bluuebunny/crossref_metadata_2025 huggingface dataset:
Fundamental parameters and evolutionary status of the magnetic chemically peculiar stars HD 188041 (V1291 Aquilae), HD 111133 (EP Virginis), and HD 204411: spectroscopy versus interferometry
Authors: Romanovskaya A , Ryabchikova T , Shulyak D , Perraut K , Valyavin G , Burlakova T , Galazutdinov G
Published: July 2019

The determination of fundamental parameters of stars is one of the main tasks of astrophysics. For magnetic chemically peculiar stars, this problem is complicated by the anomalous chemical composition of their atmospheres, which requires special analysis methods. We present the results of the effective temperature, surface gravity, abundance, and radius determinations for three CP stars HD 188041, HD 111133, and HD 204411. Our analysis is based on a self-consistent model fitting of high-resolution spectra and spectrophotometric observations over a wide wavelength range, taking into account the anomalous chemical composition of atmospheres and the inhomogeneous vertical distribution for three chemical elements: Ca, Cr, and Fe. For two stars, HD 188041 and HD 204411, we also performed interferometric observations that provided us with the direct estimates of stellar radii. Comparison of the radii determined from the analysis of spectroscopic/spectrophotometric observations with direct measurements of the radii by interferometry methods for seven CP stars shows that the radii agree within the limits of measurement errors, which proves indirect spectroscopic analysis capable of proving reliable determinations of the fundamental parameters of fainter Ap stars that are not possible to study with modern interferometric facilities.
KRAS pathway expression changes in pancreatic cancer models by conventional and experimental taxanes
Authors: Oliverius M , Flasarova D , Mohelnikova-Duchonova B , Ehrlichova M , Hlavac V , Kocik M , Strouhal O , Dvorak P , Ojima I , Soucek P
Published: July 2019

The KRAS signalling pathway is pivotal for pancreatic ductal adenocarcinoma (PDAC) development. After the failure of most conventional cytotoxic and targeted therapeutics tested so far, the combination of taxane nab-paclitaxel (Abraxane) with gemcitabine recently demonstrated promising improvements in the survival of PDAC patients. This study aimed to explore interactions of conventional paclitaxel and experimental taxane SB-T-1216 with the KRAS signalling pathway expression in in vivo and in vitro PDAC models in order to decipher potential predictive biomarkers or targets for future individualised therapy. Mouse PDAC PaCa-44 xenograft model was used for evaluation of changes in transcript and protein levels of the KRAS signalling pathway caused by administration of experimental taxane SB-T-1216 in vivo. Subsequently, KRAS wild-type (BxPc-3) and mutated (MiaPaCa-2 and PaCa-44) cell line models were treated with paclitaxel to verify dysregulation of the KRAS signalling pathway gene expression profile in vitro and investigate the role of KRAS mutation status. By comparing the gene expression profiles, this study observed for the first time that in vitro cell models differ in the basal transcriptional profile of the KRAS signalling pathway, but there were no differences between KRAS mutated and wild-type cells in sensitivity to taxanes. Generally, the taxane administration caused a downregulation of the KRAS signalling pathway both in vitro and in vivo, but this effect was not dependent on the KRAS mutation status. In conclusion, putative biomarkers for prediction of taxane activity or targets for stimulation of taxane anticancer effects were not discovered by the KRAS signalling pathway profiling in various PDAC models.
Are the intrinsically disordered linkers involved in SSB binding to accessory proteins?
Authors: Shinn Min Kyung , Kozlov Alexander G , Nguyen Binh , Bujalowski Wlodek M , Lohman Timothy M
Published: July 2019

Escherichia coli single strand (ss) DNA binding (SSB) protein protects ssDNA intermediates and recruits at least 17 SSB interacting proteins (SIPs) during genome maintenance. The SSB C-termini contain a 9 residue acidic tip and a 56 residue intrinsically disordered linker (IDL). The acidic tip interacts with SIPs; however a recent proposal suggests that the IDL may also interact with SIPs. Here we examine the binding to four SIPs (RecO, PriC, PriA and χ subunit of DNA polymerase III) of three peptides containing the acidic tip and varying amounts of the IDL. Independent of IDL length, we find no differences in peptide binding to each individual SIP indicating that binding is due solely to the acidic tip. However, the tip shows specificity, with affinity decreasing in the order: RecO > PriA ∼ χ > PriC. Yet, RecO binding to the SSB tetramer and an SSB–ssDNA complex show significant thermodynamic differences compared to the peptides alone, suggesting that RecO interacts with another region of SSB, although not the IDL. SSB containing varying IDL deletions show different binding behavior, with the larger linker deletions inhibiting RecO binding, likely due to increased competition between the acidic tip interacting with DNA binding sites within SSB.
Novel enzymatic single-nucleotide modification of DNA oligomer: prevention of incessant incorporation of nucleotidyl transferase by ribonucleotide-borate complex
Authors: Jang Eui Kyoung , Son Ryeo Gang , Pack Seung Pil
Published: July 2019

Terminal deoxynucleotidyl transferase (TdT), which mediates template-independent polymerization with low specificity for nucleotides, has been used for nucleotide extension of DNA oligomers. One concern is that it is difficult to control the number of incorporated nucleotides, which is a limitation on the use of TdT for single-nucleotide incorporation of DNA oligomers. Herein, we uncovered an interesting inhibitory effect on TdT when ribonucleotide substrates (rNTPs) were employed in a borate buffer. On the basis of unique inhibitory effects of the ribonucleotide–borate complex, we developed a novel enzymatic method for single-nucleotide incorporation of a DNA oligomer with a modified rNTP by TdT. Single-nucleotide incorporation of a DNA oligomer with various modified rNTPs containing an oxanine, biotin, aminoallyl or N6-propargyl group was achieved with a high yield. The ‘TdT in rNTP-borate’ method is quite simple and efficient for preparing a single-nucleotide modified DNA oligomer, which is useful for the design of functional DNA-based systems.
Leptomeningeal dissemination of low-grade neuroepithelial CNS tumors in adults: a 15-year experience
Authors: Karschnia, Philipp , Barbiero Frank J , Schwaiblmair Michaela H , Kaulen Leon D , Piepmeier Joseph M , Huttner Anita J , Becker Kevin P , Fulbright Robert K , Baehring Joachim M
Published: July 2019

Background

Leptomeningeal dissemination (LD) in adults is an exceedingly rare complication of low-grade neuroepithelial CNS tumors (LGNs). We aimed to determine relative incidence, clinical presentation, and predictors of outcome.

Methods

We searched the quality control database of the Section of Neuro-Oncology, Yale Cancer Center, for patients with LGN (WHO grade I/II) seen between 2002 and 2017. For cases complicated by LD, we recorded demographics, clinical signs, histopathological diagnosis, and imaging findings. A comprehensive literature review was performed.

Results

Eleven consecutive patients with LD were identified, representing 2.3% of individuals with LGN seen at our institution between 2002 and 2017 (n = 475). Ependymoma was the predominant histological entity. Mean time interval from diagnosis of LGN to LD was 38.6 ± 10 months. Symptoms were mostly attributed to communicating hydrocephalus. Tumor deposits of LD were either nodular or linear with variable enhancement (nonenhancing lesions in 4 of 11 patients). Localized (surgery, radiosurgery, involved-field, or craniospinal radiation therapy) or systemic treatments (chemotherapy) were provided. All patients progressed radiographically. Median overall survival after LD was 102 months. Survival was prolonged when a combination of localized and systemic therapies was administered (188.5 vs 25.5 months; P = .03). Demographics and tumor spectrum reported in the literature were similar to our cohort.

Conclusions

LD is a rare complication of LGNs. A high level of suspicion is required for timely diagnosis as early symptoms are nonspecific and commonly do not occur until years after initial tumor diagnosis. Repeated aggressive treatment appears to be beneficial in improving survival.
Ongoing improvements in postoperative survival of glioblastoma in the temozolomide era: a population-based data linkage study
Authors: Johnston Amy , Creighton Nicola , Parkinson Jonathon , Koh Eng-Siew , Wheeler Helen , Hovey Elizabeth , Rodriguez Michael , Currow David C
Published: July 2019

Background

Translating outcomes achieved by clinical trials into routine care is crucial to improving outcomes of glioblastoma (GBM). This study examines the extent to which an advance in treatment for GBM has translated into meaningful, population-level survival benefits in New South Wales (NSW), Australia.

Methods

This retrospective cohort study used linked population-based cancer registry, admitted patient, and mortality datasets. The cohort (n = 2604) included NSW residents aged ≥18 years with a histologically confirmed GBM and a surgical resection between July 2001 and December 2012. The study outcome was all-cause survival, examined using multivariable proportional hazard models. The main study factor was period of surgery, categorized into 4 periods corresponding to different eras in temozolomide (TMZ) use. Survival was examined over time by age (≤70 and >70 years) and for a subcohort selected to approximate the seminal European Organisation for Research and Treatment of Cancer (Stupp) protocol trial cohort. TMZ use was estimated using aggregate prescription claims data.

Results

Median survival in 2001-2003, 2004-2006, 2007-2009, and 2010-2012 was 7.4, 9.0, 9.8, and 10.6 months, and risk-adjusted 2-year survival was 8.2%, 13.8%, 15.5%, and 18.3%, respectively. Survival improved for those aged ≤70 years and those aged >70 years. In the proxy trial subcohort, median and 2-year survival were 14.3 months and 27.3%, respectively. The volume of TMZ prescribed annually increased rapidly from 2005.

Conclusions

Introduction of TMZ into standard care in 2005 coincided with improvements in survival and a rapid increase in TMZ prescribing. Optimization of care has continued to improve survival of people with GBM in subsequent years.
Patterns of bevacizumab use in patients with glioblastoma: an online survey among experts in neuro-oncology
Authors: Ranjan Surabhi , Skorupan Nebojša , Ye Xiaobu , Sivakumar Ananyaa , Yankulina Olga , Kamson David , Grossman Stuart A , Dzaye Omar , Holdhoff Matthias
Published: July 2019

Background

Bevacizumab (BEV) received accelerated FDA approval in 2009 for the treatment of recurrent glioblastoma (rGBM). Unfortunately, prospective randomized controlled phase 3 studies (AVAglio and Radiation Therapy Oncology Group 0825 in newly diagnosed, European Organisation for Research and Treatment of Cancer 26101 in rGBM) failed to show an overall survival benefit with BEV added to standard therapy. In light of these data, we aimed to capture current utilization patterns and perceived value of BEV in the treatment of GBM among experts in the field.

Methods

An online questionnaire comprising 14 multiple choice questions was sent out in spring 2017 to 207 oncologists/neuro-oncologists treating patients with GBM at all National Cancer Institute–designated cancer centers in the United States.

Results

Sixty-two of 207 (30%) invitees responded (by training, 70% neuro-oncologists, 20% medical oncologists, 10% pediatric oncologists/neuro-oncologists). Participants reported use of BEV most frequently in rGBM for control of edema (85% of respondents) and/or when no other treatment options were available (68%). BEV is rarely used in newly diagnosed GBM (<5% of cases by 78% respondents and in 5% to 10% cases by 15% respondents). Sixty-six percent of participants indicated that they thought BEV improved symptoms, 30% that it improved symptoms and survival, 3% that it had no benefit in GBM patients.

Conclusion

In this cross-sectional online survey we found that among neuro-oncology experts in the United States in 2017, BEV is predominantly utilized in select patients with rGBM, and is only rarely used in a small subgroup of patients with newly diagnosed GBM for control of edema. The low response rate may have introduced a nonresponse bias.
Shedding and Transmission Modes of Severe Fever With Thrombocytopenia Syndrome Phlebovirus in a Ferret Model
Authors: Yu Kwang-Min , Jeong Hye-Won , Park Su-Jin , Kim Young-Il , Yu Min-Ah , Kwon Hyeok-Il , Kim Eun-Ha , Kim Se-Mi , Lee Seung-Hun , Kim Seong-Gyu , Choi Young-Ki
Published: July 2019

Background

Although human-to-human transmission of severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) via direct contact with body fluids has been reported, the role of specific body fluids from SFTSV-infected hosts has not been investigated in detail.

Methods

To demonstrate the virus transmission kinetics in SFTSV-infected hosts, we adapted the ferret infection model and evaluated the virus shedding periods, virus titers, and transmission modes from various specimens of infected ferrets.

Results

Large amounts of infectious SFTSV are shed through nasal discharge, saliva, and urine from SFTSV-infected ferrets. Virus could be detected from 2 dpi and persisted until 12 dpi in these specimens, compared with the relatively short virus-shedding period in sera. Further, transmission studies revealed that SFTSV can be transmitted to close direct and indirect contact naïve animals through various mediums, especially through contact with serum and urine. Further, ferrets contacted with human urine specimens from SFTSV-positive patients were successfully infected with SFTSV, suggesting that urine specimens could be a source of SFTSV infection in humans.

Conclusions

Our results demonstrate that the SFTSV can be shed in various body fluids for more than 12 days and that these specimens could be a source for direct or indirect transmission through close personal contact.
Radiative shocks in spherical accretion
Authors: Fukue Jun
Published: July 2019

In order to explore various aspects of radiative shocks, we examine standing radiative shock waves in spherical accretion flows onto a central gravitating body under the equilibrium diffusion approximation. In contrast to the usual one-dimensional shock, in radiative shocks a radiative precursor appears in the pre-shock region before the shock front, due to the radiative diffusion effect. Furthermore, in spherical flows around a central object the gravitational potential varies in this radiative precursor, and a curvature effect also exists. We first formulate such radiative shocks in spherical flows, derive the overall jump conditions, and solve the structure of the radiative precursor for both the gas and radiation pressure dominated cases. Since the jump conditions contain the coordinates of both ends of the radiative precursor, we must obtain both the solution and the endpoints of the precursor simultaneously. We find that the gravitational effect is not significant, although it cannot be ignored. The curvature effect exerts a strong influence on the structure and width of the precursor. The precursor starting point x1 normalized by the shock radius is roughly expressed by $x_1={\cal M}_1^{1/7}$ for a radiation pressure dominated shock, while $x_1=1.21^{({\cal M}_1-1)}$ for a gas pressure one, where ${\cal M}_1$ is the pre-shock Mach number.
Loss of buoyancy control in the copepod Calanus finmarchicus
Authors: Cohen Jonathan H , Last Kim S , Waldie Jack , Pond David W
Published: July 2019

A mechanism is demonstrated that could explain large-scale aggregations of lipid-rich copepods in the surface waters of marine environments. Laboratory experiments establish that changes in salinity and temperature induce lipid-mediated buoyancy instability that entrains copepods in surface waters. Reduced hydrostatic pressure associated with forced ascent of copepods at fjordic sills, shelf breaks and seamounts would also reduce the density of the lipid reserves, forcing copepods and particularly those in diapause to the surface. We propose that salinity, temperature and hydrodynamics of the physical environment, in conjunction with the biophysical properties of lipids, explain periodic high abundances of lipid-rich copepods in surface waters.
RNA-seq-based identification of Star upregulation by islet amyloid formation
Authors: Hogan Meghan F , Ziemann Mark , K N Harikrishnan , Rodriguez Hanah , Kaspi Antony , Esser Nathalie , Templin Andrew T , El-Osta Assam , Kahn Steven E
Published: July 2019

Aggregation of islet amyloid polypeptide (IAPP) into islet amyloid results in β-cell toxicity in human type 2 diabetes. To determine the effect of islet amyloid formation on gene expression, we performed ribonucleic acid (RNA) sequencing (RNA-seq) analysis using cultured islets from either wild-type mice (mIAPP), which are not amyloid prone, or mice that express human IAPP (hIAPP), which develop amyloid. Comparing mIAPP and hIAPP islets, 5025 genes were differentially regulated (2439 upregulated and 2586 downregulated). When considering gene sets (reactomes), 248 and 52 pathways were up- and downregulated, respectively. Of the top 100 genes upregulated under two conditions of amyloid formation, seven were common. Of these seven genes, only steroidogenic acute regulatory protein (Star) demonstrated no effect of glucose per se to modify its expression. We confirmed this differential gene expression using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and also demonstrated the presence of STAR protein in islets containing amyloid. Furthermore, Star is a part of reactomes representing metabolism, metabolism of lipids, metabolism of steroid hormones, metabolism of steroids and pregnenolone biosynthesis. Thus, examining gene expression that is differentially regulated by islet amyloid has the ability to identify new molecules involved in islet physiology and pathology applicable to type 2 diabetes.
Is Virtual Reality Effective in Orthopedic Rehabilitation? A Systematic Review and Meta-Analysis
Authors: Gumaa Mohammed , Rehan Youssef Aliaa
Published: July 2019

Background

Virtual reality (VR) is an interactive technology that allows customized treatment and may help in delivering effective person-centered rehabilitation.

Purpose

The purpose of this review was to systematically review and critically appraise the controlled clinical trials that investigated VR effectiveness in orthopedic rehabilitation.

Data Sources

Pubmed, CINAHL, Embase, PEDro, REHABDATA, and Sage publications were searched up to September 2018. In addition, manual searching and snowballing using Scopus and Web of Science were done.

Study Selection

Two reviewers screened studies for eligibility first by title and abstract and then full text.

Data Extraction

Articles were categorized into general or region-specific (upper limbs, lower limbs, and spine) orthopedic disorders. Study quality was assessed using the Evaluation Guidelines for Rating the Quality of an Intervention Study scoring. Meta-analysis quantified VR effectiveness, compared with no treatment, in back pain.

Data Synthesis

Nineteen studies were included in the quality assessment. The majority of the studies were of moderate quality. Fourteen studies showed that VR did not differ compared with exercises. Compared with the no-treatment control, 5 studies favored VR and 3 other studies showed no differences. For low back pain, the meta-analysis revealed no significant difference between VR and no-treatment control (n = 116; standardized mean difference = −0.21; 95% confidence interval = −0.58 to 0.15).

Limitations

Limitations included heterogeneity in interventions and the outcome measures of reviewed studies. Only articles in English were included.

Conclusion

The evidence of VR effectiveness is promising in chronic neck pain and shoulder impingement syndrome. VR and exercises have similar effects in rheumatoid arthritis, knee arthritis, ankle instability, and post-anterior cruciate reconstruction. For fibromyalgia and back pain, as well as after knee arthroplasty, the evidence of VR effectiveness compared with exercise is absent or inconclusive.
Does Climate Change Affect Real Estate Prices? Only If You Believe In It
Authors: Baldauf Markus , Garlappi Lorenzo , Yannelis Constantine
Published: July 2019

This paper studies whether house prices reflect belief differences about climate change. We show that in an equilibrium model of housing choice in which agents derive utility from ownership in a neighborhood of similar agents, prices exhibit different elasticities to climate risk. We use comprehensive transaction data to relate prices to inundation projections of individual homes and measures of beliefs about climate change. We find that houses projected to be underwater in believer neighborhoods sell at a discount compared to houses in denier neighborhoods. Our results suggest that house prices reflect heterogeneity in beliefs about long-run climate change risks.
Financial Literacy Externalities
Authors: Haliassos Michael , Jansson Thomas , Karabulut Yigitcan
Published: July 2019

We use unique administrative data and a quasi-field experiment of exogenous allocation in Sweden to estimate medium- and longer-run effects of peoples’ exposure to financially literate neighbors on their financial behavior. We contribute evidence of (1) a causal impact of exposure and of a social multiplier of financial knowledge and (2) unfavorable distributional aspects of externalities. Exposure promotes saving in private retirement accounts and stockholding, especially when neighbors have economics or business education, but only for educated households and for substantial interaction possibilities. Findings point to a transfer of knowledge rather than mere imitation or effects through labor, education, or mobility channels.

Received October 25, 2017; editorial decision December 24, 2018 by Editor Lauren Cohen. Authors have furnished code/data/an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
IL-16 expression is increased in the skin and sera of patients with systemic sclerosis
Authors: Kawabata Kazuo , Makino Takamitsu , Makino Katsunari , Kajihara Ikko , Fukushima Satoshi , Ihn Hironobu
Published: July 2019

Objectives

SSc is an autoimmune disease with chronic and persistent inflammation in its pathogenesis. To examine the expression pattern of IL-16 in SSc lesions, the serum concentration of IL-16 in SSc patients and the relationship between serum IL-16 levels and the clinical symptoms of SSc were investigated.

Methods

Using immunohistochemical analysis, we examined the quantity and localization of IL-16 in affected skin obtained from SSc patients. We also measured serum levels of IL-16 in SSc patients using an ELISA. We then validated the correlation between serum IL-16 levels and clinical symptoms in patients with SSc.

Results

In the skin, IL-16 was expressed on the lymphocytes around the capillaries. Furthermore, the proportion of IL-16-positive cells was statistically higher in patients with dcSSc than in those with lcSSc patients (43.9 vs 29.1%, P < 0.05). The serum IL-16 levels in SSc patients were statistically significant elevated compared with healthy controls (297.0 vs 194.9 pg/ml, P < 0.05). Increased serum IL-16 levels in SSc patients were correlated with the proportion classified as dcSSc, skin score and the presence of cutaneous symptoms of erythema and pigmentation.

Conclusion

The regional up-regulation of IL-16 in the skin is not only associated with skin sclerosis, but also with systemic IL-16 activation. IL-16 may play a role in the pathogenesis of SSc. Moreover, serum IL-16 levels may be useful as a biomarker for determining the severity of the skin sclerosis. Inhibiting IL-16 activation may be effective in treating SSc.
Adenosine Kinase Expression in the Frontal Cortex in Schizophrenia
Authors: Moody Cassidy L , Funk Adam J , Devine Emily , Devore Homan Ryan C , Boison Detlev , McCullumsmith Robert E , O’Donovan Sinead M
Published: July 2019

The adenosine hypothesis of schizophrenia posits that reduced availability of the neuromodulator adenosine contributes to dysregulation of dopamine and glutamate transmission and the symptoms associated with schizophrenia. It has been proposed that increased expression of the enzyme adenosine kinase (ADK) may drive hypofunction of the adenosine system. While animal models of ADK overexpression support such a role for altered ADK, the expression of ADK in schizophrenia has yet to be examined. In this study, we assayed ADK gene and protein expression in frontocortical tissue from schizophrenia subjects. In the dorsolateral prefrontal cortex (DLPFC), ADK-long and -short splice variant expression was not significantly altered in schizophrenia compared to controls. There was also no significant difference in ADK splice variant expression in the frontal cortex of rats treated chronically with haloperidol-decanoate, in a study to identify the effect of antipsychotics on ADK gene expression. ADK protein expression was not significantly altered in the DLPFC or anterior cingulate cortex (ACC). There was no significant effect of antipsychotic medication on ADK protein expression in the DLPFC or ACC. Overall, our results suggest that increased ADK expression does not contribute to hypofunction of the adenosine system in schizophrenia and that alternative mechanisms are involved in dysregulation of this system in schizophrenia.
INSTRAL: Discordance-Aware Phylogenetic Placement Using Quartet Scores
Authors: Rabiee Maryam , Mirarab Siavash
Published: July 2019

Phylogenomic analyses have increasingly adopted species tree reconstruction using methods that account for gene tree discordance using pipelines that require both human effort and computational resources. As the number of available genomes continues to increase, a new problem is facing researchers. Once more species become available, they have to repeat the whole process from the beginning because updating species trees is currently not possible. However, the de novo inference can be prohibitively costly in human effort or machine time. In this article, we introduce INSTRAL, a method that extends ASTRAL to enable phylogenetic placement. INSTRAL is designed to place a new species on an existing species tree after sequences from the new species have already been added to gene trees; thus, INSTRAL is complementary to existing placement methods that update gene trees. [ASTRAL; ILS; phylogenetic placement; species tree reconstruction.]
Evaluation of feedlot performance, carcass characteristics, carcass retail cut distribution, Warner-Bratzler shear force, and fatty acid composition of purebred Jersey and crossbred Jersey steers
Authors: Jaborek Jerad R , Zerby Henry N , Moeller Steven J , Fluharty Francis L , Relling Alejandro E
Published: July 2019

Feedlot performance, carcass yield, fatty acid composition, and tenderness of crossbred Jersey steers compared with purebred Jersey steers was investigated. Purebred Jersey (n = 21) and crossbred Jersey steers sired by Angus (n = 9), SimAngus (n = 10), and Red Wagyu (n = 15) bulls were assessed. Adjusted to a common initial body weight (BW), crossbred Jersey steers had a greater rate of BW gain (P ≤ 0.01) compared with purebred Jersey steers. Angus sired steers had a greater daily dry matter intake (P ≤ 0.01) compared with Wagyu and Jersey sired steers, whereas SimAngus sired steers had a greater daily dry matter intake compared with Jersey sired steers. Wagyu sired steers were more feed efficient (P ≤ 0.03) compared with Jersey sired steers. Even with a greater (P ≤ 0.01) number of days on feed, off-test BW of purebred Jersey steers was less (P ≤ 0.01) compared with crossbred Jersey steers. Adjusted to a common hot carcass weight, Angus sired steers had a greater backfat thickness (P ≤ 0.01) compared with steers from the other sire breeds. Kidney fat percentage (P ≤ 0.01) was greatest for Jersey sired steers, with SimAngus and Wagyu sired steers being intermediate, and the lowest for Angus sired steers. Carcasses from Angus and Wagyu sired steers had a greater marbling score (P ≤ 0.03) compared with carcasses from Jersey sired steers. Carcasses from Wagyu sired steers had a greater (P ≤ 0.01) total red meat yield compared with Angus and Jersey sired steers, whereas SimAngus sired steers had a greater total red meat yield compared with Jersey sired steers. Carcasses from Angus sired steers tended (P = 0.07) to have a greater percentage of fat trim compared with Wagyu sired steer carcasses. There were no sire breed differences (P = 0.38) for the percentage of total bone from the carcasses. Tenderness, measured by Warner-Bratzler shear force (WBSF), was improved (P ≤ 0.01) with 14 d of postmortem aging compared with 7 d. Wagyu and SimAngus sired steers produced steaks with a lesser (P ≤ 0.01) WBSF compared with steaks from Angus and Jersey sired steers. Steaks from Angus sired steers tended (P = 0.10) to have a greater percentage of total lipid and had a greater (P ≤ 0.05) percentage of 16:0 compared with steaks from Jersey sired steers. Overall, crossbred Jersey steers improved economically relevant production parameters of feedlot performance, carcass quality, carcass yield, and instrumental predictors of eating quality compared with purebred Jersey steers.
Misclassification of a whole genome sequence reference defined by the Human Microbiome Project: a detrimental carryover effect to microbiome studies
Authors: Bandoy DJ Darwin R. , Huang B Carol , Weimer Bart C.
Published: July 2019

Taxonomic classification is an essential step in the analysis of microbiome data that depends on a reference database of whole genome sequences. Taxonomic classifiers are built on established reference species, such as the Human Microbiome Project database, that is growing rapidly. While constructing a population wide pangenome of the bacterium Hungatella, we discovered that the Human Microbiome Project reference species Hungatella hathewayi (WAL 18680) was significantly different to other members of this genus. Specifically, the reference lacked the core genome as compared to the other members. Further analysis, using average nucleotide identity (ANI) and 16s rRNA comparisons, indicated that WAL18680 was misclassified as Hungatella. The error in classification is being amplified in the taxonomic classifiers and will have a compounding effect as microbiome analyses are done, resulting in inaccurate assignment of community members and will lead to fallacious conclusions and possibly treatment. As automated genome homology assessment expands for microbiome analysis, outbreak detection, and public health reliance on whole genomes increases this issue will likely occur at an increasing rate. These observations highlight the need for developing reference free methods for epidemiological investigation using whole genome sequences and the criticality of accurate reference databases.
A Single-Cell Immune Atlas of Triple Negative Breast Cancer Reveals Novel Immune Cell Subsets
Authors: Qiu Si , Hong Ruoxi , Zhuang Zhenkun , Li Yuan , Zhu Linnan , Lin Xinxin , Zheng Qiufan , Liu Shang , Zhang Kai , Huang Mengxian , Lee Kaping , Lu Qianyi , Xia Wen , Xu Fei , Wang Xi , Tang Jun , Xiao Xiangsheng , Wei Weidong , Yuan Zhongyu , Shi Yanxia , Hou Yong , Zhang Xiuqing , Wang Jian , Yang Huanming , Zhan Qimin , Li Bo , Wang Shusen
Published: July 2019

Triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype, which recently attracts great interest for immune therapeutic development. In this context, in-depth understanding of TNBC immune landscape is highly demanded. Here we report single-cell RNA sequencing results of 9683 tumor-infiltrated immune cells isolated from 14 treatment naïve TNBC tumors, where 22 immune cell subsets, including T cells, macrophages, B cells, and DCs have been characterized. We identify a new T cell subset, CD8+CXCL8+ naïve T cell, which associates with poor survival. A novel immune cell subset comprised of TCR+ macrophages, is found to be widely distributed in TNBC tumors. Further analyses reveal an up-regulation of molecules associated with TCR signaling and cytotoxicity in these immune cells, indicating TCR signaling activation. Altogether, our study provides a valuable resource to understand the immune ecosystem of TNBC. The novel immune cell subsets reported herein might be functionally important in cancer immunity.

SIGNIFICANCE

This work demonstrates a single-cell transcriptome atlas of immune cells in treatment naïve TNBC tumors, revealing novel immune cell subsets. This study provides a valuable resource to understand the immune ecosystem of TNBC, which will be helpful for the immunotherapeutic strategy design of TNBC.
Spin∞ an improved miniaturized spinning bioreactor for the generation of human cerebral organoids from pluripotent stem cells
Authors: Romero-Morales Alejandra I. , O’Grady Brian J. , Balotin Kylie M. , Bellan Leon M. , Lippmann Ethan S. , Gama Vivian
Published: July 2019

Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), have become a powerful system to study early development events and to model human disease. Cerebral organoids are generally produced in static culture or in a culture vessel with active mixing, and the two most widely used systems for mixing are a large spinning flask and a miniaturized multi-well spinning bioreactor (also known as Spin Omega (SpinΩ)). The SpinΩ provides a system that is amenable to drug testing, has increased throughput and reproducibility, and utilizes less culture media. However, technical limitations of this system include poor stability of select components and an elevated risk of contamination due to the inability to sterilize the device preassembled. Here, we report a new design of the miniaturized bioreactor system, which we term Spin∞ that overcomes these concerns to permit long-term experiments.
Assessing neurophysiological changes associated with combined transcranial direct current stimulation and cognitive emotional training for treatment-resistant depression
Authors: Nikolin Stevan , Martin Donel , Loo Colleen K. , Iacoviello Brian M. , Boonstra Tjeerd W.
Published: July 2019

Transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, is a promising treatment for depression. Recent research suggests that tDCS efficacy can be augmented using concurrent cognitive emotional training (CET). However, the neurophysiological changes associated with this combined intervention remain to be elucidated. We therefore examined the effects of tDCS combined with CET using electroencephalography (EEG). A total of 20 participants with treatment resistant depression took part in this open-label study and received 18 sessions over 6 weeks of tDCS and concurrent CET. Resting-state and task-related EEG during a 3-back working memory task were aquired at baseline and immediately following the treatment course. Results showed an improvement in mood and working memory accuracy, but not response time, following the intervention. We did not find significant effects of the intervention on resting-state power spectral density (frontal theta and alpha asymmetry), time-frequency power (alpha event-related desynchronization and theta event-related synchronisation), or event-related potentials (P2 and P3 components). We therefore identified little evidence of neurophysiological changes associated with treatment using tDCS and concurrent CET, despite significant improvements in mood and near transfer effects of cognitive training to working memory accuracy. Further research incorporating a sham controlled group may be necessary to identify the neurophysiological effects of the intervention.
Functionally Distinct Subgroups of Oligodendrocyte Precursor Cells Integrate Neural Activity and Execute Myelin Formation
Authors: Hoche Tobias , Marisca Roberta , Agirre Eneritz , Hoodless Laura Jane , Barkey Wenke , Auer Franziska , Castelo-Branco Gonçalo , Czopka Tim
Published: July 2019

Recent reports revealed heterogeneity of oligodendrocyte precursor cells (OPCs). It remains unclear if heterogeneity reflects different types of cells with distinct functions, or rather transiently acquired states of cells with the same function. By integrating lineage formation of individual OPC clones, single-cell transcriptomics, calcium imaging and manipulation of neural activity, we show that OPCs in the zebrafish spinal cord can be divided into two functionally distinct entities. One subgroup forms elaborate networks of processes and exhibits a high degree of calcium signalling, but infrequently differentiates, despite contact to permissive axons. Instead, these OPCs divide in an activity and calcium dependent manner to produce another subgroup with higher process motility and less calcium signaling, which readily differentiates. Our data show that OPC subgroups are functionally diverse in responding to neurons and reveal that activity regulates proliferation of a subset of OPCs that is distinct from the cells that generate differentiated oligodendrocytes.
Muscarinic modulation of spike-timing dependent plasticity at recurrent layer 2/3 synapses in mouse auditory cortex
Authors: Rao Deepti , Kratz Megan B. , Manis Paul B.
Published: July 2019

Cholinergic systems contribute to the refinement of auditory cortical receptive fields by activating muscarinic acetylcholine receptors (mAChRs). However, the specific cellular and synaptic mechanisms underlying acetylcholine’s effects on cortical circuits are not fully understood. In this study, we investigate the effects of muscarinic receptor modulation on spike-timing dependent plasticity (STDP) at synapses onto layer 2/3 pyramidal neurons in mouse auditory cortex (AC). Synapses onto layer 2/3 pyramidal neurons exhibit a STDP rule for pairing of postsynaptic spike bursts with single presynaptic stimuli. Pre-before-post pairing at +10 ms results in a timing-dependent long-term potentiation (tLTP), whereas pre-before-post pairing at +50 ms intervals, and post-before-pre pairing at -10 to -20 ms produce a timing-dependent long-term depression. We also characterize how mAChR activation affects plasticity at these synapses, focusing on the induction of tLTP. During pre-before-post pairing at +10 ms, mAChR activation by either carbachol or oxotremorine-M suppresses tLTP. mAChR activation also reduces the NMDA-receptor dependent synaptically evoked increase in calcium in dendrites, apparently without affecting presynaptic transmitter release. Pharmacological experiments suggest that M1 and M3 receptors are not involved in the mAChR-mediated suppression of tLTP. Taken together, these results suggest activating mAChRs in layer 2/3 intracortical circuits can modify the circuit dynamics of AC by depressing tLTP mediated by NMDA receptors, and depressing calcium influx at excitatory synapses onto layer 2/3 pyramidal cells.
Metagenomic analysis of virus diversity and relative abundance in a eutrophic freshwater harbour
Authors: Palermo Christine N. , Fulthorpe Roberta R. , Saati Rosemary , Short Steven M.
Published: July 2019

Aquatic viruses have been extensively studied over the past decade, yet fundamental aspects of freshwater virus communities remain poorly described. Our goal was to characterize particle-associated virus communities seasonally and spatially in a freshwater harbour. Community DNA was extracted from water samples and sequenced on an Illumina HiSeq platform. Assembled contigs were annotated as belonging to the virus families Caudovirales, Mimiviridae, Phycodnaviridae, and virophages (Lavidaviridae), or to other groups of undefined viruses. Diverse Mimiviridae contigs were detected in the samples, but the two sites contained distinct Mimiviridae communities. Virophages were often the most abundant group, and discrete virophage taxa were remarkably stable across sites and dates despite fluctuations in Mimiviridae community composition. Caudovirales were present at low abundances in most samples, contrasting other studies of freshwater environments. Similarly, Phycodnaviridae abundances were surprisingly low in all samples despite the harbour’s capacity to support high algal biomass during the summer and autumn months, suggesting that Mimiviridae are the dominant algae-infecting viruses in this system. Overall, our findings provided insights into freshwater virus community assemblages by expanding the documented diversity of freshwater virus communities, highlighting the potential ecological importance of virophages, and revealing distinct communities over small spatial scales.
Genetically encoded nanostructures enable acoustic manipulation of engineered cells
Authors: Wu Di , Baresch Diego , Cook Colin , Malounda Dina , Maresca David , Abundo Maria Paulene , Mittelstein David Reza , Shapiro Mikhail G.
Published: July 2019

The ability to mechanically manipulate and control the spatial arrangement of biological materials is a critical capability in biomedicine and synthetic biology. Ultrasound has the ability to manipulate objects with high spatial and temporal precision via acoustic radiation force, but has not been used to directly control biomolecules or genetically defined cells. Here, we show that gas vesicles (GVs), a unique class of genetically encoded gas-filled protein nanostructures, can be directly manipulated and patterned by ultrasound and enable acoustic control of genetically engineered GV-expressing cells. Due to their differential density and compressibility relative to water, GVs experience sufficient acoustic radiation force to allow these biomolecules to be moved with acoustic standing waves, as demonstrated within microfluidic devices. Engineered variants of GVs differing in their mechanical properties enable multiplexed actuation and act as sensors of acoustic pressure. Furthermore, when expressed inside genetically engineered bacterial cells, GVs enable these cells to be selectively manipulated with sound waves, allowing patterning, focal trapping and translation with acoustic fields. This work establishes the first genetically encoded nanomaterial compatible with acoustic manipulation, enabling molecular and cellular control in a broad range of contexts.
Modeling the Role of Hypoxia in Glioblastoma Growth and Recurrence Patterns
Authors: Curtin Lee , Hawkins-Daarud Andrea , Porter Alyx B. , Owen Markus R. , van der Zee Kristoffer G. , Swanson Kristin R.
Published: July 2019

A typical feature of glioblastoma (GBM) growth is local recurrence after surgery. However, some GBMs recur distally. It has been noted that GBM patients with perioperative ischemia are more likely to have distal recurrence and that GBM cells migrate faster under hypoxic conditions. We apply the Proliferation Invasion Hypoxia Necrosis Angiogenesis (PIHNA) model to examine the effect of faster hypoxic cell migration on simulated GBM growth. Results suggest that a highly migratory hypoxic cell population drives the growth of the whole tumor and leads to distant recurrence, as do higher normoxic tumor cell migration and low cellular proliferation rates.
Protocols for all-atom reconstruction and high-resolution refinement of protein-peptide complex structures
Authors: Badaczewska-Dawid Aleksandra , Khramushin Alisa , Kolinski Andrzej , Schueler-Furman Ora , Kmiecik Sebastian
Published: July 2019

Structural characterizations of protein-peptide complexes may require further improvements. These may include reconstruction of missing atoms and/or structure optimization leading to higher accuracy models. In this work, we describe a workflow that generates accurate structural models of peptide-protein complexes starting from protein-peptide models in C-alpha representation generated using CABS-dock molecular docking. First, protein-peptide models are reconstructed from their C-alpha traces to all-atom representation using MODELLER. Next, they are refined using RosettaFlexPepDock. The described workflow allows for reliable all-atom reconstruction of CABS-dock models and their further improvement to high-resolution models.
Evaluation of longitudinal time-lapsedin vivomicro-CT for monitoring fracture healing in mouse femur defect models
Authors: Wehrle Esther , Tourolle né Betts Duncan C , Kuhn Gisela A , Scheuren Ariane C , Hofmann Sandra , Müller Ralph
Published: July 2019

Longitudinalin vivomicro-computed tomography (micro-CT) is of interest to non-invasively capture the healing process of individual animals in preclinical fracture healing studies. However, it is not known whether longitudinal imaging itself has an impact on callus formation and remodeling. In this study, a scan group received weekly micro-CT measurements (week 0-6), whereas controls were only scanned post-operatively and at week 5 and 6. Registration of consecutive scans using a branching scheme (bridged vs. unbridged defect) combined with a two-threshold approach enabled assessment of localized bone turnover and mineralization kinetics relevant for monitoring callus remodeling. Weekly micro-CT application did not significantly change any of the assessed callus parameters in the defect and periosteal volumes. This was supported by histomorphometry showing only small amounts of cartilage residuals in both groups, indicating progression towards the end of the healing period. Also, immunohistochemical staining of Sclerostin, previously associated with mediating adverse radiation effects on bone, did not reveal differences between groups.

The established longitudinalin vivomicro-CT-based approach allows monitoring of healing phases in mouse femur defect models without significant effects of anesthesia, handling and radiation on callus properties. Therefore, this study supports application of longitudinalin vivomicro-CT for healing-phase-specific monitoring of fracture repair in mice.