bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypobaric hypoxia aggravates osteoarthritis via the alteration of the oxygen environment and bone remodeling in the subchondral zone
Authors: Li Qianhao , Yang Zhouyuan , Zhu Mengli , Zhang Wanli , Chen Liyile , Chen Hongying , Kang Pengde
Published: April 2024

A high prevalence of osteoarthritis (OA) has been observed among individuals living at high altitudes, and hypobaric hypoxia (HH) can cause bone mass and strength deterioration. However, the effect of HH on OA remains unclear. In this study, we aimed to explore the impact of HH on OA and its potential mechanisms. A rat knee OA model was established by surgery, and the rats were bred in an HH chamber simulating a high‐altitude environment. Micro‐computed tomography (Micro‐CT), histological analysis, and RNA sequencing were performed to evaluate the effects of HH on OA in vivo. A hypoxic co‐culture model of osteoclasts and osteoblasts was also established to determine their effects on chondrogenesis in vitro. Cartilage degeneration significantly worsened in the HH‐OA group compared to that in the normoxia‐OA (N‐OA) group, 4 weeks after surgery. Micro‐CT analysis revealed more deteriorated bone mass in the HH‐OA group than in the N‐OA group. Decreased hypoxia levels in the cartilage and enhanced hypoxia levels in the subchondral bone were observed in the HH‐OA group. Furthermore, chondrocytes cultured in a conditioned medium from the hypoxic co‐culture model showed decreased anabolism and extracellular matrix compared to those in the normoxic model. RNA sequencing analysis of the subchondral bone indicated that the glycolytic signaling pathway was highly activated in the HH‐OA group. HH‐related OA progression was associated with alterations in the oxygen environment and bone remodeling in the subchondral zone, which provided new insights into the pathogenesis of OA.
Full-body Postural Alignment Analysis Through Barycentremetry
Authors: Khalifé Marc , Vergari Claudio , Assi Ayman , Guigui Pierre , Attali Valérie , Valentin Rémi , Vafadar Saman , Ferrero Emmanuelle , Skalli Wafa
Published: April 2024

Study Design.

A multicentric retrospective study.

Objective.

The study of center of mass (COM) locations (ie, barycentremetry) can help us understand postural alignment. The goal of this study was to determine relationships between COM locations and global postural alignment x-ray parameters in healthy subjects. The second objective was to determine the impact on the spinopelvic alignment of increased distance between the anterior body envelope and spine at the lumbar apex level.

Summary of Background Data.

Unexplored relationship between COM location and spinopelvic parameters.

Methods.

This study included healthy volunteers with full-body biplanar radiographs, including body envelope reconstruction, allowing the estimation of COM location. The following parameters were analyzed: lumbar lordosis (LL), thoracic kyphosis (TK), cervical lordosis (CL), pelvic tilt (PT), sacro-femoral angle (SFA), knee flexion angle (KFA), and sagittal odontoid-hip axis angle (ODHA). The following COM in the sagittal plane were located: whole body, at a thoracolumbar inflection point, and body segment above TK apex. The body envelope reconstruction also provided the distance between the anterior skin and the LL apex vertebral body center (“SV-L distance”).

Results.

This study included 124 volunteers, with a mean age of 44±19.3. Multivariate analysis confirmed the posterior translation of COM above TK apex with increasing LL (P=0.002) through its proximal component and posterior shift of COM at the inflection point with increasing TK (P=0.008). Increased SV-L distance was associated with greater ODHA (r=0.4) and more anterior body COM (r=0.5), caused by increased TK (r=0.2) and decreased proximal and distal LL (both r=0.3), resulting in an augmentation in SFA (r=0.3) (all P<0.01).

Conclusions.

Barycentremetry showed that greater LL was associated with a posterior shift of COM above the thoracic apex, while greater TK was correlated with more posterior COM at inflection point. Whole-body COM was strongly correlated with ODHA. This study also exhibited significant alignment disruption associated with increased abdominal volume, with compensatory hip extension.

Level of Evidence.

Level—II.
Head and neck cancer patients treated with concomitant chemoradiotherapy involving the oral cavity and oropharynx: is another choice possible than prophylactic gastrostomy?
Authors: Senesse Pierre , Briant Jeanne , Boisselier Pierre , Bensadoun René-Jean , Vinches Marie , Faravel Kerstin
Published: April 2024

Purpose of review

Recent recommendations on cachexia highlight, in head and neck cancers, the heterogeneity of studies, focusing on weight loss and sequelae including swallowing disorders. The current national guidelines emphasize that, in cases of concurrent chemoradiotherapy (cCRT) involving the oral cavity and oropharynx, prophylactic gastrostomy placement should be carried out systematically. We review why this technique is particularly relevant in this specific location for the feasibility of cCRT.

Recent findings

A randomized trial is underway on swallowing disorders and the quality of life of patients after prophylactic vs. reactive gastrostomy in advanced oropharyngeal cancer patients treated with CRT. Concurrently, recent literature reviews emphasize the importance of the cumulative dose of chemotherapy for local control and survival. In cases of cCRT involving the oral cavity or the oropharynx, nutritional support could have a beneficial or detrimental impact on chemotherapy.

Specifically for patients treated with cCRT involving the oral cavity and oropharynx, prophylactic gastrostomy would be able to fulfill the three objectives of local control, survival, and quality of life, minimizing complications related to nutritional support. Studies need to be more homogeneous. In clinical practice, nutrition should primarily assist in carrying out cancer treatment when survival is the main goal.
A Novel Large Deletion in the EVER1 Gene in a Family With Epidermodysplasia Verruciformis From India
Authors: Godfred Adithya Christopher , Thomas Zachariah , Peter Dincy , Joseph Anjana , Ravichandran Lavanya , George Anu Anna , Pulimood Susanne A. , Gaikwad Pranay , Babu Ramesh , Thomas Meera , Thomas Nihal , Chapla Aaron
Published: April 2024

Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis due to mutations in EVER1 and EVER2 genes. The genetic profile of Indian patients with EV has not been previously studied. This report describes the clinical presentation and molecular analysis of a family with EV. Using genomic DNA from two affected probands and healthy controls (two other siblings), conventional polymerase chain reaction (PCR) was conducted with novel primer sets designed to amplify the coding and splice-site regions in the genes EVER1 and EVER 2. This revealed no amplification with a primer set for exons 16 to 18 in the EVER1 gene of both the probands. Subsequently, long-range PCR spanning the length of exon 15–20 and next-generation sequencing demonstrated a homozygous deletion of 2078 bp in the EVER1 gene (EVER1:c.2072_2278del). Screening the family revealed the same homozygous deletion (similar to index cases) in two other affected siblings. The parents and two asymptomatic siblings were heterozygous carriers for the deletion while one healthy sibling was negative. These results were validated with Sanger sequencing. This deletion in exons 17 and 18 of the EVER1 gene results in a frameshift, followed by a premature termination resulting in a severe phenotype. The identification and validation of this large deletion was detected using stepwise amplicon-based target enrichment and long-range PCR, respectively. In this family, this simple strategy greatly enhanced genetic counseling as well as early genetic diagnosis and screening. However, functional assays and larger studies are required to characterize and validate the genetic diversity among Indians with EV.
Granulomatous Slack Skin With Lung and Esophagus Involvement: A Case Report and Molecular Analysis
Authors: Pereira Filipa Galante , Esteves Gonçalo , Costa Rosa Joaninha , Cabeçadas José , Cravo Mariana , Pereira Maria Inês Matos Silva Barbosa , Robson Alistair
Published: April 2024

Granulomatous slack skin (GSS) is a rare subtype of mycosis fungoides, and few cases have been known to spread to the blood, lymph nodes, or viscera. We present a case with early dissemination to the lung. A 27-year-old woman, previously healthy, presented with scattered disseminated scaly patches, associated with vulvar and intergluteal firm swelling and groin-skin induration for 1 year. She also reported mild fatigue and breathlessness on moderate exertion. The patient underwent blood tests, skin biopsies, and computed tomography scan. The skin biopsy showed a mildly atypical T-cell lymphoid infiltrate involving the dermis/hypodermis, with focal epidermotropism, associated with a granulomatous infiltrate and elastophagocytosis. The computed tomography scan revealed bilateral ground-glass lung nodular opacities. Positron emission tomography showed an increased signal in the skin and subcutis around the buttocks, inguinal and mediastinal lymph nodes, and lungs. The lung biopsy confirmed a dense T-cell infiltrate with numerous multinucleated giant cells. Subsequently, esophageal involvement was also observed following biopsy. Molecular analyses demonstrated identical T-cell clones in the skin and lung. After 6 cycles of chemotherapy/localized external radiotherapy, the patient had a partial skin response and stable lung disease. A preferred diagnosis of GSS with systemic spread was made based on clinical/histologic/molecular findings, after considering granulomatous mycosis fungoides and peripheral T-cell lymphoma, not otherwise specified. This case highlights the frequent diagnostic difficulty in distinguishing GSS from an inflammatory granulomatous dermatitis. Pulmonary and esophageal involvements are rare in GSS, and the simultaneous presentation of characteristic cutaneous GSS with systemic disease poses an additional classification challenge.
Oxyberberine sensitizes liver cancer cells to sorafenib via inhibiting NOTCH1-USP7-c-Myc pathway
Authors: Sun Liangbo , He Meng , Li Feng , Wu Di , Zheng Ping , Zhang Cong , Liu Yang , Liu Dong , Shan Meihua , Yang Mingzhen , Ma Yuanhang , Lian Jiqin , Xiong Haojun
Published: April 2024

Background:

Sorafenib is the first-line therapy for patients with advanced-stage HCC, but its clinical cure rate is unsatisfactory due to adverse reactions and drug resistance. Novel alternative strategies to overcome sorafenib resistance are urgently needed. Oxyberberine (OBB), a major metabolite of berberine in vivo, exhibits potential antitumor potency in various human malignancies, including liver cancer. However, it remains unknown whether and how OBB sensitizes liver cancer cells to sorafenib.

Methods:

Cell viability, trypan blue staining and flow cytometry assays were employed to determine the synergistic effect of OBB and sorafenib on killing HCC cells. PCR, western blot, co-immunoprecipitation and RNA interference assays were used to decipher the mechanism by which OBB sensitizes sorafenib. HCC xenograft models and clinical HCC samples were utilized to consolidate our findings.

Results:

We found for the first time that OBB sensitized liver cancer cells to sorafenib, enhancing its inhibitory effect on cell growth and induction of apoptosis in vitro. Interestingly, we observed that OBB enhanced the sensitivity of HCC cells to sorafenib by reducing ubiquitin-specific peptidase 7 (USP7) expression, a well-known tumor-promoting gene. Mechanistically, OBB inhibited notch homolog 1-mediated USP7 transcription, leading to the downregulation of V-Myc avian myelocytomatosis viral oncogene homolog (c-Myc), which synergized with sorafenib to suppress liver cancer. Furthermore, animal results showed that cotreatment with OBB and sorafenib significantly inhibited the tumor growth of liver cancer xenografts in mice.

Conclusions:

These results indicate that OBB enhances the sensitivity of liver cancer cells to sorafenib through inhibiting notch homolog 1-USP7-c-Myc signaling pathway, which potentially provides a novel therapeutic strategy for liver cancer to improve the effectiveness of sorafenib.
Zonulopathy and Its Relation to Primary Angle Closure Disease: A Review
Authors: Huang Jie , Huang Chukai
Published: April 2024

Précis:

This paper aims to discuss the anatomical features of zonule fibers that center the lens in the eye and summarizes the relationship between zonulopathy and PACD.

The increasing lens vault (LV) and lens thickness (LT) is a recognized mechanism for primary angle closure glaucoma (PACG). Zonulopathy, causing the abnormal lens position, is an important factor in this mechanism. Several anatomically distinct sets of zonular fibers are present in primate eyes, including ciliary zonules, vitreous zonules, and attachments between the posterior insertion zone of the vitreous zonules and the posterior lens equator (PVZ INS-LE strands). Zonulopathy, as a clinical diagnosis, exhibits zonular laxity and loss, long anterior lens zonules (LAZ). Slit lamp, gonioscopy, ultrasound biomicroscopy (UBM), anterior segment optical coherence tomography (AS-OCT) aid in the diagnosis of zonulopathy. The proportion of underdiagnosed zonulopathy among primary angle closure disease (PACD) patients before operation is high. According to the intraoperative signs, zonulopathy could be determined better. There is a high prevalence of zonulopathy among PACD patients compared with the general population. Because of the different insertion zone in lens capsules, different zonular fibers play different parts in lens position and shape. Zonular laxity and loss cause the lens to be thicker and move anteriorly, forming narrow-angle and high intraocular pressure, and then the higher intraocular pressure damages zonule fibers further and causes angle closure. Loss of vitreous zonules may make the ciliary body rotate anterior excessively and pull iris forward, leading to iridotrabecular contact. LAZ eyes tend to be hyperopic and have short axial length, increased LT and anterior lens position, plateau iris configuration, and characteristics that are consistent with elevated risk for angle closure. Zonulopathy may be a risk for PACD. A clear knowledge of zonulopathy and its relation to PACD would be helpful to the diagnosis and treatment.
Superinfections in COVID-19
Authors: Saha Arunava , Siew Michelle , Chaudhuri Sirshendu , Agiwal Varun , Abraham George M.
Published: April 2024

Introduction

Bacterial superinfection rates in SARS-CoV-2 (COVID-19) range from 8% to 49.6%, but the diagnosis remains a challenge. We conducted a study to determine the utility of the Pneumonia Severity Index (PSI) to predict the risk of superinfections and outcomes in COVID-19 patients.

Methods

A cross-sectional retrospective study was conducted on COVID-19 positive patients admitted during 2020–2022. The PSI scores were calculated at admission and at every 72-hour intervals. Data regarding clinical course, antibiotic use and overall outcome were collected.

Results

A total of 149 patients were included, with a mean age of 67 years. The PSI score at admission and the mean PSI score were higher for those who required antibiotics, intensive care unit (ICU) admission, or succumbed. Patients with a PSI score >107 at admission had a high risk of ICU admission, >113 had a high risk of antibiotic requirements, and >110 had a higher risk of death. An increase in PSI score ≥25 between the day of admission and day 3 of hospitalization; or between day 3 and day 6 of hospitalization, predicted a higher chance of mortality; but had no association with the development of superinfections.

Discussion

The PSI score at admission can be used to predict the severity of disease requiring ICU admission, antibiotic requirement, and overall mortality, with serial monitoring of the score predicting possible clinical deterioration and increased mortality. However, it was not helpful in predicting the chances of developing superinfections and the need for antibiotic therapy.

Conclusions

The PSI score can be used to prognosticate the outcome in patients admitted with COVID-19, but further studies are needed to determine its utility in predicting the risk of superinfections.
Pancreatic cancer: new approaches to drug therapy
Authors: Picozzi Vincent J.
Published: April 2024

Outcomes in pancreatic ductal adenocarcinoma (PDAC) remain poor due to a variety of biological, clinical, and societal factors. However, in recent years, PDAC has seen 1) increased precision of initial evaluation, 2) increased emphasis on supportive care, 3) deeper understanding of the translation biology of PDAC, especially as pertains to genomic alterations, and 4) foundational combination chemotherapy clinical trials across all disease stages. These advances have led to a wide range of new approaches to drug therapy for PDAC. Currently available drugs are showing added benefit, both by resequencing them with each other and also with respect to other therapeutic modalities. Molecular strategies are being developed to predict response to known therapeutic agents and to identify others. Additionally, a wide range of new drugs for PDAC are under development, including drugs which inhibit critical molecular pathways, drugs which attempt to capitalize on homologous repair deficiencies, immunotherapeutic approaches, antimetabolic agents, and drugs which attack the extracellular matrix which supports PDAC growth. These new approaches offer the promise of improved survival for future PDAC patients.
The value of cholinesterase inhibitors for improving neuropsychiatric and functional assessment scores in patients with Alzheimer disease: a systematic review and meta-analysis of on placebo-controlled RCTs
Authors: Zhang Yamin , Sun Yanqing , Hu Xiaojuan , Yao Yuping , Wang Jianping
Published: April 2024

Introduction:

At present, increasing reports from different aspects indicated that cholinesterase inhibitors (ChEIs) may be effective on improving neuropsychiatric and functional assessment scores in patients with Alzheimer disease (AD). However, no studies comprehensively and detailedly evaluated the effect of ChEIs on AD. The present analysis was designed to comprehensively evaluate the efficacy and safety of ChEIs for AD.

Methods:

Two independent researchers systematically reviewed 1096 searching records in PubMed, Embase, Cochrane Library, and Web of Science from inception to 10 May 2023, and finally identified 12 randomized, double-blind, placebo-controlled trials with 6908 participants according to predetermined inclusion and exclusion criteria. The effects were assessed with standardized mean difference (SMD) or odds ratio (OR). The primary outcomes were the mean change and least squares (LS) mean change from baseline to endpoint of neuropsychiatric and functional assessment scores. The secondary outcome was adverse events of ChEIs when compared to placebo for patients with AD. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2 and and Stata 12.0.

Results:

Pooled analysis indicated that ChEIs significantly improved the assessment scores of the AD Assessment Scale (ADAS) (SMD −1.57; 95% CI: −2.64 to −0.51), Clinician’s Interview-Based Impression of Change-Plus caregiver input (CIBIC-Plus) (SMD −0.28; 95% CI: −0.41 to −0.15), the Neuropsychiatric Inventory (NPI) (both SMD −1.67; 95% CI: −2.88 to −0.47 for 10-tiem total score and SMD −1.83; 95% CI: −3.25 to −0.42 for 12-tiem total score), and the AD Cooperative Study–Activities of Daily Living (ADCS-ADL) total score (SMD 2.44; 95% CI: 1.29–3.59), evaluated with mean change from baseline to endpoint. In addition, when evaluated with the LS mean change from baseline to endpoint, ChEIs significantly improved Mini-Mental State Examination (MMSE) total score, the Clinician Interview-Based Impression of Severity, CIBIC-Plus, ADCS-ADL total score, NPI, ADAS. Regarding to adverse events (AEs) of patients with AD, it indicated that compared to placebo, ChEIs did not increase the frequency of severe and serious AEs (fatal or nonfatal) as well as the incidence of death.

Conclusions:

Our analysis indicated that ChEIs treatment generally improved neuropsychiatric and functional assessment scores in patients with AD though opposite result was observed in Wechsler Memory Scale. ChEIs had an acceptable safety profile in patients with AD without increasing of any crucial adverse or outcomes.
Quality of Life and Loneliness Among American Military Veterans
Authors: Schafer Katherine Musacchio , Campione Marie , Joiner Thomas
Published: April 2024

Quality of life and loneliness are closely associated with mental and physical health outcomes. This relationship is particularly important in Veterans who experience elevated rates of disabilities, comorbidities, and chronic health conditions as compared with non-Veterans. In the present project, we use data from the Military Health and Well-Being Project (n = 1469, 67.2% men, 32.3% women, 0.5% transgender, nonbinary, prefer not to say) to investigate the link between five domains of quality of life (i.e., general quality of life, physical health, psychological health, social relationships, and environment) with loneliness in American Military Veterans. Findings indicated that every domain of quality of life was negatively and significantly associated with loneliness (r's < −0.45, p's < 0.001), such that quality of life decreased as loneliness increased. We further found, using linear regression, that quality social relationships (β = −0.385, t = −13.23), psychological functioning (β = −0.196, t = −5.28), and physical health (β = −0.133, t = −4.174) were related to low levels of loneliness. Taken together, these findings indicate that in this sample of Veterans 1) general quality of life, physical health, psychological health, social relationships, and environment are all strongly connected with loneliness, and 2) of these, social relationships, psychological health, and physical health seem to protect most against loneliness, with large robust effect sizes. We recommend that intervention and policy researchers continue to investigate and develop feasible, acceptable, and cost-effective ways to promote social relationships, psychological health, and physical health among Veterans. Data were collected during the COVID-19 pandemic, which may limit generalizability of these findings.
Behavioral-Social Rhythms and Cardiovascular Disease Risk in Retired Night Shift Workers and Retired Day Workers
Authors: Tracy Eunjin Lee , Chin Brian N. , Lehrer H. Matthew , Hasler Brant P. , Thomas Mark C. , Smagula Stephen , Kimutis Sarah , Hall Martica H. , Buysse Daniel J.
Published: April 2024

Objective

Stability in the timing of key daily routine behaviors such as working/doing housework, sleeping, eating, and engaging in social interactions (i.e., behavioral-social rhythms) contributes to health. This study examined whether behavioral-social rhythms were associated with cardiovascular disease (CVD) risk factors in retired night shift workers and retired day workers and explored whether past night shift work exposure moderated this association.

Methods

A total of 154 retired older adults participated in this study. Multiple logistic regression models were used to examine associations between behavioral-social rhythms and CVD risk factors. Independent variables included Social Rhythm Metric (SRM)-5 score and actigraphy rest-activity rhythm intradaily variability (IV) and interdaily stability (IS). Dependent variables were metabolic syndrome prevalence and its five individual components.

Results

More regular behavioral-social rhythms were associated with lower odds of prevalent metabolic syndrome (SRM: odds ratio [OR] = 0.57, 95% confidence interval [CI] = 0.35–0.88; IV: OR = 4.00, 95% CI = 1.86–8.58; IS: OR = 0.42, 95% CI = 0.24–0.73) and two of its individual components: body mass index (SRM: OR = 0.56, 95% CI = 0.37–0.85; IV: OR = 2.84, 95% CI = 1.59–5.07; IS: OR = 0.42, 95% CI = 0.26–0.68) and high-density lipoprotein cholesterol (SRM: OR = 0.49, 95% CI = 0.30–0.80; IV: OR = 2.49, 95% CI = 1.25–4.96; IS: OR = 0.35, 95% CI = 0.19–0.66). Past shift work history did not moderate the association between behavioral-social rhythms and metabolic syndrome.

Conclusions

Behavioral-social rhythms were related to CVD risk factors in retired adults regardless of prior night shift work exposure. Older retired workers may benefit from education and interventions aiming to increase behavioral-social rhythm regularity.
An improved genome editing system for Sphingomonadaceae
Authors: García-Romero Inmaculada , de Dios Rubén , Reyes-Ramírez Francisca
Published: April 2024

The sphingomonads encompass a diverse group of bacteria within the Sphingomonadaceae family, with the presence of sphingolipids on their cell surface instead of lipopolysaccharide as their main common feature. They are particularly interesting for bioremediation purposes due to their capability to degrade or metabolise a variety of recalcitrant organic pollutants. However, the research and development of their full bioremediation potential has been hampered because of the limited number of tools available to investigate and modify their genome. Here, we present a markerless genome editing method for Sphingopyxis granuli, which can be further optimised for other sphingomonads. This procedure is based on a double recombination triggered by a DNA double strand break in the chromosome. The strength of this protocol lies in forcing the second recombination rather than favouring it by pressing a counterselection marker, thus avoiding laborious re-streaking or passaging screenings. Additionally, we introduce a modification with respect to the original protocol to increase the efficiency of the screening after the first recombination event. We show this procedure step by step and compare our modified method with respect to the original one by deleting ecfG2, the master regulator of the general stress response in S. granuli. This adds onto the genetic tool repertoire that can be applied to sphingomonads and stands as an efficient option for fast genome editing of this bacterial group.
Seroprevalence of Herpes simplex virus Type-1 IgG antibodies among pregnant women with recurrent abortions
Authors: Ibrahim Hiba Siddig , Mohamed Dalal Abdelhamid , Ahmed Fatima , Hashim Hiba , Saeed Mohammed Ibrahim
Published: April 2024

Herpes Simplex Virus Type 1 (HSV-1) is a nuclear replicating enveloped virus, usually acquired through direct contact with infected lesions or body fluids (typically saliva). The prevalence of HSV-1 infection increases progressively from childhood, and inversely related to socioeconomic background.
The infections among children are either asymptomatic or following an incubation period of about 1 week gives rise to mucocutaneous vesicular eruptions.
Herpetic gingivostomatitis typically affects the tongue, lips, gingival, buccal mucosa and the hard and soft palate.
The main aim of this study is to study the seroprevalence of herpes simplex virus type-1 IgG antibodies among pregnant women with recurrent abortions.
The study demonstrated a 29 (58%) were positive HSV-1-IgG and 21 (42%) were negative among cases (pregnant women) while 25 (100%) in control subject were negatives, and the possible risk factors i.e. age, Abortion, Blood transfusion, Contraceptive, Rash, have been examined in this study and showed no effect except previous history of TORCH test examination.,
The study concluded more than half  pregnant women was found to be infected in our study, and we recommended to screen both  IgM and IgG  followed by viral detection and load by  molecular technique in case of positive ELISA.
Brooklawnia propionicigenes sp. nov., a facultatively anaerobic, propionate-producing bacterium isolated from a methanogenic reactor treating waste from cattle farms
Authors: Akita Yasumitsu , Ueki Atsuko , Tonouchi Akio , Sugawara Yoshimichi , Honma Sachi , Kaku Nobuo , Ueki Katsuji
Published: April 2024

Facultatively anaerobic bacterial strains were isolated from samples of a methanogenic reactor and, based on 16S rRNA gene sequences, found to be affiliated with the family Propionibacteriaceae in the phylum Actinomycetota. Four strains with almost-identical 16S rRNA gene sequences were comprehensively characterized. The most closely related species to the strains was Brooklawnia cerclae BL-34T (96.4 % sequence similarity). Although most of the phenotypic characteristics of the four strains were identical, distinct differences in some cellular and physiological properties were also detected. Cells of the strains were Gram-stain-positive, non-spore-forming, pleomorphic rods. The strains utilized carbohydrates and organic acids. The strains produced acetate, propionate and lactate from glucose, but the molar ratios of the products were variable depending on the strains. The strains grew at 10–40 °C (optimum at 35 °C) and pH 5.3–8.8 (optimum at pH 6.8–7.5.) The major cellular fatty acids of the strains were anteiso-C15 : 0, C15 : 0 and C15 : 0 dimethylacetal (as a summed feature). The major respiratory quinone was menaquinone MK-9(H4) and the diagnostic diamino acid in the peptidoglycan was meso-diaminopimelic acid. The genome size of the type strain (SH051T) was 3.21 Mb and the genome DNA G+C content was 65.7 mol%. Genes responsible for propionate production through the Wood–Werkman pathway were detected in the genome of strain SH051T. Based on the results of phylogenetic, genomic and phenotypic analyses of the novel strains, the name Brooklawnia propionicigenes sp. nov. is proposed to accommodate the four strains. The type strain of the novel species is SH051T (=NBRC 116195T=DSM 116141T).
The Relationship Between Suspected Adverse Drug Reactions Of HMG-Coa Reductase Inhibitors And Polypharmacology Using A National Registry Approach
Authors: Yousaf Hasan , Jones Alan M.
Published: April 2024

Aims

The aim of this study was to explore the suspected adverse drug reaction (ADR) data of five licensed statins in the UK: atorvastatin, fluvastatin, pravastatin, rosuvastatin and simvastatin. A secondary aim was to determine if there was a link between the polypharmacological properties of the statins and their associated muscle-related side effects.

Methods

The chemical database of bioactive molecules with drug-like properties, European Molecular Biology Laboratory (ChEMBL) was used to obtain data on the pharmacological interactions of statins with human proteins. The Medicines and Healthcare products Regulatory Agency’s (MHRA) Yellow Card Scheme was used to obtain reports of suspected ADRs from 2018 to 2022. The OpenPrescribing database was used to obtain the prescribing rates for statistical interpretation.

Results

The study found no significant difference between the statins in causing ADRs across all organ classes (X2,P> .05). Fluvastatin was found to have a higher incidence of ADRs/100,000Rxacross multiple organ classes.

Conclusion

No significant difference was found between the suspected ADR incidence of the statins across all organ classes. No evidence of higher intensity statins causing more muscle symptoms than moderate intensity statins was found.
After Reaching Its Highest Levels since 1950s, Incidence of Syphilis Among US Adults Declined in 2023
Authors: Do Duy , Rodriguez Patricia J. , Gratzl Samuel , Cartwright Brianna M. Goodwin , Baker Charlotte , Stucky Nicholas L
Published: April 2024

Recent reports showed that the incidence of syphilis in the US reached a 70-year high. Using 2019-2023 data from Truveta, this study demonstrated that while the incidence of syphilis increased from 2020 to 2022, it started to decline in 2023. The decline was driven by population subgroups that are commonly considered higher-risk for syphilis infection. Findings also highlighted growing trends among lower-risk population subgroups.
In-Flights of Outbreak Populations of Mountain Pine Beetle Alter the Local Genetic Structure of Established Populations a Decade After Range Expansion
Authors: Thompson Kirsten M. , Huber Dezene P. W. , Sperling Felix A. H. , Murray Brent W.
Published: April 2024

Mountain pine beetles began to appear at epidemic levels in Alberta, Canada, in 2006, following six years of extensive outbreaks in neighboring British Columbia. We assessed the effect of genetic MPB in-flights from the peak of the outbreak on the genetic structure of established populations of MPB and the change over time in novel regions colonized by these inflights. We used five locations sampled during the peak of the outbreak (2005/2007) and re-sampled in 2016. We performed a ddRADseq protocol to generate a SNP dataset via single-end Illumina sequencing. We detected a northern and southern genetic cluster in both sampling sets (2005/2007 and 2016) and a demographic shift in cluster assignment after ∼10 generations from south to north in two of the sites in the path of the northern outbreak. Fst values were significantly different between most sites in the same years and between the same sites at different years, with some exceptions for northern sites established by inflights. Overall, sites in the spreading path of the MPB outbreak have taken on the genetic structure of the contiguous northern outbreak except for an isolated site in Golden, BC, and in Mount Robson Provincial Park where populations are admixed between north and south. Our results suggest that range expansion during insect outbreaks can alter the genetic structure of established populations and lead to interbreeding between populations.
Selectivity of Complex Coacervation in Multi-Protein Mixtures
Authors: Ahn So Yeon , Obermeyer Allie C.
Published: April 2024

Liquid-liquid phase separation of biomolecules is increasingly recognized as relevant to various cellular functions, and complex coacervation of biomacromolecules, particularly proteins, is emerging as a key mechanism for this phenomenon. Complex coacervation is also being explored as a potential protein purification method due to its potential scalability, aqueous operation, and ability to produce a highly concentrated product. However, to date most studies of complex coacervation have evaluated the phase behavior of a binary mixture of two oppositely charged macromolecules. Therefore, a comprehensive understanding of the phase behavior of complex biological mixtures has yet to be established. To address this, a panel of engineered proteins was designed to allow for quantitative analysis of the complex coacervation of individual proteins within a multi-component mixture. The behavior of individual proteins was evaluated using a defined mixture of proteins that mimics the charge profile of theE. coliproteome. To allow for direct quantification of proteins in each phase, spectrally separated fluorescent proteins were used to construct the protein mixture. From this quantitative analysis, we observed that the coacervation behavior of individual proteins in the mixture was consistent with each other, which was distinctive from the behavior when each protein was evaluated in a single-protein system. Subtle differences in biophysical properties between the proteins became noticeable in the mixture, which allowed us to elucidate parameters for protein complex coacervation. With this understanding, we successfully designed methods to enrich a range of proteins of interest from a mixture of proteins.
Expressive modeling and fast simulation for dynamic compartments
Authors: Köster Till , Henning Philipp , Warnke Tom , Uhrmacher Adelinde
Published: April 2024

Compartmentalization is vital for cell biological processes. The field of rule-based stochastic simulation has acknowledged this, and many tools and methods have capabilities for compartmentalization. However, mostly, this is limited to a static compartmental hierarchy and does not integrate compartmental changes. Integrating compartmental dynamics is challenging for the design of the modeling language and the simulation engine. The language should support a concise yet flexible modeling of compartmental dynamics. Our work is based on ML-Rules, a rule-based language for multi-level cell biological modeling that supports a wide variety of compartmental dynamics, whose syntax we slightly adapt. To develop an efficient simulation engine for compartmental dynamics, we combine specific data structures and new and existing algorithms and implement them in the Rust programming language. We evaluate the concept and implementation using two case studies from existing cell-biological models. The execution of these models outperforms previous simulations of ML-Rules by two orders of magnitude. Finally, we present a prototype of a WebAssembly-based implementation to allow for a low barrier of entry when exploring the language and associated models without the need for local installation.

Author summary

Biochemical dynamics are constrained by and influence the dynamics of cellular compartments. Basic constraints are considered by many modeling and simulation tools, e.g., certain reactions may only occur in specific cellular compartments and at a speed influenced by the compartmental volume. However, to capture the functioning of complex compartmental dynamics such as cell proliferation or the fission or fusion of mitochondria, additional efforts are required from tool designers. These refer to how the modeler can specify these dynamics succinctly and unambiguously and how the resulting model can be executed efficiently. For modeling, we rely on ML-Rules, an expressive, formal rule-based language for modeling biochemical systems, which ships with the required features and which we only slightly adapt in our re-implementation. We design a new simulation engine that combines efficient data structures and various algorithms for efficient simulation. The achieved efficiency will enable thorough analysis, calibration, and validation of compartmental dynamics and, thus, allow the “in-silico” pursuit of research questions for which compartmental dynamics are essential. To further facilitate exploring the interplay of compartmental and non-compartmental dynamics, we exploit recent advances in web technology so that ML-Rules models can be run efficiently in the web browser.
iScore: A ML-Based Scoring Function forde novoDrug Discovery
Authors: Mahdizadeh Sayyed Jalil , Eriksson Leif A.
Published: April 2024

In the quest for acceleratingde novodrug discovery, the development of efficient and accurate scoring functions represents a fundamental challenge. This study introduces iScore, a novel machine learning (ML)-based scoring function designed to predict the binding affinity of protein-ligand complexes with remarkable speed and precision. Uniquely, iScore circumvents the conventional reliance on explicit knowledge of protein-ligand interactions and full picture of atomic contacts, instead leveraging a set of ligand and binding pocket descriptors to evaluate binding affinity. This approach avoids the inefficient and slow conformational sampling stage, thereby enabling the rapid screening of ultra-huge molecular libraries, a crucial advancement given the practically infinite dimensions of chemical space. iScore was rigorously trained and validated using the PDBbind 2020 refined set, CASF 2016, and CSAR NRC-HiQ Set1/2, employing three distinct ML methodologies: Deep Neural Network (iScore-DNN), Random Forest (iScore-RF), and eXtreme Gradient Boosting (iScore-XGB). A hybrid model, iScore-Hybrid, was subsequently developed to incorporate the strengths of these individual base learners. The hybrid model demonstrated a Pearson correlation coefficient (R) of 0.78 and a root mean square error (RMSE) of 1.23 in cross-validation, outperforming the individual base learners and establishing new benchmarks for scoring power (R= 0.814, RMSE=1.34), ranking power (ρ= 0.705), and screening power (success rate at top 10% = 73.7%).
Geometry theory of distribution shapes for autoregulatory gene circuits
Authors: Sheng Ying , Lin Genghong , Jiao Feng , Jia Chen
Published: April 2024

In this study, we provide a complete mathematical characterization of the phase diagram of distribution shapes in an extension of the two-state telegraph model of stochastic gene expression in the presence of positive or negative autoregulation. Using the techniques of second-order difference equations and nonlinear discrete dynamical systems, we prove that the feedback loop can only produce three shapes of steady-state protein distributions (decaying, bell-shaped, and bimodal), corresponding to three distinct parameter regions in the phase diagram. The boundaries of the three regions are characterized by two continuous curves, which can be constructed geometrically by the contour lines of a series of ratio operators. Based on the geometric structure of the phase diagram, we then provide some simple and verifiable sufficient and/or necessary conditions for the existence of the bimodal parameter region, as well as the conditions for the steady-state distribution to be decaying, bell-shaped, or bimodal. Finally, we also investigate how the phase diagram is affected by the strength of positive or negative feedback.
Strategies of resource sharing in clonal plants: A conceptual model and an example of contrasting strategies in two closely related species
Authors: Duchoslavová Jana , Jansa Jan
Published: April 2024

Background and Aims

Clonal growth helps plants to cope with environmental heterogeneity through resource integration via connecting organs. Such integration is considered to balance heterogeneity by the translocation of resources from rich to poor patches. However, such an ‘equalisation’ strategy is only one of several possible strategies, as we discuss in a brief conceptual analysis. Under certain conditions, a strategy emphasising acropetal movement and exploration of new areas or a strategy accumulating resources in older ramets may be preferred. The optimal strategy may be determined by environmental conditions, such as resource availability and level of light competition. Therefore, species from different habitats may exhibit distinct resource translocation strategies.

Methods

Resource translocation was compared between two closely related species from different habitats with contrasting productivity. The study examined the bidirectional translocation of carbon and nitrogen in pairs of mother and daughter ramets grown under light heterogeneity (one ramet shaded) at two developmental stages using stable-isotope labelling.

Key results

At the early developmental stage, both species translocated resources toward daughters and the translocation was modified by shading. Later, the species of low-productivity habitats,Fragaria viridis, translocated carbon to shaded ramets, according to the ‘equalisation’ strategy. The species of high-productivity habitats,Potentilla reptans, did not support shaded older ramets. Nitrogen translocation remained mainly acropetal in both species. These findings confirmed our expectations.

Conclusions

The two studied species exhibited different translocation strategies, which may be linked to the habitat conditions experienced by each species. The ‘equalisation’ strategy may occur in habitats with lower productivity and lower light competition, than the strategy emphasising acropetal movement. The results indicate that we need to consider different possible strategies. We emphasise the importance of bidirectional tracing in translocation studies and the need for further studies to investigate the translocation patterns in species from contrasting habitats.
Resilience in a time of stress: revealing the molecular underpinnings of coral survival following thermal bleaching events
Authors: Nunn Brook L. , Brown Tanya , Timmins-Schiffman Emma B , Mudge Miranda , Riffle Michael , Axworthy Jeremy , Dilwort Jenna , Kenkel Carly D , Zaneveld Jesse , Rodrigues Lisa , Padilla-Gamiño Jacqueline Robert
Published: April 2024

Coral bleaching events from thermal stress are increasing globally in duration, frequency, and intensity. Bleaching occurs when a coral's algal symbionts are expelled, resulting in a loss of color. Some coral colonies survive bleaching, reacquire their symbionts and recover. In this study, we experimentally bleached Montipora capitata colonies to examine molecular and physiological signatures of intrinsic differences between corals that recover (resilient) compared to those that die (susceptible). All colonies were collected from the same bay and monitored for eight months post-bleaching to identify specific colonies exhibiting long-term resilience and survival. Using an integrated systems-biology approach that included quantitative mass spectrometry-based proteomics, 16S rRNA of the microbiome, total lipids, symbiont density and diversity, we explored molecular-level mechanisms of tolerance in pre- and post-bleached colonies and found biomarkers of resilience that can confidently identify resilient and susceptible corals before thermal-induced bleaching events. Prior to thermal stress, resilient corals were characterized by a more diverse microbiome and increased abundances of proteins involved in multiple carbon and nitrogen acquisition strategies, symbiont retention and acquisition, and pathogen resistance. Susceptible corals had early signs of symbiont rejection and had resorted to utilizing urea uptake pathways for carbon and nitrogen. Further, molecular signatures identified prior to bleaching were amplified after bleaching, suggesting these pathways may be deterministic in a colony's fate. Our results have important implications for the future of reefs, revealing molecular factors necessary for survival through thermally-induced bleaching events and providing diagnostic biomarkers for coral reef management.
Does ecology shape geographical parthenogenesis? Evidence from the facultatively parthenogenetic stick insectMegacrania batesii
Authors: Miller Soleille , Wilner Daniela , Boldbataar Jigmidmaa , Bonduriansky Russell
Published: April 2024

Closely related sexual and parthenogenetic species often show distinct distribution patterns, known as geographical parthenogenesis. These patterns, characterized by a mosaic of separate sexual and parthenogenetic populations across their natural range, can also be found in facultative parthenogens – species in which every female is capable of both sexual and parthenogenetic reproduction. The underlying mechanisms driving this phenomenon in nature remain unclear. Features of the habitat, such as differences in host plant phenotypes or niche breadth, could favour sexual or asexual reproductive modes and thus help to explain geographical parthenogenesis in natural insect populations.Megacrania batesiiis a facultatively parthenogenetic stick insect that displays geographical parthenogenesis in the wild. We aimed to explore whether sexual and parthenogenetic populations ofM. batesiidisplayed niche differentiation or variations in niche breadth that could explain the separation of the two population types. To do this, we sampled host plants from across the range ofM. batesiiand quantified phenotypic traits that might affect palatability or accessibility forM. batesii, including leaf thickness, toughness, spike size and density, height, and chemical composition. We also quantified host plant density, which could affectM. batesiidispersal. We found little evidence of phenotypic differences between host plants supporting sexual versus asexualM. batesiipopulations, and no difference in host-plant density or niche breadth between the two population types. Our results suggest that habitat parameters do not play a substantial role in shaping patterns of geographical parthenogenesis in wild populations ofM. batesii. Instead, population sex ratio variation could result from interactions between the sexes or dispersal dynamics.