bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stably expressed genes in single-cell RNA sequencing
Authors: Deeke Julie M. , Gagnon-Bartsch Johann A. 
Published: February 2020

Motivation: In single-cell RNA-sequencing (scRNA-seq) experiments, RNA transcripts are extracted and measured from isolated cells to understand gene expression at the cellular level. Measurements from this technology are affected by many technical artifacts, including batch effects. In analogous bulk gene expression experiments, external references, e.g. synthetic gene spike-ins often from the External RNA Controls Consortium (ERCC), may be incorporated to the experimental protocol for use in adjusting measurements for technical artifacts. In scRNA-seq experiments, the use of external spike-ins is controversial due to dissimilarities with endogenous genes and uncertainty about sufficient precision of their introduction. Instead, endogenous genes with highly stable expression could be used as references within scRNA-seq to help normalize the data. First, however, a specific notion of stable expression at the single-cell level needs to be formulated; genes could be stable in absolute expression, in proportion to cell volume, or in proportion to total gene expression. Different types of stable genes will be useful for different normalizations and will need different methods for discovery. Results: We compile gene sets whose products are associated with cellular structures and record these gene sets for future reuse and analysis. We find that genes whose final products are associated with the cytosolic ribosome have expressions that are highly stable with respect to the total RNA content. Notably, these genes appear to be stable in bulk measurements as well. Supplementary information: Supplementary data are available through GitHub (johanngb/sc-stable).
Coding for voting
Authors: Hill Robin K. 
Published: February 2020

The
Communications
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Communications
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Robin K. Hill explains the ethical responsibility of the computing professional with respect to voting systems.
Complexity column
Authors: Immerman Neil 
Published: February 2020

This column concerns the complexity of evaluating database queries. In particular, for which conjunctive queries can we, after linear preprocessing, enumerate the query answer with only constant delay between entries? There is a beautiful answer, plus some lower bounds, extensions to dynamic databases and more.
I thank Christoph Berkholz, Fabian Gerhardt and Nicole Schweikardt for their clearly written tutorial. It is a wonderful, self-contained introduction to this area.
Biomedical Research Meets Toxicology: How In Vitro Chromosome Instability Methods Can Contribute to Carcinogenicity Prediction
Authors: Stolz Ailine , Becker Markus , Wistorf Elisa , Ertych Norman 
Published: February 2020

Abstract
Cancer is a major health concern and a leading cause of mortality. The reliable identification of carcinogens and understanding of carcinogenicity has become a main focus of biomedical research and regulatory toxicology. While biomedical research applies cellular in vitro methods to uncover the underlying mechanisms causing cancer, regulatory toxicology relies on animal testing to predict carcinogenicity of chemicals, often with limited human relevance. Exemplified by chromosome instability–mediated carcinogenicity, we discuss the need to combine the strengths of both fields to develop highly predictive and mechanism-derived in vitro methods that facilitate risk assessment in respect to relevant human diseases.
Targeting the SAGA and ATAC Transcriptional Coactivator Complexes in MYC-Driven Cancers
Authors: Mustachio Lisa Maria , Roszik Jason , Farria Aimee , Dent Sharon Y.R. 
Published: February 2020

AbstractTargeting epigenetic regulators, such as histone-modifying enzymes, provides novel strategies for cancer therapy. The GCN5 lysine acetyltransferase (KAT) functions together with MYC both during normal development and in oncogenesis. As transcription factors, MYC family members are difficult to target with small-molecule inhibitors, but the acetyltransferase domain and the bromodomain in GCN5 might provide alternative targets for disruption of MYC-driven functions. GCN5 is part of two distinct multiprotein histone-modifying complexes, SAGA and ATAC. This review summarizes key findings on the roles of SAGA and ATAC in embryo development and in cancer to better understand the functional relationships of these complexes with MYC family members, as well as their future potential as therapeutic targets.
A Novel Splice Variant of HYAL-4 Drives Malignant Transformation and Predicts Outcome in Patients with Bladder Cancer
Authors: Lokeshwar Vinata B. , Morera Daley S. , Hasanali Sarrah L. , Yates Travis J. , Hupe Marie C. , Knapp Judith , Lokeshwar Soum D. , Wang Jiaojiao , Hennig Martin J.P. , Baskar Rohitha , Escudero Diogo O. , Racine Ronny R. , Dhir Neetika , Jordan Andre R. , Hoye Kelly , Azih Ijeoma , Manoharan Murugesan , Klaassen Zachary , Kavuri Sravan , Lopez Luis E. , Ghosh Santu , Lokeshwar Bal L. 
Published: February 2020

Abstract

Purpose:
Poor prognosis of patients with muscle-invasive bladder cancer that often metastasizes drives the need for discovery of molecular determinants of bladder cancer progression. Chondroitin sulfate proteoglycans, including CD44, regulate cancer progression; however, the identity of a chondroitinase (Chase) that cleaves chondroitin sulfate from proteoglycans is unknown. HYAL-4 is an understudied gene suspected to encode a Chase, with no known biological function. We evaluated HYAL-4 expression and its role in bladder cancer.

Experimental Design:
In clinical specimens, HYAL-4 wild-type (Wt) and V1 expression was evaluated by RT-qPCR, IHC, and/or immunoblotting; a novel assay measured Chase activity. Wt and V1 were stably expressed or silenced in normal urothelial and three bladder cancer cell lines. Transfectants were analyzed for stem cell phenotype, invasive signature and tumorigenesis, and metastasis in four xenograft models, including orthotopic bladder.

Results:
HYAL-4 expression, specifically a novel splice variant (V1), was elevated in bladder tumors; Wt expression was barely detectable. V1 encoded a truncated 349 amino acid protein that was secreted. In bladder cancer tissues, V1 levels associated with metastasis and cancer-specific survival with high efficacy and encoded Chase activity. V1 cleaved chondroitin-6-sulfate from CD44, increasing CD44 secretion. V1 induced stem cell phenotype, motility/invasion, and an invasive signature. CD44 knockdown abrogated these phenotypes. V1-expressing urothelial cells developed angiogenic, muscle-invasive tumors. V1-expressing bladder cancer cells formed tumors at low density and formed metastatic bladder tumors when implanted orthotopically.

Conclusions:
Our study discovered the first naturally-occurring eukaryotic/human Chase and connected it to disease pathology, specifically cancer. V1-Chase is a driver of malignant bladder cancer and potential predictor of outcome in patients with bladder cancer.
Os termos da política de Roberto Esposito
Authors: Cordeiro Roan Costa 
Published: February 2020

Esta resenha apresenta o livro Termos da política, do filósofo italiano Roberto Esposito. Destacando-se o caráter abrangente de sua abordagem, tal obra permite vislumbrar o pensamento de seu autor enquanto crítica dos conceitos que desafiam o pensamento político contemporâneo, articulando-o por meio dos termos comunidade, imunidade e biopolítica.
On the taxonomy and distribution of Varanus salvator andamanensis Deraniyagala, 1944 (Reptilia: Varanidae), including a redescription of the type specimens and a discussion about its allopatric co-occurrence with V. s. macromaculatus on the Nicobar Islands
Authors: SAMARASINGHE DINAL J. S. , KOCH ANDRÉ , HARIKRISHNAN SURENDRAN , MANAMENDRA-ARACHCHI KELUM , CHANDI MANISH 
Published: February 2020

We provide a detailed redescription of the two original type specimens of the little-known, endemic Andaman water monitor, Varanus salvator andamanensis Deraniyagala, 1944. Examination of further voucher specimens allows for an expanded morphological diagnosis of this island taxon and comparison with other currently recognized subspecies of the wide-spread Southeast Asian water monitor. Based on the specimens examined, V. s andamanensis is characterized by a homogenous black dorsal background colour, with five to seven, more or less distinctive transverse rows of small spots or ocelli, light yellowish dots arranged sporadically between transverse spot/ocelli rows on the body, light yellowish coloured spots distributed sporadically throughout both forelimbs and hind limbs; 17–18 prominent rows of light spots continuing from base of tail to its tip dorsally with sporadically arranged dots on lateral sides of tail; and higher scale counts in transverse dorsal scale rows. Based on photographic evidence and examination of museum specimens, V. s. andamanensis inhabits both the Andaman and southern Nicobar Islands, which politically belong to the Republic of India. In addition, we confirm the presence of V. s. macromaculatus in the northern and central Nicobar Islands, thus providing evidence for the allopatric co-occurrence of two different water monitor subspecies in these remote archipelagos.
Complications After Distal Biceps Tendon Repair: A Systematic Review
Authors: Amarasooriya Melanie , Bain Gregory Ian , Roper Tom , Bryant Kimberley , Iqbal Karim , Phadnis Joideep 
Published: February 2020

Background: Distal biceps tendon injuries typically occur in the dominant arm of men in their fourth decade of life. Surgical repair restores flexion and supination strength, resulting in good functional outcome. The complication profile of each surgical approach and fixation technique has not been widely studied in the literature. Purpose: To report the rate of complications after repair of complete distal biceps ruptures, to classify them according to surgical approach and fixation technique, and to analyze risk factors and outcomes of the individual complications. Study Design: Systematic review. Methods: Studies published in English on primary repair of the distal biceps between January 1998 and January 2019 were identified. Data on complications were extracted and classified as major and minor for analysis. A quantitative synthesis of data was done to compare the complication rates between (1) limited anterior incision, extensile anterior incision, and double incision and (2) 4 fixation methods. Results: Seventy-two articles including 3091 primary distal biceps repairs were identified. The overall complication rate was 25% (n = 774). The major complication rate was 4.6% (n = 144) and included a 1.6% (n = 51) rate of posterior interosseous nerve injury; 0.3% (n = 10), median nerve injury; 1.4% (n = 43), rerupture; and a 0.1% (n = 4), synostosis. Brachial artery injury, ulnar nerve injury, compartment syndrome, proximal radius fracture, and chronic regional pain syndrome occurred at a rate of <0.1% each. The majority of nerve injuries resolved with an expectant approach. The minor complication rate was 20.4% (n = 630). The most common complication was lateral cutaneous nerve injury (9.2%, n = 283). An extensile single incision was associated with a higher rate of superficial radial nerve injury when compared to limited single incision(6% vs 2.1%, P = .002). Limited anterior single incision technique had a higher rate of lateral antebrachial cutaneous nerve injury compared to extensile single incision. (9.7% vs 5.2%, P = .03). Synostosis occurred only with double incision. Fixation technique had no significant effect on rerupture rate and posterior interosseous nerve injury rate. Conclusion: This is the largest analysis of complications after distal biceps repair, indicating a major complication rate of 4.6%. This study provides valuable data with regard to the choice of technique, surgical approach, and rate of complications, which is essential for surgical planning and patient consent. Registration: CRD42017074066 (PROSPERO).
Thrombin Suppresses Matrix Metalloproteinase 2 Activity and Increases Tissue Inhibitor of Metalloproteinase 1 Synthesis in Cultured Human Peritoneal Mesothelial Cells
Authors: Haslinger Bettina , Mandl–Weber Sonja , Sitter Thomas 
Published: February 2020

Objective Recently, high levels of intraperitoneally generated thrombin were found in the effluent of patients treated with continuous ambulatory peritoneal dialysis (CAPD). The aim of the present study was to investigate in human peritoneal mesothelial cells (HMCs) the effect of thrombin on the activity and synthesis of matrix metalloproteinases (MMPs), which regulate the degradation of basement membrane collagen. Methods Cultured HMCs were isolated from omental tissue and used at confluence for the experiments. Conditioned media were obtained by incubating cells with serum-free M199 containing the relevant doses of thrombin. Activity of MMP-2 and MMP-9 were determined by an activity assay system. The antigen levels of MMPs and of the specific tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by ELISA. Northern blot analysis was applied to analyze mRNA expression of MMP-2 and TIMP-1. Results Incubation of HMCs with increasing doses of thrombin resulted in a concentration- and time-dependent suppression of MMP-2 activity. No changes in MMP-9 activity were seen. After a 48-hour stimulation period with thrombin (5 U/mL), MMP-2 activity decreased to 53% of that seen in control conditions. Antigen measurements revealed that this decrease was paralleled by a slight reduction in MMP-2 levels, which became significant at a thrombin dose of 5 U/mL [50.65 ± 7.5 ng/105 cells (48 hours, 5 U/mL) vs 64.6 ± 10.1 ng/105 cells (control)]. Under the same conditions, TIMP-1 levels were considerably increased [3.9 ± 0.46 μg/105 cells (48 hours, 5 U/mL) vs 1.2 ± 0.14 μg/105 cells (control)]. Hirudin (10 U/mL) completely inhibited the thrombin-induced effects on MMP-2 and TIMP-1 synthesis. These results were also reflected by Northern blot hybridization, where a slight decrease in MMP-2 and an increase in TIMP-1 mRNA expression were observed in response to thrombin. Conclusions Our results suggest that high thrombin levels suppress MMP-2 activity through decreased MMP-2 and increased TIMP-1 synthesis. Thus, thrombin may promote the accumulation of basement membrane collagen. In addition to fibrin formation, this mechanism may represent a further contribution by thrombin to peritoneal thickening during CAPD.
Emodin Ameliorates Glucose-Induced Morphologic Abnormalities and Synthesis of Transforming Growth Factor β1 and Fibronectin by Human Peritoneal Mesothelial Cells
Authors: Yung Susan , Liu Zhi-Hong , Lai Kar-Neng , Li Lei-Shi , Chan Tak-Mao 
Published: February 2020

♦ Objective Excessive synthesis and deposition of matrix proteins by peritoneal mesothelial cells can lead to structural and functional changes in the peritoneal membrane, jeopardizing the long-term efficacy of peritoneal dialysis (PD). Prolonged exposure to high glucose concentrations in PD fluid has been implicated as a major stimulus to matrix accumulation, through the induction of transforming growth factor β1 (TGFβ 1). This study investigated the effect of emodin (3-methyl-1,6,8-trihydroxyanthraquinone) on TGFβ 1 and fibronectin (FN) synthesis in human peritoneal mesothelial cells (HPMCs) under high glucose concentration. ♦ Design The HPMCs were preconditioned in either 5 mmol/L or 30 mmol/L d-glucose for 2 weeks prior to the addition of emodin. Cell viability was assessed by MTT assay and lactate dehydrogenase (LDH) release. Morphology of HPMCs was studied by phase-contrast microscopy. Modulation of TGFβ 1 and FN synthesis at transcription and translation were investigated by reverse transcriptase polymerase chain reaction (RT-PCR), ELISA, and Western blot analysis. ♦ Results When cultured under 30 mmol/L d-glucose, HPMCs demonstrated increased cell volume, multi-nucleation, and denudation of the monolayer, as compared with cells cultured under a physiologic (5 mmol/L) glucose concentration. High glucose concentration induced TGFβ 1 synthesis by HPMCs (217.17 ± 14.88 pg/mL at 5 mmol/L d-glucose vs 370.33 ± 20.67 pg/mL at 30 mmol/L d-glucose, p < 0.0001), and FN synthesis was induced at transcription and translation. Mannitol at 30 mmol/L did not affect HPMC morphology; matrix synthesis was also unaltered. Administration of emodin together with 30 mmol/L d-glucose resulted in amelioration of cell enlargement and exfoliation, and abrogation of TGFβ 1 induction (370.33 ± 20.67 pg/mL for 30 mmol/L d-glucose alone vs 260.50 ± 17.89 pg/mL for 30 mmol/L d-glucose + emodin, p < 0.0001). Synthesis of FN induced by high glucose was also reduced by 40% in the presence of emodin. ♦ Conclusions These findings provide the first evidence that emodin can ameliorate high glucose–induced matrix synthesis in HPMCs by suppression of TGFβ 1. Emodin may thus be useful in preserving peritoneal integrity in PD.
Bisphosphonates in Dialysis and Transplantation Patients: Efficacy and Safety Issues
Authors: Rodd Celia 
Published: February 2020

Bisphosphonates are an old class of compounds. They were used in the 1930s as antiscaling and anticorrosion agents in washing powders and water to prevent the deposition of calcium crystals. Those basic functions were later utilized in an attempt to prevent ectopic calcifications in humans. The early studies demonstrated that bisphosphonates had a strong affinity for bone. That property was first exploited when the compounds were used for “bone scans.” Currently, the drugs are used for treatment of hypercalcemic conditions, abnormal bone remodelling, Paget disease, malignancy, and osteoporosis. Bisphosphonates have several important toxicities: acute renal failure, worsening renal function, reduced bone mineralization, and osteomalacia. For those reasons and others, this class of drugs has not yet been approved for use in children or in patients with severe renal insufficiency. The present review covers several aspects of bisphosphonates: molecular structure, routes of administration, pharmacology, mechanisms of action, toxicities, and exceptional uses in children with renal disease.
Accumulation of Omental Mast Cells during Peritoneal Dialysis
Authors: Zareie Mohammad , Hekking Liesbeth H.P. , Driesprong Bas A.J. , Ter Wee Piet M. , Beelen Robert H.J. , van den Born Jacob 
Published: February 2020

Objective New vessel formation has been reported in various tissues during peritoneal dialysis (PD). In that line, mast cells can produce factors such as tryptase, chymase, or basic fibroblast growth factor that might contribute to the formation of new vessels. In the present study, the association of mast cells with neovascularization during PD was investigated. Methods Rats received daily 10 mL infusions of conventional 3.86% glucose-containing PD fluid over a 10-week period. The infusions were delivered through a subcutaneously implanted mini access port that was connected by catheter to the peritoneal cavity. Untreated rats served as a control group. The number of blood vessels and of mast cells in the omentum were counted. Also, the number of peritoneal mast cells was determined. Results Chronic exposure to PD fluid resulted in an increased number of mast cells in the omentum. However, no clear correlation was found between the elevated number of omental blood vessels and the number of mast cells in the omentum or in the peritoneal cavity. Conclusions Omental mast cells accumulated dramatically upon exposure to PD fluid. The actual role of accumulated omental mast cells in the induction of angiogenesis during PD should, however, be further investigated.
Expression of Aquaporin-1 in the Peritoneal Tissues: Localization and Regulation by Hyperosmolality
Authors: Ota Tomoko , Kuwahara Michio , Fan Shuling , Terada Yoshio , Akiba Takashi , Sasaki Sei , Marumo Fumiaki 
Published: February 2020

Objective The purpose of this study was to determine the localization of the aquaporin-1 (AQP1) water channel in peritoneal tissues and the effect of hyperosmolality on the peritoneal expression and function of AQP1. Methods Immunohistochemical localization of AQP1 was identified in rat peritoneal tissues. Cultured rat peritoneal mesothelial cells (RPMCs) were exposed to hyperosmolality by adding 4% glucose to the culture medium. After 1 hour, 4 hours, 24 hours, and 48 hours, AQP1 was identified by semiquantitative immunoblot and immunocytochemistry. Osmotic water permeability was measured using a light-scattering method. Results Immunohistochemistry of rat peritoneal tissues showed the presence of AQP1 in mesothelial cells, venular endothelial cells, and capillary endothelial cells, but not in arteriole and interstitial cells. Semiquantitative immunoblot revealed that exposure to hyperosmolality significantly increased AQP1 expression after 24 hours in whole RPMC lysates (3.3-fold at 24 hours and 3.9-fold at 48 hours). Consistent with the immunoblot, osmotic water permeability of RPMC was augmented 1.7-fold and 2.7-fold after 1 hour and 24 hours, respectively, in a hyperosmotic environment. In RPMC membrane fractions, AQP1 expression was significantly increased after 1 hour of exposure to hyperosmolality (3.9-fold at 1 hour, 7.1-fold at 4 hours, and 8.7-fold at 24 hours). Immunocytochemistry of RPMCs showed that AQP1 was gradually redistributed from the perinuclear area to the peripheral cytoplasm, and then to the plasma membrane after a 1-hour hyperosmotic challenge, suggesting hyperosmolality-induced translocation of AQP1. Upregulation of AQP1 was also observed in the omentum of rats loaded intraperitoneally with hyperosmotic dialysate every day for 10 weeks. Conclusion AQP1 is widely distributed in the peritoneal cavity and may provide the major aqueous pathway across the peritoneal barrier. In addition, our findings suggested that hyperosmolality increases AQP1-dependent water permeability in peritoneal tissues by regulating the translocation and synthesis of AQP1 protein.