bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of association of gene variants with obesity traits in New Zealand European children at 6 years of age
Authors: Krishnan Mohanraj , Thompson John M. D. , Mitchell Edwin A. , Murphy Rinki , McCowan Lesley M. E. , Shelling Andrew N. , on behalf of the Children of SCOPE study group g
Published: May 2017

Childhood obesity is a public health problem, which is associated with a long-term increased risk of cardiovascular disease and premature mortality.
Ni and Cu-catalyzed one pot synthesis of unsymmetrical 1,3-di(hetero)aryl-1H-indazoles from hydrazine, o-chloro (hetero)benzophenones, and (hetero)aryl bromides
Authors: Wiethan Carson , Lavoie Christopher M. , Borzenko Andrey , Clark Jillian S. K. , Bonacorso Helio G. , Stradiotto Mark
Published: May 2017

A new nickel-catalyzed cyclization of ortho-chlorobenzophenone hydrazones, to afford 3-aryl-1H-indazoles, is applied in a one-pot synthesis of 1,3-diaryl-1H-indazoles.
Inhibition of HDAC3 prevents diabetic cardiomyopathy in OVE26 mice via epigenetic regulation of DUSP5-ERK1/2 pathway
Authors: Xu Zheng , Tong Qian , Zhang Zhiguo , Wang Shudong , Zheng Yang , Liu Qiuju , Qian Ling-bo , Chen Shao-yu , Sun Jian , Cai Lu
Published: May 2017

Inhibition of total histone deacetylases (HDACs) was phenomenally associated with the prevention of diabetic cardiomyopathy (DCM). However, which specific HDAC plays the key role in DCM remains unclear. The present study was designed to determine whether DCM can be prevented by specific inhibition of HDAC3 and to elucidate the mechanisms by which inhibition of HDAC3 prevents DCM. Type 1 diabetes OVE26 and age-matched wild-type (WT) mice were given the selective HDAC3 inhibitor RGFP966 or vehicle for 3 months. These mice were then killed immediately or 3 months later for cardiac function and pathological examination. HDAC3 activity was significantly increased in the heart of diabetic mice. Administration of RGFP966 significantly prevented DCM, as evidenced by improved diabetes-induced cardiac dysfunction, hypertrophy, and fibrosis, along with diminished cardiac oxidative stress, inflammation, and insulin resistance, not only in the mice killed immediately or 3 months later following the 3-month treatment. Furthermore, phosphorylated extracellular signal-regulated kinases (ERK) 1/2, a well-known initiator of cardiac hypertrophy, was significantly increased, while dual specificity phosphatase 5 (DUSP5), an ERK1/2 nuclear phosphatase, was substantially decreased in diabetic hearts. Both of these changes were prevented by RGFP966. Chromatin immunoprecipitation (ChIP) assay showed that HDAC3 inhibition elevated histone H3 acetylation on the DUSP5 gene promoter at both two time points. These findings suggest that diabetes-activated HDAC3 inhibits DUSP5 expression through deacetylating histone H3 on the primer region of DUSP5 gene, leading to the derepression of ERK1/2 and the initiation of DCM. The present study indicates the potential application of HDAC3 inhibitor for the prevention of DCM.
Can plume-induced internal gravity waves regulate the core rotation of subgiant stars?
Authors: Pinçon C. , Belkacem K. , Goupil M. J. , Marques J. P.
Published: May 2017

Context.The seismic data provided by the space-borne missions CoRoT andKeplerenabled us to probe the internal rotation of thousands of evolved low-mass stars. Subsequently, several studies showed that current stellar evolution codes are unable to reproduce the low core rotation rates observed in these stars. These results indicate that an additional angular momentum transport process is necessary to counteract the spin up due to the core contraction during the post-main sequence evolution. For several candidates, the transport induced by internal gravity waves (IGW) could play a non-negligible role.

Aims.We aim to investigate the effect of IGW generated by penetrative convection on the internal rotation of low-mass stars from the subgiant branch to the beginning of the red giant branch.

Methods.A semi-analytical excitation model was used to estimate the angular momentum wave flux. The characteristic timescale associated with the angular momentum transport by IGW was computed and compared to the contraction timescale throughout the radiative region of stellar models at different evolutionary stages.

Results.We show that IGW can efficiently counteract the contraction-driven spin up of the core of subgiant stars if the amplitude of the radial-differential rotation (between the center of the star and the top of the radiative zone) is higher than a threshold value. This threshold depends on the evolutionary stage and is comparable to the differential rotation rates inferred for a sample of subgiant stars observed by the satelliteKepler. Such an agreement can therefore be interpreted as the consequence of a regulation mechanism driven by IGW. This result is obtained under the assumption of a smooth rotation profile in the radiative region and holds true even if a wide range of values is considered for the parameters of the generation model. In contrast, on the red giant branch, we find that IGW remain insufficient, on their own, to explain the observations because of an excessive radiative damping.

Conclusions.IGW generated by penetrative convection are able to efficiently extract angular momentum from the core of stars on the subgiant branch and accordingly have to be taken into account. Moreover, agreements with the observations reinforce the idea that their effect is essential to regulate the amplitude of the radial-differential rotation in subgiant stars. On the red giant branch, another transport mechanism must likely be invoked.
Accretion-ejection morphology of the microquasar SS 433 resolved at sub-au scale
Authors:   GRAVITY Collaboration, Petrucci P.-O. , Waisberg I. , Le Bouquin J.-B. , Dexter J. , Dubus G. , Perraut K. , Kervella P. , Abuter R. , Amorim A. , Anugu N. , Berger J. P. , Blind N. , Bonnet H. , Brandner W. , Buron A. , Choquet É. , Clénet Y. , de Wit W. , Deen C. , Eckart A. , Eisenhauer F. , Finger G. , Garcia P. , Garcia Lopez R. , Gendron E. , Genzel R. , Gillessen S. , Gonte F. , Haubois X. , Haug M. , Haussmann F. , Henning Th. , Hippler S. , Horrobin M. , Hubert Z. , Jochum L. , Jocou L. , Kok Y. , Kolb J. , Kulas M. , Lacour S. , Lazareff B. , Lèna P. , Lippa M. , Mérand A. , Müller E. , Ott T. , Panduro J. , Paumard T. , Perrin G. , Pfuhl O. , Ramos J. , Rau C. , Rohloff R.-R. , Rousset G. , Sanchez-Bermudez J. , Scheithauer S. , Schöller M. , Straubmeier C. , Sturm E. , Vincent F. , Wank I. , Wieprecht E. , Wiest M. , Wiezorrek E. , Wittkowski M. , Woillez J. , Yazici S. , Zins G.
Published: May 2017

We present the first optical observation of the microquasar SS 433 at sub-milliarcsecond (mas) scale obtained with the GRAVITY instrument on the Very Large Telescope interferometer (VLTI). The 3.5-h exposure reveals a rich K-band spectrum dominated by hydrogen Brγand He i lines, as well as (red-shifted)emission lines coming from the jets. The K-band-continuum-emitting region is dominated by a marginally resolved point source (<1 mas) embedded inside a diffuse background accounting for 10% of the total flux. The jet line positions agree well with the ones expected from the jet kinematic model, an interpretation also supported by the consistent sign (i.e., negative/positive for the receding/approaching jet component) of the phase shifts observed in the lines. The significant visibility drop across the jet lines, together with the small and nearly identical phases for all baselines, point toward a jet that is offset by less than 0.5 mas from the continuum source and resolved in the direction of propagation, with a typical size of 2 mas. The jet position angle of ~80° is consistent with the expected one at the observation date. Jet emission so close to the central binary system would suggest that line locking, if relevant to explain the amplitude and stability of the 0.26c jet velocity, operates on elements heavier than hydrogen. The Brγprofile is broad and double peaked. It is better resolved than the continuum and the change of the phase signal sign across the line on all baselines suggests an East-West-oriented geometry similar to the jet direction and supporting a (polar) disk wind origin.
Open Carpal Tunnel Release Outcomes: Performed Wide Awake versus with Sedation
Authors: Kim Nayoung , Abboudi Jack , Jones Christopher , Liss Frederic , Kirkpatrick William , Rivlin Michael , Wang Mark , Matzon Jonas , Ilyas Asif , Tulipan Jacob
Published: May 2017

Background Carpal tunnel release (CTR) is the most common surgery of the hand, and interest is growing in performing it under local anesthesia without tourniquet. To better understand differences, we hypothesized that patients undergoing CTR under wide-awake local anesthesia with no tourniquet (WALANT) versus sedation (monitored anesthesia care [MAC]) would not result in a difference in outcome.

Methods Consecutive cases of electrodiagnostically confirmed open CTR across multiple surgeons at a single center were prospectively enrolled. Data included demographic data, visual analog scale, Levine-Katz carpal tunnel syndrome scale, QuickDASH questionnaire, customized Likert questionnaire, and complications.

Results There were 81 patients enrolled in the WALANT group and 149 patients in the MAC group. There were no reoperations in either group or any epinephrine-related complications in the WALANT group. Disability and symptom scores did not differ significantly between WALANT and sedation groups at 2 weeks or 3 months. Average postoperative QuickDASH, Levine-Katz, and VAS pain scales were the same in both groups. Both groups of patients reported high levels of satisfaction at 91 versus 96% for the WALANT versus MAC groups, respectively (p > 0.05). Patients in each group were likely to request similar anesthesia if they were to undergo surgery again.

Conclusion Patients undergoing open CTR experienced similar levels of satisfaction and outcomes with either the WALANT or MAC techniques. There was no statistically significant difference between either group relative to the tested outcome measures. These data should facilitate surgeons and patients' choosing freely between WALANT and MAC techniques relative to complications and outcomes.
Different Kinematics of Knees with Varus and Valgus Deformities
Authors: Benditz A. , Koeck F. , Keshmiri A. , Grifka J. , Maderbacher G. , Baier C.
Published: May 2017

Few data exist of kinematics of knees with varus and valgus deformities combined with osteoarthritis. The purpose of this study was to reveal different (1) tibiofemoral kinematics, (2) medial and lateral gaps, and (3) condylar liftoff of osteoarthritic knees with either varus or valgus deformity before and after total knee arthroplasty (TKA). For this purpose, 40 patients for TKA were included in this study, 23 knees with varus deformity and 17 knees with valgus deformity. All patients underwent computer navigation, and kinematics was assessed before making any cuts or releases and after implantation. Osteoarthritic knees with valgus deformity showed a significant difference in tibia rotation relative to the femur with flexion before and after TKA, whereas knees with varus deformity did not. Knees with a valgus deformity showed femoral external rotation in extension and femoral internal rotation in flexion, whereas knees with a varus deformity revealed femoral internal rotation in extension and femoral external rotation in flexion. In both groups, gaps increased after TKA. Condylar liftoff was not observed in the varus deformity group after TKA. In the valgus deformity group, condylar liftoff was detected after TKA at knee flexion of 50 degrees and more. This study revealed significant differences in tibiofemoral kinematics between osteoarthritic knees with a varus or valgus deformity before and after TKA. Valgus deformities showed a paradoxic movement pattern. These in vivo intraoperative results need to be confirmed using fluoroscopic or radiographic three-dimensional matching before and after TKA.
Präoperative Vorbereitung: Patient Blood Management – Was ist optimal?
Authors: Meybohm Patrick , Müller Markus , Zacharowski Kai
Published: May 2017

Patient Blood Management (PBM) fokussiert auf ein umfassendes Anämiemanagement, die Minimierung (unnötiger) iatrogener Blutverluste und die Ausschöpfung der natürlichen Anämietoleranz mit rationalem Einsatz von Erythrozytenkonzentrat-Transfusionen. Im Mittelpunkt des aktuellen Beitrags stehen die in der präoperativen Phase entscheidenden PBM-Komponenten: Management einer Anämie, prätransfusionelle Vorbereitungen und Management von Antikoagulanzien. Die präoperative Anämie ist ein unabhängiger Risikofaktor für eine erhöhte perioperative Morbidität und Sterblichkeit. Zum frühestmöglichen Zeitpunkt sollte daher vor elektiven Eingriffen die Ursachen der Anämie abgeklärt und bei behandelbaren Ursachen der Anämie eine spezifische Behandlung eingeleitet werden. Die präoperative prätransfusionelle Analytik sollte in Abhängigkeit von der Transfusionswahrscheinlichkeit (und dem Ausgangshämoglobinwert) einem Stufenkonzept folgen und aktuelle hausinterne Daten berücksichtigen. Im Umgang mit (oralen) Antikoagulanzien sollte bereits in der präoperativen Phase eine individuelle Risikostratifizierung erfolgen. Anhand des individuellen Blutungs- und Thromboembolierisikos wird sodann entschieden, ob die Medikation fortgeführt, pausiert oder überbrückt werden muss. Ohne klar definierte Verantwortlichkeiten im präoperativen PBM-Team, Kommunikation und Schulung aller Beteiligten ist langfristig kein Erfolg des präoperativen PBM-Programms zu erwarten.
Experimental results from an X-ray imaging crystal spectrometer utilizing multi-wire proportional counter for KSTAR
Authors: Lee S. G. , Yoo J. W. , Kim Y. S. , Nam U. W. , Moon M. K.
Published: May 2017

The inconsistency of the first experimental results from the X-ray imaging crystal spectrometer for the Korea Superconducting Tokamak Advanced Research device utilizing a multi-wire proportional counter (MWPC) is clarified after improving the photon-count rate of the data acquisition system for the MWPC and ground loop isolator for the whole spectrometer system. The improved MWPC is successfully applied to pure Ohmic plasmas as well as plasmas with high confinement modes.
Effects of turbulence, resistivity and boundary conditions on helicoidal flow collimation: Consequences for the Von-Kármán-Sodium dynamo experiment
Authors: Varela J. , Brun S. , Dubrulle B. , Nore C.
Published: May 2017

We present hydrodynamic and magneto-hydrodynamic simulations of a liquid sodium flow using the compressible MHD code PLUTO to investigate the magnetic field regeneration in the Von-Kármán-Sodium dynamo experiment. The aim of the study is to analyze the influence of the fluid resistivity and turbulence level on the collimation by helicoidal motions of a remnant magnetic field. We use a simplified Cartesian geometry to represent the flow dynamics in the vicinity of one cavity of a multi-blades impeller inspired by those used in the Von-Kármán-Sodium (VKS) experiment. We perform numerical simulations with kinetic Reynolds numbers up to 1000 for magnetic Prandtl numbers between 30 and 0.1. Our study shows that perfect ferromagnetic walls favour enhanced collimation of flow and magnetic fields even if the turbulence degree of the model increases. More specifically, the location of the helicoidal coherent vortex in between the blades changes with the impinging velocity. It becomes closer to the upstream blade and the impeller base if the flow incident angle is analogous to the TM73 impeller configuration rotating in the unscooping direction. This result is also obtained at higher kinetic Reynolds numbers when the helicoidal vortex undergoes a precessing motion, leading to a reinforced effect in the vortex evolution and in the magnetic field collimation when using again perfect ferromagnetic boundary conditions. Configurations with different materials used for the impeller blades and the impeller base confirm a larger enhancement of the magnetic field when perfect ferromagnetic boundary conditions are used compared with the perfect conductor case, although smaller compared to a perfect ferromagnetic impeller, as it was observed in the VKS experiment. We further estimate the efficiency of a hypothetical dynamo loop occurring in the vicinity of the impeller and discuss the relevance of our findings in the context of mean field dynamo theory.
A Novel Eco-Friendly Scale and Corrosion Inhibitor Modified by β-Cyclodextrin
Authors: Tang Mingjin , Li Jianbo , Ye Zhengrong , Kou Zimin , Fu Luoping
Published: May 2017

A polymer, β-MEA, was synthesised from β-cyclodextrin (β-CD), 3-chloro-2-methylpropene (MAC), epoxysuccinic acid (ESA), and 2-acrylamido-2-methyl propane sulfonic acid (AMPS) with a (NH4)2S2O8-NaHSO3 redox initiator system by aqueous solution radical polymerisation. β-MEA was characterised by means of IR spectroscopy, time-of-flight mass spectrometry, gel permeation chromatography, and thermogravimetric analysis. Its structure, molecular weight, thermal stability, scale and corrosion inhibition performance and mechanism were investigated. The results verified that β-MEA achieves a better scale inhibition efficiency for BaSO4 compared with poly(aspartic acid) (PASP) (100 % cf. 94.9 % at a concentration of 20 mg L−1) and a better corrosion inhibition efficiency of N80 carbon steel in saline water compared with PESA (91.2 % cf. 79.7 % at a concentration of 1 g L−1). The BaSO4 was characterised by scanning electron microscopy (SEM) and X-ray diffraction to investigate the crystal morphology of the scale. Primary research on the mechanism for corrosion inhibition was carried by SEM-chemical analysis.
Effects of Alternative Food Types on Body Size and Survival of Hatchery-Reared Lake Sturgeon Larvae
Authors: Valentine Shaley A , Bauman John M , Scribner Kim T
Published: May 2017

Aquaculture programs benefit from feeding protocols that result in large larval body size and high survival. Despite high labor, processing, and material costs relative to alternative foods, feeding live foods generally results in high larval growth and survival. For many species, studies that identify alternative food types or feeding regimens that produce larvae with high survival and size comparable with wild cohorts are lacking. In a 35-d study, the effects of alternative food types (previously frozen Artemia and trout crumble starter diet (trout diet) on TL, weight per fish, and survival of larval Lake Sturgeon Acipenser fulvescens were quantified. From days 14 to 21 postexogenous feeding, larvae were transitioned from live Artemia to one of the alternative food types or remained feeding on live Artemia as the control. At the end of the study, TL and weight per fish of larvae fed live Artemia were significantly greater than larvae fed the alternative foods. Survival of larvae fed live or frozen Artemia was higher than larvae fed the trout diet. Lower body growth and survival of larvae fed the alternative foods demonstrate that the frozen and formulated foods are not appropriate diets for Lake Sturgeon larvae.
Differences in responses to X-ray exposure between osteoclast and osteoblast cells
Authors: Zhang Jian , Wang Ziyang , Wu Anqing , Nie Jing , Pei Hailong , Hu Wentao , Wang Bing , Shang Peng , Li Bingyan , Zhou Guangming
Published: May 2017

Radiation-induced bone loss is a potential health concern for cancer patients undergoing radiotherapy. Enhanced bone resorption by osteoclasts and decreased bone formation by osteoblasts were thought to be the main reasons. In this study, we showed that both pre-differentiating and differentiating osteoclasts were relatively sensitive to X-rays compared with osteoblasts. X-rays decreased cell viability to a greater degree in RAW264.7 cells and in differentiating cells than than in osteoblastic MC3T3-E1 cells. X-rays at up to 8 Gy had little effects on osteoblast mineralization. In contrast, X-rays at 1 Gy induced enhanced osteoclastogenesis by enhanced cell fusion, but had no effects on bone resorption. A higher dose of X-rays at 8 Gy, however, had an inhibitory effect on bone resorption. In addition, actin ring formation was disrupted by 8 Gy of X-rays and reorganized into clusters. An increased activity of Caspase 3 was found after X-ray exposure. Actin disorganization and increased apoptosis may be the potential effects of X-rays at high doses, by inhibiting osteoclast differentiation. Taken together, our data indicate high radiosensitivity of osteoclasts. X-ray irradiation at relatively low doses can activate osteoclastogenesis, but not osteogenic differentiation. The radiosensitive osteoclasts are the potentially responsive cells for X-ray-induced bone loss.
Paratrigeminal, Paraclival, Precavernous, or All of the Above? A Circumferential Anatomical Study of the C3-C4 Transitional Segment of the Internal Carotid Artery
Authors: Marcati Eleonora , Andaluz Norberto , Froelich Sebastien C , Zimmer Lee A , Leach James L , Fernandez-Miranda Juan Carlos , Kurbanov Almaz , Keller Jeffrey T
Published: May 2017

BACKGROUND

Although the term paraclival carotid pervades recent skull base literature, no clear consensus exists regarding boundaries or anatomical segments.

OBJECTIVE

To reconcile various internal carotid artery (ICA) nomenclatures for transcranial and endoscopic-endonasal perspectives, we reexamined the transition between lacerum (C3) and cavernous (C4) segments using a C1-C7 segments schema. In this cadaveric study, we obtained a 360°-circumferential view integrating histological, microsurgical, endoscopic, and neuroradiological analyses of this C3-C4 region and identified a distinct transitional segment.

METHODS

In 13 adult, silicone-injected, formalin-fixed cadaveric heads (26 sides), transcranial-extradural-subtemporal and endoscopic-endonasal CT­guided dissections were performed. A quadrilateral area was noted medial to Meckel's cave between cranial nerve VI, anterolateral and posterolateral borders of the lateral-paratrigeminal aspect of the precavernous ICA, and posterior longitudinal ligament. Endoscopically, a medial-paraclival aspect was defined. Anatomical correlations were made with histological and neuroradiological slides.

RESULTS

We identified a distinct precavernous C3-C4 transitional segment. In 18 (69%) specimens, venous channels were absent at the quadrilateral area, on the paratrigeminal border of the precavernous ICA. A trigeminal membrane, seen consistently on the superior border of V2, defined the lateral aspect of the cavernous sinus floor. The medial aspect of the precavernous ICA corresponded with the paraclival ICA.

CONCLUSION

Our study revealing the juncture of 2 complementary borders of the ICA, endoscopic endonasal (paraclival) and transcranial (paratrigeminal), reconciles various nomenclature. A precavernous segment may clarify controversies about the paraclival ICA and support the concept of a “safe door” for lesions involving Meckel's cave, cavernous sinus, and petrous apex.
Utilization of Quantitative Susceptibility Mapping for Direct Targeting of the Subthalamic Nucleus During Deep Brain Stimulation Surgery
Authors: Rasouli Jonathan , Ramdhani Ritesh , Panov Fedor E , Dimov Alexey , Zhang Yan , Cho Catherine , Wang Yi , Kopell Brian Harris
Published: May 2017

BACKGROUND

Deep brain stimulation of the subthalamic nucleus (STN) has demonstrated efficacy in improving motor disability in Parkinson's disease. The recently developed quantitative susceptibility mapping (QSM) technique, which can accurately map iron deposits in deep brain nuclei, promises precise targeting of the STN.

OBJECTIVE

To demonstrate the use of QSM to target STN effectively by correlating with classical physiological-based targeting measures in a prospective study.

METHODS

The precision and accuracy of direct targeting with QSM was examined in a total of 25 Parkinson's disease patients between 2013 and 2015 at our institution. QSM was utilized as the primary magnetic resonance imaging (MRI) method to perform direct STN targeting on a stereotactic planning station utilizing computed tomography/MR fusion. Intraoperative microelectrode recordings (MER) were obtained to confirm appropriate trajectory through the sensorimotor STN.

RESULTS

Estimations of STN thickness between the MER and QSM methods appeared to be correlated. Mean STN thickness was 5.3 mm. Kinesthetic responsive cells were found in > 90% of electrode runs. The mean radial error (±SEM) was 0.54 ± 0.1 mm. Satisfactory clinical response as determined by Unified Parkinson's Disease Rating Scale (UPDRS III) was seen at 12 mo after surgery.

CONCLUSION

Direct targeting of the sensorimotor STN using QSM demonstrates MER correlation and can be safely used for deep brain stimulation lead placement with satisfactory clinical response. These results imply that targeting based on QSM signaling alone is sufficient to obtain reliable and reproducible outcomes in the absence of physiological recordings.
Identification of Sources of Resistance to Blackleg (Leptosphaeria maculans) in a Brassica napus Germplasm Collection
Authors: Mansouripour Seyedmojtaba , Mendoza Luis E. del Río
Published: May 2017

The increased prevalence of strains of pathogenicity group 4 of Leptosphaeria maculans, causal agent of blackleg, represents a serious threat to the canola (Brassica napus L.) industry in North Dakota, a state that contributes >85% of U.S. canola production. The objective of this study was to identify sources of resistance to PG-4 in a collection of 559 B. napus plant introduction materials (PIs). Replicated trials were conducted twice in the greenhouse using a mixture of five PG-4 isolates to evaluate the reaction at seedling stage; then, an elite group of PIs was evaluated in replicated field trials between 2014 and 2016 at Langdon, ND, using a combination of lab-produced inoculum and blackleg-infested canola residues. Combined analysis of field data indicated three PIs had on average 73 to 80% less (P < 0.05) internal stem tissue discoloration than the commercial hybrids used as the controls. These PIs could be used in canola breeding programs as good sources of resistance against PG-4; in addition, efforts should be made to characterize the resistance they carry.
Diagnosis, Treatment, and Surgical Repair in a Case of Isolated Conjunctival Lichen Planus Causing Cicatricial Entropion
Authors: Cretara Elizabeth A. , Swan Robert T. , Hill Robert H.
Published: May 2017

A 50-year-old male presented with bilateral cicatricial entropion with subepithelial fibrosis and fornix foreshortening. Conjunctival biopsy showed lymphocytic infiltrate along the interface of the epithelium and lamina propria with linear, shaggy fibrinogen deposition along the epithelial basement membrane zone, supporting a diagnosis of lichen planus. The patient was treated with commercially available topical cyclosporine for 5 months after which bilateral lower eyelid splitting procedure with recession of the anterior lamella and complete excision of the lower eyelid lashes was performed.
Graft Function and Intermediate-Term Outcomes of Kidney Transplants Improved in the Last Decade: Analysis of the United States Kidney Transplant Database
Authors: Keith Douglas Scott , Vranic Gayle , Nishio-Lucar Angie
Published: May 2017

Background

Previous analyses of the United States transplant database regarding long-term outcomes in kidney transplantation have shown minimal improvement in the rate of long-term graft loss. This study sought to analyze intermediate-term outcomes and graft function at 6 months in kidney transplantation in adult living and deceased donor recipients in the last decade.

Methods

Survival analysis was performed based on the year of transplant between 6 months and 3 years’ posttransplant. The Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) was determined at 6 months.

Results

The unadjusted graft survival between 6 months and 3 years improved significantly in the latter half of the decade in both deceased and living donor kidney recipients. Cox analysis showed a 33% reduction in the rate of graft loss and that the improvement in graft survival was due to similar improvements in both death-censored graft and death with graft function survival. A 10% improvement in median eGFR occurred despite worsening donor demographics over time in both donor types. This improvement in eGFR and graft survival occurred in association with a consolidation of chronic discharge immunosuppression from a variety of combinations to over 85% of recipients receiving tacrolimus and mycophenolate derivative immunosuppression.

Conclusions

In the latter half of last decade graft survival improved in adult kidney transplant recipients. The improvement in graft survival occurred in temporal association with an improvement in median eGFR at 6 months and consolidation of discharge immunosuppression in most patients to tacrolimus and mycophenolate derivatives.
Discovery of novel representatives of bilaterian neuropeptide families and reconstruction of neuropeptide precursor evolution in ophiuroid echinoderms
Authors: Zandawala Meet , Moghul Ismail , Yañez Guerra Luis Alfonso , Delroisse Jérôme , Abylkassimova Nikara , Hugall Andrew F. , O’Hara Timothy D. , Elphick Maurice R.
Published: May 2017

Neuropeptides are a diverse class of intercellular signaling molecules that mediate neuronal regulation of many physiological and behavioural processes. Recent advances in genome/transcriptome sequencing are enabling identification of neuropeptide precursor proteins in species from a growing variety of animal taxa, providing new insights into the evolution of neuropeptide signaling. Here detailed analysis of transcriptome sequence data from three brittle star species,Ophionotus victoriae, Amphiura filiformisandOphiopsila aranea, has enabled the first comprehensive identification of neuropeptide precursors in the class Ophiuroidea of the phylum Echinodermata. Representatives of over thirty bilaterian neuropeptide precursor families were identified, some of which occur as paralogs. Furthermore, homologs of endothelin/CCHamide, eclosion hormone, neuropeptide-F/Y and nucleobinin/nesfatin were discovered here in a deuterostome/echinoderm for the first time. The majority of ophiuroid neuropeptide precursors contain a single copy of a neuropeptide, but several precursors comprise multiple copies of identical or non-identical, but structurally-related, neuropeptides. Here we performed an unprecedented investigation of the evolution of neuropeptide copy-number over a period of ~270 million years by analysing sequence data from over fifty ophiuroid species, with reference to a robust phylogeny. Our analysis indicates that the composition of neuropeptide “cocktails” is functionally important, but with plasticity over long evolutionary time scales.
Mapping the malaria parasite drug-able genome usingin vitroevolution and chemogenomics
Authors: Cowell Annie N. , Istvan Eva S. , Lukens Amanda K. , Gomez-Lorenzo Maria G. , Vanaerschot Manu , Sakata-Kato Tomoyo , Flannery Erika L. , Magistrado Pamela , Abraham Matthew , LaMonte Gregory , Williams Roy M. , Franco Virginia , Linares Maria , Arriaga Ignacio , Bopp Selina , Corey Victoria C. , Gnädig Nina F. , Coburn-Flynn Olivia , Reimer Christin , Gupta Purva , Murithi James M. , Fuchs Olivia , Sasaki Erika , Kim Sang W. , Teng Christine , Wang Lawrence T. , Willis Paul , Siegel Dionicio , Tanaseichuk Olga , Zhong Yang , Zhou Yingyao , Ottilie Sabine , Gamo Francisco-Javier , Lee Marcus C.S. , Goldberg Daniel E. , Fidock David A. , Wirth Dyann F. , Winzeler Elizabeth A.
Published: May 2017

Chemogenetic characterization throughin vitroevolution combined with whole genome analysis is a powerful tool to discover novel antimalarial drug targets and identify drug resistance genes. Our comprehensive genome analysis of 262Plasmodium falciparumparasites treated with 37 diverse compounds reveals how the parasite evolves to evade the action of small molecule growth inhibitors. This detailed data set revealed 159 gene amplifications and 148 nonsynonymous changes in 83 genes which developed during resistance acquisition. Using a new algorithm, we show that gene amplifications contribute to 1/3 of drug resistance acquisition events. In addition to confirming known multidrug resistance mechanisms, we discovered novel multidrug resistance genes. Furthermore, we identified promising new drug target-inhibitor pairs to advance the malaria elimination campaign, including: thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This deep exploration of theP. falciparumresistome and drug-able genome will guide future drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms of the deadliest malaria parasite.

One Sentence Summary

Whole genome sequencing reveals howPlasmodium falciparumevolves resistance to diverse compounds and identifies new antimalarial drug targets.
Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T Cell Decline and Per-Parasite Pathogenicity
Authors: Bertels Frederic , Marzel Alex , Leventhal Gabriel , Mitov Venelin , Fellay Jacques , Günthard Huldrych F , Böni Jürg , Yerly Sabine , Klimkait Thomas , Aubert Vincent , Battegay Manuel , Rauch Andri , Cavassini Matthias , Calmy Alexandra , Bernasconi Enos , Schmid Patrick , Scherrer Alexandra U , Müller Viktor , Bonhoeffer Sebastian , Kouyos Roger , Regoes Roland R ,   the Swiss HIV Cohort Study
Published: May 2017

Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as “per-parasite pathogenicity”. Using viral load and CD4+ T cell measures from 2014 HIV-1 subtype B infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence — measured as the rate of decline of CD4+ T cells — and per-parasite pathogenicity are heritable from donor to recipient. We estimated heritability by donor-recipient regressions applied to 196 previously identified transmission pairs, and by phylogenetic mixed models applied to a phylogenetic tree inferred from HIVpolsequences. Regressing the CD4+ T cell declines and per-parasite pathogenicities of the transmission pairs did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model, however, our best estimate for the heritability of the CD4+ T cell decline is 17% (5%–30%), and that of the per-parasite pathogenicity is 17% (4%–29%). Further, we confirm that the set-point viral load is heritable, and estimate a heritability of 29% (12%–46%). Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection for the set-point viral load, and with directional selection for the CD4+ T cell decline and the per-parasite pathogenicity. Our analysis shows that the viral genetype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor.
Investigating The Functional Consequence Of White Matter Damage: An Automatic Pipeline To Create Longitudinal Disconnection Tractograms
Authors: Jordan Kesshi Marin , Keshavan Anisha , Caverzasi Eduardo , Osorio Joseph , Papinutto Nico , Amirbekian Bagrat , Berger Mitchel S. , Henry Roland G.
Published: May 2017

Neurosurgical resection is one of the few opportunities researchers have to image the human brain both prior to and following focal damage. One of the challenges associated with studying brains undergoing surgical resection is that they often do not fit the brain templates most image-processing methodologies are based on, so manual intervention is required to reconcile the pathology and the most extreme cases must be excluded. Manual intervention requires significant time investment and introduces reproducibility concerns. We propose an automatic longitudinal pipeline based on High Angular Resolution Diffusion Imaging acquisitions to facilitate a Pathway Lesion Symptom Mapping analysis relating focal white matter injury to functional deficits. This two-part approach includes (i) automatic segmentation of focal white matter injury from anisotropic power differences, and (ii) modeling disconnection using tractography on the single-subject level, which specifically identifies the disconnections associated with focal white matter damage. The advantages of this approach stem from (1) objective and automatic lesion segmentation and tractogram generation, (2) objective and precise segmentation of affected tissue likely to be associated with damage to long-range white matter pathways (defined by anisotropic power), (3) good performance even in the cases of anatomical distortions by use of nonlinear tensor-based registration in the patient space, which aligns images using white matter contrast. Mapping a system as variable and complex as the human brain requires sample sizes much larger than the current technology can support. This pipeline can be used to execute large-scale, sufficiently powered analyses by meeting the need for an automatic approach to objectively quantify white matter disconnection.
Transparency in Authors’ Contributions and Responsibilities to Promote Integrity in Scientific Publication
Authors: McNutt Marcia , Bradford Monica , Drazen Jeffrey , Hanson Brooks , Howard Bob , Jamieson Kathleen Hall , Kiermer Véronique , Magoulias Michael , Marcus Emilie , Pope Barbara Kline , Schekman Randy , Swaminathan Sowmya , Stang Peter , Verma Inder
Published: May 2017

In keeping with the growing movement in scientific publishing toward transparency in data and methods, we argue that the names of authors accompanying journal articles should provide insight into who is responsible for which contributions, a process should exist to confirm that the list is complete, clearly articulated standards should establish whether and when the contributions of an individual justify authorship credit, and those involved in the generation of scientific knowledge should follow these best practices.

To accomplish these goals, we recommend that journals adopt common and transparent standards for authorship, outline responsibilities for corresponding authors, adopt the CRediT (Contributor Roles Taxonomy)1methodology for attributing contributions, include this information in article metadata, and encourage authors to use the digital persistent identifier ORCID.2Furthermore, we suggest that research institutions have regular open conversations on authorship criteria and ethics and that funding agencies adopt ORCID and accept CRediT. Scientific societies should further authorship transparency by promoting these recommendations through their meetings and publications programs.
Consequences of NMDA receptor deficiency can be rescued in the adult brain
Authors: Mielnik Catharine A. , Binko Mary A. , Funk Adam J. , Johansson Emily M. , Intson Katheron , Sivananthan Nirun , Chen Yuxiao , Islam Rehnuma , Milenkovic Marija , Horsfall Wendy , Ross Ruth A. , Tripathy Shreejoy , Groc Laurent , Salahpour Ali , McCullumsmith Robert E. , Lambe Evelyn K. , Ramsey Amy J.
Published: May 2017

N-methyl-D-aspartate receptors (NMDARs) are required to shape activity-dependent connections in the developing and adult brain. Impaired NMDAR signaling through genetic or environmental insults causes a constellation of neurodevelopmental disorders that manifest as intellectual disability, epilepsy, autism, or schizophrenia. It is not clear whether the developmental impacts of NMDAR dysfunction can be overcome by interventions in adulthood. This question is paramount for neurodevelopmental disorders arising from mutations that occur in theGRINgenes, which encode NMDAR subunits, and the broader set of mutations that disrupt NMDAR function. We developed a mouse model where a congenital loss-of-function allele ofGrin1is restored to wildtype by gene editing with Cre recombinase. Rescue of NMDARs in adult mice yields surprisingly robust improvements in cognitive behaviors, including those that are refractory to treatment with current medications. These results suggest that neurodevelopmental disorders arising from NMDAR deficiency can be effectively treated in adults.
Oscillatory default mode network coupling in concussion
Authors: Dunkley B.T , Urban K. , Da Costa L. , Wong S. , Pang E.W. , Taylor M.J.
Published: May 2017

Background

Concussion is a common form of mild traumatic brain injury (mTBI). Despite the descriptor ‘mild’, a single injury can leave long-lasting and sustained alterations to brain function, including changes to localised activity and large-scale interregional communication. Cognitive complaints are thought to arise from such functional deficits. We investigated the impact of injury on neurophysiological and functionally-specialised resting networks, known as intrinsic connectivity networks (ICNs), using MEG.

Methods

We assessed neurophysiological connectivity in 40 males, 20 with concussion, 20 without, using MEG. Regions-of-interest that comprise nodes of ICNs were defined, and their time courses derived using a beamformer approach. Pairwise fluctuations and covariations in band-limited amplitude envelopes were computed reflecting measures of functional connectivity. Intra-network connectivity was compared between groups using permutation testing, and correlated with symptoms.

Results

We observedincreasedresting spectral connectivity in the default mode and motor networks in our concussion group when compared with controls, across alpha through gamma ranges. Moreover, these differences were not explained by power spectrum density (absolute changes in the spectral profiles within the ICNs). Furthermore, this increased coupling was significantly associated with symptoms in the DMN and MOT networks – but once accounting for comorbid symptoms (including, depression, anxiety, and ADHD) only the DMN continued to be associated with symptoms.

Conclusion

The DMN network plays a critical role in shifting between cognitive tasks. These data suggest even a single concussion can perturb the intrinsic coupling of functionally-specialised networks in the brain and may explain persistent and wide-ranging symptomatology.
A robust dissociation among the language, multiple demand, and default mode networks: evidence from inter-region correlations in effect size
Authors: Mineroff Zachary , Blank Idan , Mahowald Kyle , Fedorenko Evelina
Published: May 2017

Complex cognitive processes, including language, rely on multiple mental operations that are carried out by several large-scale functional networks in the frontal, temporal, and parietal association cortices of the human brain. The central division of cognitive labor is between two fronto-parietal bilateral networks: (a) the multiple demand (MD) network, which supports executive processes, such as working memory and cognitive control, and is engaged by diverse task domains, including language, especially when comprehension gets difficult; and (b) the default mode network (DMN), which supports introspective processes, such as mind wandering, and is active when we are not engaged in processing external stimuli. These two networks are strongly dissociated in both their functional profiles and their patterns of activity fluctuations during naturalistic cognition. Here, we focus on the functional relationship between these two networks and a third network: (c) the fronto-temporal left-lateralized “core” language network, which is selectively recruited by linguistic processing. Is the language network distinct and dissociated from both the MD network and the DMN, or is it synchronized and integrated with one or both of them? Recent work has provided evidence for a dissociation between the language network and the MD network. However, the relationship between the language network and the DMN is less clear, with some evidence for coordinated activity patterns and similar response profiles, perhaps due to the role of both in semantic processing. Here we use a novel fMRI approach to examine the relationship among the three networks: we measure the strength of activations in different language, MD, and DMN regions to functional contrasts typically used to identify each network, and then test which regions co-vary in their contrast effect sizes across 60 individuals. We find that effect sizes correlate strongly within each network (e.g., one language region and another language region, or one DMN region and another DMN region), but show little or no correlation for region pairs across networks (e.g., a language region and a DMN region). Thus, we replicate the language/MD network dissociation discovered previously with other methods, and also show that the language network is robustly dissociated from the DMN, overall suggesting that these three networks support distinct computations and contribute to high-level cognition in different ways. Inter-individual differences in effect sizes therefore do not simply reflect general differences in vascularization or attention, but exhibit sensitivity to the functional architecture of the brain. The strength of activation in each network can thus be probed separately in studies that attempt to link neural variability to behavioral or genetic variability.
High-NA open-top selective-plane illumination microscopy for biological imaging
Authors: McGorty Ryan , Xie Dan , Huang Bo
Published: May 2017

Selective-plane illumination microscopy (SPIM) provides unparalleled advantages for volumetric imaging of living organisms over extended times. However, the spatial configuration of a SPIM system often limits its compatibility with many widely used biological sample holders such as multi-well chambers and plates. To solve this problem, we developed a high numerical aperture (NA) open-top configuration that places both the excitation and detection objectives on the opposite of the sample coverglass. We carried out a theoretical calculation to analyze the structure of the system-induced aberrations. We then experimentally compensated the system aberrations using adaptive optics combined with static optical components, demonstrating near-diffraction-limited performance in imaging fluorescently labeled cells.

© 2017 Optical Society of America

OCIS codes:(080.080) Geometric Optics; (110.0110) Imaging systems; (110.0180) Microscopy.
Assigning function to natural allelic variation via dynamic modeling of gene network induction
Authors: Richard Magali , Chuffart Florent , Duplus-Bottin Hélène , Pouyet Fanny , Spichty Martin , Fulcrand Etienne , Entrevan Marianne , Barthelaix Audrey , Springer Michael , Jost Daniel , Yvert Gaёl
Published: May 2017

More and more natural DNA variants are being linked to physiological traits. Yet, understanding what differences they make on molecular regulations remains challenging. Important properties of gene regulatory networks can be captured by computational models. If model parameters can be ‘personalized’ according to the genotype, their variation may then reveal how DNA variants operate in the network. Here, we combined experiments and computations to visualize natural alleles of the yeastGAL3gene in a space of model parameters describing the galactose response network. Alleles altering the activation of Gal3p by galactose were discriminated from those affecting its activity (production/degradation or efficiency of the activated protein). The approach allowed us to correctly predict that a non-synonymous SNP would change the binding affinity of Gal3p with the Gal80p transcriptional repressor. Our results illustrate how personalizing gene regulatory models can be used for the mechanistic interpretation of genetic variants.