bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complementary endozoochorous seed dispersal by large mammals in the Golestan National Park, Iran
Authors: Karimi Sorour , Hemami Mahmoud-Reza , Tarkesh Esfahani Mostafa , Akhani Hossein , Baltzinger Christophe 
Published: October 2018

AbstractLarge animals tend to disperse seeds over long distances via ingestion and defecation due to their large home range and capacity to move among different habitats for feeding. The aim of this study was to investigate the potential of endozoochorous seed dispersal by five herbivores: Ovis vignei, Capra aegagrus, Gazella subgutturosa, Cervus elaphus, Capreolus capreolus and two omnivores: Sus Scrofa and Ursus arctos in the Golestan National Park, northeast of Iran, by a greenhouse germination experiment. A total of 3107 seedlings belonging to 154 different plant taxa were germinated from 655 dung samples collected in three different habitats. Plant families that most frequently germinated were Poaceae and Brassicaceae. Urtica dioica was the most abundant germinating seed, accounting for 20% of all the seedlings recorded in our dung samples, whereas the most frequently observed species was Portulaca oleracea, which occurred in 24% of our samples. We showed that 54% of the seeds germinating were dispersed by only one of the mammals studied. Herbs and graminoids were the most frequently dispersed growth forms by the herbivores and the wild boar, whereas brown bears mostly dispersed shrubs. The seedling composition in the dung samples was strongly correlated with the local flora especially for non-selective feeders, like red deer. The differences observed in the number of plants and frequency of different growth forms dispersed among the studied mammals reflect their body size, digestive physiology, and dietary and habitat preferences. Our findings highlight the different and complementary roles of large herbivores and omnivores as long-distance seed dispersal vectors.
Online grocery shopping: promise and pitfalls for healthier food and beverage purchases
Authors: Jilcott Pitts Stephanie B , Ng Shu Wen , Blitstein Jonathan L , Gustafson Alison , Niculescu Mihai 
Published: October 2018

AbstractObjectives(i) To determine the current state of online grocery shopping, including individuals’ motivations for shopping for groceries online and types of foods purchased; and (ii) to identify the potential promise and pitfalls that online grocery shopping may offer in relation to food and beverage purchases.DesignPubMed, ABI/INFORM and Google Scholar were searched to identify published research.SettingTo be included, studies must have been published between 2007 and 2017 in English, based in the USA or Europe (including the UK), and focused on: (i) motivations for online grocery shopping; (ii) the cognitive/psychosocial domain; and (iii) the community or neighbourhood food environment domain.SubjectsOur search yielded twenty-four relevant papers.ResultsFindings indicate that online grocery shopping can be a double-edged sword. While it has the potential to increase healthy choices via reduced unhealthy impulse purchases, nutrition labelling strategies, and as a method to overcome food access limitations among individuals with limited access to a brick-and-mortar store, it also has the potential to increase unhealthy choices due to reasons such as consumers’ hesitance to purchase fresh produce online.ConclusionsAdditional research is needed to determine the most effective ways to positively engage customers to use online grocery shopping to make healthier choices.
Estimating the Economic Value of Interannual Reservoir Storage in Water Resource Systems
Authors: Khadem M. , Rougé C. , Harou J. J. , Hansen K. M. , Medellin‐Azuara J. , Lund J. R. 
Published: October 2018

AbstractReservoir operators face pressures on timing releases of water. Releasing too much water immediately can threaten future supplies and costs, but not releasing enough creates immediate economic hardship downstream. This paper examines how the economic valuation of end‐of‐year carryover storage can lead to optimal amounts of carryover storage in complex large water resource systems. Economic carryover storage value functions (COSVFs) are developed to represent the value of storage in the face of interannual inflow uncertainty and variability within water resource optimization models. The approach divides a perfect foresight optimization problem into year‐long (limited foresight) subproblems solved sequentially by a within‐year optimization engine to find optimal short‐term operations. The final storage state from the previous year provides the initial condition to each annual problem, and end‐of‐year COSVFs are the final condition. Here the COSVF parameters that maximize the interannual benefits from river basin operations are found by evolutionary search. This generalized approach can handle nonconvexity in large‐scale water resources systems. The approach is illustrated with a regional model of the California Central Valley water system including 30 reservoirs, 22 aquifers, and 51 urban and agricultural demand sites. Head‐dependent pumping costs make the optimization problem nonconvex. Optimized interannual reservoir operation improves over more cautious operation in the historical approximation, reducing the average annual scarcity volume and costs by 80% and 98%, respectively, with more realistic representation of hydrologic foresight for California's Mediterranean climate. The economic valuation of storage helps inform water storage decisions.
Isotopic Constraints on Nitrogen Transformation Rates in the Deep Sedimentary Marine Biosphere
Authors: Buchwald C. , Homola K. , Spivack A. J. , Estes E. R. , Murray R. W. , Wankel S. D. 
Published: October 2018

AbstractLittle is known about the nature of microbial community activity contributing to the cycling of nitrogen in organic‐poor sediments underlying the expansive oligotrophic ocean gyres. Here we use pore water concentrations and stable N and O isotope measurements of nitrate and nitrite to constrain rates of nitrogen cycling processes over a 34‐m profile from the deep North Atlantic spanning fully oxic to anoxic conditions. Using a 1‐D reaction‐diffusion model to predict the distribution of nitrogen cycling rates, results converge on two distinct scenarios: (1) an exceptionally high degree of coupling between nitrite oxidation and nitrate reduction near the top of the anoxic zone or (2) an unusually large N isotope effect (~60‰) for nitrate reduction that is decoupled from the corresponding O isotope effect, which is possibly explained by enzyme‐level interconversion between nitrite and nitrate.
Early effects of exposure-based cognitive behaviour therapy on the neural correlates of anxiety
Authors: Reinecke Andrea , Thilo Kai V. , Croft Alison , Harmer Catherine J. 
Published: October 2018

AbstractExposure-based cognitive-behaviour therapy (CBT) for anxiety disorders is an effective intervention, but the brain mechanisms driving recovery are largely unknown. In this experimental medicine study, we investigated to what degree CBT affects neural markers of anxiety at an early stage of treatment, to identify dynamic mechanistic changes which might be crucial in the process of recovery as opposed to those seen following full treatment completion. In a randomised controlled trial, unmedicated patients with panic disorder either received four weekly sessions of exposure-based CBT (N = 14) or were allocated to a waiting group (N = 14). Symptom severity was measured before and after the intervention. During functional magnetic resonance imaging (fMRI), patients performed an emotion regulation task, either viewing negative images naturally, or intentionally down-regulating negative affect using previously taught strategies. Four-session CBT led to marked reductions in symptoms and 71% of patients reached recovery status (versus 7% in the control group). This intervention normalised brain hyperactivation previously seen in panic disorder, particularly in areas linked to threat monitoring, fear memory, and maladaptive emotion regulation, such as amygdala, dorsomedial and dorsolateral prefrontal cortex, and temporal gyrus. Our findings suggest that optimal treatment doses for panic disorder might be much lower than previously thought. Furthermore, this is the first study to show that neural markers of anxiety change very early during CBT, highlighting potential neural mechanisms that might drive clinical recovery. Such knowledge is important for the development of more compact combination treatments targeting these mechanisms more effectively. (Neural Effects of Cognitive-behaviour Therapy in Panic Disorder; clinicaltrials.gov; NCT03251235)
MicroRNA-495-3p inhibits multidrug resistance by modulating autophagy through GRP78/mTOR axis in gastric cancer
Authors: Chen Sheng , Wu Jian , Jiao Kai , Wu Qiong , Ma Jiaojiao , Chen Di , Kang Jianqin , Zhao Guodong , Shi Yongquan , Fan Daiming , Zhao Guohong 
Published: October 2018

AbstractMultidrug resistance (MDR) accounts for poor prognosis in gastric cancer (GC). MicroRNAs (miRNAs) are critical regulators of MDR via modulation of the target genes. The present study revealed that miR-495-3p could act via a target gene, GRP78, to regulate the process of autophagy and inhibit MDR. Based on the in vitro and in vivo gain-of-function or loss-of-function experiments, overexpression of miR-495-3p was sufficient to reverse the MDR to four chemotherapeutics in vitro and inhibit the tumor growth in vivo. Moreover, GRP78 was positively associated with the occurrence of autophagy. Thus, reducing the expression of GRP78 by siRNA resulted in autophagy-suppressive activity similar to that of miR-495-3p on mammalian target of rapamycin (mTOR) and its substrates activation and autophagy inhibition, while restoring GRP78 attenuated the anti-autophagy effects caused by miR-495-3p. Clinically, either miR-495-3p downregulation or GRP78 upregulation was associated with malignant phenotypes in patients with GC. In conclusion, these findings demonstrate that miR-495-3p is an important regulator of autophagy balance and MDR by modulating the GRP78/mTOR axis. In addition, miR-495-3p and GRP78 could be used as prognostic factors for overall survival in GC, which implicates miR-495-3p as a therapeutic target in cancer.
Activation of the interferon type I response rather than autophagy contributes to myogenesis inhibition in congenital DM1 myoblasts
Authors: Rizzo Milena , Beffy Pascale , Del Carratore Renata , Falleni Alessandra , Pretini Virginia , D’Aurizio Romina , Botta Annalisa , Evangelista Monica , Stoccoro Andrea , Coppedè Fabio , Furling Denis , Simili Marcella 
Published: October 2018

AbstractCongenital myotonic dystrophy type 1 (CDM1) is characterized by severe symptoms that affect patients from birth, with 40% mortality in the neonatal period and impaired skeletal muscle development. In this paper, we examined the relationship between autophagy and abnormal myogenic differentiation of CDM1 myoblasts. We investigated these pathological features at both ultrastructural and molecular levels, utilizing two CDM1 foetal myoblasts, CDM13 and CDM15, with 1800 and 3200 repeats, respectively. The congenital nature of these CDM1 myoblasts was confirmed by the high methylation level at the DMPK locus. Our results indicated that abnormal autophagy was independent of myogenic differentiation, as CDM13 myoblasts differentiated as well as control myoblasts but underwent autophagy like CDM15, displaying impaired differentiation. miRNA expression profiles revealed that CDM15 myoblasts failed to upregulate the complex network of myo-miRNAs under MYOD and MEF2A control, while this network was upregulated in CDM13 myoblasts. Interestingly, the abnormal differentiation of CDM15 myoblasts was associated with cellular stress accompanied by the induction of the interferon type 1 pathway (innate immune response). Indeed, inhibition of the interferon (IFN) type I pathway restores myogenic differentiation of CDM15 myoblasts, suggesting that the inappropriate activation of the innate immune response might contribute to impaired myogenic differentiation and severe muscle symptoms observed in some CDM1 patients. These findings open up the possibility of new therapeutic approaches to treat CDM1.
AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields)
Authors: Shteingauz Anna , Porat Yaara , Voloshin Tali , Schneiderman Rosa S. , Munster Mijal , Zeevi Einav , Kaynan Noa , Gotlib Karnit , Giladi Moshe , Kirson Eilon D. , Weinberg Uri , Kinzel Adrian , Palti Yoram 
Published: October 2018

AbstractTumor Treating Fields (TTFields), an approved treatment modality for glioblastoma, are delivered via non-invasive application of low-intensity, intermediate-frequency, alternating electric fields. TTFields application leads to abnormal mitosis, aneuploidy, and increased cell granularity, which are often associated with enhancement of autophagy. In this work, we evaluated whether TTFields effected the regulation of autophagy in glioma cells. We found that autophagy is upregulated in glioma cells treated with TTFields as demonstrated by immunoblot analysis of the lipidated microtubule-associated protein light chain 3 (LC3-II). Fluorescence and transmission electron microscopy demonstrated the presence of LC3 puncta and typical autophagosome-like structures in TTFields-treated cells. Utilizing time-lapse microscopy, we found that the significant increase in the formation of LC3 puncta was specific to cells that divided during TTFields application. Evaluation of selected cell stress parameters revealed an increase in the expression of the endoplasmic reticulum (ER) stress marker GRP78 and decreased intracellular ATP levels, both of which are indicative of increased proteotoxic stress. Pathway analysis demonstrated that TTFields-induced upregulation of autophagy is dependent on AMP-activated protein kinase (AMPK) activation. Depletion of AMPK or autophagy-related protein 7 (ATG7) inhibited the upregulation of autophagy in response to TTFields, as well as sensitized cells to the treatment, suggesting that cancer cells utilize autophagy as a resistance mechanism to TTFields. Combining TTFields with the autophagy inhibitor chloroquine (CQ) resulted in a significant dose-dependent reduction in cell growth compared with either TTFields or CQ alone. These results suggest that dividing cells upregulate autophagy in response to aneuploidy and ER stress induced by TTFields, and that AMPK serves as a key regulator of this process.
Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation
Authors: Colonna Lucrezia , Peterson Christopher W. , Schell John B. , Carlson Judith M. , Tkachev Victor , Brown Melanie , Yu Alison , Reddy Sowmya , Obenza Willi M. , Nelson Veronica , Polacino Patricia S. , Mack Heather , Hu Shiu-Lok , Zeleski Katie , Hoffman Michelle , Olvera Joe , Furlan Scott N. , Zheng Hengqi , Taraseviciute Agne , Hunt Daniel J. , Betz Kayla , Lane Jennifer F. , Vogel Keith , Hotchkiss Charlotte E. , Moats Cassie , Baldessari Audrey , Murnane Robert D. , English Christopher , Astley Cliff A. , Wangari Solomon , Agricola Brian , Ahrens Joel , Iwayama Naoto , May Andrew , Stensland Laurence , Huang Meei-Li W. , Jerome Keith R. , Kiem Hans-Peter , Kean Leslie S. 
Published: October 2018

AbstractAllogeneic transplantation (allo-HCT) has led to the cure of HIV in one individual, raising the question of whether transplantation can eradicate the HIV reservoir. To test this, we here present a model of allo-HCT in SHIV-infected, cART-suppressed nonhuman primates. We infect rhesus macaques with SHIV-1157ipd3N4, suppress them with cART, then transplant them using MHC-haploidentical allogeneic donors during continuous cART. Transplant results in ~100% myeloid donor chimerism, and up to 100% T-cell chimerism. Between 9 and 47 days post-transplant, terminal analysis shows that while cell-associated SHIV DNA levels are reduced in the blood and in lymphoid organs post-transplant, the SHIV reservoir persists in multiple organs, including the brain. Sorting of donor-vs.-recipient cells reveals that this reservoir resides in recipient cells. Moreover, tetramer analysis indicates a lack of virus-specific donor immunity post-transplant during continuous cART. These results suggest that early post-transplant, allo-HCT is insufficient for recipient reservoir eradication despite high-level donor chimerism and GVHD.
RhoGAP domain-containing fusions and PPAPDC1A fusions are recurrent and prognostic in diffuse gastric cancer
Authors: Yang Hanna , Hong Dongwan , Cho Soo Young , Park Young Soo , Ko Woo Ri , Kim Ju Hee , Hur Hoon , Lee Jongkeun , Kim Su-Jin , Kwon Sun Young , Lee Jae-Hyuk , Park Do Youn , Song Kyu Sang , Chang Heekyung , Ryu Min-Hee , Cho Kye Soo , Kang Jeong Won , Kook Myeong-Cherl , Thiessen Nina , He An , Mungall Andy , Han Sang-Uk , Kim Hark Kyun 
Published: October 2018

AbstractWe conducted an RNA sequencing study to identify novel gene fusions in 80 discovery dataset tumors collected from young patients with diffuse gastric cancer (DGC). Twenty-five in-frame fusions are associated with DGC, three of which (CLDN18-ARHGAP26, CTNND1-ARHGAP26, and ANXA2-MYO9A) are recurrent in 384 DGCs based on RT-PCR. All three fusions contain a RhoGAP domain in their 3’ partner genes. Patients with one of these three fusions have a significantly worse prognosis than those without. Ectopic expression of CLDN18-ARHGAP26 promotes the migration and invasion capacities of DGC cells. Parallel targeted RNA sequencing analysis additionally identifies TACC2-PPAPDC1A as a recurrent and poor prognostic in-frame fusion. Overall, PPAPDC1A fusions and in-frame fusions containing a RhoGAP domain clearly define the aggressive subset (7.5%) of DGCs, and their prognostic impact is greater than, and independent of, chromosomal instability and CDH1 mutations. Our study may provide novel genomic insights guiding future strategies for managing DGCs.
Structural dynamics of the E6AP/UBE3A-E6-p53 enzyme-substrate complex
Authors: Sailer Carolin , Offensperger Fabian , Julier Alexandra , Kammer Kai-Michael , Walker-Gray Ryan , Gold Matthew G. , Scheffner Martin , Stengel Florian 
Published: October 2018

AbstractDeregulation of the ubiquitin ligase E6AP is causally linked to the development of human disease, including cervical cancer. In complex with the E6 oncoprotein of human papillomaviruses, E6AP targets the tumor suppressor p53 for degradation, thereby contributing to carcinogenesis. Moreover, E6 acts as a potent activator of E6AP by a yet unknown mechanism. However, structural information explaining how the E6AP-E6-p53 enzyme-substrate complex is assembled, and how E6 stimulates E6AP, is largely missing. Here, we develop and apply different crosslinking mass spectrometry-based approaches to study the E6AP-E6-p53 interplay. We show that binding of E6 induces conformational rearrangements in E6AP, thereby positioning E6 and p53 in the immediate vicinity of the catalytic center of E6AP. Our data provide structural and functional insights into the dynamics of the full-length E6AP-E6-p53 enzyme-substrate complex, demonstrating how E6 can stimulate the ubiquitin ligase activity of E6AP while facilitating ubiquitin transfer from E6AP onto p53.
A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease
Authors: Arnadottir Gudny A. , Norddahl Gudmundur L. , Gudmundsdottir Steinunn , Agustsdottir Arna B. , Sigurdsson Snaevar , Jensson Brynjar O. , Bjarnadottir Kristbjorg , Theodors Fannar , Benonisdottir Stefania , Ivarsdottir Erna V. , Oddsson Asmundur , Kristjansson Ragnar P. , Sulem Gerald , Alexandersson Kristjan F. , Juliusdottir Thorhildur , Gudmundsson Kjartan R. , Saemundsdottir Jona , Jonasdottir Adalbjorg , Jonasdottir Aslaug , Sigurdsson Asgeir , Manzanillo Paolo , Gudjonsson Sigurjon A. , Thorisson Gudmundur A. , Magnusson Olafur Th. , Masson Gisli , Orvar Kjartan B. , Holm Hilma , Bjornsson Sigurdur , Arngrimsson Reynir , Gudbjartsson Daniel F. , Thorsteinsdottir Unnur , Jonsdottir Ingileif , Haraldsson Asgeir , Sulem Patrick , Stefansson Kari 
Published: October 2018

AbstractMutations in genes encoding subunits of the phagocyte NADPH oxidase complex are recognized to cause chronic granulomatous disease (CGD), a severe primary immunodeficiency. Here we describe how deficiency of CYBC1, a previously uncharacterized protein in humans (C17orf62), leads to reduced expression of NADPH oxidase’s main subunit (gp91phox) and results in CGD. Analyzing two brothers diagnosed with CGD we identify a homozygous loss-of-function mutation, p.Tyr2Ter, in CYBC1. Imputation of p.Tyr2Ter into 155K chip-genotyped Icelanders reveals six additional homozygotes, all with signs of CGD, manifesting as colitis, rare infections, or a severely impaired PMA-induced neutrophil oxidative burst. Homozygosity for p.Tyr2Ter consequently associates with inflammatory bowel disease (IBD) in Iceland (P = 8.3 × 10−8; OR = 67.6), as well as reduced height (P = 3.3 × 10−4; −8.5 cm). Overall, we find that CYBC1 deficiency results in CGD characterized by colitis and a distinct profile of infections indicative of macrophage dysfunction.
Women with prolonged nausea in pregnancy have increased risk for depressive symptoms postpartum
Authors: Iliadis Stavros I. , Axfors Cathrine , Johansson Sara , Skalkidou Alkistis , Mulic-Lutvica Ajlana 
Published: October 2018

AbstractThe aim of this population-based, longitudinal study was to assess the association between nausea and vomiting in pregnancy (NVP) and perinatal depressive symptoms. Pregnant women (N = 4239) undergoing routine ultrasound at gestational week (GW) 17 self-reported on NVP and were divided into those without nausea (G0), early (≤17 GW) nausea without medication (G1), early nausea with medication (G2), and prolonged (>17 GW) nausea (G3). The Edinburgh Postnatal Depression Scale at GW 17 and 32 (cut-off ≥13) and at six weeks postpartum (cut-off ≥12) was used to assess depressive symptoms. Main outcome measures were depressive symptoms at GW 32 and at six weeks postpartum. NVP was experienced by 80.7%. The unadjusted logistic regression showed a positive association between all three nausea groups and depressive symptoms at all time-points. After adjustment, significant associations with postpartum depressive symptoms remained for G3, compared to G0 (aOR = 1.66; 95% CI 1.1–2.52). After excluding women with history of depression, only the G3 group was at higher odds for postpartum depressive symptoms (aOR = 2.26; 95% CI 1.04–4.92). In conclusion, women with prolonged nausea have increased risk of depressive symptoms at six weeks postpartum, regardless of history of depression.