bluuebunny/crossref_metadata_2025 huggingface dataset:
YhcB (DUF1043), a novel cell division protein conserved across gamma-proteobacteria
Authors: Mehla Jitender , Liechti George , Morgenstein Randy M. , Caufield J. Harry , Hosseinnia Ali , Gagarinova Alla , Phanse Sadhna , Brockett Mary , Sakhawalkar Neha , Babu Mohan , Xiao Rong , Montelione Gaetano T. , Vorobiev Sergey , den Blaauwen Tanneke , Hunt John F. , Uetz Peter
Published: January 2021

YhcB, an uncharacterized protein conserved across gamma-proteobacteria, is composed predominantly of a single Domain of Unknown Function (DUF 1043) with an N-terminal transmembrane α-helix. Here, we show that E. coli YhcB is a conditionally essential protein that interacts with the proteins of the cell divisome (e.g., FtsI, FtsQ) and elongasome (e.g., RodZ, RodA). We found 7 interactions of YhcB that are conserved in Yersinia pestis and/or Vibrio cholerae. Furthermore, we identified several point mutations that abolished interactions of YhcB with FtsI and RodZ. The yhcB knock-out strain does not grow at 45°C and is hypersensitive to cell-wall acting antibiotics even in stationary phase. The deletion of yhcB leads to filamentation, abnormal FtsZ ring formation, and aberrant septa development. The 2.8 Å crystal structure for the cytosolic domain from Haemophilus ducreyi YhcB shows a unique tetrameric α-helical coiled-coil structure that combines parallel and anti-parallel coiled-coil intersubunit interactions. This structure is likely to organize interprotein oligomeric interactions on the inner surface of the cytoplasmic membrane, possibly involved in regulation of cell division and/or envelope biogenesis/integrity in proteobacteria. In summary, YhcB is a conserved and conditionally essential protein that is predicted to play a role in cell division and consequently or in addition affects envelope biogenesis.

Importance

Only 0.8 % of the protein annotations in the UniProt are based on experimental evidence and thus, functional characterization of unknown proteins remains a rate-limiting step in molecular biology. Herein, the functional properties of YhcB (DUF1043) were investigated using an integrated approach combining X-ray crystallography with genetics and molecular biology. YhcB is a conserved protein that appears to be needed for the transition from exponential to stationary growth and is involved in cell division and/or envelope biogenesis/integrity. This study will serve as a starting point for future studies on this protein family and on how cells transit from exponential to stationary survival.
Transcriptomics data availability and reusability in the transition from microarray to next-generation sequencing
Authors: Rustici Gabriella , Williams Eleanor , Barzine Mitra , Brazma Alvis , Bumgarner Roger , Chierici Marco , Furlanello Cesare , Greger Liliana , Jurman Giuseppe , Miller Michael , Ouellette B.F. Francis , Quackenbush John , Reich Michael , Stoeckert Christian J. , Taylor Ronald C. , Trutane Stephen Chervitz , Weller Jennifer , Wilhelm Brian , Winegarden Neil
Published: January 2021

Over the last two decades, molecular biology has been changed by the introduction of high-throughput technologies. Data sharing requirements have prompted the establishment of persistent data archives. A standardized approach for recording and managing these data was first proposed in the Minimal Information About a Microarray Experiment (MIAME) guidelines. The Minimal Information about a high throughput nucleotide Sequencing Experiment (MINSEQE) proposal was introduced in 2008 as a logical extension of the guidelines to next-generation sequencing (NGS) technologies used for transcriptome analysis.

We present a historical snapshot of the data-sharing situation focusing on transcriptomics data from both microarray and RNA-sequencing experiments published between 2009 and 2013, a period during which RNA-seq studies became increasingly popular for transcriptome analysis. We assess how much data from RNA-seq based experiments is actually available in persistent data archives, compared to data derived from microarray based experiments, and evaluate how these types of data differ. Based on this analysis, we provide recommendations to improve RNA-seq data availability, reusability, and reproducibility.
Genome-wide characterization and identification of synonymous codon usage patterns in Plasmodium knowlesi
Authors: Yadav Manoj Kumar , Gajbhiye Shivani
Published: January 2021

Codon usage bias is a ubiquitous phenomenon occurring at both, interspecies and intraspecies level in different organisms. P. knowlesi, whose natural host is long-tailed Macaque monkeys, has recently started infecting humans as well. The genome as well as coding sequence data of P. knowlesi is used to understand their codon usage pattern in the light of other human infecting Plasmodium species: P. vivax and P. falciparum. The different codon usage indicators: GC content, relative synonymous codon usage, effective number of codon and codon adaptation index are studied to analyze codon usage in the Plasmodium species. The codon usage pattern is found to be less conserved in studied Plasmodium species, and changes species to species at the genus level. The codon usage pattern of P. knowlesi shows similarity to P. vivax as compared to P. falciparum. The ENC vs. GC3 study indicates that compositional constraints and translation selection is the decisive forces responsible for shaping their codon usage. The studies Plasmodium species shows a higher usage of A/T ending optimal codons. This favors the codon bias in P. knowlesi and P. vivax is due to high selection pressure and in P. falciparum, the compositional mutational pressure is a dominant force. In a nutshell, our finding suggests that the more or less similar codon usage pattern of P. knowlesi and P. vivax may suggest the similar host invasion and immune evasion strategies for disease establishment.
Homology between the flagellar export apparatus and ATP synthetase: evidence from synteny predating the Last Universal Common Ancestor
Authors: Matzke Nicholas J. , Lin Angela , Stone Micaella , Baker Matthew A. B.
Published: January 2021

Evidence of homology between proteins in the ATP synthetase and the bacterial flagellar motor (BFM) has been accumulating since the 1980s. Specifically, the BFM’s Type 3 Secretion System (T3SS) export apparatus FliH, FliI, and FliJ are considered homologous to FO-b + F1-δ, F1-α/β, and F1-γ, and have similar structure and interactions. We review the discoveries that advanced the homology hypothesis and then conduct a further test by examining gene order in the two systems and their relatives. Conservation of gene order, or synteny, is often observed between closely related prokaryote species, but usually degrades with phylogenetic distance. As a result, observed conservation of synteny over vast phylogenetic distances can be evidence of shared ancestral coexpression, interaction, and function. We constructed a gene order dataset by examining the order offliH,fliI, andfliJgenes across the phylogenetic breadth of flagellar and nonflagellar T3SS. We compared this to published surveys of gene order in the F1FO-ATP synthetase, its N-ATPase relatives, and the bacterial/archaeal V- and A-type ATPases. Strikingly, thefliHIJgene order was deeply conserved, with the few exceptions appearing derived, and exactly matching the widely conserved F-ATPase gene orderatpFHAG, coding for subunitsb-δ-α-γ. The V/A-type ATPases have a similar conserved gene order shared for homologous components. Our results further strengthen the argument for homology between these systems, and suggest a rare case of synteny conserved over billions of years, dating back to well before the Last Universal Common Ancestor (LUCA).
SARS-CoV-2 infects lung epithelial cells and induces senescence and an inflammatory response in patients with severe COVID-19
Authors: Evangelou Konstantinos , Veroutis Dimitris , Foukas Periklis G. , Paschalaki Koralia , Lagopati Nefeli , Dimitriou Marios , Papaspyropoulos Angelos , Hazapis Orsalia , Polyzou Aikaterini , Havaki Sophia , Kotsinas Athanassios , Kittas Christos , Tzioufas Athanasios G. , de Leval Laurence , Vassilakos Demetris , Tsiodras Sotirios , Karakasiliotis Ioannis , Barnes Peter J , Gorgoulis Vassilis G.
Published: January 2021

Rationale

SARS-CoV-2 infection of the respiratory system can progress to a life threatening multi-systemic disease, mediated via an excess of cytokines (“cytokine storm”), but the molecular mechanisms are poorly understood.

Objectives

To investigate whether SARS-CoV-2 may induce cellular senescence in lung epithelial cells, leading to secretion of inflammatory cytokines, known as the senescence-associated secretory phenotype (SASP).

Methods

Autopsy lung tissue samples from eleven COVID-19 patients and sixty age-matched non-infected controls were analysed by immunohistochemistry for SARS-CoV-2 and markers of cellular senescence (SenTraGor, p16INK4A) and key SASP cytokines (interleukin-1β, interleukin-6). We also investigated whether SARS-CoV-2 infection of an epithelial cell line induces senescence and cytokine secretion.

Measurements and Main Results

SARS-CoV-2 was detected by immunocytochemistry and electron microscopy predominantly in alveolar type-2 (AT2) cells, which also expressed the angiotensin-converting-enzyme 2 (ACE2), a critical entry receptor for this virus. In COVID-19 samples, AT2 cells displayed increased markers of senescence [p16INK4A, SenTraGor staining positivity in 12±1.2% of cells compared to 1.7±0.13% in non-infected controls (p<0.001)], with markedly increased expression of interleukin-1β and interleukin-6 (p<0.001). Infection of epithelial cells (Vero E6) with SARS-CoV-2in-vitroinduced senescence and DNA damage (increased SenTraGor and γ-H2AX), and reduced proliferation (Ki67) compared to uninfected control cells (p<0.01).

Conclusions

We demonstrate that in severe COVID-19 patients, AT2 cells are infected with SARS-CoV-2 and show senescence and expression of proinflammatory cytokines. We also show that SARS-CoV-2 infection of epithelial cells may induce senescence and inflammation, indicating that cellular senescence may be an important molecular mechanism of severe COVID-19.
Human brain region-specific variably methylated regions (VMRs) are enriched for heritability of distinct neuropsychiatric traits
Authors: Rizzardi Lindsay F. , Hickey Peter F. , Idrizi Adrian , Tryggvadóttir Rakel , Callahan Colin M. , Stephens Kimberly E. , Taverna Sean D. , Zhang Hao , Ramazanoglu Sinan ,   GTEx Consortium, Hansen Kasper D. , Feinberg Andrew P.
Published: January 2021

BACKGROUND

DNA methylation dynamics in the brain are associated with normal development and neuropsychiatric disease and differ across functionally distinct brain regions. Previous studies of genome-wide methylation differences among human brain regions focused on limited numbers of individuals and one to two brain regions.

RESULTS

Using GTEx samples, we have generated a resource of DNA methylation in purified neuronal nuclei from 8 brain regions as well as lung and thyroid tissues from 12-23 donors. We identified differentially methylated regions between brain regions (DMRs) among neuronal nuclei in both CpG (181,146) and non-CpG (264,868) contexts, few of which were unique to a single pair-wise comparison. This significantly expands the knowledge of differential methylation across the brain by 10-fold. In addition, we present the first differential methylation analysis among neuronal nuclei from basal ganglia tissues and identified 2,295 unique CpG DMRs, many associated with ion transport. Consistent with prior studies, CpG DMRs were enriched in regulatory regions while non-CpG DMRs were enriched in intergenic regions. We also identified 81,130 regions of variably CpG methylated regions (VMRs), i.e. variable methylation among individuals in the same brain region, which were enriched in regulatory regions and in CpG DMRs. Many VMRs were unique to a specific brain region, with only 202 common across all brain regions, as well as lung and thyroid. VMRs identified in the amygdala, anterior cingulate cortex, and hippocampus were enriched for heritability of schizophrenia.

CONCLUSIONS

These data suggest that epigenetic variation in these particular human brain regions could be associated with the risk for this neuropsychiatric disorder.
Functional insights of two MATE transporters fromVibrio fluvialis
Authors: Mohanty Priyabrata , Shah Aneri , Bhardwaj Ashima Kushwaha
Published: January 2021

Functional characterization of H- and D-MATE (Multidrug and Toxin Extrusion) transporters from clinical isolates ofVibrio fluvialisrevealed H-type conferred resistance to fluoroquinolones, ethidium bromide and safranin whereas D-type exhibited marginal resistance towards ethidium bromide only. Both H-/D-type transporters were inhibited by reserpine resulting in increased intracellular norfloxacin concentration. The efflux was facilitated by both Na+/K+ions, suggesting that these efflux pumps were ion-dependent. In presence of various classes of EPIs, there was decrease in MIC exhibited by H-/D-type efflux pumps towards norfloxacin which didn’t translate into transport inhibition. But reserpine presented a conclusive pattern with decrease in MIC towards norfloxacin and increased norfloxacin accumulation inferring maximum inhibition. Substrate binding and electrostatic charge distribution of both the transporters was similar to other known MATE transporters. The H-type exhibited 10 transmembranes and D-type exhibited 11 TMs which was different from other MATE transporters known to have 12 TMs (Transmembranes). Data derived from molecular docking and ion binding studies revealed that Aspartic Acid residue in 1stTM acts as ion binding site with transport mechanism similar to NorM. Electrostatic potential map of both the transporters revealed that there is a cavity formation within the transporters surrounded by charged electronegative amino acid residues. Interestingly, surface models of both transporters revealed that 1stTM forms covalent bond with 7thTM towards extracellular space. Docking studies also revealed that reserpine covalently binds to central pocket of both transporters and serves as excellent EPI against these transporters as evidenced by MIC and drug accumulation assays.
In vivolentiviral vector gene therapy to cure hereditary tyrosinemia type 1 and prevent development of precancerous and cancerous lesions
Authors: Nicolas Clara T , VanLith Caitlin J , Allen Kari L , Hickey Raymond D , Du Zeji , Hillin Lori G , Guthman Rebekah M , Cao William J , Bhagwate Aditya , O’Brien Daniel , Kocher Jean-Pierre , Kaiser Robert A , Russell Stephen J , Lillegard Joseph B
Published: January 2021

Conventional therapy for hereditary tyrosinemia type-1 (HT1) with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) delays and in some cases fails to prevent disease progression to liver fibrosis, liver failure, and activation of tumorigenic pathways. Here we demonstrate for the first time a cure of HT1 by direct,in vivoadministration of a therapeutic lentiviral vector targeting the expression of a human fumarylacetoacetate hydrolase (FAH) transgene in the porcine model of HT1. This therapy was well tolerated and provided stable long-term expression of FAH in pigs with HT1. Genomic integration displayed a benign profile, with subsequent fibrosis and tumorigenicity gene expression patterns similar to wild-type animals as compared to NTBC-treated or diseased untreated animals. Indeed, the phenotypic and genomic data followingin vivolentiviral vector administration demonstrate comparative superiority over other therapies includingex vivocell therapy and therefore support clinical application of this approach.
Loss of mutually protective effects between osteoclasts and chondrocytes in damaged joints drives osteoclast-mediated cartilage degradation via matrix metalloproteinases
Authors: Larrouture Quitterie C , Cribbs Adam P , Snelling Sarah J , Knowles Helen J
Published: January 2021

Osteoclasts are large multinucleated cells that resorb bone to regulate bone remodelling during skeletal maintenance and development. It is overlooked that osteoclasts also digest cartilage during this process, as well as in degradative conditions including osteoarthritis, rheumatoid arthritis and primary bone sarcomas such as giant cell tumour of bone. This study explores the poorly understood mechanisms behind the interaction between osteoclasts and cartilage. Morphologically, osteoclasts differentiated on acellular human cartilage formed multinucleated cells expressing characteristic osteoclast marker genes (e.g.CTSK, MMP9) and proteins (TRAP, VNR) that visibly damaged the cartilage surface by SEM, but without the formation of resorption pits. Osteoclasts caused increased glycosaminoglycan (GAG) release from acellular and cellular human cartilage that was dependent on direct contact with the substrate. Direct co-culture with chondrocytes during osteoclast differentiation increased the number of large osteoclasts formed. When osteoclasts were cultured on dentine, direct co-culture with chondrocytes inhibited osteoclast formation and reduced basal degradation of cartilage. This suggests a mutually protective effect on their ‘native’ tissue between bone-resident osteoclasts and chondrocytes, that is reversed when the joint structure breaks down and osteoclasts are in contact with non-native substrates. Mechanistically, osteoclast-mediated cartilage degradation was inhibited by the pan-MMP inhibitor GM6001 and by TIMP1, indicative of a role for soluble MMPs. RNA sequencing and RT-qPCR analysis identifiedMMP8as overexpressed in osteoclasts differentiated on cartilage versus dentine, whileMMP9was the most highly expressed MMP on both substrates. Inhibition of eitherMMP8orMMP9by siRNA in mature osteoclasts reduced GAG release, confirming their involvement in cartilage degradation. Immunohistochemical expression of MMP8 and MMP9 was evident in osteoclasts in osteosarcoma tissue sections. Understanding and controlling the activity of osteoclasts might represent a new therapeutic approach for pathologies characterized by cartilage degeneration and presents an attractive target for further research.
LiquidCNA: tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations
Authors: Lakatos Eszter , Hockings Helen , Mossner Maximilian , Huang Weini , Lockley Michelle , Graham Trevor A.
Published: January 2021

Cell-free DNA (cfDNA) measured via liquid biopsies provides a way for minimally-invasive monitoring of tumour evolutionary dynamics during therapy. Here we present liquidCNA, a method to track subclonal evolution from longitudinally collected cfDNA samples based on somatic copy number alterations (SCNAs). LiquidCNA utilises SCNA profiles derived through cost-effective low-pass whole genome sequencing to automatically and simultaneously genotype and quantify the size of the dominant subclone without requiring prior knowledge of the genetic identity of the emerging clone. We demonstrate the accuracy of liquidCNA in synthetically generated sample sets andin vitroandin silicomixtures of cancer cell lines. Applicationin vivoin patients with metastatic lung cancer reveals the progressive emergence of a novel tumour sub-population. LiquidCNA is straightforward to use, computationally inexpensive and enables continuous monitoring of subclonal evolution to understand and control therapy-induced resistance.
Fast and Accurate Influenza Forecasting in the United States with Inferno
Authors: Osthus Dave
Published: January 2021

Infectious disease forecasting is an emerging field and has the potential to improve public health through anticipatory resource allocation, situational awareness, and mitigation planning. By way of exploring and operationalizing disease forecasting, the U.S. Centers for Disease Control and Prevention (CDC) has hosted FluSight since the 2013/14 flu season, an annual flu forecasting challenge. Since FluSight’s onset, forecasters have developed and improved forecasting models in an effort to provide more timely, reliable, and accurate information about the likely progression of the outbreak. While improving the predictive performance of these forecasting models is often the primary objective, it is also important for a forecasting model to run quickly, facilitating further model development, improvement, and scalability. In this vein I introduce Inferno, a fast and accurate flu forecasting model inspired by Dante, the top performing model in the 2018/19 FluSight challenge. When compared to all models that participated in FluSight 2018/19, Inferno would have placed 2nd in both the national and state challenges, behind only Dante. Inferno, however, runs in minutes and is trivially parallelizable, while Dante takes hours to run, representing a significant operational improvement with minimal impact to performance. A future consideration for forecasting competitions like FluSight will be how to encourage improvements to secondarily important properties of forecasting models, such as runtime, generalizability, and interpretability.
Psoriasis: Recent progress in molecular‐targeted therapies
Authors: Honma Masaru , Hayashi Kei
Published: January 2021

Psoriasis is a multifactorial recalcitrant inflammatory skin disease characterized by bothersome scaly reddish plaques especially on frequently chafed body parts, such as the extensor sites of the extremities and scalp. Nonetheless, through recent advance in molecular‐targeted therapies including biologics and small‐molecule inhibitors, even the severest symptoms of psoriasis and its comorbidities, such as psoriatic arthritis, can be excellently treated. The superb clinical effects lead to not only remarkable alleviation of symptoms but also a deep understanding of patients’ impaired “quality of life” caused by this disease. Along with the development of novel treatment options targeting various specific molecules, such as proinflammatory cytokines and signal transduction‐associated molecules, clinicians have thoroughly understood the molecular mechanism of psoriasis, and discovered that the IL‐23/IL‐17 axis mainly depending on Th17 cell function is a crucial pathogenesis of this disease. Accumulation of knowledge about the working mechanism and clinical effect of molecular‐targeted therapies is indispensable for clinicians to establish a more refined therapeutic strategy for treating psoriasis.
Bacterial metabolosomes: new insights into their structure and bioengineering
Authors: Liu Lu‐Ning
Published: January 2021

Bacterial metabolosomes have been discovered for over 25 years. They play essential roles in bacterial metabolism and pathogenesis. In this crystal ball paper, I will discuss the recent advances in the fundamental understanding and synthetic engineering of bacterial metabolosomes.
Specific cutaneous infiltrates in patients with haematological neoplasms: a retrospective study with 49 patients
Authors: Calado Rebeca , Relvas Maria , Morgado Francisca , Cardoso José Carlos , Tellechea Oscar
Published: January 2021

Background

Haematological neoplasms account for around 9% of all cancers, and they are recognised as an important cause of skin infiltration. However, studies analysing cutaneous metastasis of haematological neoplasms are scarce. We describe the clinical spectrum and outcomes of specific cutaneous manifestations of leukaemias, lymphomas, multiple myeloma (MM), and blastic plasmacytoid dendritic cell neoplasm (BPDN) and make a review of the literature.

Methods

Data from 49 patients diagnosed with secondary cutaneous infiltration of systemic haematological neoplasms over the last 10 years in a tertiary dermatology centre were retrospectively collected, and clinical‐evolutive features were analysed.

Results

Most cases were lymphoma (44.9%, n = 22), followed by leukaemia cutis (38.8%, n = 19), secondary plasmacytoma (10.2%, n = 5) and BPDN (6.1%, n = 3). Nodules were the predominant type of lesion, and most patients presented with multiple (≥3) lesions. In 51% (n = 25) of cases, cutaneous infiltration was detected before the diagnosis of the underlying malignancy. The patients in diverse nosological groups did not differ in terms of survival (P = 0.052).

Conclusions

We recognise the clinical heterogeneity of specific cutaneous infiltrates. The high proportion of cases in which skin involvement was key to the diagnosis of systemic malignancy emphasises the role of the dermatologist in recognising and correctly managing these patients.
Controversial Industries, Regional Differences, and Risk: Role of CSR*
Authors: Jo Hoje , Park Kwangwoo
Published: January 2021

Controversial industries such as the alcohol, gambling, tobacco, and firearms sectors have long suffered from organizational legitimacy problems. Using data covering 32 countries, we show that controversial industry firms’ engagement in CSR initiatives has a substantial risk‐decreasing effect, thereby increasing the probability of maintaining the social license to operate. The effect of CSR on firm risk, however, is more pronounced for firms in Europe and North America than in the Asia‐Pacific region, suggesting that the CSR–risk association varies by region. Our results are consistent with the view of the “social license to operate” and the “differential recognition” hypotheses.
Pubectomy and urinary reconstruction provides definitive treatment of urosymphyseal fistula following prostate cancer treatment
Authors: Andrews Jack R. , Hebert Kevin J. , Boswell Timothy C. , Avant Ross A. , Boonipatt Thanapoom , Kreutz‐Rodrigues Lucas , Bakri Karim , Houdek Matthew T. , Karnes R. Jeffery , Viers Boyd R.
Published: January 2021

Objective

To describe the natural history, reconstructive solutions, and functional outcomes of those men undergoing pubectomy and urinary reconstruction after prostate cancer treatment.

Patients and Methods

This study retrospectively identified 25 patients with a diagnosis of urosymphyseal fistula (UF) following prostate cancer therapy who were treated with urinary reconstruction with pubectomy. This study describes the natural history, reconstructive solutions, and functional outcomes of this cohort.

Results

All 25 patients had a history of pelvic radiotherapy for prostate cancer. The median (interquartile range [IQR]) time from prostate cancer treatment to diagnosis of UF was 11 (6, 16.5) years. The vast majority of men (24/25; 96%) presented with debilitating groin pain during ambulation. Posterior urethral stenosis was common (20/25; 80%), with 60% having repetitive endoscopic treatments. Culture of pubic bone specimens demonstrated active infection in 80%. Discordance between preoperative urine and intraoperative bone cultures was common, 21/22 (95.5%). After surgery, major 90‐day complications (Clavien–Dindo Grade III and IV) occurred in eight (32%) patients. Pain was significantly improved, with resolution of pain (24/25; 96%) and restoration of function, the median (IQR) preoperative Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 3 (2, 3) vs median postoperative ECOG PS score of 0 (0, 1).

Conclusion

Endoscopic urethral manipulation after radiation for prostate cancer is a risk factor for UF. Conservative management will not provide symptom resolution. Fistula decompression, bone resection, and urinary reconstruction effectively treats chronic infection, improves pain and ECOG PS scores.
Community‐based sugar‐sweetened beverage intervention associated with short‐term improvements in self‐rated oral health
Authors: Wang Monica L. , Minyé Helena M. , Egan Kelsey A. , Heaton Brenda
Published: January 2021

Objectives

To assess the efficacy of a community‐based childhood obesity prevention intervention targeting Sugar‐sweetened beverage (SSB) consumption on self‐rated oral health among children and their parents/caregivers.

Methods

This study is a secondary analysis of data from a pilot site‐randomized intervention (H2GO!) targeting SSB consumption and obesity risk among children. The 6‐week SSB behavioural intervention was implemented in two Massachusetts Boys and Girls Club sites that were matched for size and racial/ethnic composition. Children ages 9‐12 years and their parents/caregivers were eligible to participate. Data on self‐rated oral health and sociodemographics were obtained via self‐report surveys at baseline, 2 and 6 months. Generalized linear mixed regression models were used to estimate 2‐ and 6‐month change in oral health associated with the intervention.

Results

Data are from 100 child participants (46% female; 38% Black, 20% Hispanic, 13% White, 12% Multiracial, 11% Asian) and 87 parent participants (78.2% female; 37.9% Hispanic, 29.9% Black, 14.9% Asian, 10.3% White). At baseline, 47% of child participants rated their oral health as good, followed by very good (32%), fair (11%) and excellent (10%). Among parents, 46.3% rated their oral health as good, followed by very good (29.3%), excellent (9.8%), fair (9.7%) and poor (4.9%). The intervention was associated with 2‐ and 6‐month improvements in child participants' mean self‐rated oral health scores (β = 0.78; 95% CI: 0.48, 1.087;P < .001; β = 0.98; 95% CI: 0.61, 1.34;P < .001, respectively) and with 2‐month improvements in parent participants' mean self‐rated oral health (β = 0.42; 95% CI: 0.016, 0.82;P = .042).

Conclusion

Short‐term improvements in oral health among children and their parents/caregivers were observed among those participating in a SSB behavioural intervention. Community‐based behavioural programmes targeting SSB consumption may be a promising approach to promote oral health as well as prevent childhood obesity.
Neurovascular Unit: A critical role in ischemic stroke
Authors: Wang Liyun , Xiong Xiaoxing , Zhang Luyuan , Shen Jian
Published: January 2021

Ischemic stroke (IS), a common cerebrovascular disease, results from a sudden blockage of a blood vessel in the brain, thereby restricting blood supply to the area in question, and making a significantly negative impact on human health. Unfortunately, current treatments, that are mainly based on a recanalization of occluded blood vessels, are insufficient or inaccessible to many stroke patients. Recently, the profound influence of the neurovascular unit (NVU) on recanalization and the prognosis of IS have become better understood; in‐depth studies of the NVU have also provided novel approaches for IS treatment. In this article, we review the intimate connections between the changes in the NVU and IS outcomes, and discuss possible new management strategies having practical significance to IS. We discuss the concept of the NVU, as well as its roles in IS blood‐brain barrier regulation, cell preservation, inflammatory immune response, and neurovascular repair. Besides, we also summarize the influence of noncoding RNAs in NVU, and IS therapies targeting the NVU. We conclude that both the pathophysiological and neurovascular repair processes of IS are strongly associated with the homeostatic state of the NVU and that further research into therapies directed at the NVU could expand the range of treatments available for IS.
Comparative bioinformatics analysis between proteomes of rabbit aneurysm model and human intracranial aneurysm with label‐free quantitative proteomics
Authors: Liu Yingjun , Song Yaying , Liu Peixi , Li Sichen , Shi Yuan , Yu Guo , Quan Kai , Fan Zhiyuan , Li Peiliang , An Qingzhu , Zhu Wei
Published: January 2021

Aims

This study aimed to find critical proteins involved in the development of intracranial aneurysm by comparing proteomes of rabbit aneurysm model and human aneurysms.

Methods

Five human intracranial aneurysm samples and 5 superficial temporal artery samples, and 4 rabbit aneurysm samples and 4 control samples were collected for protein mass spectrometry. Four human intracranial aneurysm samples and 4 superficial temporal artery samples, and 6 rabbit aneurysm samples and 6 control samples were used for immunochemistry.

Results

Proteomic analysis revealed 180 significantly differentially expressed proteins in human intracranial aneurysms and 716 significantly differentially expressed proteins in rabbit aneurysms. Among them, 57 proteins were differentially expressed in both species, in which 24 were increased and 33 were decreased in aneurysms compared to the control groups. Proteins were involved in focal adhesion and extracellular matrix‐receptor interaction pathways. We found that COL4A2, MYLK, VCL, and TAGLN may be related to aneurysm development.

Conclusion

Proteomics analysis provided fundamental insights into the pathogenesis of aneurysm. Proteins related to focal adhesion and extracellular matrix‐receptor interaction pathways play an important role in the occurrence and development of intracranial aneurysm.
Gesture Helps, Only If You Need It: Inhibiting Gesture Reduces Tip‐of‐the‐Tongue Resolution for Those With Weak Short‐Term Memory
Authors: Pyers Jennie E. , Magid Rachel , Gollan Tamar H. , Emmorey Karen
Published: January 2021

People frequently gesture when a word is on the tip of their tongue (TOT), yet research is mixed as to whether and why gesture aids lexical retrieval. We tested three accounts: the lexical retrieval hypothesis, which predicts that semantically related gestures facilitate successful lexical retrieval; the cognitive load account, which predicts that matching gestures facilitate lexical retrieval only when retrieval is hard, as in the case of a TOT; and the motor movement account, which predicts that any motor movements should support lexical retrieval. In Experiment 1 (a between‐subjects study;N = 90), gesture inhibition, but not neck inhibition, affected TOT resolution but not overall lexical retrieval; participants in the gesture‐inhibited condition resolved fewer TOTs than participants who were allowed to gesture. When participants could gesture, they produced more representational gestures during resolved than unresolved TOTs, a pattern not observed for meaningless motor movements (e.g., beats). However, the effect of gesture inhibition on TOT resolution was not uniform; some participants resolved many TOTs, while others struggled. In Experiment 2 (a within‐subjects study;N = 34), the effect of gesture inhibition was traced to individual differences in verbal, not spatial short‐term memory (STM) span; those with weaker verbal STM resolved fewer TOTs when unable to gesture. This relationship between verbal STM and TOT resolution was not observed when participants were allowed to gesture. Taken together, these results fit the cognitive load account; when lexical retrieval is hard, gesture effectively reduces the cognitive load of TOT resolution for those who find the task especially taxing.
Chronic transplant glomerulopathy: New insights into pathogenesis
Authors: Gokhale Avantee , Chancay Jorge , Shapiro Ron , Randhawa Parmjeet , Menon Madhav C.
Published: January 2021

There have been recent significant advances in short‐term outcomes in renal transplantation, however, long‐term allograft survival remains a challenge. With reported incidences as high of 74.5% of chronic graft loss in patients with biopsies showing transplant glomerulopathy (TG), this syndrome represents an important factor for chronic allograft complications. In this review we show an overview of the novel mechanistic insights into pathogenesis of TG, as well as a brief description of the pathology, diagnosis and newer prognostic indices within TG diagnosis. These data raise intriguing roles for cell‐mediated immunity and podocyte stress in TG as well as reinforce previous associations of TG with ABMR. We also delve into management strategies for TG and report the paucity of existing clinical trial data for this prevalent condition in renal transplants.
Drug‐induced psoriasiform alopecia associated with interleukin‐17 inhibitor therapy
Authors: Tan Timothy L. , Taglia Lauren , Yazdan Pedram
Published: January 2021

Drug‐induced psoriasiform alopecia is an increasingly recognized form of alopecia mostly reported in association with TNF‐alpha inhibitors. However, drug‐induced psoriasiform alopecia in association with IL‐17A inhibitors has not been described. We present a 62‐year‐old woman with severe psoriasis who developed new psoriatic plaques on the scalp with alopecia after initiating ixekizumab (anti‐IL‐17A). Scalp biopsy specimens revealed a non‐cicatricial alopecia with increased telogen/catagen follicles, atrophy of the sebaceous glands, peribulbar and perifollicular inflammation with frequent lymphocytes, plasma cells, eosinophils, psoriasiform dermatitis, and lack of intra‐corneal or intra‐epidermal neutrophils. Overall, the clinical and histopathologic findings were most compatible with a drug‐induced psoriasiform alopecia in association with IL‐17A inhibitor therapy. Our case shows that drug‐induced psoriasiform alopecia can paradoxically occur in patients on IL‐17A inhibitor therapy and contributes to the growing list of cutaneous eruptions associated with biologic agents.
Non‐linear reduction of photosynthetic ability in oak trees infected with Tubakia koreana causing Quercus leaf blight
Authors: Park Minjee , Yun Hye Young , Kim Young Ho , Kim Kunhyo , Kim Hyun Seok
Published: January 2021

Tubakia species are fungi causing leaf spots and blights and are reported worldwide, mainly in Asia, Europe and North America. These diseases often occur on Quercus (oak) trees, which constitute one of the dominant broad‐leaved tree genera in the world, so forest structure, function and dynamics could be affected by Tubakia infection. However, few data about the negative impacts of Tubakia on key leaf functional traits are available. This study was conducted to investigate the changes in photosynthetic capacity, morphological, and chemical traits of sawtooth oak (Quercus acutissima Carruth.) leaves infected with Tubakia koreana causing Quercus leaf blight. Two control and four treatment seedlings were used for this study. It was found that maximum photosynthetic rate and maximum rates of carboxylation and electron transport showed exponential reductions with increasing disease severity (p < .001). However, leaf mass per area (LMA) showed no noticeable changes, while leaf nitrogen concentration (Nmass) increased linearly with increasing disease severity (p < .001), suggesting that Tubakia disease may underlay the inconsistent patterns of LMA and Nmass. These findings contribute to the understanding of fundamental effects of disease development on physiological traits of oak leaves.
Demographic consequences of foraging ecology explain genetic diversification in Neotropical bird species
Authors: Miller Matthew J. , Bermingham Eldredge , Turner Benjamin L. , Touchon Justin C. , Johnson Andrew B. , Winker Kevin
Published: January 2021

Despite evidence that species’ traits affect rates of bird diversification, biogeographic studies tend to prioritise earth history in Neotropical bird speciation. Here we compare mitochondrial genetic differentiation among 56 co‐distributed Neotropical bird species with varying ecologies. The trait ‘diet’ best predicted divergence, with plant‐dependent species (mostly frugivores and nectivores) showing lower levels of genetic divergence than insectivores or mixed‐diet species. We propose that the greater vagility and demographic instability of birds whose diets rely on fruit, seeds, or nectar  known to vary in abundance seasonally and between years  relative to birds that eat primarily insects, drives episodic re‐unification of otherwise isolated populations, resetting the divergence ‘clock’. Testing this prediction using coalescent simulations, we find that plant‐dependent species show stronger signals of recent demographic expansion compared to insectivores or mixed‐diet species, consistent with this hypothesis. Our study provides evidence that localised ecological phenomena scale up to generate larger macroevolutionary patterns.
Quantitative estimates of freshwater fish stocking practices by recreational angling clubs in France
Authors: Cucherousset Julien , Lassus Rémy , Riepe Carsten , Millet Paul , Santoul Frédéric , Arlinghaus Robert , Buoro Mathieu
Published: January 2021

Although freshwater fish stocking is widely used by managers, quantitative assessments of stocking practices are lacking in many countries. The general objective of the present study was to determine the quantity and characteristics of fish stocking in metropolitan France. Using a survey‐based approach, stocking practices for 2013 by recreational angling clubs in France were quantified, which represented the bulk of fish stocking undertaken in that year. Stocking was found to be practiced by 88.6% of angling clubs in France, representing, on average, 65% of their annual budget. Overall, 22 species were stocked, including 13 native and nine non‐native species, with strong variations among species in terms of life stages and body sizes used for stocking. Using Bayesian modelling, a total biomass of 2.029 t, representing approximately 90 million fishes, was estimated to be stocked in France in 2013. In terms of biomass, the most widely stocked species were rainbow troutOncorhynchus mykiss(Walbaum), brown troutSalmo truttaL., roachRutilus rutilus(L.), common carpCyprinus carpioL. and northern pikeEsox luciusL. A stocking volume of approximately 60 fishes or 1.5 kg of fish biomass per angler per year seems commonplace in industrialised countries for which data are available.
Performance evaluation of the new hematology analyzer UniCel DxH 900
Authors: Martinez‐Iribarren Alicia , Tejedor Xavier , Sala Sanjaume Àngels , Leis Alba , Doladé Botias Maria , Morales‐Indiano Cristian
Published: January 2021

Introduction

UniCel DxH900 (Beckman Coulter, Miami, Florida, USA) is a quantitative, multi‐parameter, automated hematology analyzer for in vitro diagnostic use in clinical laboratories. The aim of this study was to evaluate the analytical performance of the new DxH900 analyzer to verify its diagnostic and clinical utility in the hematology laboratory of a tertiary care hospital in Spain. The most important and novel feature offered by DxH900 analyzer is providing MDW (monocyte distribution width), a new hematologic parameter which is being clinically validated as an early sepsis indicator with promising results.

Methods

We evaluated imprecision (including MDW), linearity, and carryover of DxH900. Method comparison for cell blood count (CBC) was performed in relation to DxH800 with 100 samples. We compared leukocyte differential (DIFF) from DxH900 with manual 400‐cell differential. 390 samples were assessed for flag performance.

Results

Results obtained for between days and within‐run imprecision were good. DxH900 showed excellent linearity (R = 1.00) over analytical range for white blood cells, red blood cells, hemoglobin, platelets, and reticulocyte count (RET) (R = 0.96) and no significant carryover effect. CBC and RET on the DxH900 correlated well with DxH800 (R ≥ 0.99). Comparison with manual differential showed excellent correlation (R ≥ 0.88), except for basophils. Flagging performance exhibited sensitivity over 90% for majority of alarm messages and very high negative predictive value (over 95%).

Conclusion

UniCel DxH900 Coulter analyzer provides reliable results and fully comparable to DxH800. DxH900 is an accurate, highly precise analyzer with good analytical performances to be used effectively in high‐volume laboratories.
Variations in blood pressure control by medical comorbidities prior to sudden death
Authors: Keen Susan K. , Chang Albert , Gupta Suhani , Lin Feng‐Chang , Simpson Ross J.
Published: January 2021

Patients with hypertension have increased risk of sudden death, but the impact of blood pressure control in sudden death is not clear. To better understand potential opportunities to prevent sudden, we assessed blood pressure control, comorbidities, and the number of recent medical encounters among all‐cause sudden death victims. Less than 40% of sudden death victims with hypertension had controlled blood pressure prior to death. Furthermore, increased frequency of medical visits and number of comorbidities were associated with better blood pressure control Strategies to address clinical inertia in hypertension treatment particularly for patients with fewer comorbidities may attenuate the risk of sudden death.
Recent, small beginnings: genetic analysis suggests Catostomus rimiculus (Klamath smallscale sucker) in the Smith River, California, are introduced
Authors: Kinziger Andrew P. , White Jason L. , Nakamoto Rodney J. , Harvey Bret C.
Published: January 2021

Identification of introduced species can be important to understanding ecological systems and meeting conservation and management goals, but the process can be surprisingly challenging. The Klamath smallscale sucker Catostomus rimiculus seems likely to be native to the Smith River because the drainage separates two basins believed to be within the fish's native range, the Rogue and Klamath rivers. Further, C. rimiculus is broadly distributed in the Smith River, and the indigenous Dee‐ni’ People of the Smith River have a unique word for sucker. Nonetheless, a historical survey of fishes that described C. rimiculus from the Rogue and Klamath rivers did not include C. rimiculus among the fishes of the Smith River. To determine whether the genetic structure of the Smith River C. rimiculus reflects expectations for a native sucker population, the authors of this study examined variation in microsatellite and mitochondrial genetic markers from the Smith River and surrounding drainages. The genetic analyses revealed a pattern consistent with extreme founder effects in Smith River C. rimiculus, as would be expected from a single introduction of six or fewer effective individuals. The sharing of a high‐frequency haplotype between the Smith River and Klamath River that is not detected in the Rogue River suggests the Klamath River as the likely source for the introduction. The findings highlight that local‐scale introductions can be easily overlooked because the newly established populations can appear to be parts of contiguous natural distributions.
Cyclooxygenase inhibition attenuates brain angiogenesis and independently decreases mouse survival under hypoxia
Authors: Seeger Drew R. , Golovko Svetlana A. , Grove Bryon D. , Golovko Mikhail Y.
Published: January 2021

Although cyclooxygenase (COX) role in cancer angiogenesis has been studied, little is known about its role in brain angioplasticity. In the present study, we chronically infused mice with ketorolac, a non‐specific COX inhibitor that does not cross the blood–brain barrier (BBB), under normoxia or 50% isobaric hypoxia (10% O2 by volume). Ketorolac increased mortality rate under hypoxia in a dose‐dependent manner. Using in vivo multiphoton microscopy, we demonstrated that chronic COX inhibition completely attenuated brain angiogenic response to hypoxia. Alterations in a number of angiogenic factors that were reported to be COX‐dependent in other models were assayed at 24‐hr and 10‐day hypoxia. Intriguingly, hypoxia‐inducible factor 1 was unaffected under COX inhibition, and vascular endothelial growth factor receptor type 2 (VEGFR2) and C‐X‐C chemokine receptor type 4 (CXCR4) were significantly but slightly decreased. However, a number of mitogen‐activated protein kinases (MAPKs) were significantly reduced upon COX inhibition. We conclude that additional, angiogenic factor‐independent mechanism might contribute to COX role in brain angioplasticity, probably including mitogenic COX effect on endothelium. Our data indicate that COX activity is critical for systemic adaptation to chronic hypoxia, and BBB COX is essential for hypoxia‐induced brain angioplasticity. These data also indicate a potential risk for using COX inhibitors under hypoxia conditions in clinics. Further studies are required to elucidate a complete mechanism for brain long‐term angiogenesis regulation through COX activity.

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