bluuebunny/crossref_metadata_2025 huggingface dataset:
From globular clusters to the disc: the dual life of our Galaxy
Authors: Recio-Blanco Alejandra
Published: November 2018

The halo and disc globular cluster population can be used as a tracer of the primordial epochs of the Milky Way formation. In this work, literature data of globular clusters ages, chemical abundances, and structural parameters are studied, explicitly focussing on the origin of the known split in the age-metallicity relation (AMR) of globular clusters. When the α-element abundances, which are less strongly affected by the internal light-element spread of globular clusters (Si, Ca), are considered, a very low observational scatter among metal-poor clusters is observed. A plateau at [SiCa/Fe],∼ 0.35 dex, with a dispersion of only 0.05 dex (including abundance errors) is observed up to a metallicity of about −0.75 dex. Only a few metal-poor clusters in this metallicity interval present low [SiCa/Fe] abundances. Moreover, metal-rich globular clusters show a knee in the [α/Fe] vs. [Fe/H] plane around [Fe/H] ∼ −0.75 dex. As a consequence, if a substantial fraction of galactic globular clusters has an external origin, they have to be mainly formed either in galaxies that are massive enough to ensure high levels of α-element abundances even at intermediate metallicity, or in lower mass dwarf galaxies accreted by the Milky Way in their early phases of formation. Finally, clusters in the metal-poor branch of the AMR present an anti-correlation of [SiCa/Fe] with the total cluster magnitude, while this is not the case for metal-rich branch clusters. In addition, this lack of faint high-α clusters in the young metal-poor population is in contrast with what is observed for old and more metal-poor clusters, possibly reflecting a higher heterogeneity of formation environments at lower metallicity. Accretion of high-mass satellites, as a major contribution to the current Milky Way globular cluster system both in the metal-poor and the metal-intermediate regime is compatible with the observations.
Exploring the stellar properties of M dwarfs with high-resolution spectroscopy from the optical to the near-infrared
Authors: Rajpurohit A. S. , Allard F. , Rajpurohit S. , Sharma R. , Teixeira G. D. C. , Mousis O. , Kamlesh R.
Published: November 2018

Context. Being the most numerous and oldest stars in the galaxy, M dwarfs are objects of great interest for exoplanet searches. The presence of molecules in their atmosphere complicates our understanding of their atmospheric properties. But great advances have recently been made in the modeling of M dwarfs due to the revision of solar abundances.

Aims. We aim to determine stellar parameters of M dwarfs using high resolution spectra (R ∼ 90 000) simultaneously in the visible and the near-infrared. The high resolution spectra and broad wavelength coverage provide an unique opportunity to understand the onset of dust and cloud formation at cool temperatures. Furthermore, this study will help in understanding the physical processes which occur in a cool atmospheres, particularly, the redistribution of energy from the optical to the near-infrared.

Methods. The stellar parameters of M dwarfs in our sample have been determined by comparing the high resolution spectra both in the optical and in the near-infrared simultaneously observed by CARMENES with the synthetic spectra obtained from the BT-Settl model atmosphere. The detailed spectral synthesis of these observed spectra both in the optical and in the near-infrared helps to understand the missing continuum opacity.

Results. For the first time, we derive fundamental stellar parameters of M dwarfs using the high resolution optical and near-infrared spectra simultaneously. We determine Teff, log g and [M/H] for 292 M dwarfs of spectral type M0 to M9, where the formation of dust and clouds are important. The derived Teff for the sample ranges from 2300 to 4000 K, values of log g ranges from 4.5 ≤ logg ≤ 5.5 and the resulting metallicity ranges from −0.5 ≤ [M/H] ≤ +0.5. We have also explored the possible differences in Teff, log g and [M/H] by comparing them with other studies of the same sample of M dwarfs.
Klinischer Nutzen der molekularen Diagnostik pädiatrischer Hirntumore
Authors: Milde Till , Witt Olaf
Published: November 2018

Die Fortschritte der molekularen Diagnostik haben neue Türen für die Diagnosestellung, Risikostratifizierung und Präzisionsonkologie für Kinder mit Hirntumoren aufgestoßen. Dieses Wissen konsequent und systematisch in einen klinischen Nutzen zu übertragen wird Aufgabe der kommenden Jahre sein.
Morphological, environmental and management factors affecting nutritive value of tall fescue (Lolium arundinaceum)
Authors: Insua J. R. , Agnusdei M. G. , Utsumi S. A. , Berone G. D.
Published: November 2018

The aim of this study was to quantify the relative importance of leaf age and leaf length on the dynamics of neutral detergent fibre (NDF), and 24-h in vitro digestibility of NDF (NDFD) and dry matter (DMD) of tall fescue (Lolium arundinaceum (Schreb) Darbysh.). Mini-swards were conditioned and used to conduct two experiments, the first with 4-cm plant stubble height in spring–summer 2009 and autumn–winter 2011, and the second with 4-cm or 10-cm plant stubble height in spring–summer 2011. Plants were harvested at consecutive leaf-appearance intervals to measure nutritive value up to the four-leaf stage. In parallel, leaf morphogenetic traits (appearance, elongation and lifespan) and sheath length of the successive leaves produced on marked tillers were measured. Leaf NDF contents remained stable with increasing leaf age and length but showed a marked variation across seasons. Leaf NDFD and DMD showed a consistent decrease with increasing leaf age and length, and irrespective of growing season or residual pasture height. The negative effect of leaf age and length on digestibility was related to variations in sheath tube length and associated differences in leaf appearance and elongation rates. These findings highlight the relevance of monitoring the sheath tube length as a complementary measure to leaf stage for further management of the NDFD and DMD of grass forages. Although the focus of this study was tall fescue swards, the same morphogenetic implications on forage nutritive value could apply to other temperate and tropical grass species; however, the testing of this hypothesis warrants carefully controlled investigations.
First record of a dugong (Dugong dugon Müller, 1776) in Fiji
Authors: Hill-Lewenilovo Renee , Vuiyasawa Roko , Piovano Susanna
Published: November 2018

We report the first record of a dugong (Dugong dugon Müller, 1776) in Fiji. The dugong, probably a vagrant, was found dead on 20 May 2018 at more than 600 km from the nearest known dugong population, which is in Vanuatu. The dugong, a 2-m-long female, was 13 years old.
A prospective evaluation of contingent loans as a means of financing wild dog exclusion fences
Authors: Cockfield Geoff , Botterill Linda Courtenay , Kelly Simon
Published: November 2018

Invasive species, such as wild dogs can be considered an externality arising from the activities of pastoral enterprises, with producers having limited responsibility for the problem and limited capacity to mitigate it. There are therefore arguments for government intervention through encouraging both individual and collective control measures. Governments are however increasingly inclined to ensure recipients of support make some contribution where there are private benefits. An example of this, in Australia, is the requirement that students repay some of the cost of their tertiary education. Using the issue of wild dog exclusion fencing in south-west Queensland as a case study, this paper considers if and how a policy instrument adopted for higher education (HECS-HELP), contingent loans, could be adapted to address problems of externalities in rural Australia. Central to the issue of exclusion fences are high upfront costs and highly variable incomes that limit the ability to recoup those costs according to a predictable timeline. Considering a range of incomes and a variety of private/government shares of the cost of the fences, we examine the effects of revenue contingent loans for the construction of these fences, using model farms developed from survey data for farm businesses in south-west Queensland. We find that contingent loans could mitigate the hardship effects of additional debt and variable incomes. Businesses with smaller properties and relatively lower incomes may however struggle to pay back larger loans. Using south-west Queensland as a case study, we show how different shares of contributions change the time to pay back loans, outline how a contingent loan scheme might be administered and note some issues with integrating personal contingent loans into a collective fence arrangement.
Physical and microclimate characteristics of Nyctophilus gouldi and Vespadelus vulturnus maternity-roost cavities
Authors: Rueegger Niels , Goldingay Ross , Law Brad
Published: November 2018

Context Tree cavities suitable to rear young are a key resource in managed landscapes to support viable populations of tree cavity-roosting bats. Little is known about the selection of cavities for maternity roosts, presumably because of the difficulty in accessing such roosts. Aims Our study investigated physical and microclimate characteristics of maternity roosts of two species, namely, Gould’s long-eared bat (Nyctophilus gouldi) and little forest bat (Vespadelus vulturnus). Methods Maternity-roost cavities were identified in a timber-production landscape in south-eastern Australia. Roost trees (V. vulturnus n=5; N. gouldi n=9) and a subsample of available cavity-bearing trees (n=16) were climbed to obtain cavity characteristics. Key results Vespadelus vulturnus used tree hollows exclusively, whereas N. gouldi used both tree hollows (n=7) and thick loose bark (n=2). No significant difference in roost-cavity characteristics was detected between the species. However, V. vulturnus selected significantly narrower cavity entrances (mean: 16±3mm) than those of the available cavities. Temperature did not differ between maternity roosts and available cavities when investigated after the maternity season. However, a V. vulturnus maternity roost occupied for 33 consecutive days was warmer than mean roost and available cavities, suggesting that long-term roost use may be influenced by the thermal property of a cavity. Conclusions Our study has provided the first detailed tree-cavity description of maternity roosts of N. gouldi and V. vulturnus. The nightly roost switching and the large variation of tree-cavity characteristics used by N. gouldi suggest that this species requires a high density of non-specific tree cavities that are large enough for colony formation, whereas preferred roost cavities for V. vulturnus are likely to be hollows comprising narrow entrances that facilitate long-term use. Implications Our results highlighted the likely importance of narrow roost entrances for V. vulturnus, presumably for predator protection, and the conservation of tree cavities large enough for colonies to congregate. The formation of such hollows is likely to take many decades. Poor silvicultural practices, land clearing and inappropriate management of veteran trees have the potential to have an impact on this hollow resource. Our study also highlighted the need to further assess the importance of cavity microclimate for maternity-roost selection in warm climates.
Excitability of oxytocin neurons in paraventricular nucleus is regulated by voltage-gated potassium channels Kv4.2 and Kv4.3
Authors: Imai Ryota , Yokota Shoko , Horita Shoichiro , Ueta Yoichi , Maejima Yuko , Shimomura Kenju
Published: November 2018

Oxytocin is produced by neurons in the paraventricular nucleus (PVN) and the supraoptic nucleus in the hypothalamus. Various ion channels are considered to regulate the excitability of oxytocin neurons and its secretion. A-type currents of voltage-gated potassium channels (Kv channels), generated by Kv4.2/4.3 channels, are known to be involved in the regulation of neuron excitability. However, it is unclear whether the Kv4.2/4.3 channels participate in the regulation of excitability in PVN oxytocin neurons. Here, we investigated the contribution of the Kv4.2/4.3 channels to PVN oxytocin neuron excitability. By using transgenic rat brain slices with the oxytocin-monomeric red fluorescent protein 1 fusion transgene, we examined the excitability of oxytocin neurons by electrophysiological technique. In some oxytocin neurons, the application of Kv4.2/4.3 channel blocker increased firing frequency and membrane potential with extended action potential half-width. Our present study indicates the contribution of Kv4.2/4.3 channels to PVN oxytocin neuron excitability regulation.

Abbreviation: PVN, paraventricular nucleus; Oxt-mRFP1, Oxt-monometric red fluorescent protein 1; PaTx-1, Phrixotoxin-1; TEA, Tetraethylammonium Chloride; TTX, tetrodotoxin; aCSF, artificial cerebrospinal fluid;PBS, phosphate buffered saline 3v, third ventricle.
BiXGBoost: a scalable, flexible boosting-based method for reconstructing gene regulatory networks
Authors: Zheng Ruiqing , Li Min , Chen Xiang , Wu Fang-Xiang , Pan Yi , Wang Jianxin
Published: November 2018

Motivation

Reconstructing gene regulatory networks (GRNs) based on gene expression profiles is still an enormous challenge in systems biology. Random forest-based methods have been proved a kind of efficient methods to evaluate the importance of gene regulations. Nevertheless, the accuracy of traditional methods can be further improved. With time-series gene expression data, exploiting inherent time information and high order time lag are promising strategies to improve the power and accuracy of GRNs inference.

Results

In this study, we propose a scalable, flexible approach called BiXGBoost to reconstruct GRNs. BiXGBoost is a bidirectional-based method by considering both candidate regulatory genes and target genes for a specific gene. Moreover, BiXGBoost utilizes time information efficiently and integrates XGBoost to evaluate the feature importance. Randomization and regularization are also applied in BiXGBoost to address the over-fitting problem. The results on DREAM4 and Escherichia coli datasets show the good performance of BiXGBoost on different scale of networks.

Availability and implementation

Our Python implementation of BiXGBoost is available at https://github.com/zrq0123/BiXGBoost.

Supplementary information

Supplementary data are available at Bioinformatics online.
“The British Soldier is no Bolshevik”: The British Army, Discipline, and the Demobilization Strikes of 1919
Authors: Butler William
Published: November 2018

This article considers the breakdown in discipline in the British Army which occurred in Britain and on the Western Front during the process of demobilization at the end of the First World War. Many soldiers, retained in the army immediately after the Armistice, went on strike, and some formed elected committees, demanding their swifter return to civilian life. Their perception was that the existing demobilization system was unjust, and men were soon organized by those more politically conscious members of the armed forces who had enlisted for the duration of the war. At one stage in January 1919, over 50,000 soldiers were out on strike, a fact that was of great concern to the British civilian and military authorities who miscalculated the risk posed by soldiers. Spurred on by many elements of the press, especially the Daily Mail and Daily Herald, who both fanned and dampened the flames of discontent, soldiers’ discipline broke down, demonstrating that the patriotism which had for so long kept them in line could only extend so far. Though senior members of the government, principally Winston Churchill, and the military, especially Douglas Haig and Henry Wilson, were genuinely concerned that Bolshevism had ‘infected’ the army, or, at the very least, the army had been unionized, their fears were not realized. The article examines the government’s strategy regarding demobilization, its efforts to assess the risk of politicization and manage the press, and its responses to these waves of strikes, arguing that, essentially, these soldiers were civilians first and simply wanted to return home, though, in the post-war political climate, government fears were very real.
Phylogeny, Distribution, and Pathogenicity of Lasiodiplodia Species Associated With Cankers and Dieback Symptoms of Persian Lime in Mexico
Authors: Bautista-Cruz M. A. , Almaguer-Vargas G. , Leyva-Mir S. G. , Colinas-León M. T. , Correia K. C. , Camacho-Tapia M. , Robles-Yerena L. , Michereff S. J. , Tovar-Pedraza J. M.
Published: November 2018

Persian lime (Citrus latifolia Tan.) is an important and widely cultivated fruit crop in several regions of Mexico. In recent years, severe symptoms of gummosis, stem cankers, and dieback were detected in the Persian lime-producing region in the states of Veracruz and Puebla, Mexico. The aims of this study were to identify the species of Lasiodiplodia associated with these symptoms, determine the distribution of these species, and test their pathogenicity and virulence on Persian lime plants. In 2015, symptomatic samples were collected from 12 commercial Persian lime orchards, and 60 Lasiodiplodia isolates were obtained. Fungal identification of 32 representative isolates was performed using a phylogenetic analysis based on DNA sequence data of the internal transcribed spacer region and part of the translation elongation factor 1-α and β-tubulin genes. Sequence analyses were carried out using the Maximum Likelihood and Bayesian Inference methods. Six Lasiodiplodia species were identified as Lasiodiplodia pseudotheobromae, Lasiodiplodia theobromae, Lasiodiplodia brasiliense, Lasiodiplodia subglobosa, Lasiodiplodia citricola, and Lasiodiplodia iraniensis. All Lasiodiplodia species of this study are reported for the first time in association with Persian lime in Mexico and worldwide. L. pseudotheobromae (46.9% of isolates) was the most frequently isolated species followed by L. theobromae (28.1%) and L. brasiliense (12.5%). Pathogenicity on Persian lime young plants using a mycelial plug inoculation method showed that all identified Lasiodiplodia species were able to cause necrotic lesions and gummosis, but L. subglobosa, L. iraniensis, and L. pseudotheobromae were the most virulent.
Serial Third-Trimester Ultrasonography Compared With Routine Care in Uncomplicated Pregnancies
Authors: Ashimi Balogun Olaide , Sibai Baha M. , Pedroza Claudia , Blackwell Sean C. , Barrett Tyisha L. , Chauhan Suneet P.
Published: November 2018

OBJECTIVE:

Among uncomplicated pregnancies, serial third-trimester ultrasound examinations identified significantly more cases with a composite of fetal growth or amniotic fluid abnormalities (27%) than did routine fundal height measurements (8%).

METHODS:

Women without complications between 24 0/7 and 30 6/7 weeks of gestation were randomized (NCT0270299) to either routine care (control arm) or ultrasound examination every 4 weeks (intervention arm). The primary outcome was a composite of abnormalities of fluid volume and growth: oligohydramnios or polyhydramnios; fetal growth restriction; or large for gestational age. The secondary outcome was the presence of composite maternal or neonatal morbidity among the two groups. A total of 206 participants was needed to have 80% power to detect an increase in the primary composite outcome from 10% in control to 25% in the intervention group (baseline rate 10%; two-tailed; α=0.05; loss to follow-up 5%). All women were included in the intent-to-treat analysis. Fisher exact, χ2 tests, or two-sample t tests were used to assess group differences.

RESULTS:

From July 11, 2016, to May 24, 2017, 852 women were screened for eligibility and 206 were randomized as follows: 102 in routine care and 104 in serial ultrasound examinations. The two groups were comparable in baseline characteristics. The primary composite outcome was significantly higher among women who were in the ultrasound examination group than the routine care group (27% vs 8%; relative risk 3.43, 95% CI 1.64–7.17); five women (95% CI 3–11) were needed to identify at least one of the composite ultrasound abnormalities. Although we were underpowered to detect a significant difference, the following secondary endpoints occurred with similar frequency in the ultrasound examination group than the routine care group: induction resulting from abnormal ultrasound examination findings (14% vs 6%), cesarean delivery in labor (5% vs 6%), and prespecified composite maternal morbidity (9% in both groups) and composite neonatal morbidity (1% vs 4%).

CONCLUSION:

Among uncomplicated pregnancies between 24 0/7 and 30 6/7 weeks of gestation, serial third-trimester ultrasound examinations were significantly more likely to identify abnormalities of fetal growth or amniotic fluid than measurements of fundal height and indicated ultrasound examination. No differences in maternal and neonatal outcomes were noted, although we were underpowered for these endpoints.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02702999.
Obesity Is Associated with Driveline Infection of Left Ventricular Assist Devices
Authors: Akay Mehmet H. , Nathan Sriram S. , Radovancevic Rajko , Poglajen Gregor , Jezovnik Mateja K. , Candelaria Isabella N. , Averill Barbara L. , Patel Manish K. , Kar Biswajit , Gregoric Igor D.
Published: November 2018

In patients with left ventricular assist devices (LVADs), the association of driveline infection (DLI) and body mass index (BMI) remains controversial. The aim of this study was to explore a potential correlation between BMI and DLI in the LVAD patient population. A retrospective, single-center study evaluated patients who underwent LVAD implantation between May 2012 and July 2016. Driveline infection was evaluated per Interagency Registry for Mechanically Assisted Circulatory Support established criteria. Of 222 included patients, 80% were male, the average age was 55 years, and the main underlying heart failure diagnosis was nonischemic cardiomyopathy (56%). The majority of patients (65%) received LVAD as destination therapy and 35% as a bridge to transplantation. Average time-to-first DLI was 296 days after LVAD implantation. In comparison to non-DLI group (80%, N = 177), patients in DLI group (20%, N = 45) had a higher BMI (33.5 ± 8.3 kg/m2 in DLI group vs. 28.8 ± 7.5 kg/m2 in non-DLI group, p = 0.0003) and were younger (51 ± 12 years in DLI group vs. 56 ± 12 years in non-DLI group, p = 0.013). There was a significant correlation between BMI and DLI (p < 0.0001), and age was negatively correlated with DLI (p = 0.01). Analysis revealed no correlation between time-to-first DLI and BMI. Our data confirm that higher BMI is associated with increased prevalence of DLI in LVAD population, particularly in younger patients. Addressing excessive body weight in this patient cohort may significantly reduce DLI and thereby improve long-term outcomes.
Prognosis of a rare subtype of thyroid cancer
Authors: Liu Zeming , Zhao Qiuyang , Zeng Wen , Wang Shuntao , Xiong Yiquan , Guo Hui , Huang Tao , Cheng Hongtao , Guo Liang
Published: November 2018

Systemic illustrations of spindle cell thyroid cancer (SCTC), based on a large cohort, are few. We investigated the prognosis of SCTC compared to the most common subtypes, papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC).

Information of patients with a diagnosis of SCTC, PTC, or FTC, between 2004 and 2013, was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Patient survival curves were investigated using Kaplan–Meier analyses, log-rank tests, and Cox proportional hazards regression analyses.

In a Kaplan–Meier analysis of the entire cohort of thyroid cancer patients, cancer specific survival declined sharply for patients with SCTC, but declined more modestly for patients with PTC and FTC. Unadjusted Cox regression analysis and Kaplan–Meier curve analysis showed that SCTC had a poorer cancer-specific mortality and all-cause mortality compared to PTC and FTC. Similar results were obtained after adjustment for different confounding factors.

Our study assessed the prognosis of SCTC, based on a large cohort, compared to PTC and FTC, and found relatively accurate hazard ratios of death rate in SCTC as compared to PTC and FTC. Thus, our findings would provide beneficial insights on patients with SCTC, and aid in treatment decision making, more radical treatment like total-thyoridectomy and/or plus central lymph node dissection should be performed for patients with SCTC.
Layer-specific strain analysis of left ventricular myocardium after alcohol septal ablation for hypertrophic obstructive cardiomyopathy
Authors: Zhang Juan , Zhu Linlin , Jiang Xiaomin , Hu Zuoying
Published: November 2018

Introduction:

We aimed to explore the layer-specific systolic strain of left ventricular (LV) myocardium in patients with hypertrophic obstructive cardiomyopathy (HOCM) before and after alcohol septal ablation (ASA).

The routine 2D (frame rate: >50 Hz) data sets were acquired using GE Vivi7 system for 44 consecutive HOCM patients and 21 matched normal subjects. Fifteen of HOCM patients had serial echocardiograms available for speckle tracking analyses before and 1 year after ASA. 2D strain was analyzed by EchoPAC software.

The layer strain from inner to mid-myocardial and outer layers in basal and middle segments in HOCM patients continuously declined. The absolute values of peak systolic strains from the endocardium to mid-myocardium and epicardium in the basal septum of the HOCM group were significantly lower than those of the normal group (P <.01). Meanwhile, the layer systolic strain of LV endocardium in the basal septum increased significantly during a 1-year follow-up (P <.05).

Conclusions:

The layer-specific strains of HOCM patients measured by tissue Doppler echocardiography decreased significantly compared to those of normal individuals. The increased specific layer strain of LV endocardium in the basal septum may be a valid marker of echocardiographic improvement in HOCM patients receiving ASA.
Routine coagulation test abnormalities caused by rivaroxaban
Authors: Song Zikai , Wu Haidi , Cao Hongyan , Yang Shuo , Tang Minglong , Qin Ling
Published: November 2018

Rationale:

Rivaroxaban is a non-vitamin K antagonist oral anticoagulant. Current recommendations state that coagulation monitoring is not required, and neither the dose nor dosing interval requires adjustment in response to changes in coagulation parameters when rivaroxaban is used for approved indications. Guidelines mainly discuss the indications for rivaroxaban and non-vitamin K antagonist oral anticoagulants in general; they offer less guidance regarding how to use these medications in specific clinical situations to bridge the gulf between guidelines and clinical practice.

Patient concerns:

An 88-year-old man with a long history of atrial fibrillation presented to the hospital with worsening dyspnea and chest pain. Significantly, he had an estimated glomerular filtration rate of 46.7 mL/min. He was prescribed oral rivaroxaban 20 mg once daily. After 7 days, the patient complained of maroon colored stools.

Diagnosis:

Laboratory investigations revealed that the patient's prothrombin time (PT) and activated partial thromboplastin time (aPTT) were elevated. Rivaroxaban induced gastrointestinal bleeding was suspected.

Interventions:

Rivaroxaban was discontinued and routine coagulation tests were monitored daily.

Outcomes:

Two days following the discontinuation of the drug, the bleeding was controlled and hemoglobin was normal, but the PT and aPTT remained abnormal. On the third day after discontinuing rivaroxaban, the patient experienced sudden syncope and pulselessness and expired.

Lessons:

This case indicates that in real-world situations, a small number of patients may develop changes in both PT and aPTT during rivaroxaban therapy. Therefore, coagulation monitoring should be considered in patients with risk factors for bleeding, such as elderly patients with renal insufficiency.
Chylous Ascites: Complication of Laparoscopic Donor Nephrectomy. Case Report and Review of Literature
Authors: Seth Abhinav , Sharma Ashish , Kenwar Deepesh Benjamin , Singh Sarbpreet
Published: November 2018

Background.

Chylous ascites (CA) is an extremely rare complication after laparoscopic donor nephrectomy (LDN). It can increase the hospital stay, morbidity in postoperative period and thus negating the benefits of laparoscopic surgery. Most of the cases were managed conservatively, but surgical intervention may be occasionally required. This report describes the importance of accurate localization of the leaking chyle duct and its repair by endosuturing in a renal donor not responding to conservative treatment.

Methods.

A comprehensive review of literature regarding this rare complication after LDN was performed with Pubmed/Medline and Google Scholar using “chyle,” “complications,” and “laparoscopic donor nephrectomy” as keywords. The demographic profile and management of patients is discussed in detail. The various surgical modalities used to manage these patients are described.

Results.

Fifty-four cases of chyle leak/ascites have been reported after LDN in literature to date. Around 77% donors with CA could be successfully managed conservatively with dietary measures and total parenteral nutrition. Surgical intervention was required in nearly 23% donors ranging from clip application, use of argon coagulation, endosuturing with application of glue after 36.1 ± 19.07 days of failed conservative treatment. Donors with massive ascites or requiring frequent large-volume paracentesis on conservative treatment are likely to require surgical therapy. The present case was successfully managed with laparoscopic endosuturing and has no recurrence at 6 month follow-up.

Conclusions.

Chylous ascites is a rare complication after donor nephrectomy in experienced centers. Although conservative management remains the first line of treatment, early surgical treatment shall be undertaken in cases of massive ascites.
Regulatory mechanisms for the axonal localization of tau in neurons
Authors: Iwata Minori , Watanabe Shoji , Yamane Ayaka , Miyasaka Tomohiro , Misonou Hiroaki
Published: November 2018

Tau is a microtubule (MT)-associated protein, which precisely localizes to the axon of a mature neuron. Although it has been widely used as an axonal marker, the mechanisms for its axonal localization have been elusive. This might be largely due to the lack of an experimental system, as exogenously expressed tau, such as GFP-tau, mis-localizes to the soma and dendrites. In this study, we found that the expression of endogenous tau and its axonal localization in cultured rat hippocampal neurons mainly occur during early neuronal development and are coupled. By mimicking this early expression, we demonstrate that exogenously expressed human tau can be properly localized to the axon, thereby providing the first experimental model to study the mechanisms of tau localization. Using this model, we obtained surprising findings that the axonal localization of tau did not require the MT-binding domain nor correlate with the MT-binding ability. Instead, we identified a transport mechanism mediated by the proline-rich region 2 (PRR2), which contains a number of important phosphorylation sites. Mimicking phosphorylation and dephosphorylation in PRR2 disrupts the axonal localization, suggesting that it is regulated by the phosphorylation state of PRR2. These results shed new lights on the mechanism for the axonal localization of tau and indicate a link between the hyperphosphorylation and mis-localization of tau observed in tauopathies.

Significance statement

In this paper, we present a first experimental system, in which expressed tau is properly localized to the axon, and which can therefore be used to study the mechanisms of tau localization and mis-localization. Using this system, we provide evidence that the microtubule binding domain of tau nor stable binding of tau to microtubules is not necessary for its axonal localization. Instead, we identified the proline-rich region and its phosphorylation-state dictate the localization of tau in neurons. These results provide a novel foundation to consider how axonal tau mis-localize to the soma and dendrites during early pathogenesis of Alzheimer’s disease.
Accumulation of prelamin A drives inflammation in the heart with implications for treatment of inherited and acquired cardiomyopathies
Authors: Brayson Daniel , Frustaci Andrea , Verardo Romina , Chimenti Cristina , Russo Matteo Antonio , Hayward Robert , Ahmad Sadia Munir , Vizcay-Barrena Gema , Protti Andrea , Zammit Peter S. , dos Remedios Cristobal G. , Ehler Elisabeth , Shah Ajay M. , Shanahan Catherine M.
Published: November 2018

Cardiomyopathies are complex heart muscle diseases that can be inherited e.g. dilated cardiomyopathy resulting from LMNA gene mutations, or acquired, e.g. cardiomyopathy associated with HIV. In both cases the lamin A precursor, prelamin A, may play a central role: mutations in LMNA and certain HIV protease inhibitors acting via the enzyme ZMPSTE24 both inhibit prelamin A processing. Firstly, we show that myocardial prelamin A accumulation occurs in both these cardiomyopathies in patients. Secondly, we developed a novel mouse model of cardiac specific prelamin A accumulation which mimicked tissue and molecular features of HIV associated cardiomyopathy, including inflammation. These findings: (1) confirm a central pathological role of prelamin A common to genetic and acquired cardiomyopathies; (2) have implications for the management of HIV patients with cardiac disease in whom protease inhibitors with low/no binding to ZMPSTE24 may be preferred; and (3) suggest that targeting inflammation may be a useful treatment strategy for some forms of inherited cardiomyopathy.
Ultra-sensitive sequencing for cancer detection reveals progressive clonal selection in normal tissue over a century of human lifespan
Authors: Salk Jesse J. , Loubet-Senear Kaitlyn , Maritschnegg Elisabeth , Valentine Charles C. , Williams Lindsey N. , Horvat Reinhard , Vanderstichele Adriaan , Nachmanson Daniela , Baker Kathryn T. , Emond Mary J. , Loter Emily , Soussi Thierry , Loeb Lawrence A. , Zeillinger Robert , Speiser Paul , Risques Rosa Ana
Published: November 2018

High accuracy next-generation DNA sequencing promises a paradigm shift in early cancer detection by enabling the identification of mutant cancer molecules in minimally-invasive body fluid samples. We demonstrate 80% sensitivity for ovarian cancer detection using ultra-accurate Duplex Sequencing to identify TP53 mutations in uterine lavage. However, in addition to tumor DNA, we also detect low frequency TP53 mutations in nearly all lavages from women with and without cancer. These mutations increase with age and share the selection traits of clonal TP53 mutations commonly found in human tumors. We show that low frequency TP53 mutations exist in multiple healthy tissues, from newborn to centenarian, and progressively increase in abundance and pathogenicity with older age across tissue types. Our results illustrate that subclonal cancer evolutionary processes are a ubiquitous part of normal human aging and great care must be taken to distinguish tumor-derived, from age-associated mutations in high sensitivity clinical cancer diagnostics.
Using Computer-vision and Machine Learning to Automate Facial Coding of Positive and Negative Affect Intensity
Authors: Haines Nathaniel , Southward Matthew W. , Cheavens Jennifer S. , Beauchaine Theodore , Ahn Woo-Young
Published: November 2018

Facial expressions are fundamental to interpersonal communication, including social interaction, and allow people of different ages, cultures, and languages to quickly and reliably convey emotional information. Historically, facial expression research has followed from discrete emotion theories, which posit a limited number of distinct affective states that are represented with specific patterns of facial action. Much less work has focused on dimensional features of emotion, particularly positive and negative affect intensity. This is likely, in part, because achieving inter-rater reliability for facial action and affect intensity ratings is painstaking and labor-intensive. We use computer-vision and machine learning (CVML) to identify patterns of facial actions in 4,648 video recordings of 125 human participants, which show strong correspondences to positive and negative affect intensity ratings obtained from highly trained coders. Our results show that CVML can both (1) determine the importance of different facial actions that human coders use to derive positive and negative affective ratings, and (2) efficiently automate positive and negative affect intensity coding on large facial expression databases. Further, we show that CVML can be applied to individual human judges to infer which facial actions they use to generate perceptual emotion ratings from facial expressions.
Multiscale causal network models of Alzheimer’s disease identify VGF as a key regulator of disease
Authors: Beckmann Noam D. , Lin Wei-Jye , Wang Minghui , Cohain Ariella T. , Wang Pei , Ma Weiping , Wang Ying-Chih , Jiang Cheng , Audrain Mickael , Comella Phillip , Hariharan Siddharth P. , Belbin Gillian M. , Levey Allan I. , Seyfried Nicholas T. , Dammer Eric B. , Duong Duc , Lah James J. , Haure-Mirande Jean-Vianney , Shackleton Ben , Charney Alexander W. , Kenny Eimear , Zhu Jun , Haroutunian Vahram , Katsel Pavel , Gandy Sam , Tu Zhidong , Ehrlich Michelle , Zhang Bin , Salton Stephen R. , Schadt Eric E.
Published: November 2018

Though discovered over 100 years ago, the molecular foundation of sporadic Alzheimer’s disease (AD) remains elusive. To elucidate its complex nature, we constructed multiscale causal network models on a large human AD multi-omics dataset, integrating clinical features of AD, DNA variation, and gene and protein expression into probabilistic causal models that enabled detection and prioritization of high-confidence key drivers of AD, including the top predicted key driver VGF. Overexpression of neuropeptide precursor VGF in 5xFAD mice partially rescued beta-amyloid-mediated memory impairment and neuropathology. Molecular validation of network predictions downstream of VGF was achieved, with significant enrichment for homologous genes identified as differentially expressed in 5xFAD brains overexpressing VGF versus controls. Our findings support a causal and/or protective role for VGF in AD pathogenesis and progression.

One sentence summary

VGF protects against Alzheimer’s disease
Genome-wide association study of piscine myocarditis virus (PMCV) robustness in Atlantic salmon (Salmo salar)
Authors: Hillestad Borghild , Moghadam Hooman K.
Published: November 2018

Cardiomyopathy syndrome is a sever, viral disease of Atlantic salmon that mostly affects farmed animals during their late production stage at sea. Caused by piscine myocarditis virus (PMCV), over the past few years, the outbreaks due to this disease have resulted in significant losses to the aquaculture industry. However, there are currently no vaccine that has proven effective against this virus. In this study, using a challenge model, we investigate the genetic variation for robustness to PMCV, by screening large number of animals using a 55 K SNP array. In particular, we aimed to identify genetic markers that are tightly linked to higher disease resistance and can potentially be used in breeding programs. Using genomic information, we estimated heritability of 0.41 ±0.05, suggesting that robustness against this virus is largely controlled by genetic factors. Through association analysis, we identified a major QTL on chromosome 27, explaining approximately 57% of the total additive genetic variation. The region harbouring this putative QTL contains various immune related candidate genes, many of which have previously been shown to have a differential expression profile between the naïve and infected animals. We also identified a suggestive association on chromosome 12, where the QTL linked markers are located within two putatively immune related genes. These findings are important as they can be readily implemented into the breeding programs but also the results can further help in fine-mapping the causative mutation, in better understanding the biology of the disease and refine the mechanics of resistance against PMCV.
pyMeSHSim: an integrative python package for biomedical named entity recognition, normalization and comparison
Authors: Luo Zhi-Hui , Shi Meng-Wei , Yang Zhuang , Zhang Hong-Yu , Chen Zhen-Xia
Published: November 2018

Motivation

Increasing disease causal genes have been identified through different methods, while there are still no uniform biomedical named entity (bio-NE) annotations of the disease phenotypes. Furthermore, semantic similarity comparison between two bio-NE annotations, like disease descriptions, has become important for data integration or system genetics analysis.

Methods

The package pyMeSHSim realizes bio-NEs recognition using MetaMap, which produces Unified Medical Language System (UMLS) concepts in natural language process. To map the UMLS concepts to MeSH, pyMeSHSim embedded a house made dataset containing the Medical Subject Headings (MeSH) main headings (MHs), supplementary concept records (SCRs) and relations between them. Based on the dataset, pyMeSHSim implemented four information content (IC) based algorithms and one graph-based algorithm to measure the semantic similarity between two MeSH terms.

Results

To evaluate its performance, we used pyMeSHSim to parse OMIM and GWAS phenotypes. The inclusion of SCRs and the curation strategy of non-MeSH-synonymous UMLS concepts used by pyMeSHSim improved the performance of pyMeSHSim in the recognition of OMIM phenotypes. In the curation of GWAS phenotypes, pyMeSHSim and previous manual work recognized the same MeSH terms from 276/461 GWAS phenotypes, and the correlation between their semantic similarity calculated by pyMeSHSim and another semantic analysis tool meshes was as high as 0.53-0.97.

Conclusion

With the embedded dataset including both MeSH MHs and SCRs, the integrative MeSH tool pyMeSHSim realized the disease recognition, normalization and comparison in biomedical text-mining.

Availability

Package’s source code and test datasets are available under the GPLv3 license at https://github.com/luozhhub/pyMeSHSim
The Aryl Hydrocarbon Receptor senses the Henna pigment Lawsone and mediates Yin-Yang effects on skin homeostasis
Authors: Lozza Laura , Moura-Alves Pedro , Domaszewska Teresa , Lage Crespo Carolina , Streata Ioana , Kreuchwig Annika , Bechtle Marina , Klemm Marion , Zedler Ulrike , Ungureanu Bogdan Silviu , Guhlich-Bornhof Ute , Koehler Anne-Britta , Staeber Manuela , Mollenkopf Hans-Joachim , Hurwitz Robert , Furkert Jens , Krause Gerd , Weiner January , Jacinto Antonio , Mihai Ioana , Leite-de-Moraes Maria , Siebenhaar Frank , Maurer Marcus , Kaufmann Stefan H.E.
Published: November 2018

As a first host barrier, the skin is constantly exposed to environmental insults that perturb its integrity. Tight regulation of skin homeostasis is largely controlled by the aryl hydrocarbon receptor (AhR). Here, we demonstrate that Henna and its major pigment, the naphthoquinone Lawsone activate AhR, both in vitro and in vivo. In human keratinocytes and epidermis equivalents, Lawsone exposure enhances the production of late epidermal proteins, impacts keratinocyte differentiation and proliferation, and regulates skin inflammation. To determine the potential use of Lawsone for therapeutic application, we harnessed human, murine and zebrafish models. In skin regeneration models, Lawsone interferes with physiological tissue regeneration and inhibits wound healing. Conversely, in a human acute dermatitis model, topical application of a Lawsone-containing cream ameliorates skin irritation. Altogether, our study reveals how a widely used natural plant pigment is sensed by the host receptor AhR, and how the physiopathological context determines beneficial and detrimental outcomes.
The transcriptome-wide landscape and modalities of EJC binding in adult Drosophila
Authors: Obrdlik Ales , Lin Gen , Haberman Nejc , Ule Jernej , Ephrussi Anne
Published: November 2018

Splicing-dependent assembly of the exon junction complex (EJC) at canonical sites −20 to −24 nucleotides upstream of exon-exon junctions in mRNAs occurs in all higher eukaryotes and affects most major regulatory events in the life of a transcript. In mammalian cell cytoplasm, EJC is essential for efficient RNA surveillance, while in Drosophila the most essential cytoplasmic EJC function is in localization of oskar mRNA. Here we developed a method for isolation of protein complexes and associated RNA-targets (ipaRt), which provides a transcriptome-wide view of RNA binding sites of the fully assembled EJC in adult Drosophila. We find that EJC binds at canonical positions, with highest occupancy on mRNAs from genes comprising multiple splice sites and long introns. Moreover, the occupancy is highest at junctions adjacent to strong splice sites, CG-rich hexamers and RNA structures. These modalities have not been identified by previous studies in mammals, where more binding was seen at non-canonical positions. The most highly occupied transcripts in Drosophila have increased tendency to be maternally localized, and are more likely to derive from genes involved in differentiation or development. Taken together, we identify the RNA modalities that specify EJC assembly in Drosophila on a biologically coherent set of transcripts.
Convergent evolution inArabidopsis halleriandArabidopsis arenosaon calamine metalliferous soils
Authors: Preite Veronica , Sailer Christian , Syllwasschy Lara , Bray Sian , Krämer Ute , Yant Levi
Published: November 2018

It is a plausible hypothesis that parallel adaptation events to the same environmental challenge should result in genetic changes of similar or identical effects, depending on the underlying fitness landscapes. However, systematic testing of this is scarce. Here we examine this hypothesis in two closely related plant species,Arabidopsis halleriandArabidopsis arenosa, which co-occur at two calamine metalliferous sites harbouring toxic levels of the heavy metals zinc and cadmium. We conduct individual genome resequencing alongside soil elemental analysis for 64 plants from 8 populations on metalliferous and non-metalliferous soils, and identify genomic footprints of selection and local adaptation. Selective sweep and environmental association analyses indicate a modest degree of gene as well as functional network convergence, whereby the proximal molecular factors mediating this convergence mostly differ between site pairs and species. Notably, we observe repeated selection on identical SNPs in severalA. hallerigenes at two independently colonized metalliferous sites. Our data suggest that species-specific metal handling and other biological features could explain a low degree of convergence between species. The parallel establishment of plant populations on calamine metalliferous soils involves convergent evolution, which will likely be more pervasive across sites purposely chosen for maximal similarity in soil composition.