bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription Factor KLF2 in Dendritic Cells Downregulates Th2 Programming via the HIF-1α/Jagged2/Notch Axis
Authors: Xiong Ye , Lingrel Jerry B. , Wüthrich Marcel , Klein Bruce S. , Vasudevan Neelakantan T. , Jain Mukesh K. , George Mariam , Deepe George S. 
Published: June 2016

ABSTRACTThe adaptive immune response is tightly regulated by complex signals in dendritic cells (DCs). Although Th2 polarization is dictated by defined functional DC subsets, the molecular factors that govern the amplitude of these responses are not well understood. Krüppel-like factor 2 (KLF2) is a transcription factor that negatively regulates the activation of numerous immune cells in response to stimuli. Here, we demonstrate that suppression of KLF2 in conditioned DCs preferentially amplifies Th2 responses in two model systems, one of which is a prototypical intracellular pathogen and the other an allergen. This elevation in Th2 responses was dependent on contact-mediated Notch signalingin vitroandin vivo. A deficiency of KLF2 increased the expression of Notch ligand Jagged2 via hypoxia-inducible factor 1α (HIF-1α), which led to Th2 amplification. Our results revealed a novel circuit in DCs for Th2 polarization that is governed by KLF2.IMPORTANCEDendritic cells are the key element that bridges innate and adaptive immunity. A complex and not-well-understood area in dendritic cell biology is the regulatory network that predetermines or moderates their function to shape the adaptive immune response. Our study for the first time demonstrates that KLF2, a transcription factor, conditions dendritic cells to regulate Th2 responses via a Jagged2/Notch axis. Downregulation of KLF2 expression in dendritic cells may provide a beneficial effect for treatment of diseases such as obesity or parasitic infections but may be deleterious in the case of invasion by intracellular pathogens. Strategies to tune KLF2 may be useful for future therapeutic approaches to particular diseases of mankind.
Associations among Wine Grape Microbiome, Metabolome, and Fermentation Behavior Suggest Microbial Contribution to Regional Wine Characteristics
Authors: Bokulich Nicholas A. , Collins Thomas S. , Masarweh Chad , Allen Greg , Heymann Hildegarde , Ebeler Susan E. , Mills David A. 
Published: June 2016

ABSTRACTRegionally distinct wine characteristics (terroir) are an important aspect of wine production and consumer appreciation. Microbial activity is an integral part of wine production, and grape and wine microbiota present regionally defined patterns associated with vineyard and climatic conditions, but the degree to which these microbial patterns associate with the chemical composition of wine is unclear. Through a longitudinal survey of over 200 commercial wine fermentations, we demonstrate that both grape microbiota and wine metabolite profiles distinguish viticultural area designations and individual vineyards within Napa and Sonoma Counties, California. Associations among wine microbiota and fermentation characteristics suggest new links between microbiota, fermentation performance, and wine properties. The bacterial and fungal consortia of wine fermentations, composed from vineyard and winery sources, correlate with the chemical composition of the finished wines and predict metabolite abundances in finished wines using machine learning models. The use of postharvest microbiota as an early predictor of wine chemical composition is unprecedented and potentially poses a new paradigm for quality control of agricultural products. These findings add further evidence that microbial activity is associated with wineterroir.IMPORTANCEWine production is a multi-billion-dollar global industry for which microbial control and wine chemical composition are crucial aspects of quality.Terroiris an important feature of consumer appreciation and wine culture, but the many factors that contribute toterroirare nebulous. We show that grape and wine microbiota exhibit regional patterns that correlate with wine chemical composition, suggesting that the grape microbiome may influenceterroir. In addition to enriching our understanding of how growing region and wine properties interact, this may provide further economic incentive for agricultural and enological practices that maintain regional microbial biodiversity.
Deciphering Clostridium tyrobutyricum Metabolism Based on the Whole-Genome Sequence and Proteome Analyses
Authors: Lee Joungmin , Jang Yu-Sin , Han Mee-Jung , Kim Jin Young , Lee Sang Yup 
Published: June 2016

ABSTRACT

Clostridium tyrobutyricum
is a Gram-positive anaerobic bacterium that efficiently produces butyric acid and is considered a promising host for anaerobic production of bulk chemicals. Due to limited knowledge on the genetic and metabolic characteristics of this strain, however, little progress has been made in metabolic engineering of this strain. Here we report the complete genome sequence of
C. tyrobutyricum
KCTC 5387 (ATCC 25755), which consists of a 3.07-Mbp chromosome and a 63-kbp plasmid. The results of genomic analyses suggested that
C. tyrobutyricum
produces butyrate from butyryl-coenzyme A (butyryl-CoA) through acetate reassimilation by CoA transferase, differently from
Clostridium acetobutylicum
, which uses the phosphotransbutyrylase-butyrate kinase pathway; this was validated by reverse transcription-PCR (RT-PCR) of related genes, protein expression levels,
in vitro
CoA transferase assay, and fed-batch fermentation. In addition, the changes in protein expression levels during the course of batch fermentations on glucose were examined by shotgun proteomics. Unlike
C. acetobutylicum
, the expression levels of proteins involved in glycolytic and fermentative pathways in
C. tyrobutyricum
did not decrease even at the stationary phase. Proteins related to energy conservation mechanisms, including Rnf complex, NfnAB, and pyruvate-phosphate dikinase that are absent in
C. acetobutylicum
, were identified. Such features explain why this organism can produce butyric acid to a much higher titer and better tolerate toxic metabolites. This study presenting the complete genome sequence, global protein expression profiles, and genome-based metabolic characteristics during the batch fermentation of
C. tyrobutyricum
will be valuable in designing strategies for metabolic engineering of this strain
.

IMPORTANCE
Bio-based production of chemicals from renewable biomass has become increasingly important due to our concerns on climate change and other environmental problems.
C. tyrobutyricum
has been used for efficient butyric acid production. In order to further increase the performance and expand the capabilities of this strain toward production of other chemicals, metabolic engineering needs to be performed. For this, better understanding on the metabolic and physiological characteristics of this bacterium at the genome level is needed. This work reporting the results of complete genomic and proteomic analyses together with new insights on butyric acid biosynthetic pathway and energy conservation will allow development of strategies for metabolic engineering of
C. tyrobutyricum
for the bio-based production of various chemicals in addition to butyric acid.
Functional Analysis of the Rhoptry Kinome during Chronic Toxoplasma gondii Infection
Authors: Knoll Laura J. 
Published: June 2016

ABSTRACT

Toxoplasma gondii
is one of the most common parasitic infections of humans worldwide. Once exposed, humans remain infected with
T. gondii
for life, and there are no therapeutics capable of eliminating a chronic infection. In the search for novel drug targets,
T. gondii
is known to contain several unique secretory organelles, one of which is called the rhoptries. Rhoptry organelles contain and secrete numerous proteins with kinase domains, but the roles of most of these kinases during infection remain unknown. In a recent mBio article, B. A. Fox et al. [mBio 7(3):e00193-16, 2016,
http://dx.doi.org/10.1128/mBio.00193-16
] performed a tour de force deletion analysis of 31 rhoptry kinases and examined their roles in the development of chronic infection. While rhoptry kinase deletion strains that displayed an acute infection defect also showed a reduction in chronic infection cyst burden, two rhoptry kinase deletion strains had decreased cyst burden without any change in acute virulence. These results indicate the necessity of the rhoptry kinases for the establishment and perhaps maintenance of chronic infection. They also highlight the potential of these kinases as drug targets to clear chronic infection or as candidates to generate a nonpersisting vaccine.
Physical impairments in symptomatic femoroacetabular impingement: a systematic review of the evidence
Authors: Freke Matthew , Kemp Joanne L , Svege Ida , Risberg May Arna , Semciw Adam Ivan , Crossley Kay M 
Published: June 2016

BackgroundFemoroacetabular impingement (FAI) and associated pathologies are associated with pain and reduced quality of life. Physical impairments can be associated with worse symptoms and may be an important target of rehabilitation programmes in this patient group. Knowledge regarding physical impairments in people with symptomatic FAI is limited.HypothesisIn adults aged 18–50 years with symptomatic FAI: (1) to identify physical impairments in range of motion (ROM), hip muscle function and functional tasks; (2) to compare physical impairments with healthy controls; and (3) to evaluate the effects of interventions targeting physical impairments.Study designSystematic review.MethodsA systematic review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The modified Downs and Black checklist was used for quality appraisal. Studies of adults aged 18–50 years with symptomatic FAI that examined ROM, hip muscle function and functional tasks were included. Standardised mean differences were calculated where possible or best evidence synthesis and study conclusions were presented.ResultsTwenty-two studies fulfilled all inclusion criteria. Methodological quality was varied. Results for hip joint ROM differences between people with symptomatic FAI compared and control subjects were varied. People with symptomatic FAI demonstrated some deficits in hip muscle strength and reduced balance on one leg when compared with control subjects. For hip joint ROM and hip muscle strength results for within-group differences between preintervention and postintervention time points were limited and inconclusive. No randomised controlled trials evaluated the effect of different types of interventions for symptomatic patients with symptomatic FAI.ConclusionsPeople with symptomatic FAI demonstrate impairments in some hip muscle strength and single leg balance. This information may assist therapists in providing targeted rehabilitation programmes for people with FAI and associated pathology. Further research is needed to determine whether symptomatic FAI affects other aspects of functional performance; and to evaluate whether targeted interventions are effective in symptomatic FAI.Clinical relevanceThis information may assist therapists in providing targeted rehabilitation programmes for people with symptomatic FAI.
Multistrategy childcare-based intervention to improve compliance with nutrition guidelines versus usual care in long day care services: a study protocol for a randomised controlled trial
Authors: Seward Kirsty , Wolfenden Luke , Finch Meghan , Wiggers John , Wyse Rebecca , Jones Jannah , Gillham Karen , Yoong Sze Lin 
Published: June 2016

IntroductionInterventions to improve child diet are recommended as dietary patterns developed in childhood track into adulthood and influence the risk of chronic disease. For child health, childcare services are required to provide foods to children consistent with nutrition guidelines. Research suggests that foods and beverages provided by services to children are often inconsistent with nutrition guidelines. The primary aim of this study is to assess, relative to a usual care control group, the effectiveness of a multistrategy childcare-based intervention in improving compliance with nutrition guidelines in long day care services.Methods and analysisThe study will employ a parallel group randomised controlled trial design. A sample of 58 long day care services that provide all meals (typically includes 1 main and 2 mid-meals) to children while they are in care, in the Hunter New England region of New South Wales, Australia, will be randomly allocated to a 6-month intervention to support implementation of nutrition guidelines or a usual care control group in a 1:1 ratio. The intervention was designed to overcome barriers to the implementation of nutrition guidelines assessed using the theoretical domains framework. Intervention strategies will include the provision of staff training and resources, audit and feedback, ongoing support and securing executive support. The primary outcome of the trial will be the change in the proportion of long day care services that have a 2-week menu compliant with childcare nutrition guidelines, measured by comprehensive menu assessments. As a secondary outcome, child dietary intake while in care will also be assessed. To assess the effectiveness of the intervention, the measures will be undertaken at baseline and ∼6 months postbaseline.Ethics and disseminationThe study was approved by the Hunter New England Human Research Ethics Committee. Study findings will be disseminated widely through peer-reviewed publications.
Effects of pork differentiation strategies in Canada on pig performance and carcass characteristics
Authors: Zhang H. , Aalhus J.L. , Gariépy C. , Uttaro B. , López-Campos O. , Prieto N. , Dugan M.E.R. , Jin Y. , Juárez M. 
Published: June 2016

Performance and quality traits were measured in carcasses from combinations of genotype, diet supplement, slaughter weight, and carcass chilling regime. Iberian-crossed pigs had lower live animal performance than Duroc and Lacombe. From 70 to 115 kg, Lacombe pigs grew slightly faster than Duroc. Duroc carcasses had a higher lean percentage, heavier ham and picnic primals, and lighter loins and bellies, compared with Lacombe and Iberian. Heavier carcasses had lower lean yield, except those from Iberian-crossed pigs, and bigger bellies. Meat from Duroc-crossed pigs was lighter in colour and higher in marbling, with intermediate values for fat hardness. Iberian carcasses displayed dark meat with intermediate marbling and the hardest fat. Meat from Lacombe pigs was the leanest although, like in all three breeds, marbling scores were higher in heavier carcasses. Generally, supplementing with canola and flax decreased and blast chilling increased fat hardness values. Dietary canola also seemed to affect meat colour traits, but these effects were not consistent among breeds and slaughter weights. The commercial combination of Duroc breed, control diet, and 115-kg slaughter weight showed a balance in terms of performance, carcass, and quality traits. Other combinations evaluated in this study showed potential to efficiently produce differentiated pork.
Effects of extracted rice bran supplementation on growth performance, nutrient digestibility, diarrhea score, blood profiles, and fecal microbial shedding in comparison with apramycin (antibiotic growth promoter) in weanling pigs
Authors: Hossain M.M. , Park J.W. , Nyachoti C.M. , Kim I.H. 
Published: June 2016

This study evaluated the efficacy of extracted rice bran (ERB) in weanling piglets. One hundred forty weanling pigs [(Yorkshire × Landrace) × Duroc] with an average BW of 5.70 ± 1.41 kg (21 d of age) were fed in two phases in a 6-wk experiment. Weanling pigs were allotted to diets containing 0 or 0.1 g kg−1 of ERB, and 0 or 165 mg kg−1 of apramycin according to a 2 × 2 factorial arrangement of treatments. Both apramycin and ERB supplementation increased growth efficiency (G:F) during phase 1 and overall, respectively (P < 0.05). The apparent total tract digestibility (ATTD) of dry matter (DM) was increased in response to either ERB or apramycin at wk 2 and 6 (P < 0.05). Supplementation of ERB decreased total cholesterol (TC) and increased high-density lipoprotein cholesterol (HDL-C) in diets lacking ERB at wk 6 (P < 0.05). Pigs receiving diets supplemented with apramycin reduced Escherichia coli at wk 2 and 6, and Salmonella counts at wk 6 (P < 0.05). Supplementation of ERB increased fecal Lactobacillus and reduced Salmonella counts at wk 6 (P < 0.05). In conclusion, results indicated that dietary supplementation of ERB improved performance in weanling pigs.
China’s Embrace of the UN Post-2015 Development Agenda
Authors: Zhu Dandan , Xu Qiyuan 
Published: June 2016

Since the 1990s, the United Nations has issued three agendas for global development cooperation. China’s attitude toward these agendas has also undergone three phases: from cautious passivity at first, to active yet restrained involvement, and to fully embracing them. On January 1, 2016, the Sustainable Development Goals (SDGs) replaced the Millennium Development Goals (MDGs) as the primary goals for global development cooperation in the next 15 years. But there are substantial differences between the SDGs and MDGs, which will inevitably exert significant impacts on China’s domestic development and its involvement in international cooperation. In its response, China should carefully examine its strengths and constraints before making a comprehensive national strategy for sustainable development, so as to advance domestic structural reforms and facilitate its commitment to the implementation of the SDGs. Meanwhile, China should actively push forward international collaboration in line with its opening-up policy, including South-South and South-North cooperation, as well as new mechanisms for trilateral cooperation. All these efforts will contribute to the establishment of new global partnerships for common development and the fulfillment of the SDGs.
Inhibiting DX2-p14/ARF Interaction Exerts Antitumor Effects in Lung Cancer and Delays Tumor Progression
Authors: Oh Ah-Young , Jung Youn Sang , Kim Jiseon , Lee Jee-Hyun , Cho Jung-Hyun , Chun Ho-Young , Park Soyoung , Park Hyunchul , Lim Sikeun , Ha Nam-Chul , Park Jong Sook , Park Choon-Sik , Song Gyu-Yong , Park Bum-Joon 
Published: June 2016

Abstract
The aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) splice variant designated DX2 is induced by cigarette smoke carcinogens and is often detected in human lung cancer specimens. However, the function of DX2 in lung carcinogenesis is obscure. In this study, we found that DX2 expression was induced by oncogenes in human lung cancer tissues and cells. DX2 prevented oncogene-induced apoptosis and senescence and promoted drug resistance by directly binding to and inhibiting p14/ARF. Through chemical screening, we identified SLCB050, a novel compound that blocks the interaction between DX2 and p14/ARF in vitro and in vivo. SLCB050 reduced the viability of human lung cancer cells, especially small cell lung cancer cells, in a p14/ARF-dependent manner. Moreover, in a mouse model of K-Ras–driven lung tumorigenesis, ectopic expression of DX2 induced small cell and non–small cell lung cancers, both of which could be suppressed by SLCB050 treatment. Taken together, our findings show how DX2 promotes lung cancer progression and how its activity may be thwarted as a strategy to treat patients with lung cancers exhibiting elevated DX2 levels. Cancer Res; 76(16); 4791–804. ©2016 AACR.
Mathematical Modeling of Cancer Immunotherapy and Its Synergy with Radiotherapy
Authors: Serre Raphael , Benzekry Sebastien , Padovani Laetitia , Meille Christophe , André Nicolas , Ciccolini Joseph , Barlesi Fabrice , Muracciole Xavier , Barbolosi Dominique 
Published: June 2016

Abstract
Combining radiotherapy with immune checkpoint blockade may offer considerable therapeutic impact if the immunosuppressive nature of the tumor microenvironment (TME) can be relieved. In this study, we used mathematical models, which can illustrate the potential synergism between immune checkpoint inhibitors and radiotherapy. A discrete-time pharmacodynamic model of the combination of radiotherapy with inhibitors of the PD1–PDL1 axis and/or the CTLA4 pathway is described. This mathematical framework describes how a growing tumor first elicits and then inhibits an antitumor immune response. This antitumor immune response is described by a primary and a secondary (or memory) response. The primary immune response appears first and is inhibited by the PD1–PDL1 axis, whereas the secondary immune response happens next and is inhibited by the CTLA4 pathway. The effects of irradiation are described by a modified version of the linear-quadratic model. This modeling offers an explanation for the reported biphasic relationship between the size of a tumor and its immunogenicity, as measured by the abscopal effect (an off-target immune response). Furthermore, it explains why discontinuing immunotherapy may result in either tumor recurrence or a durably sustained response. Finally, it describes how synchronizing immunotherapy and radiotherapy can produce synergies. The ability of the model to forecast pharmacodynamic endpoints was validated retrospectively by checking that it could describe data from experimental studies, which investigated the combination of radiotherapy with immune checkpoint inhibitors. In summary, a model such as this could be further used as a simulation tool to facilitate decision making about optimal scheduling of immunotherapy with radiotherapy and perhaps other types of anticancer therapies. Cancer Res; 76(17); 4931–40. ©2016 AACR.
Remodeling of the Epithelial–Connective Tissue Interface in Oral Epithelial Dysplasia as Visualized by Noninvasive 3D Imaging
Authors: Pal Rahul , Shilagard Tuya , Yang Jinping , Villarreal Paula , Brown Tyra , Qiu Suimin , McCammon Susan , Resto Vicente , Vargas Gracie 
Published: June 2016

Abstract
Early neoplastic features in oral epithelial dysplasia are first evident at the basal epithelium positioned at the epithelial–connective tissue interface (ECTI), separating the basal epithelium from the underlying lamina propria. The ECTI undergoes significant deformation in early neoplasia due to focal epithelial expansion and proteolytic remodeling of the lamina propria, but few studies have examined these changes. In the present study, we quantitated alterations in ECTI topography in dysplasia using in vivo volumetric multiphoton autofluorescence microscopy and second harmonic generation microscopy. The label-free method allows direct noninvasive visualization of the ECTI surface without perturbing the epithelium. An image-based parameter, “ECTI contour,” is described that indicates deformation of the ECTI surface. ECTI contour was higher in dysplasia than control or inflamed specimens, indicating transition from flat to a deformed surface. Cellular parameters of nuclear area, nuclear density, coefficient of variation in nuclear area in the basal epithelium and collagen density in areas adjacent to ECTI were measured. ECTI contour differentiated dysplasia from control/benign mucosa with higher sensitivity and specificity than basal nuclear density or basal nuclear area, comparable with coefficient of variation in nuclear area and collagen density. The presented method offers a unique opportunity to study ECTI in intact mucosa with simultaneous assessment of cellular and extracellular matrix features, expanding opportunities for studies of early neoplastic events near this critical interface and potentially leading to development of new approaches for detecting neoplasia in vivo. Cancer Res; 76(16); 4637–47. ©2016 AACR.