bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical Properties of Naturally Occurring Human Bloom Helicase Variants
Authors: Cueny Rachel R. , Varma Sameer , Schmidt Kristina H. , Keck James L. 
Published: January 2023

AbstractBloom syndrome helicase (BLM) is a RecQ-family helicase implicated in a variety of cellular processes, including DNA replication, DNA repair, and telomere maintenance. Mutations in humanBLMcause Bloom syndrome (BS), an autosomal recessive disorder that leads to myriad negative health impacts including a predisposition to cancer. BS-causing mutations inBLMoften negatively impact BLM ATPase and helicase activity. WhileBLMmutations that cause BS have been well characterized bothin vitroandin vivo, there are other less studiedBLMmutations that exist in the human population that do not lead to BS. Two of these non-BS mutations, encoding BLM P868L and BLM G1120R, when homozygous, increase sister chromatid exchanges in human cells. To characterize these naturally occurring BLM mutant proteinsin vitro, we purified the BLM catalytic core (BLMcore, residues 636-1298) with either the P868L or G1120R substitution. We also purified a BLMcoreK869A K870A mutant protein, which alters a lysine-rich loop proximal to the P868 residue. We found that BLMcoreP868L and G1120R proteins were both able to hydrolyze ATP, bind diverse DNA substrates, and unwind G-quadruplex and duplex DNA structures. Molecular dynamics simulations suggest that the P868L substitution weakens the DNA interaction with the winged-helix domain of BLM and alters the orientation of one lobe of the ATPase domain. Because BLMcoreP868L and G1120R retain helicase functionin vitro, it is likely that the increased genome instability is caused by specific impacts of the mutant proteinsin vivo. Interestingly, we found that BLMcoreK869A K870A has diminished ATPase activity, weakened binding to duplex DNA structures, and less robust helicase activity compared to wild-type BLMcore. Thus, the lysine-rich loop may have an important role in ATPase activity and specific binding and DNA unwinding functions in BLM.
Behavioral pattern separation and cognitive flexibility are enhanced in a mouse model of increased lateral entorhinal cortex-dentate gyrus circuit activity
Authors: Yun Sanghee , Soler Ivan , Tran Fionya , Haas Harley A. , Shi Raymon , Bancroft Grace L. , Suarez Maiko , de Santis Chris R. , Reynolds Ryan P. , Eisch Amelia J. 
Published: January 2023

ABSTRACTBehavioral pattern separation and cognitive flexibility are essential cognitive abilities which are disrupted in many brain disorders. Better understanding of the neural circuitry involved in these abilities will open paths to treatment. In humans and mice, discrimination and adaptation rely on integrity of the hippocampal dentate gyrus (DG) which both receive glutamatergic input from the entorhinal cortex (EC), including the lateral EC (LEC). Inducible increase of EC-DG circuit activity improves simple hippocampal-dependent associative learning and increases DG neurogenesis. Here we asked if the activity of LEC fan cells that directly project to the DG (LEC➔DG neurons) regulates behavioral pattern separation or cognitive flexibility. C57BL6/J male mice received bilateral LEC infusions of a virus expressing shRNA TRIP8b, an auxiliary protein of an HCN channel or a control virus (SCR shRNA); this approach increases the activity of LEC➔DG neurons. Four weeks later, mice underwent testing for behavioral pattern separation and reversal learning (touchscreen-based Location Discrimination Reversal [LDR] task) and innate fear of open spaces (elevated plus maze [EPM]) followed by counting of new DG neurons (doublecortin-immunoreactive cells [DCX+] cells). TRIP8b and SCR shRNA mice performed similarly in general touchscreen training and LDR training. However, in late LDR testing, TRIP8b shRNA mice reached the first reversal more quickly and had more accurate discrimination vs. SCR shRNA mice, specifically when pattern separation was challenging (lit squares close together or “small separation”). Also, TRIP8b shRNA mice achieved more reversals in late LDR testing vs. SCR shRNA mice. Supporting a specific influence on cognitive behavior, SCR shRNA and TRIP8b shRNA mice did not differ in total distance traveled or in time spent in the closed arms of the EPM. Supporting an inducible increase in LEC-DG activity, DG neurogenesis was increased. These data indicate TRIP8b shRNA mice had better pattern separation and reversal learning and more neurogenesis vs. SCR shRNA mice. This work advances fundamental and translational neuroscience knowledge relevant to two cognitive functions critical for adaptation and survival — behavioral pattern separation and cognitive flexibility — and suggests the activity of LEC➔DG neurons merits exploration as a therapeutic target to normalize dysfunctional DG behavioral output.
The Omicron variant BQ.1* with mutations at positions 28,311 and 28,312 in the SARS-CoV-2 N gene have minimal impact on CDC N1 target detection
Authors: Ren Guoping , Langhorst Bradley W. , Patton Gregory C. 
Published: January 2023

AbstractEnsuring COVID-19 testing remains accurate and reliable is of critical importance as the SARS-CoV-2 virus continues to evolve. Currently, a number of Omicron variants are dominating infection across the globe in including BQ.1 and XBB. Both variants and their sublineages (BQ.1* and XBB*) contain a 28,311 C/U mutation inherited from the original Omicron variant (BA.1). This mutation overlaps with a commonly used fluorescent probe for N gene detection in many Emergency Use Authorization (EUA) assays, as this target was originally established by the U.S. Centers for Disease Control and Prevention (CDC) in their EUA test for COVID-19 (2019-nCoV_N1). This C to U mutation was previously shown to have no impact on CDC N1 target detection. The rise of Omicron sublineages has increased the likelihood of additional point mutations occurring within the same assay target. A subpopulation of BQ.1* has an additional 28,312 C/U mutation within the CDC 2019_nCoV_N1 fluorescent probe in addition to the 28,311 C/U mutation. The double mutation could adversely affect the ability of diagnostic assays to detect the virus in patient samples and therefore it is important to verify the impacts of this additional mutation. Using in vitro transcribed (IVT) N gene RNA representing the wildtype (GenBank/GISAID IDMN908947.3) and Omicron BQ.1.1 variant (BQ.1, GISAID ID EPI_ISL_ 15155651), we evaluated the performance of two different amplification protocols, both of which include the CDC 2019-nCoV_N1 primer-probe set. Both assays successfully detected the mutant N gene sequence efficiently even at 10 copies of input, although the double mutation caused a 0.5∼1 Cqdelay on average when compared to the wild-type sequence. These data suggest that circulating BQ.1* lineage viruses with this double mutation likely have minimal impact on diagnostic assays that use the 2019-nCoV-N1 primer-probe.
Statins in pre‐eclampsia or fetal growth restriction: A systematic review and meta‐analysis on maternal blood pressure and fetal growth across species
Authors: Meijerink Lotte , Wever Kim E. , Terstappen Fieke , Ganzevoort Wessel , Lely A. Titia , Depmann Martine 
Published: January 2023

AbstractBackgroundSeveral human randomised controlled trials (RCTs) are investigating the effects of statins on pre‐eclampsia (PE) and fetal growth restriction (FGR). This cross‐species meta‐analysis summarises the preclinical evidence of statin use for PE and FGR.ObjectivesEvaluate the effects of statins on maternal blood pressure (MBP) and birthweight (BW) in pregnancies complicated by PE or FGR.Search StrategyPubMed and Embase.com were searched on 10 May 2022 using ‘statins’ and ‘pregnancy’.Selection CriteriaWe included RCTs and cohorts with matched control groups as well as animal studies.Data Collection and AnalysisThe main outcomes were MBP in mmHg and BW in grams. The standardised mean difference (SMD) with a 95% confidence interval (CI) was calculated. Subgroup analyses on species, statin, dose, timing and route of administration were performed if subgroups included at least three studies.Main ResultsOur data included one human and 12 animal studies. Prenatal administration of statins significantly reduced MBP during pregnancy (SMD  −2.49 mmHg [95% CI −4.26 to −0.71], p = 0.01). There was no significant effect of statins on BW (SMD 0.69 [95% CI −0.65 to 2.03], p = 0.28). Our subgroup analyses showed no effect on MBP of different doses, species or route of administration.ConclusionsOur cross‐species meta‐analyses demonstrate that statins only reduce maternal blood pressure in rodent pregnancies complicated by pre‐eclampsia or fetal growth restriction and have no effect on birthweight across species. The broad confidence intervals, inconsistent direction of the observed effects across the studies and large risk of bias lead us to conclude that a solid base for further human RCTs is lacking.
Production of selenium nanoparticles occurs through an interconnected pathway of sulphur metabolism and oxidative stress response in Pseudomonas putida KT2440
Authors: Avendaño Roberto , Muñoz‐Montero Said , Rojas‐Gätjens Diego , Fuentes‐Schweizer Paola , Vieto Sofía , Montenegro Rafael , Salvador Manuel , Frew Rufus , Kim Juhyun , Chavarría Max , Jiménez Jose I. 
Published: January 2023

AbstractThe soil bacterium Pseudomonas putida KT2440 has been shown to produce selenium nanoparticles aerobically from selenite; however, the molecular actors involved in this process are unknown. Here, through a combination of genetic and analytical techniques, we report the first insights into selenite metabolism in this bacterium. Our results suggest that the reduction of selenite occurs through an interconnected metabolic network involving central metabolic reactions, sulphur metabolism, and the response to oxidative stress. Genes such as sucA, D2HGDH and PP_3148 revealed that the 2‐ketoglutarate and glutamate metabolism is important to convert selenite into selenium. On the other hand, mutations affecting the activity of the sulphite reductase decreased the bacteria's ability to transform selenite. Other genes related to sulphur metabolism (ssuEF, sfnCE, sqrR, sqr and pdo2) and stress response (gqr, lsfA, ahpCF and sadI) were also identified as involved in selenite transformation. Interestingly, suppression of genes sqrR, sqr and pdo2 resulted in the production of selenium nanoparticles at a higher rate than the wild‐type strain, which is of biotechnological interest. The data provided in this study brings us closer to understanding the metabolism of selenium in bacteria and offers new targets for the development of biotechnological tools for the production of selenium nanoparticles.
Chytridiomycosis and climate change: exposure to Batrachochytrium dendrobatidis and mild winter conditions do not increase mortality in juvenile agile frogs during hibernation
Authors: Kásler A. , Holly D. , Herczeg D. , Ujszegi J. , Hettyey A. 
Published: January 2023

AbstractHibernation is often associated with high mortality, especially during early life stages, and losses can be exacerbated by unusual winter conditions or if animals enter hibernation carrying a disease. Here, we examined how overwintering amphibians may be affected by the combined effects of mild winters, which are projected to increase in frequency due to climate change, and of chytridiomycosis, a disease that has contributed to the decline of hundreds of species worldwide. We exposed juvenile agile frogs Rana dalmatina to Batrachochytrium dendrobatidis (Bd), the causative agent of chytridiomycosis, and subsequently subjected them to either a long, cold winter (1.5°C for 91 days) or a short, mild winter (4.5°C for 61 days) under laboratory conditions. Agile frogs proved to be highly resistant to Bd as only 37% of Bd‐exposed individuals became infected as determined before hibernation, and prevalence further decreased to 8% by the end of hibernation, with individuals showing very low infection intensity values. We observed lack of mortality in control and Bd‐exposed groups also, in both types of winter. The two types of winter we simulated did not result in differing body mass loss either alone or in combination with experimental infection. In the Bd‐exposed group, the two types of winter also did not cause differences in prevalence and infection intensity. However, among Bd‐exposed frogs, individuals that were Bd negative when entering hibernation lost more body mass than their conspecifics that carried the fungus at the onset of overwintering. Based on our results, warming winter climate conditions, with or without Bd infection, do not decrease body mass and survival rate of hibernating agile frogs, and do not increase susceptibility of individuals to chytridiomycosis. It remains to be seen to what extent the relatively weak effects of milder winters can be generalized to other amphibians of the temperate climate zone.
Comparative performance of a multi‐locus barcoding approach to enhance taxonomic resolution of New Zealand mosquitoes (Diptera: Culicidae)
Authors: Wu Jieyun , Li Dongmei , Boyd Ben , Balan Rebijith K. , George Sherly , Peacock Lora , Pal Chandan 
Published: January 2023

AbstractMosquitoes (Diptera: Culicidae) pose a serious threat to human health globally and the accurate identification of mosquito species is fundamental to entomological diagnostics and surveillance implementing effective vector control and management. However, cryptic species complexes, incomplete or damaged specimens, and juvenile life stages complicates the task. Molecular characterisation has shown the potential to identify the mosquito species accurately and overcomes the difficulties that morphological diagnosis face. Here, we assessed the effectiveness of a multi‐locus barcoding approach using cytochrome c oxidase subunit I (COI), internal transcribed spacer 1 (ITS1) and internal transcribed spacer 2 (ITS2) regions to identify the New Zealand mosquito species (n = 16) at the highest taxonomic resolution, which can make diagnosis more accurate and efficient. Our results show that most of the New Zealand mosquito species could be distinctly separated from each other as well as from other exotic species using either of these barcoding regions (i.e., COI, ITS1 and ITS2). The assessment of taxonomic discriminatory power of COI, ITS1 and ITS2 barcodes suggests that ITS2 can better distinguish the New Zealand closely‐related species. Two closely‐related endemic species from the Culex pervigilans species complex (Cx. rotoruae and Cx. pervigilans) were difficult to distinguish using COI and ITS1 regions. However, the ITS2 barcode could detect a greater genetic variation among individuals of those two species and demonstrate the potential to resolve the relationships among them to provide better resolution as a complementary to COI. Overall, this study provides a reference DNA barcode database of COI and ITS2 for New Zealand mosquito species, which will aid in their accurate identification at a higher taxonomic resolution and corroborate the traditional morphological approaches to perform better species discrimination among closely‐related species complex. The study also assessed the preliminary genetic diversity of the mosquito species from different regions of New Zealand, which can be used as a baseline for uncovering the environmental and geographical effect on genomic variations among New Zealand mosquito populations in the future.
Non‐linear association between testosterone and LDL concentrations in men
Authors: Lee Jun Ho , Jung Hyuk‐Dal , Choi Jae Duck , Kang Jung Yoon , Yoo Tag Keun , Park Yeon Won 
Published: January 2023

AbstractBackgroundContradictory data have been reported about the association between testosterone levels and the levels of low‐density lipoprotein cholesterol (LDL).ObjectivesThe aim of this study was to elucidate the association between testosterone and LDL levels.Materials and methodsA cross‐sectional study was conducted that included 7268 men who had participated in a health examination. Men who took agents that influence serum lipid profiles within the previous 6 months were excluded. A full metabolic work‐up and serum testosterone level checks were performed. The main outcome measures included the testosterone level and testosterone <3.5 ng/ml prevalence of each decile of LDL and their polynomial trendlines and the odds ratio (OR) of testosterone <3.5 ng/ml according to the LDL level.ResultsThe polynomial trendline suggests the inverse association of testosterone with the deciles of triglycerides, the positive association of testosterone with the deciles of high‐density lipoprotein cholesterol and the inverted U‐shaped association between testosterone and the deciles of LDL. The polynomial trendline suggests a U‐shaped curvilinear relationship between the deciles of LDL and the prevalence of testosterone <3.5 ng/ml. The adjusted ORs of testosterone <3.5 ng/ml in men in the lowest and highest deciles were significantly higher than those of men in the 10th–90th deciles of LDL (OR [95% CI], < 10th LDL: 1.4[1.2–1.8]; 10th – 90th LDL: 1.0 [reference]; >90th LDL: 1.3[1.0–1.6]), which reinforces the U‐shaped curvilinear relationship between LDL levels and the prevalence of testosterone <3.5 ng/ml.Discussion and conclusionFurther research is needed to elucidate the association of very low or very high LDL concentrations with circulating testosterone in men.
How we approach the perioperative management of patients with chronic lymphocytic leukaemia receiving continuous cancer‐directed therapies
Authors: Ma Helen , Wang Stephani , O'Brien Susan , Kern Morton , Gupta Pankaj 
Published: January 2023

SummaryHistorically, invasive procedures and surgeries were deferred in patients with haematological malignancies including advanced stage chronic lymphocytic leukaemia (CLL) because of limited life expectancy. However, novel, and often continuous, treatments have markedly improved outcomes in CLL. Some patients may expect years of treatment response and disease control, overcoming the short life expectancy that deters interventionalists. Such patients now often undergo various invasive procedures including major surgery. To inform peri‐operative management, we summarize the relevant side effects and drug interactions of continuous CLL therapies, highlight potential surgical risks, and provide recommendations on withholding specific CLL drugs around invasive procedures.
TNTversion 1.6, with a graphical interface forMacOSand Linux, including new routines in parallel
Authors: Goloboff Pablo A. , Morales Martín E. 
Published: January 2023

AbstractA new graphical user interface (GUI) for the parsimony program TNT is presented that works under the Linux and Mac operating systems, as well as the Cygwin environment (which runs under Windows). The new interface is based on the GIMP Tool Kit, GTK (version 3). Formerly, only Windows versions of TNT had a GUI. The new interface improves upon the existing Windows GUI in several respects. These changes, together with several additions to the program since the publication of version 1.5, warrant a change in minor version, thus moving from version 1.5 to 1.6. Among the most notable improvements are the possibility to access graphical user dialogs by means of simple commands, to easily save trees in SVG format (“Scalable Vector Graphics”) directly from any tree‐diagram being displayed, and to manage analyses in parallel (using multiple processors, by means of the PVM system or “Parallel Virtual Machine”), as well as a generally more stable and consistent behaviour. As the binaries for the new version are compiled as native 64‐bit applications, this removes the limitations for accessing large amounts of memory in the previous GUI Windows interface (which is a 32‐bit application).
Impact and recovery of the COVID‐19 pandemic on weight status of children and adolescents
Authors: Bond Diana M. , Seimon Radhika , Schneuer Francisco J. , Baur Louise A. , Craig Maria , Alexander Shirley , Garnett Sarah P. , Henderson Joanne , Nassar Natasha 
Published: January 2023

SummaryRecent evidence suggests the immediate effects of the COVID‐19 lockdowns and restrictions have resulted in increased weight in children and adolescents. However, the longer‐term effects have not been assessed. The aim of this study was to examine the impact and longer‐term effects of the COVID‐19 pandemic on BMI and weight status of children and adolescents. This study used routinely collected clinical data from the Sydney Children's Hospitals Network, comprising two socio‐demographically diverse children's hospitals in New South Wales, Australia from 2018 to 2021. Of 245 836 individuals ≤18‐years assessed, mean BMI percentile increased from 58.7 (SD 31.6) pre‐COVID‐19 to 59.8 (SD 31.7) (p < .05) post‐restrictions and overweight/obesity increased by 5.5% (obesity alone 6.3%), predominantly in children <12‐years and from lower socioeconomic backgrounds. The trend in BMI percentile was steady pre‐COVID‐19 (β = −0.03 [95% CI −0.07, 0.01]), peaked immediately following COVID‐19 restrictions (β = 1.28 [95% CI 0.24, 2.32]) and returned to pre‐pandemic levels over ensuing 21 months (β = −0.04 [95% CI –0.13, 0.04]). Routine anthropometric measurement facilitates ongoing monitoring and evaluation of the weight status of children and adolescents, helping to identify those at‐risk. Despite initial BMI and weight increases among children and adolescents, longer‐term follow‐up highlighted a return to pre‐pandemic rates, possibly attributed to state‐wide policies aimed at reducing childhood obesity.
Comprehensive analysis of pyroptosis‐related gene signatures for glioblastoma immune microenvironment and target therapy
Authors: Wang Zeyu , Dai Ziyu , Zhang Hao , Zhang Nan , Liang Xisong , Peng Luo , Zhang Jian , Liu Zaoqu , Peng Yun , Cheng Quan , Liu Zhixiong 
Published: January 2023

AbstractGlioblastoma (GBM) is a malignant brain tumour, but its subtypes (mesenchymal, classical, and proneural) show different prognoses. Pyroptosis is a programmed cell death relating to tumour progression, but its association with GBM is poorly understood. In this work, we collected 73 GBM samples (the Xiangya GBM cohort) and reported that pyroptosis involves tumour‐microglia interaction and tumour response to interferon‐gamma. GBM samples were grouped into different subtypes, cluster 1 and cluster 2, based on pyroptosis‐related genes. Cluster 1 samples manifested a worse prognosis and had a more complicated immune landscape than cluster 2 samples. Single‐cell RNA‐seq data analysis supported that cluster 1 samples respond to interferon‐gamma more actively. Moreover, the machine learning algorithm screened several potential compounds, including nutlin‐3, for cluster 1 samples as a novel treatment. In vitro experiments supported that cluster 1 cell line, T98G, is more sensitive to nutlin‐3 than cluster 2 cell line, LN229. Nutlin‐3 can trigger oxidative stress by increasing DHCR24 expression. Moreover, pyroptosis‐resistant genes were upregulated in LN229, which may participate against nutlin‐3. Therefore, we hypothesis that GBM may be able to upregulate pyroptosis resistant related genes to against nutlin‐3‐triggered cell death. In summary, we conclude that pyroptosis highly associates with GBM progression, tumour immune landscape, and tumour response to nutlin‐3.