bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-17A Contributes to Lung Fibrosis in a Model of Chronic Pulmonary Graft-versus-host Disease
Authors: Martinu Tereza , McManigle William C. , Kelly Francine L. , Nelson Margaret E. , Sun Jesse , Zhang Helen L. , Kolls Jay K. , Gowdy Kymberly M. , Palmer Scott M. 
Published: August 2019

Background.
Chronic pulmonary graft-versus-host disease (cpGVHD) after hematopoietic cell transplant (HCT) manifests as progressive airway and parenchymal lung fibrosis. On the basis of our prior data, mice that undergo allogeneic HCT with Tbet-knockout donors (AlloTbet−/−) have increased lung Th17 cells and IL-17A and develop fibrosis resembling human cpGVHD. The role of IL-17A in posttransplant pulmonary fibrosis remains incompletely understood. We hypothesized that IL-17A is necessary for development of murine cpGVHD in this model.

Methods.
AlloTbet−/− mice received weekly intraperitoneal anti-IL-17A or IgG (200 μg/mouse) starting 2 weeks post-HCT and were sacrificed after week 5. Histologic airway and parenchymal fibrosis were semiquantitatively graded in a blinded fashion. Lung cells and proteins were measured by flow cytometry, ELISA, and multicytokine assays.

Results.
Anti-IL-17A modestly decreased airway and parenchymal lung fibrosis, along with a striking reduction in pulmonary neutrophilia, IL-6, MIP-1α, MIP-1β, CXCL1, and CXCL5 in AlloTbet−/− mice. Additionally, anti-IL-17A decreased CCL2, inflammatory monocytes and macrophages, and Th17 cells.

Conclusions.
In the setting of murine AlloHCT with Tbet−/− donors, IL-17A blockade decreases fibrotic features of cpGVHD. This may be mediated by the observed reduction in neutrophils or specific lung monocyte and macrophage populations or alternatively via a direct effect on fibroblasts. Collectively, our results further suggest that anti-IL-17A strategies could prove useful in preventing alloimmune-driven fibrotic lung diseases.
The Comparable Efficacy of Lung Donation After Circulatory Death and Brain Death: A Systematic Review and Meta-analysis
Authors: Zhou Jian , Chen Boran , Liao Hu , Wang Zihuai , Lyu Mengyuan , Man Shulei , Pu Qiang , Liu Lunxu 
Published: August 2019

Background.
Lung transplantations (LTx) have become an effective lifesaving treatment for patients with end-stage lung diseases. While the shortage of lung donor pool and severe posttransplantation complications exaggerate the obstacle of LTx. This meta-analysis aimed to evaluate the efficacy of donation after circulatory death (DCD) in LTx for patients with end-stage lung diseases.

Methods.
PubMed, EmBase, and Web of Science were systematically searched for all relevant studies comparing the efficacy of DCD and conventional donation after brain death (DBD). The relative risk (RR) value as well as the weighted mean difference with a 95% confidence interval (CI) were pooled for dichotomous and continuous outcomes, respectively. The heterogeneity across the included studies was also assessed carefully.

Results.
Overall, 17 studies with 995 DCD recipients and 38 579 DBD recipients were included. The pooled analysis showed comparable 1-year overall survival between the 2 cohorts (RR 0.89, 95% CI, 0.74-1.07, P = 0.536, I
2 = 0%). The airway anastomotic complications rate in DCD cohort was higher than that in DBD cohorts (RR 2.00; 95% CI, 1.29-3.11, P = 0.002, I

2
= 0%). There was no significant difference between DCD and DBD regarding the occurrence of primary graft dysfunction grade 2/3, bronchiolitis obliterans syndrome, acute transplantation rejection, and length of stay. The stability of the included studies was strong.

Conclusions.
Evidence of this meta-analysis indicated that the use of lungs from DCD donors could effectively and safely expand the donor pool and therefore alleviate the crisis of organ shortage.
Patient Benefit and Risk in Anticancer Drug Development: A Systematic Review of the Ixabepilone Trial Portfolio
Authors: Carlisle Benjamin , Mattina James , Zheng Tiger , Kimmelman Jonathan 
Published: August 2019

AbstractOBJECTIVETo describe the patient burden and benefit, and the dynamics of trial success in the development of ixabepilone—a drug that was approved in the US but not in Europe.DATA SOURCESTrials were captured by searching Embase and MEDLINE on July 27, 2015.STUDY SELECTIONInclusion: 1) primary trial reports, 2) interventional trials, 3) human subjects, 4) phase 1 to phase 3, 5) trials of ixabepilone in monotherapy or combination therapy of 6) pre-licensure cancer indications. Exclusion: 1) secondary reports, 2) interim results, 3) meta-analyses, 4) retrospective/observational studies, 5) laboratory analyses (ex vivo tissues), 6) reviews, 7) letters, editorials, guidelines, interviews, abstract-only and poster presentations.DATA EXTRACTION AND SYNTHESISData were independently double-extracted and differences between coders were reconciled by discussion.MAIN OUTCOMES AND MEASURESWe measured risk using the number of drug-related adverse events that were grade 3 or higher, benefit by objective response rate and trial outcomes by whether studies met their primary endpoint with acceptable safety.RESULTSWe identified 39 publications of ixabepilone monotherapy and 23 primary publications of combination therapy, representing 5615 patients and 1598 patient-years of involvement over 11 years and involving 17 different malignancies. In total, 830 patients receiving ixabepilone experienced objective tumour response (16%, 95% CI 12.5%–20.1%), and 74 died from drug-related toxicites (2.2%, 95% CI 1.6%–2.9%). Responding indications and combinations were identified very quickly; thereafter, the search for additional responding indications or combinations did not lead to labelling additions. A total of 11 “uninformative” trials were found, representing 27% of studies testing efficacy, 208 grade 3–4 events and 226 patient-years of involvement (21% and 26% of the portfolio total, respectively). After the European Medicines Agency rejected ixabepilone for licensing, all further trial activity involving ixabepilone was pursued outside of Europe.DISCUSSIONRisk/benefit for patients who enrolled in trials of non-approved indications of ixabepilone did not improve over the course of the drug’s development. Clinical value was discovered very quickly; however, a large fraction of trials were uninformative.
A metabolic reconstruction ofLactobacillus reuteriJCM 1112 and analysis of its potential as a cell factory
Authors: Kristjansdottir Thordis , Bosma Elleke F. , Santos Filipe Branco dos , Özdemir Emre , Herrgård Markus J. , França Lucas , Ferreira Bruno Sommer , Nielsen Alex T. , Gudmundsson Steinn 
Published: August 2019

AbstractBackgroundLactobacillus reuteriis a heterofermentative Lactic Acid Bacterium (LAB) that is commonly used for food fermentations and probiotic purposes. Due to its robust properties, it is also increasingly considered for use as a cell factory. It produces several industrially important compounds such as 1,3-propanediol and reuterin natively, but for cell factory purposes, developing improved strategies for engineering and fermentation optimization is crucial. Genome-scale metabolic models can be highly beneficial in guiding rational metabolic engineering. Reconstructing a reliable and a quantitatively accurate metabolic model requires extensive manual curation and incorporation of experimental data.ResultsA genome-scale metabolic model ofL. reuteriJCM 1112Twas reconstructed and the resulting model, Lreuteri_530, was validated and tested with experimental data. Several knowledge gaps in the metabolism were identified and resolved during this process, including presence/absence of glycolytic genes. Flux distribution between the two glycolytic pathways, the phosphoketolase and Embden-Meyerhof-Parnas pathways, varies considerably between LAB species and strains. As these pathways result in different energy yields, it is important to include strain-specific utilization of these pathways in the model. We determined experimentally that the Embden-Meyerhof-Parnas pathway carried at most 7% of the total glycolytic flux. Predicted growth rates from Lreuteri_530 were in good agreement with experimentally determined values. To further validate the prediction accuracy of Lreuteri_530, the predicted effects of glycerol addition andadhEgene knock-out, which results in impaired ethanol production, were compared toin vivodata. Examination of both growth rates and uptake- and secretion rates of the main metabolites in central metabolism demonstrated that the model was able to accurately predict the experimentally observed effects. Lastly, the potential ofL. reuterias a cell factory was investigated, resulting in a number of general metabolic engineering strategies.ConclusionWe have constructed a manually curated genome-scale metabolic model ofL. reuteriJCM 1112Tthat has been experimentally parameterized and validated and can accurately predict metabolic behavior of this important platform cell factory.
Modulating the unfolded protein response: Impacts of radiation on the response of prostate cancer cells to ONC201
Authors: Amoroso Francesca , Glass Kimberley , Liberal Francisco , Steele Rebecca E. , Maguire Sarah , Tarapore Rohinton , Allen Joshua E. , Van Schaeybroeck Sandra , Butterworth Karl T. , Prise Kevin , O’Sullivan Joe M. , Jain Suneil , Waugh David J. , Mills Ian G. 
Published: August 2019

AbstractProstate cancer (PCa) is the most common non-cutaneous cancer in men and a notable cause of cancer mortality when it metastasises. Localised disease is mostly treated with surgery or radiotherapy. As PCa develops and treatment resistance emerges, the unfolded protein response (UPR) arises as an important adaptive biology co-amplifying with key cancer drivers [1]. The UPR can be cytoprotective but when acutely activated can lead to cell death. In this study we sought to enhance the acute activation of the UPR using radiation and ONC201, previously reported to be an UPR activator [2]. We found that treating PCa cells with ONC201 quickly increases the expression of components in all arms of the UPR – ATF4, ATF6 and IRE1-XBP1 – culminating in the subsequent cell death. During this time window between UPR activation and cell death we tested the priming effect of short-term administration of ONC201 on radiation responses. Pre-treatment with ONC201 for 24 hours prior to irradiation led to enhanced cytotoxicity compared to radiation alone assessed by cell viability and clonogenic assays. With priming, RNA-Seq analysis showed a sustained suppression of transcripts encoding cell cycle regulators as well as components of the DNA damage response pathways. Phenotypically this was reflected in enhanced cell cycle arrest and induction of necrosis and apoptosis. Furthermore, we demonstrated that short-term administration of inhibitors of cell cycle regulators (Dinaciclib and BI2536), could replicate this priming effect. Thus, we propose future studies to assess the impact of the short-term administration of drugs targeting the UPR and cell cycle regulation to enhance radiotherapy response.
Deep microbial community profiling along the fermentation process of pulque, a major biocultural resource of Mexico
Authors: Rocha-Arriaga Carolina , Espinal-Centeno Annie , Martinez-Sanchez Shamayim , Caballero-Pérez Juan , Alcaraz Luis D. , Cruz-Ramirez Alfredo 
Published: August 2019

AbstractSome of the biggest non-three plants endemic to Mexico were called metl in the Nahua culture. During colonial times they were renamed with the antillan word maguey. This was changed again by Carl von Linné who called them Agave (a greco-latin voice for admirable). For several Mexican prehispanic cultures, Agave species were not only considered as crops, but also part of their biocultural resources and cosmovision. Among the major products obtained from some Agave spp since pre-hispanic times is the alcoholic beverage called pulque or octli. This beverage represents a precolumbian biotechnological development obtained by the natural fermentation of the mead (aguamiel) from such plants. The pulque played a central role in mexican prehispanic cultures, mainly the Mexica and the Tolteca, where it was considered as sacred. For modern Mexicans, pulque is still part of their heritage and, in recent times, there has been a renewed interest in this ancient beverage, due to its high content in nutrients such as essential amino acids. We focus this study in the microbial diversity involved in pulque fermentation process, specially because it is still produced using classic antique technologies,. In this work, we report the microbiome of pulque fermentation stages, using massive sequencing of the 16S rRNA gene and the internal transcribed spacer (ITS) for describing bacterial and fungal diversity and dynamics along pulque production. In this study, we are providing the most diverse catalogue of microbes during pulque production with 57 identified bacterial genus and 94 fungal species, these findings allowed us to identify core microbes resilient during pulque production which point to be potential biomarkers exclusive to each fermentation stage.Our approach allowed the identification of a broader microbial diversity in PulqueWe increased 4.4 times bacteria genera and 40 times fungal species detected in mead.Newly reported bacteria genera and fungal species associated to Pulque fermentation
The two-step chemosensory system underlying the oligophagy of silkworm larvae
Authors: Tsuneto Kana , Endo Haruka , Shii Fumika , Sasaki Ken , Nagata Shinji , Sato Ryoichi 
Published: August 2019

AbstractOligophagous insect herbivores specifically identify host-plant leaves using their keen sense of taste1. Plant secondary metabolites and sugars are key chemical cues for insects to identify host plants and evaluate their nutritional value, respectively2. However, it is poorly understood how the insect chemosensory system integrates the information from various gustatory inputs. Here we report that a two-step chemosensory system is responsible for host acceptance by larvae of the silkworm Bombyx mori, a specialist for several mulberry species. The first step controlled by a gustatory organ, the maxillary palp (MP), is host-plant recognition during palpation at the leaf edge. Surprisingly, MP detects chlorogenic acid, quercetin glycosides, and β-sitosterol, which stimulate feeding by the silkworm3–6, with ultra-sensitivity (thresholds of aM to fM). Detecting a mixture of these compounds triggers test biting. The second step is evaluation of the sugar content in the leaf sap exuded by test biting. Low-sensitivity chemosensory neurons in another gustatory organ, the maxillary galea (MG), mainly detect sucrose in the leaf sap exuded by test biting, allowing larvae to accept the leaf and proceed to persistent biting. Our present work shows the behavioral and neuronal basis of host acceptance in the silkworm, mainly driven by six phytochemicals. It also reveals that the ultra-sensitive gustation via MP strictly limits initiation of feeding in the silkworm unless it detects a certain combination of host compounds, suggesting an essential role of MP in host-plant selection. The two-step chemosensory system reported herein may commonly underlie stereotyped feeding behavior in phytophagous insects and determine their feeding habits.
Microbial degradation of plastic in aqueous solutions demonstrated by CO2 evolution and quantification
Authors: Rose Ruth-Sarah , Richardson Katherine H. , Latvanen Elmeri Johannes , Hanson China A. , Resmini Marina , Sanders Ian A. 
Published: August 2019

AbstractThe environmental accumulation of plastics worldwide is a consequence of the durability of the material. Alternative polymers, marketed as biodegradable, present a potential solution to mitigate their ecological damage. However, understanding of biodegradability has been hindered by a lack of reproducible testing methods. Here, we present a new approach to assess biodegradability by monitoring bacterial respiration, in an aqueous media supplemented with a polymer as a single carbon source. Rhodococcus rhodochrous and Alcanivorax borkumensis are good model organisms for soil and marine systems respectively, allowing simulations of plastic biodegradation in these key environments. We demonstrate that polymer molecular weight reduction is the critical factor in the biodegradability of low-density polyethylene. Additionally, we tested a wide variety of plastics, including environmentally weathered and laboratory aged samples, using the same method allowing direct comparisons of the relative biodegradability of various polymers.
Network-based functional prediction augments genetic association to predict candidate genes for histamine hypersensitivity in mice
Authors: Tyler Anna L. , Raza Abbas , Krementsov Dimitry N. , Case Laure K. , Huang Rui , Ma Runlin Z. , Blankenhorn Elizabeth P. , Teuscher Cory , Mahoney J. Matthew 
Published: August 2019

ABSTRACTGenetic mapping is a primary tool of genetics in model organisms; however, many quantitative trait loci (QTL) contain tens or hundreds of positional candidate genes. Prioritizing these genes for validation is oftenad hocand biased by previous findings. Here we present a technique for computationally prioritizing positional candidates based on computationally inferred gene function. Our method uses machine learning with functional genomic networks, whose links encode functional associations among genes, to identify network-based signatures of functional association to a trait of interest. We demonstrate the method by functionally ranking positional candidates in a large locus on mouse Chr 6 (45.9 Mb to 127.8 Mb) associated with histamine hypersensitivity (Hhs). Hhs is characterized by systemic vascular leakage and edema in response to histamine challenge, which can lead to multiple organ failure and death. Although Hhs risk is strongly influenced by genetics, little is known about its underlying molecular or genetic causes, due to genetic and physiological complexity of the trait. To dissect this complexity, we ranked genes in theHhslocus by predicting functional association with multiple Hhs-related processes. We integrated these predictions with new single nucleotide polymorphism (SNP) association data derived from a survey of 23 inbred mouse strains and congenic mapping data. The top-ranked genes includedCxcl12, Ret, Cacna1c, andCntn3, all of which had strong functional associations and were proximal to SNPs segregating with Hhs. These results demonstrate the power of network-based computational methods to nominate highly plausible quantitative trait genes even in highly challenging cases involving large QTLs and extreme trait complexity.
Vimentin provides the mechanical resilience required for amoeboid migration and protection of the nucleus
Authors: Stankevicins Luiza Da Cunha , Urbanska Marta , Flormann Daniel AD. , Terriac Emmanuel , Mostajeran Zahra , Gad Annica K.B. , Cheng Fang , Eriksson John E. , Lautenschläger Franziska 
Published: August 2019

AbstractDendritic cells use amoeboid migration through constricted passages to reach the lymph nodes, and this homing function is crucial for immune responses. Amoeboid migration requires mechanical resilience, however, the underlying molecular mechanisms for this type of migration remain unknown. Because vimentin intermediate filaments (IFs) and microfilaments regulate adhesion-dependent migration in a bidirectional manner, we analyzed if they exert a similar control on amoeboid migration. Vimentin was required for cellular resilience, via a joint interaction between vimentin IFs and F-actin. Reduced actin mobility in the cell cortex of vimentin-reduced cells indicated that vimentin promotes Factin subunit exchange and dynamics. These mechano-dynamic alterations in vimentin-deficient dendritic cells impaired amoeboid migration in confined environments in vitro and blocked lymph node homing in mouse experiments in vivo. Correct nuclear positioning is important in confined amoeboid migration both to minimize resistance and to avoid DNA damage. Vimentin-deficiency also led to DNA double strand breaks in the compressed dendritic cells, pointing to a role of vimentin in nuclear positioning. Together, these observations show that vimentin IF-microfilament interactions provide both the specific mechano-dynamics required for dendritic cell migration and the protection the genome needs in compressed spaces.Summary statementVimentin — in joint action with actin — mediates the mechanical stiffness of cells required for amoeboid cell migration through confined spaces and protects the nucleus from DNA damage.
Noninvasive Prenatal Diagnosis for Duchenne Muscular Dystrophy Based on the Direct Haplotype Phasing
Authors: Chen Min , Chen Chao , Huang Xiaoyan , Sun Jun , Jiang Lu , Li Yingting , Zhu Yaping , Tian Changgeng , Li Yufan , Lu Zhe , Wang Yaoshen , Zeng Fanwei , Yang Yun , Peng Zhiyu , Yin Chenghong , Chen Dunjin 
Published: August 2019

AbstractObjectiveWe aimed to investigate the validity of noninvasive prenatal diagnosis (NIPD) based on direct haplotype phasing without the proband and its feasibility for clinical application in the case of Duchenne Muscular Dystrophy (DMD).MethodsThirteen singleton-pregnancy families affected by DMD were recruited. Firstly, we resolved maternal haplotypes for each family by performing targeted linked-read sequencing of their high molecular weight DNA, respectively. Then, we identified SNPs of the DMD gene in all carrier mothers and inferred the DMD gene mutation status of all fetuses. Finally, the fetal genotypes were further validated by using chorionic villus sampling.ResultsThe method of directly resolving maternal haplotype through targeted linked-read sequencing was smoothly performed in all participated families. The predicted mutational status of 13 fetuses was correct, which had been confirmed by invasive prenatal diagnosis.ConclusionDirect haplotyping of NIPD based on linked-read sequencing for DMD is accurate.
Ciliary phosphatidylinositol phosphatase Inpp5e plays positive and negative regulatory roles in Shh signaling
Authors: Constable Sandii , Long Alyssa B. , Floyd Katharine A. , Schurmans Stéphane , Caspary Tamara 
Published: August 2019

AbstractSonic hedgehog (Shh) signal transduction specifies ventral cell fates in the neural tube and is mediated by the Gli transcription factors that play both activator (GliA) and repressor (GliR) roles. Cilia are essential for Shh signal transduction and the ciliary phosphatidylinositol phosphatase, Inpp5e, is linked to Shh regulation. In the course of a forward genetic screen for recessive mouse mutants, we identified a functional null allele ofInpp5e,ridge top (rdg), with expanded ventral neural cell fates at E10.5. By E12.5,Inpp5erdg/rdgembryos displayed normal neural patterning and this correction over time required Gli3, the predominant repressor in neural patterning.Inpp5erdgfunction largely depended on the presence of cilia and on Smoothened, the obligate transducer of Shh signaling, indicating Inpp5e functions within the cilium to regulate the pathway. These data indicate that Inpp5e plays a more complicated role in Shh signaling than previously appreciated. We propose that Inpp5e attenuates Shh signaling in the neural tube through regulation of the relative timing of GliA and GliR production, which is important in understanding how duration of Shh signaling regulates neural tube patterning.Summary statementInpp5e attenuates Sonic hedgehog signal transduction through a combination of positive and negative regulatory roles that likely control the relative timing of Gli processing.