bluuebunny/crossref_metadata_2025_split huggingface dataset:
SNAP23 is required for constitutive and regulated exocytosis in mouse oocytes†
Authors: Mehlmann Lisa M , Uliasz Tracy F , Lowther Katie M 
Published: June 2019

AbstractMammalian oocytes are stored in the ovary for prolonged periods, and arrested in meiotic prophase. During this period, their plasma membranes are constantly being recycled by endocytosis and exocytosis. However, the function of this membrane turnover is unknown. Here, we investigated the requirement for exocytosis in the maintenance of meiotic arrest. Using Trim-away, a newly developed method for rapidly and specifically depleting proteins in oocytes, we have identified the SNARE protein, SNAP23, to be required for meiotic arrest. Degradation of SNAP23 causes premature meiotic resumption in follicle-enclosed oocytes. The reduction in SNAP23 is associated with loss of gap junction communication between the oocyte and surrounding follicle cells. Reduction of SNAP23 protein also inhibits regulated exocytosis in response to a Ca2+ stimulus (cortical granule exocytosis), as measured by lectin staining and cleavage of ZP2. Our results show an essential role for SNAP23 in two key processes that occur in mouse oocytes and eggs.
Recruitment of monocytes and mature macrophages in mouse pubic symphysis relaxation during pregnancy and postpartum recovery†
Authors: Castelucci Bianca G , Consonni Silvio R , Rosa Viviane S , Joazeiro Paulo P 
Published: June 2019

AbstractAppropriate remodeling of the female lower reproductive tract and pelvic floor is essential during normal mammalian pregnancy, labor, and postpartum recovery. During mouse pregnancy, in addition to reproductive tract modifications, the pubic symphysis (PS) is remodeled into a soft interpubic ligament (IpL) to provide safe delivery of the offspring and fast postpartum recovery. Although temporal changes in the phenotypes of myeloid cells, such as mononuclear phagocytes, are crucial to remodeling the lower reproductive tract organs in preparation for a safe delivery, little is known about the involvement of recruited monocytes or macrophages in mouse PS remodeling. We used combined light microscopy, electron microscopy, and qPCR analysis to investigate the profile of recruited monocytes and macrophage polarization markers in C57Bl6 mouse interpubic tissues during pregnancy (D12, D18, and D19) and early days postpartum (1 dpp and 3 dpp) to better identify their presence in proper remodeling of the mouse PS. Our morphological data show that the number of recruited monocytes is increased in interpubic tissues and that recruited monocytes differentiate into proinflammatory or anti-inflammatory macrophage phenotypes from D18 to 3 dpp, which may contribute to dynamic changes in the gene expression of specific inflammatory mediators involved in interpubic tissue remodeling at these time points. Therefore, our morphological and quantitative gene expression data suggest that both differentiated macrophages from recruited monocytes and polarized macrophages may collaborate for IpL relaxation at labor and the appropriate repair of the PS after the first pregnancy.
Nanopore Sequencing Significantly Improves Genome Assembly of the Protozoan Parasite Trypanosoma cruzi
Authors: Díaz-Viraqué Florencia , Pita Sebastián , Greif Gonzalo , de Souza Rita de Cássia Moreira , Iraola Gregorio , Robello Carlos 
Published: June 2019

Abstract
Chagas disease was described by Carlos Chagas, who first identified the parasite Trypanosoma cruzi from a 2-year-old girl called Berenice. Many T. cruzi sequencing projects based on short reads have demonstrated that genome assembly and downstream comparative analyses are extremely challenging in this species, given that half of its genome is composed of repetitive sequences. Here, we report de novo assemblies, annotation, and comparative analyses of the Berenice strain using a combination of Illumina short reads and MinION long reads. Our work demonstrates that Nanopore sequencing improves T. cruzi assembly contiguity and increases the assembly size in ∼16 Mb. Specifically, we found that assembly improvement also refines the completeness of coding regions for both single-copy genes and repetitive transposable elements. Beyond its historical and epidemiological importance, Berenice constitutes a fundamental resource because it now constitutes a high-quality assembly available for TcII (clade C), a prevalent lineage causing human infections in South America. The availability of Berenice genome expands the known genetic diversity of these parasites and reinforces the idea that T. cruzi is intraspecifically divided in three main clades. Finally, this work represents the introduction of Nanopore technology to resolve complex protozoan genomes, supporting its subsequent application for improving trypanosomatid and other highly repetitive genomes.
The Effects of Metformin on Age-Related Changes in the Liver Sinusoidal Endothelial Cell
Authors: Hunt Nicholas J , Lockwood Glen P , Kang Sun Woo (Sophie) , Pulpitel Tamara , Clark Ximonie , Mao Hong , McCourt Peter A G , Cooney Gregory J , Wali Jibran A , Le Couteur Frank H , Le Couteur David G , Cogger Victoria C 
Published: June 2019

Abstract
Age-related changes in the liver sinusoidal endothelium, particularly the reduction in fenestrations, contribute to insulin resistance in old age. Metformin impacts on the aging process and improves insulin resistance. Therefore, the effects of metformin on the liver sinusoidal endothelium were studied. Metformin increased fenestrations in liver sinusoidal endothelial cells isolated from both young and old mice. Mice administered metformin in the diet for 12 months had increased fenestrations and this was associated with lower insulin levels. The effect of metformin on fenestrations was blocked by inhibitors of AMP-activated protein kinase (AMPK), endothelial nitric oxide synthase, and myosin light chain kinase phosphorylation. Metformin led to increased transgelin expression and structural changes in the actin cytoskeleton but had no effect on lactate production. Metformin also generated fenestration-like structures in SK-Hep1 cells, a liver endothelial cell line, and this was associated with increased ATP, cGMP, and mitochondrial activity. In conclusion, metformin ameliorates age-related changes in the liver sinusoidal endothelial cell via AMPK and endothelial nitric oxide pathways, which might promote insulin sensitivity in the liver, particularly in old age.
Decellularized Human Gut as a Natural 3D Platform for Research in Intestinal Fibrosis
Authors: Giuffrida Paolo , Curti Marco , Al-Akkad Walid , Biel Carin , Crowley Claire , Frenguelli Luca , Telese Andrea , Hall Andrew , Tamburrino Domenico , Spoletini Gabriele , Fusai Giuseppe , Tinozzi Francesco Paolo , Pietrabissa Andrea , Corazza Gino Roberto , De Coppi Paolo , Pinzani Massimo , Di Sabatino Antonio , Rombouts Krista , Mazza Giuseppe 
Published: June 2019

Abstract

Background
The current methodologies for the identification of therapeutic targets for inflammatory bowel disease (IBD) are limited to conventional 2-dimensional (2D) cell cultures and animal models. The use of 3D decellularized human intestinal scaffolds obtained from surgically resected intestine and engineered with human intestinal cells may provide a major advancement in the development of innovative intestinal disease models. The aim of the present study was to design and validate a decellularization protocol for the production of acellular 3D extracellular matrix (ECM) scaffolds from the human duodenum.

Methods
Scaffolds were characterized by verifying the preservation of the ECM protein composition and 3D architecture of the native intestine and were employed for tissue engineering with primary human intestinal myofibroblasts for up to 14 days.

Results
Engrafted cells showed the ability to grow and remodel the surrounding ECM. mRNA expression of key genes involved in ECM turnover was significantly different when comparing primary human intestinal myofibroblasts cultured in 3D scaffolds with those cultured in standard 2D cultures on plastic dishes. Moreover, incubation with key profibrogenic growth factors such as TGFβ1 and PDGF-BB resulted in markedly different effects in standard 2D vs 3D cultures, further emphasizing the importance of using 3D cell cultures.

Conclusions
These results confirm the feasibility of 3D culture of human intestinal myofibroblasts in intestinal ECM scaffolds as an innovative platform for disease modeling, biomarker discovery, and drug testing in intestinal fibrosis.
Su salud a la mano (your health at hand): patient perceptions about a bilingual patient portal in the Los Angeles safety net
Authors: Casillas Alejandra , Perez-Aguilar Giselle , Abhat Anshu , Gutierrez Griselda , Olmos-Ochoa Tanya T , Mendez Carmen , Mahajan Anish , Brown Arleen , Moreno Gerardo 
Published: June 2019

Abstract

Objectives
Driven by beneficial patient-centered outcomes associated with patient portal use and the Affordable Care Act, portal implementation has expanded into safety nets—health systems that offer access to care to a large share of uninsured, Medicaid, and other vulnerable populations. However, little attention has been paid to the factors that affect portal accessibility by the vulnerable patients served by these health systems—including those who are limited English proficient (LEP).

Materials and Methods
The Los Angeles County Department of Health Services (LAC DHS), the second-largest safety net system in the nation, launched its first patient portal, and one of the few bilingual English-Spanish interfaces in existence, in March of 2015. To explore portal awareness and perceptions, we conducted focus groups with LAC DHS patients, in English and Spanish (LEP). The Technology Acceptance Model was used to guide thematic analysis of focus group data.

Results
Of the 46 participants, 37 were patients and 9 were caretakers; 23 were English-speaking and 23 Spanish-speaking LEP. All patients had diabetes or hypertension. Over half had an annual household income &lt;$10 000, yet 78% of English-speaking and 65% of Spanish-speaking LEP participants reported at-home Internet access. Participants’ discussion centered around 3 major thematic narratives: (1) participants’ awareness or attitudes about the LAC DHS portal; (2) role of culture, language, or community with regard to portal accessibility and utility; and (3) perceived needs for successful portal implementation.

Conclusions
Safety net participants identified concrete benefits to the portal and emphasized the need for portal engagement that offered accessible education, support, and resources in clinical and community settings. The portal offers an additional opportunity to engage the patient and family with trusted and validated health information, and should be further developed in this capacity. This study provides a better understanding of preferred improvements of patient portal engagement that guide broader health technology efforts to address electronic health disparities.
The Bacteriological Profile of Burn Wound Infections at a Tertiary Burns Center in Nepal
Authors: Pujji Ojas Jyoti Singh , Nakarmi Kiran Kishor , Shrestha Basudha , Rai Shankar Man , Jeffery Steven Leonard Alexander 
Published: June 2019

AbstractIn Nepal, burn is the third most common injury after falls and road traffic accidents. Infection is the leading cause of mortality in burn injury. A profile exploring predominant flora and antimicrobial sensitivity is important to facilitate treatment ahead of microbiology results and to aid prevention of multidrug-resistant organisms. The aim of this study was to document epidemiological and bacteriological data of burn wound infections at a tertiary level burns center in Nepal. Samples were collected from January 2017 to May 2017, over a period of 5 months. Patient notes were referred to and information regarding baseline characteristics and burn wound infection data was collected. A total of 76 patients were included in the study during the 5-month period, which resulted in 113 samples being included for review. Females were injured most with burns 70% (n = 53) compared with males 30% (n = 23). Only 6 (8%) of 77 patients lived locally in Kathmandu. The average distance traveled by patients was 233 km (median 208, range 0–765, SD 181). Average TBSA% of burn was 22% (median 20, range 3–50, SD 12). Gram-negative organisms predominated, with Acinetobacter spp. in 42 cases (55%), Pseudomonas aeruginosa in 26 cases (34%), and Enterobacter spp. in 16 cases (21%). Colistin, polymyxin B, and tigecycline were found to be most sensitive covering 108, 98, and 94 organisms. Gram-negative bacteria colonized the majority of burn wounds. Colistin, polymyxin B, and tigecycline were the most sensitive to gram-negative bacteria. Gram-positive Staphylococcus aureus was sensitive most to vancomycin and tigecycline.
The Political Economy of Public Debt: A Laboratory Study
Authors: Battaglini Marco , Nunnari Salvatore , Palfrey Thomas R 
Published: June 2019

AbstractThis paper reports the results from a laboratory experiment designed to study political distortions in the accumulation of public debt. A legislature bargains over the levels of a public good and of district specific transfers in two periods. The legislature can issue or purchase risk-free bonds in the first period and the level of public debt creates a dynamic linkage across policymaking periods. In line with the theoretical predictions, we find that public policies are inefficient and efficiency is increasing in the size of the majority requirement, with higher investment in public goods and lower debt associated with larger majority requirements. Debt is lower when the probability of a negative shock to the economy in the second period is higher indicating that even in a political equilibrium debt is used to smooth consumption and to insure against economic uncertainty. Also in line with the theoretical predictions, we find that dynamic distortions are eliminated when the first period proposer can commit to a policy for both periods. The experiment, however, highlights two phenomena that are surprising in terms of standard theory and have not been previously documented. First, balancing the budget in each period is a focal point, leading to lower distortions than predicted. Second, higher majority requirements induce significant delays in reaching an agreement.
Effect of Fluctuating High Temperatures on House Flies (Diptera: Muscidae) and Their Principal Parasitoids (Muscidifurax spp. and Spalangia spp. [Hymenoptera: Pteromalidae]) From the United States
Authors: Geden Christopher J , Biale Haim , Chiel Elad , Johnson Dana M 
Published: June 2019

Abstract
Colonies of house flies (Musca domestica L. [Diptera: Muscidae]) and four species of parasitoids (Muscidifurax raptor Girault and Sanders, Muscidifurax zaraptor Kogan and Legner, Spalangia cameroni Perkins and Spalangia endius Walker) were established by making collections from dairy farms near Bell, FL, Beatrice, NE, Minneapolis, MN, and San Jacinto, CA. Colonies were assessed for heat tolerance by comparing life history parameters at 25–27°C and fluctuating hot (26.7–41.7°C) temperatures. Muscidifurax raptor, S. cameroni, and S. endius produced 24–28% as many progeny under hot conditions as at 25°C. Colonies of M. zaraptor were more heat-tolerant and produced an average 46.9% as many progeny under the hot regime compared with moderate conditions. There was little evidence for higher heat tolerance in parasitoid populations from historically hot locations (CA desert and FL). Colonies of M. raptor and S. endius that had been in culture for 24 yr were the least heat-tolerant with regard to progeny production. House flies collected from the same locations varied little in longevity, fecundity, or egg-to-adult survival under either hot or moderate regimes. Flies reared under hot conditions laid about half as many eggs (89/female) and had about half the egg–adult survival rate (47.3%) under hot compared with moderate conditions, indicating that heat stress had less effect on flies than on all of the parasitoids except M. zaraptor. An attempt to select for heat tolerance in flies by subjecting them to incremental increases in rearing temperatures for 20 generations resulted in little change in tolerance among the selected flies.
The effects of dynamical substructure on Milky Way mass estimates from the high-velocity tail of the local stellar halo
Authors: Grand Robert J J , Deason Alis J , White Simon D M , Simpson Christine M , Gómez Facundo A , Marinacci Federico , Pakmor Rüdiger 
Published: June 2019

ABSTRACT
We investigate the impact of dynamical streams and substructure on estimates of the local escape speed and total mass of Milky-Way-mass galaxies from modelling the high-velocity tail of local halo stars. We use a suite of high-resolution magnetohydrodynamical cosmological zoom-in simulations that resolve phase space substructure in local volumes around solar-like positions. We show that phase space structure varies significantly between positions in individual galaxies and across the suite. Substructure populates the high-velocity tail unevenly and leads to discrepancies in the mass estimates. We show that a combination of streams, sample noise, and truncation of the high-velocity tail below the escape speed leads to a distribution of mass estimates with a median that falls below the true value by ${\sim } 20 {{\ \rm per\ cent}}$, and a spread of a factor of 2 across the suite. Correcting for these biases, we derive a revised value for the Milky Way mass presented in Deason et al. of $1.29 ^{+0.37}_{-0.47} \times 10^{12}\, \rm M_{\odot }$.
Fundamentals of Clinical Prediction Modeling for the Neurosurgeon
Authors: Mijderwijk Hendrik-Jan , Steyerberg Ewout W , Steiger Hans-Jakob , Fischer Igor , Kamp Marcel A 
Published: June 2019

AbstractClinical prediction models in neurosurgery are increasingly reported. These models aim to provide an evidence-based approach to the estimation of the probability of a neurosurgical outcome by combining 2 or more prognostic variables. Model development and model reporting are often suboptimal. A basic understanding of the methodology of clinical prediction modeling is needed when interpreting these models. We address basic statistical background, 7 modeling steps, and requirements of these models such that they may fulfill their potential for major impact for our daily clinical practice and for future scientific work.
Behavioral and Subjective Effects of Reducing Nicotine in Cigarettes: A Cessation Commentary
Authors: Piper Megan E , Drobes David J , Walker Natalie 
Published: June 2019

Abstract
This commentary addresses critical questions regarding the impact of the reduction of nicotine on changes in smoking behavior. There appears to be moderate evidence that use of reduced nicotine cigarettes (RNC) increases the likelihood of making a quit attempt among smokers unmotivated to quit and among smokers motivated to quit who also used nicotine replacement therapy (NRT). There was limited evidence that RNC combined with NRT increased smoking abstinence, regardless of motivation to quit. Several plausible mechanisms via which RNC may influence smoking behavior, including reducing dependence, are reviewed. The moderate evidence that abrupt reduction in nicotine reduces self-reported dependence as well as smoking behavior and likelihood of relapse is also reviewed. The data reviewed here suggest that abrupt switching to, and extended use of, RNC can reduce cigarette dependence and several related constructs, including the ability to quit smoking. The data reviewed in this commentary suggest that abrupt reduction in the level of nicotine in combustible cigarettes could reduce smoking behavior, nicotine dependence, and other related constructs and increase quit attempts and eventual smoking cessation.
A comparison between Zooglider and shipboard net and acoustic mesozooplankton sensing systems
Authors: Whitmore Benjamin M , Nickels Catherine F , Ohman Mark D 
Published: June 2019

Abstract
Some planktonic patches have markedly higher concentrations of organisms compared to ambient conditions and are <5 m in thickness (i.e. thin layers). Conventional net sampling techniques are unable to resolve this vertical microstructure, while optical imaging systems can measure it for limited durations. Zooglider, an autonomous zooplankton-sensing glider, uses a low-power optical imaging system (Zoocam) to resolve mesozooplankton at a vertical scale of 5 cm while making concurrent physical and acoustic measurements (Zonar). In March 2017, Zooglider was compared with traditional nets (MOCNESS) and ship-based acoustics (Simrad EK80). Zoocam recorded significantly higher vertically integrated abundances of smaller copepods and appendicularians, and larger gelatinous predators and mineralized protists, but similar abundances of chaetognaths, euphausiids, and nauplii. Differences in concentrations and size-frequency distributions are attributable to net extrusion and preservation artifacts, suggesting advantages of in situ imaging of organisms by Zooglider. Zoocam detected much higher local concentrations of copepods and appendicularians (53 000 and 29 000 animals m−3, respectively) than were resolvable by nets. The EK80 and Zonar at 200 kHz agreed in relative magnitude and distribution of acoustic backscatter. The profiling capability of Zooglider allows for deeper high-frequency acoustic sampling than conventional ship-based acoustics.
IgG4-related disease in a multi-ethnic community: clinical characteristics and association with malignancy
Authors: Poo S X , Tham C S W , Smith C , Lee J , Cairns T , Galliford J , Hamdulay S , Jacyna M , Levy J B , McAdoo S P , Roufosse C , Wernig F , Mason J C , Pusey C D , Tam F W K , Tomlinson J A P 
Published: June 2019

Abstract

Background
Immunoglobulin-G4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory condition that can affect multiple organs. Despite growing interest in this condition, the natural history and management of IgG4-RD remain poorly understood.

Aim
To describe the clinical characteristics, treatment and outcomes of IgG4-RD in a multi-ethnic UK cohort, and investigate its possible association with malignancy.

Design
Retrospective analysis of case-note and electronic data.

Methods
Cases were identified from sub-specialty cohorts and a systematic search of an NHS trust histopathology database using ‘IgG4’ or ‘inflammatory pseudotumour’ as search terms. Electronic records, imaging and histopathology reports were reviewed.

Results
In total, 66 identified cases of IgG4-RD showed a similar multi-ethnic spread to the local population of North West London. The median age was 59 years and 71% of patients were male. Presenting symptoms relating to mass effect of a lesion were present in 48% of cases and the mean number of organs involved was 2.4. Total of 10 patients had reported malignancies with 6 of these being haematological. 83% of those treated with steroids had good initial response; however, 50% had relapsing-remitting disease. Rituximab was administered in 11 cases and all achieved an initial serological response. Despite this, seven patients subsequently relapsed after a mean duration of 11 months and four progressed despite treatment.

Conclusions
We report a large UK-based cohort of IgG4-RD that shows no clear ethnic predisposition and a wide range of affected organs. We discuss the use of serum IgG4 concentrations as a disease marker in IgG4-RD, the association with malignant disease and outcomes according to differing treatment regimens.