bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the probability of coincidental similarity between atomic displacement parameters with machine learning
Authors: Ahlberg Gagner Viktor , Jensen Maja , Katona Gergely
Published: May 2021

High-resolution diffraction studies of macromolecules incorporate the tensor form of the anisotropic displacement parameter (ADP) of atoms from their mean position. The comparison of these parameters requires a statistical framework that can handle the experimental and modeling errors linked to structure determination. Here, a Bayesian machine learning model is introduced that approximates ADPs with the random Wishart distribution. This model allows for the comparison of random samples from a distribution that is trained on experimental structures. The comparison revealed that the experimental similarity between atoms is larger than predicted by the random model for a substantial fraction of the comparisons. Different metrics between ADPs were evaluated and categorized based on how useful they are at detecting non-accidental similarity and whether they can be replaced by other metrics. The most complementary comparisons were provided by Euclidean, Riemann and Wasserstein metrics. The analysis of ADP similarity and the positional distance of atoms in bovine trypsin revealed a set of atoms with striking ADP similarity over a long physical distance, and generally the physical distance between atoms and their ADP similarity do not correlate strongly. A substantial fraction of long- and short-range ADP similarities does not form by coincidence and are reproducibly observed in different crystal structures of the same protein.
Processing Stability of Monolayer WS2 on SiO2
Authors: Delie G , Chiappe D , Asselberghs I , Huyghebaert C , Radu I , Banerjee S , Groven B , Brems S , Afanas’ev V V
Published: May 2021

Using internal photoemission of electrons, the energy position of the valence band top edge in 1 monolayer WS2 films on top of SiO2 thermally-grown on Si was monitored to evaluate the stability of the WS2 layer with respect to two critically important technological factors: exposure to air and the transfer of WS2 from the growth substrate (sapphire) onto SiO2. Contrary to previous results obtained for WS2 and MoS2 layers synthesized by metal film thermal sulfurization in H2S, the valence band top of metal-organic chemical vapor deposition grown WS2 is found to remain at 3.7 ± 0.1 eV below the conduction band bottom edge of SiO2 through different growth runs, transfer processing, and storage in air for several months. This exceptional stability indicates WS2 as a viable candidate for the wafer-scale technology implementation.
The viability of analog-based accelerators for neuromorphic computing: a survey
Authors: Musisi-Nkambwe Mirembe , Afshari Sahra , Barnaby Hugh , Kozicki Michael , Sanchez Esqueda Ivan
Published: May 2021

Focus in deep neural network hardware research for reducing latencies of memory fetches has steered in the direction of analog-based artificial neural networks (ANN). The promise of decreased latencies, increased computational parallelism, and higher storage densities with crossbar non-volatile memory (NVM) based in-memory-computing/processing-in-memory techniques is not without its caveats. This paper surveys this rich landscape and highlights the advantages and challenges of emerging NVMs as multi-level synaptic emulators in various neural network types and applications. Current and potential methods for reliably programming these devices in a crossbar matrix are discussed, as well as techniques for reliably integrating and propagating matrix products to emulate the well-known MAC-like operations throughout the neural network. This paper complements previous surveys, but most importantly uncovers further areas of ongoing research relating to the viability of analog-based ANN implementations based on state-of-the-art NVM technologies in the context of hardware accelerators. While many previous reviews of analog-based ANN focus on device characteristics, this review presents the perspective of crossbar arrays, peripheral circuitry and the required architectural and system considerations for an emerging memory crossbar neural network.
Cefazolin and rifampin: A coagulopathy-inducing combination
Authors: Castillo Almeida Natalia E , Stevens Ryan W , Gurram Pooja , Rivera Christina G , Suh Gina A
Published: May 2021

Purpose

To identify risk factors that may predispose patients to rifampin- and cefazolin-induced coagulopathy.

An 86-year-old man with a history of rheumatoid arthritis on chronic prednisone and stage 3 chronic kidney disease, notably not on warfarin, presented to the hospital with a 10-day history of right hip pain, swelling, and drainage after a recent right total-hip arthroplasty. The patient underwent a combination of surgical intervention and medication therapy with rifampin and ceftriaxone. After discharge and at postoperative day 9, ceftriaxone was changed to cefazolin due to increasing alkaline phosphatase levels. Four weeks after the initial debridement, antibiotics, and implant retention, the patient underwent a second irrigation and debridement due to persistent infection. Cefazolin and rifampin therapy was extended. Three days later, the patient presented to the emergency room with significant bleeding at the surgical site and a profoundly elevated prothrombin time and international normalized ratio (INR). No potential contributors were identified. The Naranjo adverse drug reaction probability scale identified cefazolin and rifampin as the probable cause of elevated INR. The Liverpool adverse drug reaction avoidability assessment tool classified this adverse event as “definitely avoidable.”

Conclusion

Rifampin-containing regimens are often recommended to treat staphylococcal prosthetic joint infections when the implant is retained. In methicillin-susceptible staphylococcal infections, cefazolin is routinely employed as the β-lactam backbone of definitive antimicrobial regimens. Although rifampin- and cefazolin-induced hypoprothrombinemia seems to be rare, adverse consequences of its occurrence may be prevented with appropriate monitoring.
Hair Transplantation in Burn Scar Alopecia After Combined Non-Ablative Fractional Laser and Microfat Graft Treatment
Authors: Agaoglu Galip , Özer Fırat , Karademir Sacit , Agaoglu Esra , Erol Onur
Published: May 2021

Background

Burn scar and alopecia on hair-bearing areas can severely affect the social life of patients. Unlike healthy skin, poor biological and mechanical properties of scar tissue in the recipient area can reduce the survival rate of hair graft following hair transplantation.

Objectives

The authors sought to determine if combined non-ablative fractional laser (NAFL) and microfat injection could improve the survival rate of hair grafts on post burn scar.

Methods

Thirteen patients with alopecia resulting from burn scar in hair-bearing areas of the scalp and face were treated with combined NAFL and microfat graft and subsequent follicular unit extraction hair transplantation. Cicatricial alopecia occurred on the scalp, eyebrow, mustache, and beard areas. Patients were treated with 3 to 6 sessions of NAFL and 2 to 5 sessions of microfat graft injections, followed by 1 session of hair transplantation employing the follicular unit extraction technique.

Results

Hair transplantation was successfully performed with good to excellent results. The survival rate of transplanted follicular units ranged from 76% to 95% (mean, 85.04%), and the density success rate per square centimeter ranged from 76.9% to 95.2% (mean, 84.54%). All patients expressed high satisfaction with the results and no complication was encountered.

Conclusions

Hair transplantation, after combined NAFL and microfat injection, is a promising treatment for post burn alopecia.

Level of Evidence: 4
A case report of open-aorta, direct transcatheter valve-in-valve implantation: an innovative approach to manage the hazard of coronary flow compromise in transcatheter aortic valve re-interventions
Authors: Calcaterra Domenico , Kaur Navneet , Dasari Gopika , Daniel George
Published: May 2021

Background

Coronary flow compromise is a significant risk of transcatheter aortic valve therapy. Warranting preservation of coronary flow is even more challenging with transcatheter aortic valve re-intervention since the implantation of a transcatheter valve within a degenerated bioprosthetic or transcatheter valve increases significantly this hazard.

Case summary

We present a case of heart failure secondary to transcatheter aortic valve degeneration requiring a transcatheter aortic valve re-intervention. Pre-operative imaging studies demonstrated a high risk for iatrogenic coronary flow impairment. The patient underwent a successful surgical removal of the prosthetic valve leaflets followed by direct transcatheter aortic valve implantation.

Conclusion

We reviewed the literature on the approach to difficult coronaries in transcatheter aortic valve therapy, and we describe an innovative hybrid approach that may represent a viable alternative in cases where catheter techniques of coronary flow preservation are not applicable.
Emergency sandwich patch repair via right ventricular incision for postinfarction ventricular septal defects: a case series
Authors: Shimahara Yusuke , Fukushima Satsuki , Yajima Shin , Tadokoro Naoki , Kakuta Takashi , Asaumi Yasuhide , Kobayashi Junjiro , Fujita Tomoyuki
Published: May 2021

Background

The surgical treatment for postinfarction ventricular septal defect (VSD) remains challenging, especially in emergency cases. Several authors have reported the efficacy of a sandwich patch VSD repair via a right ventricular (RV) incision. However, this procedure remains uncommon, and its efficacy is still unknown, especially when performed under an emergency.

Case summary

We were able to perform sandwich patch VSD repair via an RV incision on seven consecutive patients with VSD following an ST-segment elevation myocardial infarction (STEMI) from March 2017 to December 2019. Bovine pericardial patches were used for sandwich patches. Two patients developed inferior STEMI, and the other patients developed anterior STEMI. Six patients received intra-aortic balloon pump prior to surgery, and the other received extracorporeal membrane oxygenation with Impella. The interval between the diagnosis of VSD and surgery was within 1 day in all patients except one (5 days). All seven patients underwent VSD repair in the emergency status. Four patients underwent concomitant coronary artery bypass grafting. The hospital mortality rate was 14.3% (1/7). Early postoperative transthoracic echocardiography revealed that only one patient developed more than trace residual shunt. The postoperative right atrial pressure was not significantly elevated at ≤12 mmHg in all patients. No patient developed early postoperative prolonged low cardiac output syndrome.

Discussion

In patients with postinfarction VSD, a sandwich patch VSD repair via an RV incision is a promising procedure with a low incidence of residual shunt development and hospital mortality, even in emergency cases.
Platypnoea–orthodeoxia syndrome after percutaneous treatment of ruptured sinus Valsalva complicated by SARS-Cov-2 pneumonia: a case report
Authors: Jenab Yaser , Hosseinsabet Ali , Vaskelyte Laura , Hosseini Kaveh
Published: May 2021

Background

Rupture of sinus of Valsalva (RSV) to right atrium (RA) causes significant left to right shunt, tricuspid regurgitation, and right ventricular failure. If left uncorrected it can lead to biventricular heart failure. Hence, early invasive management is advised. To date, there is no report about platypnoea–orthodeoxia syndrome (POS) after device closure of ruptured sinus of Valsalva.

Case summary

A 50-year-old woman with dyspnoea of exertion and rupture of sinus valsalva to right atrium was referred to our hospital. On admission, chest computed tomography (CT) was normal. After closure of the rupture, she developed orthostatic hypoxemia and frequent cough. A repeat chest CT was suggestive of COVID-19 infection which most probably occurred during the hospitalization. Although COVID-19 was thought to be the only culprit, her symptoms were not solely justified by COVID-19. Transthoracic echocardiography showed patent foramen ovale (PFO) with significant shunt. PFO device closure was performed under intracardiac echocardiography guidance.

Discussion

Interatrial septum deformation may happen after RSV correction and right to left shunt from PFO may become more significant. POS is an important indication for PFO closure which should be noticed by careful examination. As COVID-19 is the most frequent pathology these days, it may delay other probable diagnosis, and hence detailed history taking and physical examination is mandatory.
Histological Inflammation in the Endoscopically Uninflamed Mucosa is Associated With Worse Outcomes in Limited Ulcerative Colitis
Authors: de Frias Gomes Catarina Geraldes , de Almeida Alexandra Sofia Ribeiro , Mendes Catarina Callé Lucas , Ellul Pierre , Burisch Johan , Buhagiar Tiffany , Attard Abigail , Lo Bobby , Ungaro Ryan C , da Silva Morão Bárbara Tonilhas , Gouveia Catarina Ferreira , de Carvalho e Branco Joana Milheiro Delgado , Rodrigues Jaime Manuel Martins Pereira , Teixeira Cristina , Dias de Castro Maria Francisca Faria , Nunes Gonçalo Filipe Domingos , Brito Mariana , de Sousa Antunes Marília Cristina , Borralho Nunes Paula Maria Ferreira Brinca , da Silva Torres Joana Maria Tinoco
Published: May 2021

Background

The Montreal classification categorizes patients with ulcerative colitis (UC) based on their macroscopic disease extent. Independent of endoscopic extent, biopsies through all colonic segments should be retrieved during index colonoscopy. However, the prognostic value of histological inflammation at diagnosis in the inflamed and uninflamed regions of the colon has never been assessed.

Methods

This was a multicenter retrospective cohort study of newly diagnosed patients with treatment-naïve proctitis and left-sided UC. Biopsies from at least 2 colonic segments (endoscopically inflamed and uninflamed mucosa) were retrieved and reviewed by 2 pathologists. Histological features in the endoscopically inflamed and uninflamed mucosa were scored using the Nancy score. The primary outcomes were disease complications (proximal disease extension, need for hospitalization or colectomy) and higher therapeutic requirements (need for steroids or for therapy escalation).

Results

Overall, 93 treatment-naïve patients were included, with a median follow-up of 44 months (range, 2-329). The prevalence of any histological inflammation above the endoscopic margin was 71%. Proximal disease extension was more frequent in patients with histological inflammation in the endoscopically uninflamed mucosa at diagnosis (21.5% vs 3.4%, P = 0.04). Histological involvement above the endoscopic margin was the only predictor associated with an earlier need for therapy escalation (adjusted hazard ratio, 3.69; 95% confidence interval, 1.05-13.0); P = 0.04) and disease complications (adjusted hazard ratio, 4.79; 95% confidence interval, 1.10-20.9; P = 0.04).

Conclusions

The presence of histological inflammation in the endoscopically uninflamed mucosa at the time of diagnosis was associated with worse outcomes in limited UC.
Adverse clinical outcomes associated with infections by Enterobacterales producing ESBL (ESBL-E): a systematic review and meta-analysis
Authors: Ling Weiping , Furuya-Kanamori Luis , Ezure Yukiko , Harris Patrick N A , Paterson David L
Published: May 2021

Objectives

Enterobacterales producing ESBL (ESBL-E) have been notable for their rapid expansion in community settings. This systematic review and meta-analysis aimed to summarize evidence investigating the association between ESBL-E infection and adverse clinical outcomes, defined as bacteraemia, sepsis or septic shock, and all-cause mortality in adult patients.

Methods

Database search was conducted in PubMed, Scopus and EMBASE. In general, studies were screened for effect estimates of ESBL-E colonization or infection on clinical outcomes with non-ESBL-producing Enterobacterales as comparator, adult populations and molecular ascertainment of ESBL gene. Meta-analysis was performed using the inverse variance heterogeneity model.

Results

Eighteen studies were identified, including 1399 ESBL-E and 3200 non-ESBL-E infected patients. Sixteen of these studies included only bacteraemic patients. Mortality was studied in 17 studies and ESBL-E infection was significantly associated with higher odds of mortality compared with non-ESBL-producing Enterobacterales infection (OR = 1.70, 95% CI: 1.15–2.49, I2=58.3%). However, statistical significance did not persist when adjusted estimates were pooled (aOR = 1.67, 95% CI: 0.52–5.39, I2=78.1%). Septic shock was studied in seven studies and all included only bacteraemic patients. No association between ESBL-E infection and shock was found (OR = 1.23, 95% CI: 0.75–2.02, I2=14.8%). Only one study investigated the association between ESBL-E infection and bacteraemia.

Conclusions

Infections by ESBL-E appear to be significantly associated with mortality but not septic shock. Available studies investigating bacteraemia and shock as an intermediate outcome of ESBL-E infections are lacking. Future studies investigating the relationship between clinical outcomes and molecular characteristics of resistant strains are further warranted, along with studies investigating this in non-bacteraemic patients.
Three-dimensional structure analysis of mouse nails using synchrotron radiation
Authors: Yoo HyunJong , Jung YongJu , Jang Sang-Hun , Lee Suk-Jun , Lee OnSeok
Published: May 2021

Until now, studies on nail diseases have been performed through microscopic diagnosis and microscopic computed tomography (micro-CT). However, these kinds of conventional methods have some limitations. Firstly, the microscopic method is considered the gold standard for medical diagnosis. However, due to the use of fluorescent materials, the sample is damaged and it takes a long time to get results. Secondly, while micro-CT is a noninvasive method to get inner structure images of the sample with high resolution, the penetration and spatial resolution are insufficient for studying the microstructures of the sample, such as the sponge bone and the muscle fibers. In contrast, synchrotron radiation (SR) X-ray imaging technology has the advantage of very vividly demonstrating the anatomic structure of the sample with high penetration, sensitivity and resolution. In this study, we compared the optical microscopic method using hematoxylin and eosin staining and SR imaging to analyze the nail tissue in a mouse model. The results showed that SR could depict the inner structures of a mouse nail without any physical damage. Additionally, we could divide the important anatomical structures of the nail unit into three parts with three-dimensional (3D) images: the nail bed, nail matrix and hyponychium. The images showed that SR could be used for analyzing nails by visualizing the relatively clear and medically semantic structures in a 3D section. We expect that the results of this study will be applied to study nail diseases and conduct pharmaceutical research on their treatment.
Financial Burden of Discarded Weight-based Antineoplastic Drugs to Payers and Patients in the Private Insurance Market
Authors: Shih Ya-Chen Tina , Xu Ying , Zhao Hui , Schrag Deborah , Yao James
Published: May 2021

Background

Our study estimated insurance payments and patient out-of-pocket (OOP) expenses associated with discarded weight-based intravenous antineoplastic drugs for privately insured US adult patients with cancer.

Methods

We identified patients who received weight-based antineoplastic drugs from a 2017 MarketScan health risk assessment (IBM Corp, Armonk, NY) linked to claims data. Using weight information in the health risk assessment, we derived the recommended dose and calculated the percentage of drugs discarded. We applied β-regression to determine factors associated with the discarded percentages. To compare patients with and without high-deductible plans, we employed a generalized linear model and a 2-part model to examine insurance payment and OOP expense, respectively. All statistical tests were 2-sided.

Results

Of 27 350 claims for 58 weight-based antineoplastic drugs from 1970 patients, the median discarded percentage was 9.8% (mean [SD] = 12.8% [10.5%]). Aside from drug and tumor type, statistically significantly higher discarded percentages were found for patients in the lowest weight group (5.5% [95% confidence interval = 4.7% to 6.4%]; P < .001; weight <150 lb [68.0 kg] vs ≥200 lb [90.7 kg]). Private payers spent $5090 per patient in 2017 on discarded weight-based antineoplastic drugs, and patients’ mean OOP expense on discarded drugs was $63. In total, 39.7% of patients had high-deductible plans. The adjusted mean OOP expense for discarded drugs was statistically significantly higher for those in high-deductible plans ($95 vs $47; P < .001).

Conclusions

Private insurers incurred substantial financial burden from discarded weight-based antineoplastic drugs. Although the OOP expenses of discarded drugs were modest for most privately insured patients with cancer, approximately 5% spent more than $400 on the discarded drugs. Policies designed to reduce drug waste from single-dose, weight-based antineoplastic drugs should evaluate their financial consequences for payers and patients.
Xenogeneic Silencing and Bacterial Genome Evolution: Mechanisms for DNA Recognition Imply Multifaceted Roles of Xenogeneic Silencers
Authors: Duan Bo , Ding Pengfei , Navarre William Wiley , Liu Jun , Xia Bin
Published: May 2021

Horizontal gene transfer (HGT) is a major driving force for bacterial evolution. To avoid the deleterious effects due to the unregulated expression of newly acquired foreign genes, bacteria have evolved specific proteins named xenogeneic silencers to recognize foreign DNA sequences and suppress their transcription. As there is considerable diversity in genomic base compositions among bacteria, how xenogeneic silencers distinguish self- from nonself DNA in different bacteria remains poorly understood. This review summarizes the progress in studying the DNA binding preferences and the underlying molecular mechanisms of known xenogeneic silencer families, represented by H-NS of Escherichia coli, Lsr2 of Mycobacterium, MvaT of Pseudomonas, and Rok of Bacillus. Comparative analyses of the published data indicate that the differences in DNA recognition mechanisms enable these xenogeneic silencers to have clear characteristics in DNA sequence preferences, which are further correlated with different host genomic features. These correlations provide insights into the mechanisms of how these xenogeneic silencers selectively target foreign DNA in different genomic backgrounds. Furthermore, it is revealed that the genomic AT contents of bacterial species with the same xenogeneic silencer family proteins are distributed in a limited range and are generally lower than those species without any known xenogeneic silencers in the same phylum/class/genus, indicating that xenogeneic silencers have multifaceted roles on bacterial genome evolution. In addition to regulating horizontal gene transfer, xenogeneic silencers also act as a selective force against the GC to AT mutational bias found in bacterial genomes and help the host genomic AT contents maintained at relatively low levels.
Soil Microbial Diversity Impacts Plant Microbiota More than Herbivory
Authors: Malacrinò Antonino , Karley Alison J. , Schena Leonardo , Bennett Alison E.
Published: May 2021

Interactions between plants and microbiomes play a key role in ecosystem functioning and are of broad interest due to their influence on nutrient cycling and plant protection. However, we do not yet have a complete understanding of how plant microbiomes are assembled. Here, we tested and quantified the effect of different factors driving the diversity and composition of plant-associated microbial communities. We manipulated soil microbial diversity (high or low diversity), plant species (Solanum tuberosum or S. vernei), and herbivory (presence or absence of a phloem-feeding insect, Macrosiphum euphorbiae) and found that soil microbial diversity influenced the herbivore-associated microbiome composition but also plant species and herbivory influenced the soil microbiome composition. We quantified the relative strength of these effects and demonstrated that the initial soil microbiome diversity explained the most variation in plant- and herbivore-associated microbial communities. Our findings strongly suggest that soil microbial community diversity is a driver of the composition of multiple associated microbiomes (plant and insect), and this has implications for the importance of management of soil microbiomes in multiple systems.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Salvianolic acid B protects against MPP+-induced neuronal injury via repressing oxidative stress and restoring mitochondrial function
Authors: Zhao Yuan , Zhang Yidan , Zhang Jian , Yang Guofeng
Published: May 2021

Maintaining normal conditions in the mitochondria and repressing oxidative stress has emerged as a crucial therapeutic strategy to ameliorate neuron damage in Parkinson’s disease. Salvianolic acid B (SalB) is a polyphenolic compound isolated from Salvia miltiorrhiza, which has been prescribed for various biological properties, including antioxidative stress, anti-inflammation and neuroprotection in pathological conditions. Previously, SalB was reported to be of benefit in slowing Parkinson’s disease pathology, but whether the neuroprotective role of SalB is associated with a mitochondrial protective action is still elusive. Here we aimed to explore the effects of SalB on mitochondrial function in Parkinson’s disease to uncover the underlying cellular mechanisms. The results showed that SalB significantly alleviated 1-methyl-4-phenylpyridinium (MPP+)-induced mitochondrial disruption in line with ameliorated oxidative injury, which is evidenced by inhibited mitochondrial membrane potential collapse, reduced reactive oxygen species (ROS) generation, increased expression of NAD(P)H: quinone oxidoreductase, and enhanced mitochondrial biosynthesis – the upregulation of nuclear respiratory factor 1 and mitochondrial transcription factor A expressions. Mechanistically, SalB not only increased AMP-activated protein kinase (AMPK) activation and sirtuin3 mRNA and protein levels, but also attenuated ROS-triggered neuroinflammation by downregulating the expressions of NOD-like receptor family pyrin domain containing 3, caspase-1 and Interleukin-1β (IL-1β). In conclusion, these in-vitro findings, for the first time, demonstrate that SalB offers protection against MPP+-induced neuronal injury via upregulating sirtuin3 expression and activating the AMPK signaling to restore mitochondrial function.
Natronoglycomyces albus gen. nov., sp. nov, a haloalkaliphilic actinobacterium from a soda solonchak soil
Authors: Sorokin Dimitry Y. , Khijniak Tatjana V. , Zakharycheva Alicia P. , Elcheninov Alexander G. , Hahnke Richard L. , Boueva Olga V. , Ariskina Elena V. , Bunk Boyke , Kublanov Ilya V. , Evtushenko Lyudmila I.
Published: May 2021

A haloalkaliphilic hydrolytic actinobacterium, strain ACPA22T, was enriched and isolated in pure culture from saline alkaline soil (soda solonchak) in northeastern Mongolia. The isolate was facultatively alkaliphilic, growing at pH 6.5–10.5 (optimum at 7.3–9.0) and highly salt-tolerant, tolerating up to 3 M total Na+ as carbonates. The hydrolytic nature of ACPA22T was confirmed by two different growth-dependent methods and by the presence of multiple glycosidase-encoding genes in the genome. The 16S rRNA gene-based phylogenetic analysis demonstrated that strain ACPA22T formed a deep-branching lineage within the family Glycomycetaceae, with the highest sequence similarity value to

Glycomyces buryatensis

18T (92.1 %) and

Salininema proteolyticum

Miq-4T (91.8 %). The average amino acid identity values (56.1–61.5 %) between ACPA22T and other

Glycomycetaceae

members with available genomes did not exceed the threshold reported for different genera. The cell wall of ACPA22T contained meso-diaminopimelic acid, glycine, glutamic acid and alanine in a molar ratio, characteristic of the peptidoglycan type A1γ'. The whole-cell sugars included mannose, galactose, arabinose, ribose and xylose. The major menaquinones were MK-10(Н4) and MK-11(Н4). The identified polar lipids were represented by phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannosides. In addition, the strain had a few unidentified characteristic polar lipids, including an amine-containing phospholipid with chromatographic mobility similar to that of phosphatidylinositol. The polar lipid fatty acids were dominated by anteiso-C17 : 0 and iso-C16 : 0. The genome included a chromosome of 3.94 Mbp (G+C content 61.5 mol%) encoding 3285 proteins and two plasmids of 59.8 and 14.8 kBp. Based on the data obtained in this study, a new genus and species, Natronoglycomyces albus gen. nov., sp. nov, is proposed with the type strain ACPA22T (=DSM 106290T=VKM Ac-2771T).
COVID-19 Patients Analysis using SuperHeat Map and Bayesian Network to identify Comorbidities Correlations under Different Scenarios
Authors: Nolasco-Jáuregui O. , Quezada-Téllez L. A. , Rodriguez-Torres E. E. , Fernández-Anaya G.
Published: May 2021

Background

Given the exposure risk of comorbidities in Mexican society, the new pandemic involves the highest risk for the population in the history.

Objective

This article presents an analysis of the COVID-19 risk from Mexico’s regions.

Method

The study period runs from April 12 to June 29, 2020 (220,667 patients). The method has a nature applied and according to its level of deepening in the object of study it is framed in a descriptive and explanatory analysis type. The data used here has a quantitative and semi-quantitative characteristic because they are the result of a questionnaire instrument made up of 34 fields and the virus test. The instrument is of a deliberate type. According to the manipulation of the variables, this research is a secondary type of practices, and it has a factual inference from an inductive method because it is emphasizing the concomitant variations for each region of the country.

Results

Region 1 and Region 4 have a higher percentage of hospitalized patients, while Region 2 has a minimum of them. The average age of non-hospitalized patients is around 40 years old, while the hospitalized patients’ age it is close to 55 years. The most sensitive comorbidities in hospitalized patients are three principal: obesity, diabetes mellitus and hypertension. The patients whose needed the mechanical respirator were in ranged from 7.45% to 10.79%.

Conclusions

There is a higher risk of lose their lives in the Region 1 and Region 4 territories than in the Region 2, this information was dictated by the statistical analysis..
Cancer Metastases of 202 Kinds of Cancers via Cytocapsular Tubes
Authors: Yi Tingfang , Wagner Gerhard
Published: May 2021

BACKGROUND

Cancer metastasis is the primary source of solid cancer lethality, but the underlying mechanisms have essentially remained elusive. Recently, we found that cytocapsular tubes, a newly discovered organelle of mammalian cells, conduct cell translocation, suggesting an efficient pathway for cancer cell metastases.

METHODS

We performed immunohistochemistry staining and fluorescence microscope imaging analyses of 6 kinds of normal organs (n=14 patients), 38 subtypes of benign tumors (n= 126 patients), and 8,061 clinical solid cancer tissue samples (covering 202 types and subtypes of cancers, and including cancers, paracancer tissues and metastatic cancers) taken from 7,125 cancer patients. These solid cancers cover 30 types of organs. We characterized cytocapsular tubes (CTs), cell migration in CTs, and CT quantity, density, network, superstructures and lifecycle in clinical samples of normal tissues, benign tumors, cancers, paracancer tissues, and metastatic cancers.

RESULTS

There is no cytocapsular tubes (CTs) in normal organ tissues. Among the 126 benign tumor samples (covering 38 subtypes) from 126 patients, 86.6% do not have CTs and the other 13.4% show benign-to-malignancy transitions with CTs. Of the 8,061 solid cancer tissue and paracancer samples from 7,125 patients, 100% of cancers (including carcinomas in situ), 100% of paracancer tissues, and 100% of metastatic cancer tissues/organs, harbor large quantities (from thousands to hundreds of thousands) of CTs with many cancer cells in migration inside.

CONCLUSION

Cytocapsular tubes and networks provide membrane-enclosed physical freeway systems for clinical cancer cell metastasis to neighboring and far-distance tissues and organs.
The upper respiratory tract microbiome of Australian Aboriginal and Torres Strait Islander children in ear and nose health and disease
Authors: Coleman Andrea , Zaugg Julian , Wood Amanda , Cottrell Kyra , Håkansson Eva Grahn , Adams Jasmyn , Brown Matthew , Cervin Anders , Bialasiewicz Seweryn
Published: May 2021

Objective

To examine the nasal microbiota in relation to otitis status and nose health in Indigenous Australian children.

Methods

Children aged 2-7 years were recruited from two northern Australian (Queensland) communities. Clinical histories were obtained through parent interview and review of the medical record. Nasal cavity swabs were obtained, and the child’s ears, nose and throat were examined. DNA was extracted and analysed by 16S rRNA amplicon next generation sequencing of the V3/V4 region in combination with previously generated culture data.

Results

103 children were recruited (mean 4.7 years), 17 (16.8%) were ‘healthy’, i.e. normal examination and no history of otitis media (OM). Nasal microbiota differed significantly in relation to otitis status and nose health. Children with historical OM had higher relative abundance of Moraxella compared to healthy children, despite both having healthy ears at the time of swabbing. Children with healthy noses had higher relative abundance of S. aureus compared to those with rhinorrhoea. Dolosigranulum was correlated to Corynebacterium in healthy children. Haemophilus and Streptococcus correlated across phenotypes. Ornithobacterium was absent/low relative abundance in healthy children and clustered around otopathogens. It correlated with Helcococcus and Dichelobacter.

Conclusions

Dolosigranulum and Corynebacterium form a synergism that promotes URT/ear health in Indigenous Australian children. Ornithobacterium likely represents Candidatus Ornithobacterium hominis and in this population is correlated with a novel bacterium which appears to be related to poor upper respiratory tract/ear health.

Importance

Recurring and chronic infections of the ear (otitis media) are disproportionately prevalent in disadvantaged communities across the globe, and in particular, within Indigenous communities. Despite numerous intervention strategies, otitis media persists as a major health issue and is the leading cause of preventable hearing loss. In disadvantaged communities, this hearing loss is associated with negative educational and social development outcomes, and consequently, poorer employment prospects and increased contact with the justice system in adulthood. Thus, a better understanding of the microbial ecology is needed in order to identify new targets to treat, as well as prevent the infections. This study used a powerful combination of 16S rRNA sequencing and extended culturomics to show that Dolosigranulum pigrum, a bacterium previously identified as a candidate protective species, may require co-colonisation with Corynebacterium pseudodiptheriticum in order to prevent otitis media. Additionally, emerging and potentially novel pathogens and bacteria were identified.
South American freshwater fish diversity shaped by Andean uplift since the Late Cretaceous
Authors: Boschman Lydian M. , Cassemiro Fernanda A.S. , Carraro Luca , de Vries Jorad , Altermatt Florian , Hagen Oskar , Hoorn Carina , Pellissier Loïc
Published: May 2021

South America is home to the highest freshwater fish biodiversity on Earth1,2. The hotspot of species richness is located in the western Amazon Basin, and richness decreases downstream along the Amazon River towards the mouth at the Atlantic coast (Fig. 1b, c)3,4, which contradicts the positive relationship between stream size and biodiversity that is commonly observed in river systems across the world5,6. We investigate the role of river rerouting events caused by Andean mountain building and repeated episodes of flooding in western Amazonia in shaping the modern-day richness pattern of freshwater fishes in South America. To this end, we combine a reconstruction of river networks following Andean surface uplift since 80 million years ago with a mechanistic biological model simulating dispersal, allopatric speciation and extinction over the dynamic landscape of rivers and lakes. We show that the numerous small river rerouting events in western Amazonia resulting from mountain building produced highly dynamic riverine habitats that caused high diversification rates, shaping the exceptional present-day richness of this region. The history of marine incursions and lakes, including the Miocene Pebas megawetland system in western Amazonia, played a secondary role. This study is a major step towards the understanding of the processes involved in the interactions between the solid Earth, landscapes, and life of extraordinary biodiverse South America.
Conformational buffering underlies functional selection in intrinsically disordered protein regions
Authors: Gonzalez-Foutel Nicolas S. , Borcherds Wade M. , Glavina Juliana , Barrera-Vilarmau Susana , Sagar Amin , Estaña Alejandro , Barozet Amelie , Fernandez-Ballester Gregorio , Blanes-Mira Clara , Sánchez Ignacio E , de Prat-Gay Gonzalo , Cortés Juan , Bernadó Pau , Pappu Rohit V. , Holehouse Alex S. , Daughdrill Gary W. , Chemes Lucía B.
Published: May 2021

Many disordered proteins conserve essential functions in the face of extensive sequence variation. This makes it challenging to identify the forces responsible for functional selection. Viruses are robust model systems to investigate functional selection and they take advantage of protein disorder to acquire novel traits. Here, we combine structural and computational biophysics with evolutionary analysis to determine the molecular basis for functional selection in the intrinsically disordered adenovirus early gene 1A (E1A) protein. E1A competes with host factors to bind the retinoblastoma (Rb) protein, triggering early S-phase entry and disrupting normal cellular proliferation. We show that the ability to outcompete host factors depends on the picomolar binding affinity of E1A for Rb, which is driven by two binding motifs tethered by a hypervariable disordered linker. Binding affinity is determined by the spatial dimensions of the linker, which constrain the relative position of the two binding motifs. Despite substantial sequence variation across evolution, the linker dimensions are finely optimized through compensatory changes in amino acid sequence and sequence length, leading to conserved linker dimensions and maximal affinity. We refer to the mechanism that conserves spatial dimensions despite large-scale variations in sequence as conformational buffering. Conformational buffering explains how variable disordered proteins encode functions and could be a general mechanism for functional selection within disordered protein regions.
Integrative proteogenomics for differential expression and splicing variation in a DM1 mouse model
Authors: Solovyeva Elizaveta M. , Utzinger Stephan , Vissières Alexandra , Mitchelmore Joanna , Ahrné Erik , Hermes Erwin , Poetsch Tania , Ronco Marie , Bidinosti Michael , Merkl Claudia , Serluca Fabrizio C. , Fessenden James , Naumann Ulrike , Voshol Hans , Meyer Angelika S. , Hoersch Sebastian
Published: May 2021

Dysregulated mRNA splicing is involved in the pathogenesis of many diseases including cancer, neurodegenerative diseases, and muscular dystrophies such as myotonic dystrophy type 1 (DM1). Comprehensive assessment of dysregulated splicing on the transcriptome and proteome level has been methodologically challenging, and thus investigations have often been targeting only few genes.

Here, we performed a large-scale coordinated transcriptomic and proteomic analysis to characterize a DM1 mouse model (HSALR) in comparison to wild-type. Our integrative proteogenomics approach comprised gene- and splicing-level assessments for mRNAs and proteins. It recapitulated many known instances of aberrant mRNA splicing in DM1 and identified new ones. It enabled the design and targeting of splicing-specific peptides and confirmed the translation of known instances of aberrantly spliced disease-related genes (e.g.Atp2a1, Bin1, Ryr1), complemented by novel findings (e.g.Ywhae, Flnc, Svil). Comparative analysis of large-scale mRNA and protein expression data showed quantitative agreement of differentially expressed genes and splicing patterns between disease and wild-type.

We hence propose this work as a suitable blueprint for a robust and scalable integrative proteogenomic strategy geared towards advancing our understanding of splicing-based disorders. With such a strategy, splicing-based biomarker candidates emerge as an attractive and accessible option, as they can be efficiently asserted on the mRNA and protein level in coordinated fashion.

Graphical abstract
Reactive oxygen species mediate thylakoid membrane remodeling and triacylglycerol synthesis under nitrogen starvation in the alga Chlorella sorokiniana
Authors: Vijayan Jithesh , Wase Nishikant , Liu Kan , Zhang Chi , Riekhof Wayne R.
Published: May 2021

Many microbes accumulate energy storage molecules such as triglycerides and starch during nutrient limitation. In eukaryotic green algae grown under nitrogen limiting conditions, triglyceride accumulation is coupled with chlorosis and growth arrest. In this study we show that accumulation of reactive oxygen species (ROS) under nitrogen limitation in the microalga Chlorella sorokiniana is involved in thylakoid membrane remodeling, leading to chlorosis. We show that ROS accumulation under nitrogen limitation is an active process involving downregulation of expression of ROS-quenching enzymes, such as superoxide dismutases, catalase, peroxiredoxin, and glutathione peroxidase-like, and upregulation of enzymes involved in generating ROS, such as NADPH oxidase, xanthine oxidase and amine oxidases. Expression of enzymes involved in ascorbate and glutathione metabolism are also affected under these conditions. Quenching ROS under nitrogen limitation reduces TAG accumulation, adding additional evidence for the role of ROS signaling in the process.
A lipid-mTORC1 nutrient sensing pathway regulates animal development by peroxisome-derived hormones
Authors: Li Na , Hua Beilei , Chen Qing , Ruan Meiyu , Zhu Mengnan , Shen Huali , Zhang Li , Zhu Huanhu
Published: May 2021

Animals have developed many signaling mechanisms that alter cellular and developmental programs in response to changes in nutrients and their derived metabolites, many of which remain to be understood. We recently uncovered that glucosylceramides, a core sphingolipid, act as a critical nutrient signal for overall amino-acid level to promote development by activating the intestinal mTORC1 pathway. However, how the intestinal GlcCer-mTORC1 activity regulates development throughout the whole body is unknown. Through a large-scale genetic screen, we found that the peroxisomes are critical for antagonizing the GlcCer-mTORC1-mediated nutrient signal. Mechanistically, deficiency of glucosylceramide, inactivation of the downstream mTORC1 activity, or prolonged starvation relocated peroxisomes closer to the intestinal apical region to release peroxisomal-beta-oxidation derived hormones that targeting chemosensory neurons to arrest the animal development. Our data illustrated a new gut-brain axis for orchestrating nutrient-sensing dependent development in Caenorhabditis elegans, which may also explain why glucosylceramide and peroxisome become essential in metazoans.
Ubiquity and origins of structural maintenance of chromosomes (SMC) proteins in eukaryotes
Authors: Yoshinaga Mari , Inagaki Yuji
Published: May 2021

Structural maintenance of chromosomes (SMC) protein complexes are common in Bacteria, Archaea, and Eukaryota. SMC proteins, together with the proteins related to SMC (SMC-related proteins), constitute a superfamily of ATPases. Bacteria/Archaea and Eukaryotes are distinctive from one another in terms of the repertory of SMC proteins. A single type of SMC protein is dimerized in the bacterial and archaeal complexes, whereas eukaryotes possess six distinct SMC subfamilies (SMC1-6), constituting three heterodimeric complexes, namely cohesin, condensin, and SMC5/6 complex. Thus, to bridge the homodimeric SMC complexes in Bacteria and Archaea to the heterodimeric SMC complexes in Eukaryota, we need to invoke multiple duplications of an SMC gene followed by functional divergence. However, to our knowledge, the evolution of the SMC proteins in Eukaryota had not been examined for more than a decade. In this study, we reexamined the ubiquity of SMC1-6 in phylogenetically diverse eukaryotes that cover the major eukaryotic taxonomic groups recognized to date and provide two novel insights into the SMC evolution in eukaryotes. First, multiple secondary losses of SMC5 and SMC6 occurred in the eukaryotic evolution. Second, the SMC proteins constituting cohesin and condensin (i.e., SMC1-4), and SMC5 and SMC6 were derived from closely related but distinct ancestral proteins. Based on the above-mentioned findings, we discuss how SMC1-6 have diverged from the archaeal homologs.
SARS-CoV-2 convergent evolution cannot be reliably inferred from phylogenetic analyses
Authors: Jo Yoon-Seo , Tamuri Asif U. , Towers Greg J. , Goldstein Richard A.
Published: May 2021

A homoplasy is a trait shared between individuals that did not arise in a common ancestor, but rather is the result of convergent evolution. SARS-CoV-2 homoplasic mutations are important to characterise, because the evidence for a mutation conferring a fitness advantage is strengthened if this mutation has evolved independently and repeatedly in separate viral lineages. Yet detecting homoplasy is difficult due to insufficient variation between sequences to construct reliable phylogenetic trees. Here, we develop a method to more robustly identify confident homoplasies. We derive a maximum likelihood (ML) tree, with taxa bearing seemingly recurrent mutations dispersed across the tree, and then, for each potentially homoplasic mutation, we derive an alternative tree where the same taxa are constrained to one clade such that the mutation is no longer homoplasic. We then compare how well the two trees fit the sequence data. Applying this method to SARS-CoV-2 yields only a few instances where the constrained trees have significantly less statistical support than unconstrained tree, suggesting phylogenetics can provide limited support for homoplasy in SARS-CoV-2 and that caution is needed when inferring evidence of convergent evolution from phylogenetic methods in the absence of evidence from other sources.