bluuebunny/crossref_metadata_2025_split huggingface dataset:
Competition of calcified calmodulin N lobe and PIP2to an LQT mutation site in Kv7.1 channel
Authors: Tobelaim William Sam , Dvir Meidan , Lebel Guy , Cui Meng , Buki Tal , Peretz Asher , Marom Milit , Haitin Yoni , Logothetis Diomedes E. , Hirsch Joel Alan , Attali Bernard 
Published: January 2017

SignificanceVoltage-gated potassium 7.1 (Kv7.1) channel and KCNE1 protein coassembly forms the IKSK+current that repolarizes the cardiac action potential, and mutations inKv7.1andKCNE1genes cause cardiac arrhythmias. The proximal Kv7.1 C terminus binds calmodulin and the phospholipid phosphatidylinositol-4,5-bisphosphate (PIP2); however, it is unknown whether their binding sites overlap physically and functionally. Here, we reveal the competition of PIP2and the calcified form of the calmodulin N lobe to a previously unidentified site in helix B of the proximal Kv7.1 C terminus. Notably, this site bears a mutation causing a cardiac arrhythmia called the long-QT syndrome. Our results suggest that, after receptor-mediated PIP2depletion and increased cytosolic Ca2+, calcified calmodulin N lobe interacts with helix B in place of PIP2to limit excessive IKScurrent depression.
Conserved GTPase LepA (Elongation Factor 4) functions in biogenesis of the 30S subunit of the 70S ribosome
Authors: Gibbs Michelle R. , Moon Kyung-Mee , Chen Menglin , Balakrishnan Rohan , Foster Leonard J. , Fredrick Kurt 
Published: January 2017

Significance
The translational GTPase LepA is a highly conserved bacterial protein whose role in the cell has been elusive. Here, we show that the function of LepA lies in biogenesis of the 30S subunit of the ribosome, rather than in translation elongation, as previously supposed. Loss of LepA results in the accumulation of immature 30S particles lacking certain proteins of the 3′ (head) domain and containing precursor 17S rRNA. The GTPase activity of LepA, like that of other translational GTPases, is stimulated by interactions with both subunits of the ribosome. This implies that LepA acts at a late stage of assembly, in the context of the 70S ribosome.
Ontogenetic and life history trait changes associated with convergent ecological specializations in extinct ungulate mammals
Authors: Gomes Rodrigues Helder , Herrel Anthony , Billet Guillaume 
Published: January 2017

Significance
Estimating life history traits such as pace of growth or longevity is difficult in extinct mammals. Yet, these parameters could be helpful to better understand how herbivorous mammals adapted to changing environments. We here highlight the insights gained by studying dental growth and eruption in a clade of extinct ungulate mammals. Variation in these traits was assessed in the context of volcanism, cooling, and increasing aridity in South America starting 50 Ma. We show that ever-growing teeth combined with faster molar eruption arose several times during the evolution of these mammals, allowing them to obtain a more durable and efficient dentition in constraining environments. These innovations might represent convergent ontogenetic and physiological adjustments that contributed to their ecological specialization.
Fragility of the provision of local public goods to private and collective risks
Authors: Cárdenas Juan-Camilo , Janssen Marco A. , Ale Manita , Bastakoti Ram , Bernal Adriana , Chalermphol Juthathip , Gong Yazhen , Shin Hoon , Shivakoti Ganesh , Wang Yibo , Anderies John M. 
Published: January 2017

Significance
Smallholder farmers make a significant contribution to food security in developing countries. Those farmer communities are experiencing new challenges owing to integration with the broader economy (increasing price volatility) and climate change (increasing frequency of extreme weather events). Our study aimed to understand how smallholder agricultural communities make collective action decisions in a public good game with different types of risks. Experiments performed in 118 small-scale rice-producing communities in China, Colombia, Nepal and Thailand show that increasing the integration of those communities with the broader economic system is associated with lower investments in public goods when facing collective risks. As such, the provision of local public goods may be negatively affected by market integration and climate change.
Molecular mechanism underlying juvenile hormone-mediated repression of precocious larval–adult metamorphosis
Authors: Kayukawa Takumi , Jouraku Akiya , Ito Yuka , Shinoda Tetsuro 
Published: January 2017

SignificanceJuvenile hormone (JH) intricately controls molting and metamorphosis in holometabolous insects.Ecdysone-induced protein 93F(E93) functions as an adult specifier gene in the pupal–adult transition. JH is known to repressE93expression to prevent immature larvae from bypassing the pupal stage and progressing to precocious adult development; however, the molecular mechanism underlying JH-mediatedE93repression remains unknown. Here, we demonstrated that JH-inducible Krüppel homolog 1 functions as a direct transcriptional repressor ofE93. This study markedly advances the present understanding of the molecular basis of JH function in repressing insect metamorphosis.
Multi-institute analysis of carbapenem resistance reveals remarkable diversity, unexplained mechanisms, and limited clonal outbreaks
Authors: Cerqueira Gustavo C. , Earl Ashlee M. , Ernst Christoph M. , Grad Yonatan H. , Dekker John P. , Feldgarden Michael , Chapman Sinéad B. , Reis-Cunha João L. , Shea Terrance P. , Young Sarah , Zeng Qiandong , Delaney Mary L. , Kim Diane , Peterson Ellena M. , O’Brien Thomas F. , Ferraro Mary Jane , Hooper David C. , Huang Susan S. , Kirby James E. , Onderdonk Andrew B. , Birren Bruce W. , Hung Deborah T. , Cosimi Lisa A. , Wortman Jennifer R. , Murphy Cheryl I. , Hanage William P. 
Published: January 2017

Significance
Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent threat: as an increasing cause of disease and as the staging ground for resistance to “last line” drugs. Thus, we must understand how CRE evolve, diversify, and spread and especially the potential for asymptomatic transmission without outbreaks. Our broad sample of species and genetic determinants that defined four hospital CRE communities over 16 mo revealed a significant degree of CRE diversity, with little evidence for clonal spread but extensive movement of resistance determinants. We provide evidence for considerable asymptomatic carriage and unrecognizable mechanisms of carbapenem resistance that, together, indicate continued innovation by these organisms to thwart the action of this important class of antibiotics and underscore the need for continued surveillance of CRE.
Phylogenetic analysis of the human antibody repertoire reveals quantitative signatures of immune senescence and aging
Authors: de Bourcy Charles F. A. , Angel Cesar J. Lopez , Vollmers Christopher , Dekker Cornelia L. , Davis Mark M. , Quake Stephen R. 
Published: January 2017

SignificanceThe world’s population is growing older, and senescence of the immune system is a fundamental factor underlying morbidity and mortality. We report a direct molecular characterization of the effects of aging on the adaptive immune system by high-throughput sequencing of antibody transcripts in the peripheral blood of humans. Using a phylogenetic approach to quantify dissimilarity, we compared the immunoglobulin repertoires of young and elderly individuals at baseline and during a well-defined immunogenic perturbation in the form of influenza vaccination; we also studied the long-term effects of chronic infection. Our work reveals previously unappreciated signatures of immune senescence that may find diagnostic use and guide approaches for improving elderly patients’ antibody responses.
Stromal cues regulate the pancreatic cancer epigenome and metabolome
Authors: Sherman Mara H. , Yu Ruth T. , Tseng Tiffany W. , Sousa Cristovao M. , Liu Sihao , Truitt Morgan L. , He Nanhai , Ding Ning , Liddle Christopher , Atkins Annette R. , Leblanc Mathias , Collisson Eric A. , Asara John M. , Kimmelman Alec C. , Downes Michael , Evans Ronald M. 
Published: January 2017

Significance
Stromal fibroblasts of the pancreatic tumor microenvironment (TME) have been shown to play both tumor-supportive and tumor-suppressive roles in enacting a dysregulated wound-healing response. This apparent complexity suggests that an improved understanding of the molecular basis of cell–cell interactions in the TME is required to identify and target stroma-derived, growth-permissive mechanisms. Here we show that stromal cues induce transcriptional and metabolic changes in pancreatic cancer cells implicated in anabolic metabolism, which overlap with those previously demonstrated downstream of oncogenic Kras. Stromal signals broadly induce histone acetylation in the pancreatic cancer epigenome, and we highlight inhibition of acetyl-lysine sensing by the bromodomain and extraterminal (BET) bromodomain family, Bromodomain-containing protein 2 (BRD2) in particular, as a potential therapeutic strategy.
Role of CCT chaperonin in the disassembly of mitotic checkpoint complexes
Authors: Kaisari Sharon , Sitry-Shevah Danielle , Miniowitz-Shemtov Shirly , Teichner Adar , Hershko Avram 
Published: January 2017

Significance
The mitotic checkpoint system has an important role in ensuring correct segregation of chromosomes in mitosis. As long as not all chromosomes are attached correctly to the mitotic spindle, a mitotic checkpoint complex (MCC) is assembled and prevents chromosome separation by inhibiting the action of the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C). When the mitotic checkpoint system is turned off, MCC is disassembled to allow chromosome separation, but the mechanisms of MCC disassembly are poorly understood. Here we show that an important pathway in MCC disassembly is mediated by chaperonin containing TCP1, a complex previously known to play a role only in protein folding. The present study provides insight into molecular events responsible for mitotic checkpoint inactivation.
Induction, purification, and characterization of a thermo and pH stable laccase from Abortiporus biennis J2 and its application on the clarification of litchi juice
Authors: Yin Liang , Ye Jiayin , Kuang Sibi , Guan Yanqing , You Rong 
Published: January 2017

Abstract
A fungus J2 producing laccase with high yield was screened in soils and identified as Abortiporus biennis. The production of laccase was induced by 0.1 mM Cu2+, 0.1 mM tannic acid, and 0.5 M ethanol. The laccase from Abortiporus biennis J2 was purified to electrophoretic homogeneity by a couple of steps. The N-terminal amino acid sequence of the enzyme was AIGPTADLNISNADI. The properties of the purified laccase were investigated. The result showed the laccase from Abortiporus biennis J2 is a thermo and pH stable enzyme. The laccase activity was inhibited by Hg2+, Cd2+, Fe2+, Ag+, Cu2+, and Zn2+, while promoted by Mg2+, Mn2+ at 10 mM level. Purified laccase was used to the clarification of litchi juice. After treatment with this laccase, the phenolic content of litchi juice had been found to be greatly reduced along with an increase in the clarity of the juice. The result indicated the potential of this laccase for application in juice procession.
Anaerobic biodegradation of spiramycin I and characterization of its new metabolites
Authors: Yao Jian , Shao Lei , Chen Daijie , Liu Pengyu , Zhang Yubin 
Published: January 2017

Abstract
Activated sludge was used to treat the wastewater containing spiramycin I. Three new metabolites were isolated and identified, which produced by oxidation of C6-aldehyde, hydrolysis of C5-mycaminose-mycarose and macrolactone ring-open reaction of spiramycin I in anaerobic digestion. And their antimicrobial activities were inactivated. Our results indicated that anaerobic biodegradation metabolites of spiramycin I could not induce bacterial resistance in environment.
Enhanced Recovery Implementation in Major Gynecologic Surgeries: Effect of Care Standardization
Authors: Modesitt Susan C. , Sarosiek Bethany M. , Trowbridge Elisa R. , Redick Dana L. , Shah Puja M. , Thiele Robert H. , Tiouririne Mohamed , Hedrick Traci L. 
Published: January 2017

(Abstracted from Obstet Gynecol 2016;128:457–466)
The concept of enhanced recovery after surgery (ERAS) emerged as a multimodal approach focused on optimizing patient experience, standardizing perioperative care, and improving surgical outcomes. This concept has been refined in several different surgical fields including both colorectal and gynecologic.
Effect of Wearable Technology Combined With a Lifestyle Intervention on Long-term Weight Loss: The IDEA Randomized Clinical Trial
Authors: Jakicic John M. , Davis Kelliann K. , Rogers Renee J. , King Wendy C. , Marcus Marsha D. , Helsel Diane , Rickman Amy D. , Wahed Abdus S. , Belle Steven H. 
Published: January 2017

(Abstracted from JAMA 2016;316:1161–1171)
There is a critical need for effective long-term interventions to address the obesity epidemic. Treatments emphasizing both diet and physical activity are effective for achieving short-term weight loss (6-month weight loss of 8%–10% of initial weight).
Conundrums in the Management of Malignant Ovarian Germ-Cell Tumors: Toward Lessening Acute Morbidity and Late Effects of Treatment
Authors: Gershenson David M. , Frazier A. Lindsay 
Published: January 2017

(Abstracted from Gynecol Oncol 2016;143:428–432)
Prior to the mid-1960s, most girls and young women with malignant ovarian germ cell tumors died of the disease. The only treatments available during this era were included surgery alone or combined with postoperative treatment (consisting of radiotherapy or radioisotopes, or single alkylating agents).
Antenatal Betamethasone: A Prolonged Time Interval from Administration to Delivery Is Associated With an Increased Incidence of Severe Intraventricular Hemorrhage in Infants Born Before 28 Weeks’ Gestation
Authors: Liebowitz Melissa , Clyman Ronald I. 
Published: January 2017

(Abstracted from J Pediatr 2016;177:114–120)
Studies, including several randomized controlled trials, have reported that neonates exposed to antenatal corticosteroids have reduced incidence of death, respiratory distress syndrome (RDS), and severe grades of intraventricular hemorrhage (IVH). The present study aimed to investigate the effects of antenatal corticosteroids on severe IVH in infants born at less than 28 weeks’ gestation based on the hypothesis that the beneficial effects of antenatal steroids on severe IVH diminish with time in these infants and that retreatment with a second course of antenatal betamethasone (BMZ) can restore its beneficial effects.
Evidence for Feasibility of Fetal Trophoblastic Cell-Based Noninvasive Prenatal Testing
Authors: Breman Amy M. , Chow Jennifer C. , U’Ren Lance , Normand Elizabeth A. , Qdaisat Sadeem , Zhao Li , Henke David M. , Chen Rui , Shaw Chad A. , Jackson Laird , Yang Yaping , Vossaert Liesbeth , Needham Rachel H. V. , Chang Elizabeth J. , Campton Daniel , Werbin Jeffrey L. , Seubert Ron C. , Van den Veyver Ignatia B. , Stilwell Jackie L. , Kaldjian Eric P. , Beaudet Arthur L. 
Published: January 2017

(Abstracted from Prenat Diagn 2016;36:1–11)
The potential use of fetal cells in maternal blood for prenatal diagnosis has been a promising technology for decades. Several strategies have been tried and tested for recovering fetal cells, although they are inconsistent and not reproducible.
Association of Labor Induction With Offspring Risk of Autism Spectrum Disorders
Authors: Oberg Anna Sara , D’Onofrio Brian M. , Rickert Martin E. , Hernandez-Diaz Sonia , Ecker Jeffrey L. , Almqvist Catarina , Larsson Henrik , Lichtenstein Paul , Bateman Brian T. 
Published: January 2017

(Abstracted from JAMA Pediatr 2016;170(9):e160965)
Autism spectrum disorders (ASDs) are a collection of permanent developmental disabilities exemplified by impairments in social interaction and language development and stereotyped and repetitive behaviors. This study aimed to examine the association of labor induction with ASD by comparison of differentially exposed relatives and to follow up on their diagnosis of ASD.
Medical Students’ Perspectives on Implementing Curriculum Change at One Institution
Authors: Yengo-Kahn Aaron M. , Baker Courtney E. , Lomis and Kimberly D. 
Published: January 2017

Training physicians to be effective practitioners throughout their careers begins in undergraduate medical education with particular focus on self-directed inquiry, professional and interprofessional development, and competency-based assessment. A select number of medical schools are restructuring their curricula by placing the student at the center of content delivery to enhance the learning experience. While this restructuring may benefit the adult learner, administrators often make assumptions about how students will perceive and respond to such innovative and unfamiliar educational concepts. This can create a disconnect between students and their curriculum. Administrative mindfulness of student experiences is needed to ensure successful implementation of curricular change, facilitate the transition from old to new modalities, and train competent physician graduates.
Vanderbilt University School of Medicine (VUSM) recently completed a curriculum update, and student representatives have been essential participants in the transition, from the earliest stages in preplanning to rapid-cycle feedback as the curriculum runs. Two of the authors are members of VUSM’s Student Curriculum Committee, which facilitates gathering and relaying student feedback to the administration. Drawing from their experiences, five specific considerations to address and manage when implementing student-centered curricular change are presented: (1) Communicate the rationale, (2) acknowledge anxiety, (3) adjust extracurricular leadership roles, (4) manage “The Bulge” of learners in the clinical environment, and (5) foster ongoing collaboration of students and administrators. For each consideration, examples and proposed solutions are provided.
Paradoxical Emergence
Authors: Hambrecht-Wiedbusch Viviane S. , Li Duan , Mashour George A. 
Published: January 2017

Abstract

Background
Promoting arousal by manipulating certain brain regions and/or neurotransmitters has been a recent research focus, with the goal of trying to improve recovery from general anesthesia. The current study tested the hypothesis that a single subanesthetic dose of ketamine during isoflurane anesthesia would increase cholinergic tone in the prefrontal cortex and accelerate recovery.

Methods
Adult male rats were implanted with electroencephalography electrodes (frontal, parietal, and occipital cortex) and a microdialysis guide cannula targeted for the prefrontal cortex. After establishing general anesthesia with isoflurane, animals were randomly assigned to receive a saline control or ketamine injection. When isoflurane was discontinued nearly 90 min after drug or saline administration, recovery from anesthesia was measured by experimenters and blinded observers. During the entire experiment, electrophysiologic signals were recorded and acetylcholine was quantified by high-performance liquid chromatography with electrochemical detection.

Results
A single dose of subanesthetic ketamine caused an initial 125% increase in burst suppression ratio (last isoflurane sample: 37.48 ± 24.11% vs. isoflurane after ketamine injection: 84.36 ± 8.95%; P < 0.0001), but also a significant 44% reduction in emergence time (saline: 877 ± 335 s vs. ketamine: 494 ± 108 s; P = 0.0005; n = 10 per treatment). Furthermore, ketamine caused a significant 317% increase in cortical acetylcholine release (mean after ketamine injection: 0.18 ± 0.16 pmol vs. ketamine recovery: 0.75 ± 0.41 pmol; P = 0.0002) after isoflurane anesthesia was discontinued.

Conclusions
Administration of subanesthetic doses of ketamine during isoflurane anesthesia increases anesthetic depth but—paradoxically—accelerates the recovery of consciousness, possibly through cholinergic mechanisms.
Presepsin (sCD14-ST) Is a Novel Marker for Risk Stratification in Cardiac Surgery Patients
Authors: Bomberg Hagen , Klingele Matthias , Wagenpfeil Stefan , Spanuth Eberhard , Volk Thomas , Sessler Daniel I. , Schäfers Hans-Joachim , Groesdonk Heinrich Volker 
Published: January 2017

Abstract

Background
Presepsin (soluble cluster-of-differentiation 14 subtype [sCD14-ST]) is a humoral risk stratification marker for systemic inflammatory response syndrome and sepsis. It remains unknown whether presepsin can be used to stratify risk in elective cardiac surgery. The authors therefore determined the usefulness of presepsin for risk stratification in patients having elective cardiac surgery.

Methods
Eight hundred fifty-six cardiac surgical patients were prospectively studied. Preoperative plasma concentrations of presepsin, procalcitonin, N-terminal pro–hormone natriuretic peptide, cystatin C, and the additive European System of Cardiac Operative Risk Evaluation 2 were compared to mortality at 30 days (primary outcome), 6 months, and 2 yr. Discrimination was assessed with C statistic. Logistic regression analysis was used to calculate univariable and multivariable odds ratios.

Results
Thirty-day mortality was 3.2%, 6-month mortality was 6.1%, and 2-yr mortality was 10.4% across the population. Median preoperative presepsin concentrations were significantly greater in 30-day nonsurvivors than in survivors: 842 pg/ml (interquartile range, 306 to 1,246) versus 160 pg/ml (interquartile range, 122 to 234); difference, 167 pg/ml (interquartile range, 92 to 301; P < 0.001). The results were similar for 6-month and 2-yr mortality. Compared to the European System of Cardiac Operative Risk Evaluation 2, presepsin concentration provided better discrimination for postoperative mortality at all follow-up periods, including 30 days (C statistic 0.88 vs. 0.74), 6 months (0.87 vs. 0.76), and 2 yr (0.81 vs. 0.74). Presepsin also provided better discrimination than cystatin C, N-terminal pro–hormone natriuretic peptide, or procalcitonin. Elevated presepsin remained an independent risk predictor after adjustment for potential confounding factors.

Conclusions
Elevated preoperative plasma presepsin concentration is an independent predictor of postoperative mortality in elective cardiac surgery patients and is a stronger predictor than several other commonly used assessments.
STARGARDT DISEASE
Authors: Light Jacob G. , Fard Masoud A. , Yaseri Mehdi , Aiyetan Paul , Handa James T. , Ebrahimi Katayoon B. 
Published: January 2017

Purpose:
To identify changes in the outer retina in areas without atrophy or flecks of Stargardt disease (STGD) using spectral-domain optical coherence tomography.

Methods:
Twenty-three STGD patients and 26 control subjects were assessed for outer retina (from the outer border of Bruch membrane [BrM] to the inner border of the inner segment ellipsoid zone [EZ]), BrM–retinal pigment epithelium apex, the EZ thickness, and apical process interdigitation zone.

Results:
Patients with STGD had increased BrM–EZ thickness in areas without apparent disease versus control subjects at 1,000, 1,500, 2,000, and 2,500 μm superior and 1,500 μm, 2,000 μm, and 2,500 μm inferior to the fovea (P < 0.05 to P < 0.001), greatest difference (3.4 μm) at 2,500 μm superiorly. The BrM–retinal pigment epithelium segment showed larger fractional contribution of 0.48 to 0.51 to the overall BrM-EZ thickness compared with 0.35 to 0.42 in control subjects. The thickness of EZ and the interspace between the retinal pigment epithelium apex and EZ were smaller in the STGD patients (P < 0.05 to P < 0.001). Patients with STGD displayed an interrupted interdigitation zone in 16 (84.2%) of 19 eyes versus 6 (23.1%) of 26 eyes of the control subjects (P < 0.001). The BrM-EZ segment of the outer retina of STGD patients lacked the typical normal trilaminar pattern.

Conclusion:
Subtle changes are present within the BrM-EZ segment of the outer retina of STGD patients in areas that are devoid of atrophy and flecks. These findings suggest that pathologic changes in STGD are more widespread than that seen by clinical examination.