bluuebunny/crossref_metadata_2025 huggingface dataset:
Preperitoneal Ventral Hernia Repair
Authors: Heniford B. Todd , Ross Samuel W. , Wormer Blair A. , Walters Amanda L. , Lincourt Amy E. , Colavita Paul D. , Kercher Kent W. , Augenstein Vedra A.
Published: August 2018

Objectives:

The aim of this study was to examine the outcomes of over a decade's experience utilizing preperitoneal ventral hernia repair (PP-VHR).

Background:

PP-VHR was first described by our group in 2006, and there have been no subsequent reports of outcomes with this technique.

Methods:

A prospective study of all PP-VHR from January, 2004 to April, 2016 was performed. Multivariate stepwise logistic regression and Cox proportional-hazard models were used to identify predictors of wound complications and hernia recurrence, respectively.

Results:

There were 1023 PP-VHRs. Mean age was 57.2 ± 12.6 years, BMI 33.7 ± 11.4 kg/m2, defect size 210.0 ± 221.4 cm2; 23.7% had diabetes, 13.9% were smokers, 68.7% were recurrent, and 23.6% incarcerated. Component separation was required in 43.6%, and a panniculectomy was performed in 30.0%. Wound complication was present in 27.3% of patients, with 1.7% having a mesh infection. In all, there were 53 (5.2%) hernia recurrences and 36 (3.9%) in the synthetic repairs, with a mean follow-up of 27.0 ± 26.4 months. On multivariate regression (odds ratio or hazard ratio, 95% confidence interval), diabetes (1.9, 1.4–3.0), panniculectomy (2.6, 1.8–3.9), and operations requiring biologic mesh were predictors of wound complications, whereas recurrent hernia repair (2.69, 1.14–6.35), biologic mesh (3.1, 1.67–5.75), and wound complications (3.01, 1.69–5.39) were predictors of hernia recurrence.

Conclusions:

An open PP-VHR is a very effective means to repair large, complex, and recurrent hernias resulting in a low recurrence rate. Mesh choice in VHR is important and was associated with hernia recurrence and wound complications in this population.
Disease-free Survival and Local Recurrence for Laparoscopic Resection Compared With Open Resection of Stage II to III Rectal Cancer
Authors: Fleshman James , Branda Megan E. , Sargent Daniel J. , Boller Anne Marie , George Virgilio V. , Abbas Maher A. , Peters Walter R. , Maun Dipen C. , Chang George J. , Herline Alan , Fichera Alessandro , Mutch Matthew G. , Wexner Steven D. , Whiteford Mark H. , Marks John , Birnbaum Elisa , Margolin David A. , Larson David W. , Marcello Peter W. , Posner Mitchell C. , Read Thomas E. , Monson John R. T. , Wren Sherry M. , Pisters Peter W. T. , Nelson Heidi
Published: August 2018

Objective:

To determine the disease-free survival (DFS) and recurrence after the treatment of patients with rectal cancer with open (OPEN) or laparoscopic (LAP) resection.

Background:

This randomized clinical trial (ACOSOG [Alliance] Z6051), performed between 2008 and 2013, compared LAP and OPEN resection of stage II/III rectal cancer, within 12 cm of the anal verge (T1-3, N0-2, M0) in patients who received neoadjuvant chemoradiotherapy. The rectum and mesorectum were resected using open instruments for rectal dissection (included hybrid hand-assisted laparoscopic) or with laparoscopic instruments under pneumoperitoneum. The 2-year DFS and recurrence were secondary endpoints of Z6051.

Methods:

The DFS and recurrence were not powered, and are being assessed for superiority. Recurrence was determined at 3, 6, 9, 12, and every 6 months thereafter, using carcinoembryonic antigen, physical examination, computed tomography, and colonoscopy. In all, 486 patients were randomized to LAP (243) or OPEN (243), with 462 eligible for analysis (LAP = 240 and OPEN = 222). Median follow-up is 47.9 months.

Results:

The 2-year DFS was LAP 79.5% (95% confidence interval [CI] 74.4–84.9) and OPEN 83.2% (95% CI 78.3–88.3). Local and regional recurrence was 4.6% LAP and 4.5% OPEN. Distant recurrence was 14.6% LAP and 16.7% OPEN.

Disease-free survival was impacted by unsuccessful resection (hazard ratio [HR] 1.87, 95% CI 1.21–2.91): composite of incomplete specimen (HR 1.65, 95% CI 0.85–3.18); positive circumferential resection margins (HR 2.31, 95% CI 1.40–3.79); positive distal margin (HR 2.53, 95% CI 1.30–3.77).

Conclusion:

Laparoscopic assisted resection of rectal cancer was not found to be significantly different to OPEN resection of rectal cancer based on the outcomes of DFS and recurrence.
Stem cell transplantation for amyotrophic lateral sclerosis
Authors: Baloh Robert H. , Glass Jonathan D. , Svendsen Clive N.
Published: August 2018

Purpose of review

This review analyses the recent efforts to develop therapeutics using transplantation of stem cells for amyotrophic lateral sclerosis (ALS).

Recent findings

Stem cells are considered as a potential therapeutic for a variety of neurodegenerative diseases, in an effort to either replace cells that are lost, or to enhance the survival of the remaining cells. In ALS, meaningful attempts to verify the safety and feasibility of many cell transplantation approaches have only recently been completed or are underway. Due to the complexities of reconstructing complete motor neuron circuits in adult patients, current approaches aim rather to prolong the survival and function of existing motor neurons through paracrine effects or production of new interneurons or astrocytes. Recent trials showed that autologous mesenchymal stem cells can be safely injected intrathecally, transiently enhancing growth factor concentrations and anti-inflammatory cytokines into the cerebrospinal fluid. Likewise, a small pilot study investigating safety of autologous transplantation of regulatory T-cells for immunomodulation was recently completed. Finally, early phase trials demonstrated safety of direct surgical transplantation of heterologous fetal-derived neural progenitor cells into the spinal cord of ALS patients, as an attempt to provide a lasting source of local trophic support for motor neurons.

With clinical trials recently demonstrating that stem cell transplantation can be safe and well tolerated in ALS, the field is positioned to complete pivotal controlled trials to determine efficacy.
Sequential Specification of Oligodendrocyte Lineage Cells by Distinct Levels of Hedgehog and Notch Signaling
Authors: Ravanelli Andrew M. , Kearns Christina A. , Powers Rani K. , Wang Yuying , Hines Jacob H. , Donaldson Maranda J. , Appel Bruce
Published: August 2018

During development of the central nervous system oligodendrocyte precursor cells (OPCs) give rise to both myelinating oligodendrocytes and NG2 glia, which are the most proliferative cells in the adult mammalian brain. NG2 glia retain characteristics of OPCs, and some NG2 glia produce oligodendrocytes, but many others persist throughout adulthood. Why some OPCs differentiate as oligodendrocytes during development whereas others persist as OPCs and acquire characteristics of NG2 glia is not known. Using zebrafish spinal cord as a model, we found that OPCs that differentiate rapidly as oligodendrocytes and others that remain as OPCs arise in sequential waves from distinct neural progenitors. Additionally, oligodendrocyte and persistent OPC fates are specified during a defined critical period by small differences in Shh signaling and Notch activity, which modulates Shh signaling response. Thus, our data indicate that OPCs fated to produce oligodendrocytes or remain as OPCs during development are specified as distinct cell types, raising the possibility that the myelinating potential of OPCs is set by graded Shh signaling activity.
Changes in structural network topology correlate with severity of hallucinatory behaviour in Parkinson’s disease
Authors: Hall Julie M. , O’Callaghan Claire , Muller Alana. J. , Martens Kaylena A. Ehgoetz , Phillips Joseph R. , Moustafa Ahmed A. , Lewis Simon J. G. , Shine James M.
Published: August 2018

An inefficient integration between bottom-up visual input and higher-order visual processing regions is implicated in the manifestation of visual hallucinations (VH) in Parkinson’s disease (PD). Using graph theory, the current study aimed to investigate white matter contributions to this perceptual imbalance hypothesis. Twenty-nine PD patients reported their hallucinatory behaviour on a questionnaire and performed a behavioural test that has been shown to elicit misperceptions. A composite score derived from these measures was used as a proxy for hallucinations severity and was correlated to connectivity strength of the network using the Network Based Statistic approach. The results showed that the severity of VH was associated with reduced connectivity within a large sub-network. This network included the majority of the diverse club and showed overall greater between- and within-module scores, compared to nodes not associated with hallucination severity. Furthermore, a reduction in between-module connectivity in the lateral occipital cortex, insula and pars orbitalis, as well as decreased within-module connectivity in the prefrontal, somatosensory and primary visual cortices were associated with VH severity. In contrast, the severity of VH was associated with an increase in between- and within-module connectivity in the orbitofrontal and temporal cortex, as well as regions comprising the dorsal attentional and DMN. These results suggest that the severity of VHs is associated with marked alterations in structural network topology, highlighted by a reduction in connectivity strength across a large sub-network, as well as changes in participation across top-down visual processing centres, visual and attentional networks. Therefore, impaired integration across the perceptual hierarchy may result in the inefficient transfer of information that gives rise to VHs in PD.
Disentangling the contribution of childhood and adulthood circumstances and genetics to phenotypic aging: prospective cohort study
Authors: Liu Zuyun , Chen Xi , Gill Thomas M. , Ma Chao , Crimmins Eileen M. , Levine Morgan E.
Published: August 2018

Objectives

To evaluate the extent to which childhood and adulthood circumstances and genetics contribute to phenotypic aging, using a multi-system-based signature of aging that has been shown to capture mortality and morbidity risk.

Design

Prospective population-based cohort study.

Setting

United States (U.S.).

Participants

2,339 adults (aged 51+ years) from U.S. Health and Retirement Study, who participated in the Core Survey, the 2016 Venous Blood Study, the 2015 Life History Mail Survey, the Enhanced Face-To-Face interview (2006-2016), and were part of the genetic sample.

Main outcomes measure

Phenotypic Age, a validated aging measure based on a linear combination of chronological age and nine multi-system biomarkers. For most analyses, we examined “PhenoAgeAccel”, which represents phenotypic aging after accounting for chronological age (i.e. whether a person appears older [positive value] or younger [negative value] than expected, physiologically).

Results

The Shapley Value Decomposition approach revealed that together all 11 domains (four childhood and adulthood circumstances domains, five polygenic scores [PGSs] domains, demographics, and behaviors domains) accounted for about 30% of variance in PhenoAgeAccel. Among the four circumstances domains, adulthood adversity was the largest contributor (9%), while adulthood socioeconomic status (SES), childhood adversity, and childhood SES accounted for 2.8%, 2.1%, 0.7%, respectively. Collectively, all PGSs contributed 3.8% of variance in PhenoAgeAccel. Further, six subpopulations/clusters—identified using a hierarchical cluster analysis based on childhood and adulthood SES and adversity—showed differences in average levels of phenotypic aging. Finally, there was a significant gene-by-environment interaction between a previously validated PGS for coronary artery disease and the most apparently disadvantaged subpopulation/cluster—suggesting a multiplicative effect of adverse environment coupled with genetic risk on phenotypic aging.

Conclusions

Socioenvironmental circumstances during both childhood and adulthood account for a sizable proportion of the difference in phenotypic aging among U.S. older adults. The detrimental effects may further be exacerbated among persons with a genetic predisposition to coronary artery disease.
Two spatially distinct posterior alpha sources fulfill different functional roles in attention
Authors: Sokoliuk R. , Mayhew S.D. , Aquino K.M. , Wilson R. , Brookes M.J. , Francis S.T. , Hanslmayr S. , Mullinger K.J.
Published: August 2018

Directing attention helps to extract relevant information and suppress distracters. Alpha brain oscillations (8-12Hz) play a fundamental role in this process, with a power decrease facilitating processing of important information and power increase inhibiting brain regions processing irrelevant information. Evidence for this phenomenon arises from visual attention studies (Worden et al., 2000), however, the effect also exists in other modalities, including the somatosensory system (Haegens et al., 2011) and inter-sensory attention tasks (Foxe and Snyder, 2011). We investigated what happens when attention is divided between two modalities using both a multi- and unimodal attention paradigm while recording EEG over 128 scalp electrodes in two separate experiments. In Experiment 1 participants divided their attention between the visual and somatosensory modality to determine the temporal or spatial frequency of a target stimulus (vibrotactile stimulus or Gabor grating). In Experiment 2, participants divided attention between two visual hemifields to identify the orientation of a target Gabor grating. In both experiments, pre-stimulus alpha power in visual areas decreased linearly with increasing attention to visual stimuli. In contrast, alpha power in parietal areas showed lower pre-stimulus alpha power when attention was divided between modalities, compared to unimodal attention. These results suggest that there are two different alpha sources, where one reflects the ‘visual spotlight of attention’ and the other reflects attentional effort. To our knowledge, this is the first study to show that attention recruits two spatially distinct alpha sources in occipital and parietal brain regions, which act simultaneously but serve different functions in attention.

SIGNIFICANCE STATEMENT

Attention to one spatial location/sensory modality leads to power changes of alpha oscillations (~10Hz) with decreased power over regions processing relevant information and power increases to actively inhibit areas processing ‘to-be-ignored’ information. Here, we used detailed source modelling to investigate EEG data recorded during separate uni-modal (visual) and multi- (visual and somatosensory) attention tasks. Participants either focused their attention on one modality/spatial location or directed it to both. We show for the first time two distinct alpha sources are active simultaneously but play different roles. A sensory (visual) alpha source was linearly modulated by attention representing the ‘visual spotlight of attention’. In contrast, a parietal alpha source was modulated by attentional effort, showing lowest alpha power when attention was divided.
Spatiotemporal prediction of wildfire extremes with Bayesian finite sample maxima
Authors: Joseph Maxwell B. , Rossi Matthew W. , Mietkiewicz Nathan P. , Mahood Adam L. , Cattau Megan E. , Denis Lise Ann St. , Nagy R. Chelsea , Iglesias Virginia , Abatzoglou John T. , Balch Jennifer K.
Published: August 2018

Wildfires are becoming more frequent in parts of the globe, but predicting where and when wildfires occur remains difficult. To predict wildfire extremes across the contiguous United States, we integrate a 30 year wildfire record with meteorological and housing data in spatiotemporal Bayesian statistical models with spatially varying nonlinear effects. We compared different distributions for the number and sizes of large fires to generate a posterior predictive distribution based on finite sample maxima for extreme events (the largest fires over bounded spatiotemporal domains). A zero-inflated negative binomial model for fire counts and a lognormal model for burned areas provided the best performance. This model attains 99% interval coverage for the number of fires and 93% coverage for fire sizes over a six year withheld data set. Dryness and air temperature strongly predict extreme wildfire probabilities. Housing density has a hump-shaped relationship with fire occurrence, with more fires occurring at intermediate housing densities. Statistically, these drivers affect the chance of an extreme wildfire in two ways: by altering fire size distributions, and by altering fire frequency, which influences sampling from the tails of fire size distributions. We conclude that recent extremes should not be surprising, and that the contiguous United States may be on the verge of even larger wildfire extremes.
Host cell metabolism contributes to delayed-death kinetics of apicoplast inhibitors in Toxoplasma gondii
Authors: Amberg-Johnson Katherine , Yeh Ellen
Published: August 2018

Toxoplasma gondii and related human parasites contain an essential plastid organelle called the apicoplast. Clinically-used antibiotics and other inhibitors that disrupt apicoplast biogenesis cause a mysterious “delayed-death” phenotype, in which parasite growth is unaffected during the first lytic cycle of inhibitor treatment but is severely inhibited in the second lytic cycle even after drug removal. Critical to understanding the complex downstream cellular effects of these drug classes is the timing of apicoplast loss during inhibitor treatment and how it relates to this peculiar growth phenotype. Here we show that, upon treatment with diverse classes of apicoplast inhibitors, newly-replicated T. gondii parasites in the first lytic cycle initially form apicoplasts with defects in protein import or genome replication and eventually fail to inherit the apicoplast altogether. Despite the accumulation of parasites with defective or missing apicoplasts, growth is unaffected during the first lytic cycle, as previously observed. Strikingly, concomitant inhibition of host cell isoprenoid biosynthesis results in growth inhibition in the first lytic cycle and unmasks the apicoplast defects. These results suggest that defects in and even complete loss of the apicoplast in T. gondii are partially rescued by scavenging of host cell metabolites leading to death that is delayed. Our findings uncover host cell interactions that can alleviate apicoplast inhibition and highlight key differences in “delayed-death” inhibitors between T. gondii and Plasmodium falciparum.
Single-cell RNA-seq reveals dynamic transcriptome profiling in human early neural differentiation
Authors: Shang Zhouchun , Chen Dongsheng , Wang Quanlei , Wang Shengpeng , Deng Qiuting , Wu Liang , Liu Chuanyu , Ding Xiangning , Wang Shiyou , Zhong Jixing , Zhang Doudou , Cai Xiaodong , Zhu Shida , Yang Huanming , Liu Longqi , Fink J. Lynn , Chen Fang , Liu Xiaoqing , Gao Zhengliang , Xu Xun
Published: August 2018

Background

Investigating cell fate decision and subpopulation specification in the context of the neural lineage is fundamental to understanding neurogenesis and neurodegenerative diseases. The differentiation process of neural-tube-like rosettesin vitrois representative of neural tube structures, which are composed of radially organized, columnar epithelial cells and give rise to functional neural cells. However, the underlying regulatory network of cell fate commitment during early neural differentiation remains elusive.

Results

In this study, we investigated the genome-wide transcriptome profile of single cells from six consecutive reprogramming and neural differentiation time points and identified cellular subpopulations present at each differentiation stage. Based on the inferred reconstructed trajectory and the characteristics of subpopulations contributing the most towards commitment to the central nervous system (CNS) lineage at each stage during differentiation, we identified putative novel transcription factors in regulating neural differentiation. In addition, we dissected the dynamics of chromatin accessibility at the neural differentiation stages and revealed active c/s-regulatory elements for transcription factors known to have a key role in neural differentiation as well as for those that we suggest are also involved. Further, communication network analysis demonstrated that cellular interactions most frequently occurred among embryoid body (EB) stage and each cell subpopulation possessed a distinctive spectrum of ligands and receptors associated with neural differentiation which could reflect the identity of each subpopulation.

Conclusions

Our study provides a comprehensive and integrative study of the transcriptomics and epigenetics of human early neural differentiation, which paves the way for a deeper understanding of the regulatory mechanisms driving the differentiation of the neural lineage.
Potential Application of Bacteriophages in Enrichment Culture for Improved PrenatalStreptococcus agalactiaeScreening
Authors: Uchiyama Jumpei , Matsui Hidehito , Murakami Hironobu , Kato Shini-chiro , Watanabe Naoki , Nasukawa Tadahiro , Mizukami Keijiro , Ogata Masaya , Sakaguchi Masahiro , Matsuzaki Shigenobu , Hanaki Hideaki
Published: August 2018

Vertical transmission ofStreptococcus agalactiaecan cause neonatal infections. A culture test in the late stage of pregnancy is used to screen for the presence of maternalS. agalactiaefor intrapartum antibiotic prophylaxis. For the test, vaginal-rectal swab sampling is immediately followed by enrichment culture and bacterial identification. In some cases,Enterococcus faecaliscompetes with and overgrowthsS. agalactiaein the enrichment culture. Consequently, the identification test occasionally yields false-negative results. Bacterial viruses, bacteriophages (phages), infect and kill specific host bacteria. In the current study, we explored the feasibility of using phages to minimize the undesirableE. faecalisoutgrowth and facilitateS. agalactiaedetection in an experimental setting. Phage mixture was prepared using three phages that specifically infectE. faecalis:phiEF24C, phiEF17H, and phiM1EF22. The mixture inhibited the growth of 86.7% (26/30) ofE. faecalisstrains tested in the enrichment broth. When single strains ofE. faecalisandS. agalactiaewere inoculated in the enrichment broth containing the phage mixture, bacterial growth was inhibited or facilitated, respectively. Further, several sets ofS. agalactiaeandE. faecalisstrains were co-cultured, and bacteria were detected on chromogenic agar after the enrichment culture.S. agalactiaewas dominant after plating a phage mixture-treated co-culture, while it was barely detected after plating the untreated co-culture. Considering these observations, the phage mixture can be employed in theS. agalactiaeculture test to increase test accuracy.
Novel allosteric mechanism of p53 activation by small molecules for targeted anticancer therapy
Authors: Zawacka-Pankau Joanna , Grinkevich Vera V. , Burmakin Mikhail , Vema Aparna , Fawkner Karin , Issaeva Natalia , Andreotti Virginia , Dickinson Eleanor R. , Hedström Elisabeth , Spinnler Clemens , Inga Alberto , Larsson Lars-Gunnar , Karlén Anders , Tarasova Olga , Poroikov Vladimir , Lavrenov Sergey , Preobrazhenskaya Maria , Barran Perdita E. , Okorokov Andrei L. , Selivanova Galina
Published: August 2018

Given the immense significance of p53 restoration for anti-cancer therapy, elucidation of the mechanisms of action of p53-activating molecules is of the utmost importance. Here we report a discovery of novel allosteric modulation of p53 by small molecules, which is an unexpected turn in the p53 story. We identified a structural element involved in p53 regulation, whose targeting by RITA, PpIX and licofelone block the binding of p53 inhibitors, MDM2 and MDMX. Deletion and mutation analysis followed by molecular modeling, identified the key p53 residues S33 and S37 targeted by RITA and PpIX. We propose that the binding of small molecules to the identified site induces a conformational trap preventing p53 from the interaction with MDM2 and MDMX. These results point to a high potential of allosteric activators. Our study provides the basis for the development of therapeutics with a novel mechanism of action, thus extending the p53 pharmacological potential.
Spermatoproteasome-deficient mice are proficient in meiotic DNA repair but defective in meiotic exit
Authors: Gómez-H Laura , Felipe-Medina Natalia , Condezo Yazmine B. , Garcia-Valiente Rodrigo , Ramos Isabel , Roig Ignasi , Sánchez-Martin Manuel , de Rooij Dirk , Llano Elena , Pendas Alberto M.
Published: August 2018

Meiotic recombination generates crossovers which are essential to ensure genome haploidization. The ubiquitin proteasome system regulates meiotic recombination through its association to the synaptonemal complex, a ‘zipper’-like structure that holds homologs and provides the structural framework for meiotic recombination. Here we show that the testis-specific α4s subunit (PSMA8) of the spermatoproteasome is located at the synaptonemal complex and is essential for the assembly of its activator PA200. Accordingly, synapsis-deficient mice show delocalization of PSMA8 from the synaptonemal complex. Genetic analysis of Psma8-deficient mice shows normal meiotic DNA repair, crossing over formation and an increase of spermatocytes at metaphase I and metaphase II which either enter into apoptosis or slip to give rise to an early spermatid arrest and infertility. Thus, spermatoproteasome-dependent histone degradation is dispensable for meiotic recombination. We show that PSMA8 deficiency alters the proteostasis of several key meiotic players such as acetylated histones, SYCP3, SYCP1, CDK1 and TRIP13 which in turn leads to an aberrant meiotic exit and early spermatid arrest prior to the histone displacement process that take place subsequently.
An efficient timer and sizer of biomacromolecular motions
Authors: Chan Justin , Lin Hong-Rui , Takemura Kazuhiro , Chang Kai-Chun , Chang Yuan-Yu , Joti Yasumasa , Kitao Akio , Yang Lee-Wei
Published: August 2018

Life ticks as fast as how efficiently proteins perform their functional dynamics. Well-folded/structured biomacromolecules perform functions via large-scale intrinsic motions across multiple conformational states, which occur at timescales of nano-to milliseconds. Computationally expensive molecular dynamics (MD) simulation has been the only theoretical tool to gauge the time and sizes of these motions, though barely to their slowest ends. Here, we convert a computationally cheap elastic network model (ENM) into a molecular timer and sizer to gauge the slowest functional motions of proteins and ribosome. Quasi-harmonic analysis, fluctuation-profile matching (FPM) and the Wiener–Khintchine theorem (WKT) are used to define the “time-periods”,t, for anharmonic principal components (PCs) which are validated by NMR order parameters. The PCs with their respective “time-periods” are mapped to the eigenvalues (λENM) of the corresponding ENM modes. Thus, the power lawst(ns) = 86.9λENM−1.9and σ2(Å2) = 46.1λENM−2.5are established allowing the characterization of the time scales of NMR-resolved conformers, crystallographic anisotropic displacement parameters, and important ribosomal motions, as well as motional sizes of the latter.

GRAPHICAL ABSTRACT
A revisit to a low-cost method for the isolation of microsatellite markers: the case of the endangered Malayan tapir (Tapirus indicus)
Authors: Lim Qi Luan , Ismail Nurul Adilah , Arumugam Ramitha , Ng Wei Lun , Yien Yong Christina Seok , Ismail Ahmad , Rovie-Ryan Jeffrine J. , Rosli Norsyamimi , Annavi Geetha
Published: August 2018

There are many approaches to develop microsatellite markers. We revisited an easy and rapid Polymerase Chain Reaction (PCR)-cloning-sequencing method to design microsatellite markers for Tapirus indicus. Using six random amplified microsatellite (RAM) markers, this study had rapidly generated 45 unique genomic sequences containing microsatellites. After screening 15 terminal and seven intermediate microsatellite loci, we shortlisted five and seven which were amplified either by single- or multiplex PCR using the economical three-primer PCR method. Genotyping attempts were made with ten Tapirus indicus individuals using three of the terminal microsatellite loci and all seven intermediate loci. However, none of the terminal microsatellite loci were considered useful for population genotyping studies, while the seven intermediate loci showed good amplification but were monomorphic in the ten samples. Despite successful detection of amplified loci, we would like to highlight that, researchers who are interested in this alternative method for isolation of microsatellite loci to be cautious and be aware of the limitations and downfalls reported herein that could render these loci unsuitable for population genotyping.
Deep learning image recognition enables efficient genome editing in zebrafish by automated injections
Authors: Cordero-Maldonado Maria Lorena , Perathoner Simon , Kolk Kees-Jan van der , Boland Ralf , Heins-Marroquin Ursula , Spaink Herman P. , Meijer Annemarie H. , Crawford Alexander D. , Sonneville Jan de
Published: August 2018

One of the most popular techniques in zebrafish research is microinjection, as it is a rapid and efficient way to genetically manipulate early developing embryos, and to introduce microbes or tracers at larval stages.

Here we demonstrate the development of a machine learning software that allows for microinjection at a trained target site in zebrafish eggs at unprecedented speed. The software is based on the open-source deep-learning library Inception v3.

In a first step, the software distinguishes wells containing embryos at one-cell stage from wells to be skipped with an accuracy of 93%. A second step was developed to pinpoint the injection site. Deep learning allows to predict this location on average within 42 µm to manually annotated sites. Using a Graphics Processing Unit (GPU), both steps together take less than 100 milliseconds. We first tested our system by injecting a morpholino into the middle of the yolk and found that the automated injection efficiency is as efficient as manual injection (~ 80%). Next, we tested both CRISPR/Cas9 and DNA construct injections into the zygote and obtained a comparable efficiency to that of an experienced experimentalist. Combined with a higher throughput, this results in a higher yield. Hence, the automated injection of CRISPR/Cas9 will allow high-throughput applications to knock out and knock in relevant genes to study their mechanisms or pathways of interest in diverse areas of biomedical research.
Multilayer network analysis of miRNA and protein expression profiles in breast cancer patients
Authors: Zhang Yang , Chen Jiannan , Wang Dehua , Cong Weihui , Lai Bo Shiun , Zhao Yi
Published: August 2018

MiRNAs and proteins play important roles in different stages of tumor development and serve as biomarkers for the early diagnosis of cancer. A new algorithm that combines machine learning algorithms and multilayer complex network analysis is hereby proposed to explore the potential diagnostic values of miRNAs and proteins. XGBoost and random forest algorithms were employed to exclude unrelated miRNAs and proteins, and the most significant candidates were retained for the further analysis. Given these candidates’ possible functional relationships to one other, a multilayer complex network was constructed to identify miRNAs and proteins that could serve as biomarkers for breast cancer. Proteins and miRNAs that are nodes in the network were subsequently categorized into two network layers considering their distinct functions. Maximal information coefficient (MIC) was applied to assess intralayer and interlayer connection. The betweenness centrality was used as the first measurement of the importance of the nodes within each single layer. To further characterize the interlayer interaction between miRNAs and proteins, the degree of the nodes was chosen as the second measurement to map their signalling pathways. By combining these two measurements into one score and comparing the difference of the same candidate between normal tissue and cancer tissue, this novel multilayer network analysis could be applied to successfully identify molecules associated with breast cancer.
HERI-1 is a Chromodomain Protein that Negatively Regulates Transgenerational Epigenetic Inheritance
Authors: Perales Roberto , Pagano Daniel , Wan Gang , Fields Brandon , Saltzman Arneet L. , Kennedy Scott G.
Published: August 2018

Transgenerational epigenetic inheritance (TEI) is the inheritance of epigenetic information for two or more generations. In most cases, TEI is limited to 2-3 generations. This short-term nature of TEI could be set by innate biochemical limitations to TEI or by genetically encoded systems that actively limit TEI. dsRNA-mediated gene silencing (RNAi) can be inherited inC. elegans(termed RNAi inheritance or RNA-directed TEI). To identify systems that might actively limit RNA-directed TEI, we conducted a forward genetic screen for factors whose mutation enhanced RNAi inheritance. This screen identified the geneheritableenhancer ofRNAi(heri-1), whose mutation causes RNAi inheritance to last longer (>20 generations) than normal.heri-1encodes a protein with a chromodomain and a kinase-homology domain that is expressed in germ cells and localizes to nuclei. InC. elegans, a nuclear branch of the RNAi pathway (nuclear RNAi or NRDE pathway) is required for RNAi inheritance. We find that this NRDE pathway is hyper-responsive to RNAi inheri-1mutant animals, suggesting that a normal function of HERI-1 is to limit nuclear RNAi and that limiting nuclear RNAi may be the mechanism by which HERI-1 limits RNAi inheritance. Interestingly, we find that HERI-1 binds to genes targeted by RNAi, suggesting that HERI-1 may have a direct role in limiting nuclear RNAi and, therefore, RNAi inheritance. Surprisingly, recruitment of the negative regulator HERI-1 to genes depends upon that same NRDE factors that drive co-transcriptional gene silencing during RNAi inheritance. We therefore speculate that the generational perdurance of RNAi inheritance is set by competing pro- and anti-silencing outputs of the NRDE nuclear RNAi machinery.
Realizing the potential of blockchain technologies in genomics
Authors: Ozercan Halil Ibrahim , Ileri Atalay Mert , Ayday Erman , Alkan Can
Published: August 2018

Genomics data introduce a substantial computational burden as well as data privacy and ownership issues. Data sets generated by high-throughput sequencing platforms require immense amounts of computational resources to align to reference genomes and to call and annotate genomic variants. This problem is even more pronounced if reanalysis is needed for new versions of reference genomes, which may impose high loads to existing computational infrastructures. Additionally, after the compute-intensive analyses are completed, the results are either kept in centralized repositories with access control, or distributed among stakeholders using standard file transfer protocols. This imposes two main problems: (1) Centralized servers become gatekeepers of the data, essentially acting as an unnecessary mediator between the actual data owners and data users; and (2) servers may create single points of failure both in terms of service availability and data privacy. Therefore, there is a need for secure and decentralized platforms for data distribution with user-level data governance. A new technology, blockchain, may help ameliorate some of these problems. In broad terms, the blockchain technology enables decentralized, immutable, incorruptible public ledgers. In this Perspective, we aim to introduce current developments toward using blockchain to address several problems in omics, and to provide an outlook of possible future implications of the blockchain technology to life sciences.
Logistics practices in healthcare organizations in Bogota
Authors: Velasco Nubia , Moreno Juan-Pablo , Rebolledo Claudia
Published: August 2018

Purpose

The purpose of this paper is to explore the current state of logistics practices in healthcare organizations in Bogota, Colombia.

Design/methodology/approach

The assessment is based on case study research using open interviews, focused interviews, a questionnaire and direct observations as sources of evidence. Seven Colombian health care settings are analyzed: four public hospitals and three private clinics. Cross-case analysis allows the identification of patterns regarding supply management, inventory management, replenishment and use of information and communication technologies.

Findings

Manual procedures, poor planning, little recognition from top management and a lack of specialized personnel characterize the current situation. Innovative practices with a potential to improve the efficacy of logistics activities are rare, particularly in public hospitals.

Research avenues

Future research could replicate this study in other Colombian cities, in order to generalize the results to the whole country. It could also be interesting to document successful and less successful implementations of innovative logistics practices in Colombian hospitals to guide and promote their adoption.

Research limitations/implications

The small number of cases considered, and the fact that the research is concentrated in one city, limits the generalizability of the results.

Originality/value

To the best of the authors’ knowledge, this research is the first to explore the state of healthcare logistics practices in Colombia.
Explanatory factors and limitations of Spanish local debt
Authors: Vera Jorge Olmo
Published: August 2018

Purpose

The purpose of this paper is to evaluate the impact of the Law on Budgetary Stability of 2012 over the level of accumulated debt in Spanish municipalities. The paper also analyses the influence of the socioeconomic environment, political factors and budgetary indicators on the level of accumulated debt for the 2008–2014 period, which coincides with the economic crisis.

Design/methodology/approach

The paper uses panel data methodology. First, the t-test of difference of means is used to analyse which political variables are significant. Then, the analysis is carried out using the generalised method of moments in order to obtain the explanatory variables of the level of debt.

Findings

The results show that in 2013–2014, the Law on Budgetary Stability did not have a significant effect on reducing the accumulated debt. However, the law has led to a change of the trend in debt levels, as the debt decreased from 2013 to 2014. Moreover, population, unemployment, immigration, personnel expenditure, direct fiscal pressure and level of investment have an influence over the level of accumulated debt.

Originality/value

This paper contributes to analyse to what extent the Law on Budgetary Stability has affected accumulated debt. The study reveals a slight impact on reducing debt, although it is not significant. An original aspect of this paper is that it uses dynamic models to study the accumulated debt of Spanish municipalities. The study shows the impact of socioeconomic, environmental and political factors as well as of budgetary indicators on the level of debt in the context of economic crisis.
A real option approach for the valuation of switching output flexibility in residential property investment
Authors: Mintah Kwabena , Higgins David , Callanan Judith
Published: August 2018

Purpose

Uncertainties in residential property investment performance require that real estate assets are designed in a flexible manner to respond to impacts of market dynamics. Though estimating the cost of flexibility is straightforward, assessing the economic value of flexibility is not. The purpose of this study is to explore the potential practical application of real option analysis to determine the economic value of a switching output flexibility embedded in a residential property investment in Australia. The study involves the exploration of an optimal strategy for investment in a residential development through real option analysis and valuation of a mixed use investment.

Design/methodology/approach

The real option valuation model developed by McDonald and Siegel (1986) is adopted for the evaluation because the switching output flexibility is likened to a perpetual American call option with dividend payout.

Findings

Through real option analysis, the economic value of switching output flexibility of the mixed use building was determined to be higher than the initial upfront costs. Moreover, a payoff of about $4million was determined to be the value of the switching output flexibility, therefore justifying upfront investments in flexibility as an uncertainty and risk management tool.

Practical implications

This application is an important demonstration of the practical use of options pricing techniques (real options analysis) and delivers further evidence needed to support the adoption of real option valuation in practice. Flexibility can also enhance risks and uncertainty management in residential property investment better than the adjustment of discount rates.

Originality/value

There is limited evidence on the use of real options techniques for the valuation of switching output flexibility in practice, and this comes as an original application; both the case study and data are all initial applications of switching flexibility in the Australian property market.
High-skilled female immigrants: career strategies and experiences
Authors: Colakoglu Saba , Yunlu Dilek G. , Arman Gamze
Published: August 2018

Purpose

The purpose of this paper is to uncover career-related issues that high-skilled female immigrants face and their strategies for rebuilding their careers upon migration for a diverse range of reasons including following a spouse, furthering education and self-initiated expatriation.

Design/methodology/approach

Using grounded theory to explore this topic, the authors performed 14 in-depth interviews with female immigrants that fit pre-determined inclusion criteria for high-skilled (e.g. educated, gainfully and professionally employed). The study context of immigration is the USA, and the authors performed interviews with high-skilled immigrants from Turkey – an underrepresented nation in the US migrant population.

Findings

Content analysis of in-depth interviews revealed five primary theoretical themes that captured the career experiences of these individuals: non-linear career entry, career orientation, strong commitment and will to succeed, socialization patterns at work and support network. Integrating these findings with theories on adult learning, the authors developed an experiential learning model of career reconstruction among high-skilled immigrants.

Originality/value

This study contributes to the global mobility literature by developing an experiential learning theory of careers and taking a gendered perspective to the career experiences of high-skilled female immigrants. It answers the questions: what are the individual and situation factors associated with career success among high-skilled female immigrants? and what is the process that high-skilled immigrants go through to rebuild their careers?
Resveratrol supplementation reduces oxidative stress and modulates the immune response in free‐living animals during a viral infection
Authors: Sebastiano Manrico , Eens Marcel , Messina Simone , AbdElgawad Hamada , Pineau Kévin , Beemster Gerrit T. S. , Chastel Olivier , Costantini David
Published: August 2018

Diet quality may have an important effect on the regulation of oxidative status and the immune system during an infectious disease. However, the relationship among intake of specific dietary molecules, an individual’s oxidative status and the occurrence and progress of a viral disease remains almost unexplored in free‐living organisms.

Here, we study a wild, long‐lived animal, the Magnificent frigatebird Fregata magnificens to investigate: (a) the differences in a number of physiological traits (biomarkers of blood oxidative status, corticosterone (CORT), immunity and inflammation) between sick and healthy nestlings; and (b) whether experimentally increased intake of resveratrol (a polyphenol with antioxidant and antiviral properties) affects these physiological markers during the progress of a severe viral disease.

Birds with visible clinical signs showed higher oxidative damage, haemolysis and haemagglutination scores and lower antioxidant defences in comparison with birds without clinical signs. At the end of the experiment, supplemented birds showed the following: (a) increased plasma haptoglobin levels and circulating antioxidant defences; (b) reduced generation of lipid oxidative damage; and (c) negligible to no influence on immune markers, baseline CORT levels and activity of antioxidant enzymes.

Our work illustrates how the availability of specific organic molecules in the diet may constrain the individuals’ capacity to cope with viral infections in free‐living animals.

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Plant functional diversity and nutrient availability can improve restoration of floating fens via facilitation, complementarity and selection effects
Authors: van Zuidam Jeroen P. , van Leeuwen Casper H. A. , Bakker Elisabeth S. , Verhoeven Jos T. A. , Ijff Stéphanie , Peeters Edwin T. H. M. , van Zuidam Bastiaan G. , Soons Merel B.
Published: August 2018

Peat‐forming wetlands, particularly floating fens that form the initial stages of these ecosystems, are declining globally due to excavation, dehydration and eutrophication. Restoration typically involves reestablishment of early‐successional open‐water stages, with oligotrophic conditions that are characteristic for these systems. However, restoration success is notoriously limited. A potential improvement may be to initiate succession by reintroducing of target plant species. Knowledge is therefore needed on (a) which plant functional groups should be re‐introduced to stimulate fen formation; and (b) how to manage nutrient levels during restoration, considering that plant growth may be slow in oligotrophic conditions.

We hypothesized that increasing functional diversity of introduced species would stimulate the formation of peat‐forming target communities, their biomass accumulation and expansion onto open water. We also hypothesized that nutrient availability would mediate the relative contribution of specific functional groups to these effects. We investigated this in 36 artificial outdoor ponds by manipulating plant functional diversity (clonal dominants, clonal stress‐tolerators and interstitials) on constructed rafts with fen‐forming communities, and subjected these to a range of nutrient loadings over 2 years.

Increasing functional diversity as well as increasing nutrient loadings had stimulating effects on plant biomass accumulation, cover formation and rhizome growth onto open water. Both complementarity (due to niche partitioning or facilitation) and selection effects were mechanisms underlying the diversity effect, with a constant relative importance over the entire range of nutrient availabilities. Different functional groups were important for biomass production at different nutrient availabilities. Rhizome formation by clonal stress‐tolerators contributed disproportionately to open water colonization, identifying this functional group as key across all nutrient levels.

Synthesis and applications. Restoration of floating fen communities can be stimulated during the first 2 years by introducing a high functional diversity of plant species. These include fast‐growing clonal species, clonal stress‐tolerators and interstitials, which facilitate each other. Restoration is dependent on the presence of clonal stress‐tolerators such as Calla palustris, Comarum palustre and Menyanthes trifoliata for expansion onto the open water. Furthermore, restoration can start under a wide range of water nutrient levels, including eutrophic conditions.