR (p> 0.2) and increased strongly after a standardized test meal (300 kcal liquid meal) with a peak at 15 to 30 minutes. The increase was stronger in GR compared to PR (GLP-1, PYY:TimexGroup p< 0.05). Plasma ghrelin levels already differed between groups at fasted state, showing significantly higher levels for GR (p< 0.05). Postprandially, ghrelin secretion was suppressed in both groups, but suppression was higher in GR (TimexGroup p< 0.05). GR showed significantly higher WM scores than PR (p< 0.05). Postprandial ghrelin (iAUC), but not GLP-1 or PYY release, significantly mediated the relationship between EWL and a WM subscore (IS score, CI = 0.07 - 1.68), but not WM main score (MIS score, CI = −0.07 - 1.54).

Conclusion

Excess weight loss success after bariatric surgical procedures is associated with distinct profiles of gut-hormones at fasted and postprandial state, and differences in working memory. Working memory performance was partly mediated by postprandial incremental drops in ghrelin. Future studies need to integrate longitudinal data, larger samples and more sensitive cognitive tests.

Highlights

Fasted and postprandial gut hormone release differs between good and poor surgery responders

Good responders show higher working memory performance

Postprandial ghrelin dynamics mediate the relationship between excessive weight loss and a subscore of working memory performance

Longitudinal data are needed to investigate the gut-brain interactions with regard to cognitive functions after bariatric surgery
Beam-induced redox chemistry in iron oxide nanoparticle dispersions at ESRF–EBS
Authors: Thomä Sabrina L. J. , Zobel Mirijam
Published: December 2022

The storage ring upgrade of the European Synchrotron Radiation Facility makes ESRF–EBS the most brilliant high-energy fourth-generation light source, enabling in situ studies with unprecedented time resolution. While radiation damage is commonly associated with degradation of organic matter such as ionic liquids or polymers in the synchrotron beam, this study clearly shows that highly brilliant X-ray beams readily induce structural changes and beam damage in inorganic matter, too. Here, the reduction of Fe3+ to Fe2+ in iron oxide nanoparticles by radicals in the brilliant ESRF–EBS beam, not observed before the upgrade, is reported. Radicals are created due to radiolysis of an EtOH–H2O mixture with low EtOH concentration (∼6 vol%). In light of extended irradiation times during insitu experiments in, for example, battery and catalysis research, beam-induced redox chemistry needs to be understood for proper interpretation of insitu data.
Total scattering measurements at the Australian Synchrotron Powder Diffraction beamline: capabilities and limitations
Authors: D'Angelo Anita M. , Brand Helen E. A. , Mitchell Valerie D. , Hamilton Jessica L. , Oldfield Daniel , Liu Amelia C. Y. , Gu Qinfen
Published: December 2022

This study describes the capabilities and limitations of carrying out total scattering experiments on the Powder Diffraction (PD) beamline at the Australian Synchrotron, ANSTO. A maximum instrument momentum transfer of 19 Å−1 can be achieved if the data are collected at 21 keV. The results detail how the pair distribution function (PDF) is affected by Q
max, absorption and counting time duration at the PD beamline, and refined structural parameters exemplify how the PDF is affected by these parameters. There are considerations when performing total scattering experiments at the PD beamline, including (1) samples need to be stable during data collection, (2) highly absorbing samples with a μR > 1 always require dilution and (3) only correlation length differences >0.35 Å may be resolved. A case study comparing the PDF atom–atom correlation lengths with EXAFS-derived radial distances of Ni and Pt nanocrystals is also presented, which shows good agreement between the two techniques. The results here can be used as a guide for researchers considering total scattering experiments at the PD beamline or similarly setup beamlines.
Spatial variation of the determinants affecting urban land value in Thiruvananthapuram, India
Authors: Binoy B.V. , Naseer M.A. , Anil Kumar P.P.
Published: December 2022

Purpose

Land value varies at a micro level depending on the location’s economic, geographical and political determinants. The purpose of this study is to present a comprehensive assessment of the determinants affecting land value in the Indian city of Thiruvananthapuram in the state of Kerala.

Design/methodology/approach

The global influence of the identified 20 explanatory variables on land value is measured using the traditional hedonic price modeling approach. The localized spatial variations of the influencing parameters are examined using the non-parametric regression method, geographically weighted regression. This study used advertised land value prices collected from Web sources and screened through field surveys.

Findings

Global regression results indicate that access to transportation facilities, commercial establishments, crime sources, wetland classification and disaster history has the strongest influence on land value in the study area. Local regression results demonstrate that the factors influencing land value are not stationary in the study area. Most variables have a different influence in Kazhakootam and the residential areas than in the central business district region.

Originality/value

This study confirms findings from previous studies and provides additional evidence in the spatial dynamics of land value creation. It is to be noted that advanced modeling approaches used in the research have not received much attention in Indian property valuation studies. The outcomes of this study have important implications for the property value fixation of urban Kerala. The regional variation of land value within an urban agglomeration shows the need for a localized method for land value calculation.
Corona-phobia violated human rights? Impact of COVID-19 on patient’s well-being
Authors: Amin Saqib , Mehmood Waqas , Aman-Ullah Attia , Khan Mujahid Ameen
Published: December 2022

Purpose

This study aims to measure whether admittance in the quarantine ward due to COVID-19 can affect one’s mental health. Nowadays, many countries worldwide are battling with the threat of the COVID-19 contagion, and it is difficult to understand how the pandemic leaves psychological impacts on one’s well-being.

Design/methodology/approach

This research used qualitative and quantitative approaches to assess the psychological impacts of quarantine due to COVID-19. Population of the present study were 250 patients who were admitted in quarantine centres of Pakistan. The data analysis was conducted through univariate analysis using (ANVOVA) software.

Findings

This study found that patients who were quarantined due to the COVID-19 infection displayed multiple psychological symptoms such as a lack of self-control, anxiety, low general health and vitality, depression and negative well-being.

Practical implications

There is an urgency to provide psychological treatments to each afflicted person and their family members to establish a healthy community.

Originality/value

This research investigates whether admittance in the quarantine ward due to COVID-19 can affect mental health in Pakistan.
Serum sodium level is inversely associated with new‐onset diabetes in hypertensive patients
Authors: Cheng Qi , Liu Xiaocong , Cai Anping , Zhou Dan , Huang Yuqing , Feng Yingqing
Published: December 2022

Background

Serum sodium level is associated with cardiovascular and endocrine health. Though decreased serum sodium is considered to be associated with reduced hypertension risk, some studies also found that it may increase the risk of diabetes. This study aimed to investigate the association of serum sodium with new‐onset diabetes in hypertensive patients.

Methods

Based on the annual health examinations from 2011 to 2016 in Dongguan City, Guangdong, China, hypertensive patients without diabetes at baseline were selected. Logistic regression and restricted cubic spline were used to evaluate the association between serum sodium level and new‐onset diabetes. Subgroup analysis was also conducted.

Results

A total of 4438 hypertensive patients with a mean age of 58.65 years were included, of whom 48.9% were male. During a median follow‐up of 35.1 months, 617 (13.9%) of the subjects developed new‐onset diabetes. Per 1‐SD (3.39 mmol/L) increment of serum sodium was associated with a 14% lower risk of new‐onset diabetes (odds ratio = 0.86; 95% CI: 0.78, 0.97; p = 0.01). The lowest quartile of serum sodium was associated with the lowest diabetes risk. The restricted cubic spline showed a linear inverse relationship (nonlinear p = 0.72). Across all the subgroups, the inverse association was consistent (p for interaction >0.05).

Conclusion

An inverse association of serum sodium with new‐onset diabetes in hypertensive patients was observed.