bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive profiling of rhizome‐associated alternative splicing and alternative polyadenylation in moso bamboo (Phyllostachys edulis)
Authors: Wang Taotao , Wang Huiyuan , Cai Dawei , Gao Yubang , Zhang Hangxiao , Wang Yongsheng , Lin Chentao , Ma Liuyin , Gu Lianfeng 
Published: May 2017

SummaryMoso bamboo (Phyllostachys edulis) represents one of the fastest‐spreading plants in the world, due in part to its well‐developed rhizome system. However, the post‐transcriptional mechanism for the development of the rhizome system in bamboo has not been comprehensively studied. We therefore used a combination of single‐molecule long‐read sequencing technology and polyadenylation site sequencing (PAS‐seq) to re‐annotate the bamboo genome, and identify genome‐wide alternative splicing (AS) and alternative polyadenylation (APA) in the rhizome system. In total, 145 522 mapped full‐length non‐chimeric (FLNC) reads were analyzed, resulting in the correction of 2241 mis‐annotated genes and the identification of 8091 previously unannotated loci. Notably, more than 42 280 distinct splicing isoforms were derived from 128 667 intron‐containing full‐length FLNC reads, including a large number of AS events associated with rhizome systems. In addition, we characterized 25 069 polyadenylation sites from 11 450 genes, 6311 of which have APA sites. Further analysis of intronic polyadenylation revealed that LTR/Gypsy and LTR/Copia were two major transposable elements within the intronic polyadenylation region. Furthermore, this study provided a quantitative atlas of poly(A) usage. Several hundred differential poly(A) sites in the rhizome‐root system were identified. Taken together, these results suggest that post‐transcriptional regulation may potentially have a vital role in the underground rhizome‐root system.
Relationships between soil properties and the occurrence of the most agronomically important weed species in the field margins of eastern Arkansas – implications for weed management in field margins
Authors: Korres N E , Norsworthy J K , Brye K R , Skinner V , Mauromoustakos A 
Published: May 2017

SummaryThe work presented in this study adds to previous research on the occurrence, distribution and growth habitat of common weeds along roadsides in the Mississippi River Delta region of eastern Arkansas, USA. It addresses the relationships between soil properties (i.e. defined as a group of individual soil characteristics or attributes such as P, K, Ca, Mn and other nutrients) and the most agronomically important weeds of which the occurrence at field margins accounted for ≥ 10% of the total sampling sites. These were three broad‐leaved weeds (Amaranthus palmeri, Ipomoea spp. and Sida spinosa) and four grass weeds (Echinochloa crus‐galli, Urochloa platyphylla, Sorghum halepense and Digitaria sanguinalis). Soil properties were used as explanatory variables for weed occurrence (presence–absence) using partition analysis; the occurrences of the weeds under examination were partitioned by the application of a decision‐tree method. The most important soil properties explaining the occurrence of these weeds in field margins were extractable soil nutrients, specifically sodium, boron and copper content, as well as soil physical attributes, in order of importance, bulk density, silt content, field moisture capacity, hydraulic conductivity, wilting point, available water and clay content. Soil chemical properties proved least reliable in explaining weed occurrence at roadside field margins. Knowledge of the relationships between soil properties and weed occurrence can add to our understanding of weed biology and hence enhance the efficiency of weed management strategies. For example, the occurrence of A. palmeri, in soils with high bulk density (>1.4 g cm−3) and low organic matter content (<2.7%) and thus lower residual herbicide activity, will require integrated weed management of this species in field margins. This is of interest given the occurrence of herbicide resistance in roadside arable weeds, mainly A. palmeri, E. crus‐galli and S. halepense, in the Mississippi River Delta region of eastern Arkansas and other parts of the world.
Deciphering MCR-2 Colistin Resistance
Authors: Sun Jian , Xu Yongchang , Gao Rongsui , Lin Jingxia , Wei Wenhui , Srinivas Swaminath , Li Defeng , Yang Run-Shi , Li Xing-Ping , Liao Xiao-Ping , Liu Ya-Hong , Feng Youjun 
Published: May 2017

ABSTRACT

Antibiotic resistance is a prevalent problem in public health worldwide. In general, the carbapenem β-lactam antibiotics are considered a final resort against lethal infections by multidrug-resistant bacteria. Colistin is a cationic polypeptide antibiotic and acts as the last line of defense for treatment of carbapenem-resistant bacteria. Very recently, a new plasmid-borne colistin resistance gene,
mcr-2
, was revealed soon after the discovery of the paradigm gene
mcr-1
, which has disseminated globally. However, the molecular mechanisms for MCR-2 colistin resistance are poorly understood. Here we show a unique transposon unit that facilitates the acquisition and transfer of
mcr-2
. Evolutionary analyses suggested that both MCR-2 and MCR-1 might be traced to their cousin phosphoethanolamine (PEA) lipid A transferase from a known polymyxin producer,
Paenibacillus
. Transcriptional analyses showed that the level of
mcr-2
transcripts is relatively higher than that of
mcr-1
. Genetic deletions revealed that the transmembrane regions (TM1 and TM2) of both MCR-1 and MCR-2 are critical for their location and function in bacterial periplasm, and domain swapping indicated that the TM2 is more efficient than TM1. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) confirmed that all four MCR proteins (MCR-1, MCR-2, and two chimeric versions [TM1-MCR-2 and TM2-MCR-1]) can catalyze chemical modification of lipid A moiety anchored on lipopolysaccharide (LPS) with the addition of phosphoethanolamine to the phosphate group at the 4′ position of the sugar. Structure-guided site-directed mutagenesis defined an essential 6-residue-requiring zinc-binding/catalytic motif for MCR-2 colistin resistance. The results further our mechanistic understanding of transferable colistin resistance, providing clues to improve clinical therapeutics targeting severe infections by MCR-2-containing pathogens.

IMPORTANCE
Carbapenem and colistin are the last line of refuge in fighting multidrug-resistant Gram-negative pathogens. MCR-2 is a newly emerging variant of the mobilized colistin resistance protein MCR-1, posing a potential challenge to public health. Here we report transfer of the
mcr-2
gene by a unique transposal event and its possible origin. Distribution of MCR-2 in bacterial periplasm is proposed to be a prerequisite for its role in the context of biochemistry and the colistin resistance. We also define the genetic requirement of a zinc-binding/catalytic motif for MCR-2 colistin resistance. This represents a glimpse of transferable colistin resistance by MCR-2.
Do outcomes after kidney transplantation differ for black patients in England versus New York State? A comparative, population-cohort analysis
Authors: Tahir Sanna , Gillott Holly , Jackson-Spence Francesca , Nath Jay , Mytton Jemma , Evison Felicity , Sharif Adnan 
Published: May 2017

ObjectivesInferior outcomes for black kidney transplant recipients in the USA may not be generalisable elsewhere. In this population cohort analysis, we compared outcomes for black kidney transplant patients in England versus New York State.DesignRetrospective, comparative, population cohort study utilising administrative data registries.Settings and participantsEnglish data were derived from Hospital Episode Statistics, while New York State data were derived from Statewide Planning and Research Cooperative System. All adults receiving their first kidney-alone allograft between 2003 and 2013 were eligible for inclusion.MeasuresThe primary outcome measure was mortality post kidney transplantation (including inhospital death, 30-day mortality and 1-year mortality). Secondary outcome measures included postoperative admission length of stay, risk of rehospitalisation, development of cardiac events, stroke, cancer or fracture and finally transplant rejection/failure. Cox proportional hazards regression was used to investigate relationship between ethnicity, country and outcome.ResultsBlack patients comprised 6.5% of the English cohort (n=1215/18 493) and 23.0% of the New York State cohort (n=2660/11 602). Compared with New York State, black kidney transplant recipients in England were more likely younger, male, living-donor kidney recipients and had dissimilar medical comorbidities. Inpatient mortality was not statistically different, but death within 30 days, 1 year or kidney transplant rejection/failure was lower among black patients in England versus black patients in New York State. In adjusted regression analysis, with black ethnicity the reference group, white patients had reduced risk for 30-day mortality (OR 0.62 (95% CI 0.44 to 0.86)) and 1-year mortality (OR 0.79 (95% CI 0.63 to 0.99)) in New York State but no difference was observed in England. Compared with England, black kidney transplant patients in New York State had increased HR for kidney transplant rejection rejection/failure by median follow-up (HR 2.15, 95% CI 1.91 to 2.43).ConclusionsOutcomes after kidney transplantation for black patients may not be translatable between countries.
Association of endotoxaemia with serum free fatty acids in metabolically healthy and unhealthy abdominally obese individuals: a case–control study in northwest of Iran
Authors: Saghafi-Asl Maryam , Amiri Parichehr , Naghizadeh Mahsa , Ghavami Seyed Mostafa , Karamzad Nahid 
Published: May 2017

ObjectivesThis study aimed to compare serum free fatty acids (FFAs) and lipopolysaccharide-binding protein (LBP) between metabolically healthy abdominally obese (MHAO) and metabolically unhealthy abdominally obese (MUAO) individuals. We also examined the association between serum FFAs and LBP in the participants.MethodsIn this age-matched and gender-matched case–control study, 164 abdominally obese subjects were recruited from June to November 2015 in the northwest of Iran. Demographic data, dietary intake, body composition, anthropometric indices and physical activity (PA) were assessed. Basal blood samples were collected to determine serum metabolic parameters, FFAs and LBP. Abdominal obesity was defined as having waist circumference ≥95 cm. Those with three or more metabolic alterations were defined as MUAO and those having two or less were classified as MHAO. Data were analysed using SPSS V.17.0.ResultsThere were no significant differences in dietary intake, anthropometric indices, body composition and PA between the two groups. The odds of MUAO significantly increased by increments in serum fasting blood sugar (OR 3.79, 95% CI 2.25 to 6.40), triglycerides (OR 1.10, 95% CI 1.05 to 1.15), systolic blood pressure (OR 1.02, 95% CI 1.00 to 1.04) and diastolic blood pressure (OR 1.03, 95% CI 1.01 to 1.06) and decreased by increase in serum high-density lipoprotein cholesterol (OR 0.32, 95% CI 0.20 to 0.52). The levels of LBP and FFAs showed no significant differences between the two groups. However, significant correlations were found between LBP and FFAs in pooled population (r=0.712; p<0.001) as well as in cases (r=0.717; p<0.001) and controls (r=0.704; p<0.001). Neither FFAs nor LBP were significantly correlated with dietary intake or metabolic parameters (p>0.05).ConclusionThe results indicated that serum LBP and FFAs are highly correlated both in MHAO and MUAO states. In addition, the levels of LBP and FFAs seem to be more related to abdominal obesity than to the presence or absence of metabolic health.
Staying connected: Service-specific orientation can be successfully achieved using a mobile application for onboarding care providers
Authors: Chreiman Kristen M , Prakash Priya S , Martin Niels D , Kim Patrick K , Mehta Samir , McGinnis Kelly , Gallagher John J , Reilly Patrick M 
Published: May 2017

Communicating service-specific practice patterns, guidelines, and provider information to a new team of learners that rotate frequently can be challenging. Leveraging individual and healthcare electronic resources, a mobile device platform was implemented into a newly revised resident onboarding process. We hypothesized that offering an easy-to-use mobile application would improve communication across multiple disciplines as well as improve provider experiences when transitioning to a new rotation. A mobile platform was created and deployed to assist with enhancing communication within a trauma service and its resident onboarding process. The platform had resource materials such as: divisional policies, Clinical Practice Guidelines (CMGs), and onboarding manuals along with allowing for the posting of divisional events, a divisional directory that linked to direct dialing, text or email messaging, as well as on-call schedules. A mixed-methods study, including an anonymous survey, aimed at providing information on team member's impressions and usage of the mobile application was performed. Usage statistics over a 3-month period were analyzed on those providers who completed the survey. After rotation on the trauma service, trainees were asked to complete an anonymous, online survey addressing both the experience with, as well as the utility of, the mobile app. Thirty of the 37 (81%) residents and medical students completed the survey. Twenty-five (83%) trainees stated that this was their first experience rotating on the trauma service and 6 (20%) were from outside of the health system. According to those surveyed, the most useful function of the app were access to the directory (15, 50%), the divisional calendar (4, 13.3%), and the on-call schedules (3, 10%). Overall, the app was felt to be easy to use (27, 90%) and was accessed an average of 7 times per day (1–50, SD 9.67). Over half the survey respondents felt that the mobile app was helpful in completing their everyday tasks (16, 53.3%). Fifteen (50%) of the respondents stated that the app made the transition to the trauma service easier. Twenty-five (83.3%) stated it was valuable knowing about departmental events and announcements, and 17 (56.7%) felt more connected to the division. The evolution of mobile technology is rapidly becoming fundamental in medical education and training. We found that integrating a service-specific mobile application improved the learner's experience when transitioning to a new service and was a valuable onboarding instrument.Level of evidenceIV.
An miRNA Expression Signature for the Human Colonic Stem Cell Niche Distinguishes Malignant from Normal Epithelia
Authors: Viswanathan Vignesh , Damle Shirish , Zhang Tao , Opdenaker Lynn , Modarai Shirin , Accerbi Monica , Schmidt Skye , Green Pamela , Galileo Deni , Palazzo Juan , Fields Jeremy , Haghighat Sepehr , Rigoutsos Isidore , Gonye Greg , Boman Bruce M. 
Published: May 2017

Abstract
Malignant transformation of tissue stem cells (SC) may be the root of most cancer. Accordingly, we identified miRNA expression patterns in the normal human colonic SC niche to understand how cancer stem cells (CSC) may arise. In profiling miRNA expression in SC-enriched crypt subsections isolated from fresh, normal surgical specimens, we identified 16 miRNAs that were differentially expressed in the crypt bottom, creating an SC signature for normal colonic epithelia (NCE). A parallel analysis of colorectal cancer tissues showed differential expression of 83 miRNAs relative to NCE. Within the 16 miRNA signature for the normal SC niche, we found that miR-206, miR-007-3, and miR-23b individually could distinguish colorectal cancer from NCE. Notably, miR-23b, which was increased in colorectal cancer, was predicted to target the SC-expressed G protein-coupled receptor LGR5. Cell biology investigations showed that miR-23b regulated CSC phenotypes globally at the level of proliferation, cell cycle, self-renewal, epithelial–mesenchymal transition, invasion, and resistance to the colorectal cancer chemotherapeutic agent 5-fluorouracil. In mechanistic experiments, we found that miR-23b decreased LGR5 expression and increased ALDH+ CSCs. CSC analyses confirmed that levels of LGR5 and miR-23b are inversely correlated in ALDH+ CSCs and that distinct subpopulations of LGR5+ and ALDH+ CSCs exist. Overall, our results define a critical function for miR-23b, which, by targeting LGR5, contributes to overpopulation of ALDH+ CSCs and colorectal cancer. Cancer Res; 77(14); 3778–90. ©2017 AACR.
Monitoring Tumor Response to Antivascular Therapy Using Non-Contrast Intravoxel Incoherent Motion Diffusion-Weighted MRI
Authors: Shi Changzheng , Liu Dexiang , Xiao Zeyu , Zhang Dong , Liu Guanfu , Liu Guanshu , Chen Hanwei , Luo Liangping 
Published: May 2017

Abstract
Antivascular therapy is a promising approach to the treatment of non–small cell lung cancer (NSCLC), where an imaging modality capable of longitudinally monitoring treatment response could provide early prediction of the outcome. In this study, we sought to investigate the feasibility of using intravoxel incoherent motion (IVIM) diffusion MRI to quantitatively assess the efficacy of the treatments of a vascular-disrupting agent CA4P or its combination with bevacizumab on experimental NSCLC tumors. CA4P caused a strong but reversible effect on tumor vasculature; all perfusion-related parameters—D*, f, fD*, and Ktrans—initially showed a decrease of 30% to 60% at 2 hours and then fully recovered to baseline on day 2 for CA4P treatment or on days 4 to 8 for CA4P + bevacizumab treatment; the diffusion coefficient in tumors decreased initially at 2 hours and then increased from day 2 to day 8. We observed a good correlation between IVIM parameters and dynamic contrast-enhanced MRI (DCE-MRI; Ktrans). We also found that the relative change in f and fD* at 2 hours correlated well with changes in tumor volume on day 8. In conclusion, our results suggest that IVIM is a promising alternative to DCE-MRI for the assessment of the change in tumor perfusion as a result of antivascular agents and can be used to predict the efficacy of antivascular therapies without the need for contrast media injection. Cancer Res; 77(13); 3491–501. ©2017 AACR.
EGFR Signals through a DOCK180-MLK3 Axis to Drive Glioblastoma Cell Invasion
Authors: Misek Sean A. , Chen Jian , Schroeder Laura , Rattanasinchai Chotirat , Sample Ashley , Sarkaria Jann N. , Gallo Kathleen A. 
Published: May 2017

Abstract
A hallmark of glioblastoma (GBM) tumors is their highly invasive behavior. Tumor dissemination into surrounding brain tissue is responsible for incomplete surgical resection, and subsequent tumor recurrence. Identification of targets that control GBM cell dissemination is critical for developing effective therapies to treat GBM. A majority of GBM tumors have dysregulated EGFR signaling, due most frequently to EGFR amplification or the presence of a constitutively active EGFRvIII mutant. Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAP3K) that can activate multiple MAPK pathways. In this study, evidence is provided that MLK3 is essential for GBM cell migration and invasion, and that an MLK inhibitor blocks EGF-induced migration and invasion. MLK3 silencing or MLK inhibition blocks EGF-induced JNK activation, suggesting that MLK3-JNK signaling promotes invasion of GBM cells. Mechanistically, it is demonstrated that DOCK180, a RAC1 guanine nucleotide exchange factor (GEF) overexpressed in invasive GBM cells, activates the MLK3-JNK signaling axis in a RAC1-dependent manner. In summary, this investigation identifies an EGFR–DOCK180–RAC1–MLK3–JNK signaling axis that drives glioblastoma cell migration and dissemination.
Implications: On the basis of these findings, MLK3 emerges as a potential therapeutic target for the treatment of glioblastoma. Mol Cancer Res; 15(8); 1085–95. ©2017 AACR.
Calcium/Calmodulin-Dependent Protein Kinase II Activity Persists During Chronic β-Adrenoceptor Blockade in Experimental and Human Heart Failure
Authors: Dewenter Matthias , Neef Stefan , Vettel Christiane , Lämmle Simon , Beushausen Christina , Zelarayan Laura C. , Katz Sylvia , von der Lieth Albert , Meyer-Roxlau Stefanie , Weber Silvio , Wieland Thomas , Sossalla Samuel , Backs Johannes , Brown Joan H. , Maier Lars S. , El-Armouche Ali 
Published: May 2017

Background—
Considerable evidence suggests that calcium/calmodulin-dependent protein kinase II (CaMKII) overactivity plays a crucial role in the pathophysiology of heart failure (HF), a condition characterized by excessive β-adrenoceptor (β-AR) stimulation. Recent studies indicate a significant cross talk between β-AR signaling and CaMKII activation presenting CaMKII as a possible downstream mediator of detrimental β-AR signaling in HF. In this study, we investigated the effect of chronic β-AR blocker treatment on CaMKII activity in human and experimental HF.

Methods and Results—

Immunoblot analysis of myocardium from end-stage HF patients (n=12) and non-HF subjects undergoing cardiac surgery (n=12) treated with β-AR blockers revealed no difference in CaMKII activity when compared with non–β-AR blocker–treated patients. CaMKII activity was judged by analysis of CaMKII expression, autophosphorylation, and oxidation and by investigating the phosphorylation status of CaMKII downstream targets. To further evaluate these findings, CaMKIIδ
C
transgenic mice were treated with the β
1
-AR blocker metoprolol (270 mg/kg*d). Metoprolol significantly reduced transgene-associated mortality (n≥29;
P
<0.001), attenuated the development of cardiac hypertrophy (−14±6% heart weight/tibia length;
P
<0.05), and strongly reduced ventricular arrhythmias (−70±22% premature ventricular contractions;
P
<0.05). On a molecular level, metoprolol expectedly decreased protein kinase A–dependent phospholamban and ryanodine receptor 2 phosphorylation (−42±9% for P-phospholamban-S16 and −22±7% for P-ryanodine receptor 2-S2808;
P
<0.05). However, this was paralled neither by a reduction in CaMKII autophosphorylation, oxidation, and substrate binding nor a change in the phosphorylation of CaMKII downstream target proteins (n≥11). The lack of CaMKII modulation by β-AR blocker treatment was confirmed in healthy wild-type mice receiving metoprolol.

Conclusions—
Chronic β-AR blocker therapy in patients and in a mouse model of CaMKII-induced HF is not associated with a change in CaMKII activity. Thus, our data suggest that the molecular effects of β-AR blockers are not based on a modulation of CaMKII. Directly targeting CaMKII may, therefore, further improve HF therapy in addition to β-AR blockade.