bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designing social networks: joint tasks and the formation and endurance of network ties
Authors: Hasan Sharique , Koning Rembrand 
Published: February 2020

AbstractCan managers influence the formation of organizational networks? In this article, we evaluate the effect of joint tasks on the creation of network ties with data from a novel field experiment with 112 aspiring entrepreneurs. During the study, we randomized individuals to a set of 15 joint tasks varying in duration (week-long teams to 20-min conversations). We then evaluated the impact of these interactions on the formation and structure of individuals’ social networks. We find strong evidence that these designed interactions led to the systematic creation of new friendship and advice relations as well as changes to the participants’ network centrality. Overall, network ties formed after a randomized interaction account for about one-third the individuals a participant knows, of their friendships, and their advice relations. Nevertheless, roughly 90% of randomized interactions never become social ties of friendship or advice. A key result from our research is that while joint tasks may serve to structure the social consideration set of possible connections, individual preferences strongly shape the structure of networks. As a consequence, there will likely remain a considerable unpredictability in the presence of specific ties even when they are designed.
Evaluation of a Bacillus thuringiensis isolate-based formulation against the pod borer, Helicoverpa armigera Hübner (Lepidoptera: Noctuidae)
Authors: Bouslama Thameur , Chaieb Ikbal , Rhouma Ali , Laarif Asma 
Published: February 2020

AbstractThe present study focuses on the evaluation of the potential of a Tunisian Bacillus thuringiensis (Bt) isolate named Hr1, isolated from dead and diseased pod borer, Helicoverpa armigera Hübner (Lepidoptera: Noctuidae) larvae under laboratory and field semi-controlled conditions. The bacterial strain Hr1 showed an insecticidal activity against the pest’s neonates in comparison to the spinosad-based insecticide (Tracer 240 SC®) during bioassays under laboratory conditions. A carboxymethyl cellulose-talc (CMC-talc)-based formulation of the Bt isolate was prepared to evaluate the potential of the bacterium on tomato plants infested with H. armigera under semi-controlled field conditions with and without rain simulation. The results showed the efficacy of the formulation than the spinosad-based insecticide and the treatment with unformulated bacterium. The results also showed the persistence of Bt isolate activity even after rain-wash than the treatment with unformulated bacterium.
The clinical phenotypes and genetic characteristics of seven epilepsy patients related to heterozygous DEPDC5 variants in China
Authors: Wei Zihan , Wang Luojun , Qiao Xiaozhi , Zhang Ying , Liu Chao , Deng Yanchun 
Published: February 2020

Abstract
Objective
DEPDC5 together with NPRL2 and NPRL3 forms the GATOR1 which plays an important role in the the mechanistic target of rapamycin (mTOR) pathway. Deregulation of mTOR signalling has been associated to various neurological conditions, including epilepsy. Variants in the gene encoding GATOR1 complex, especially in DEPDC5, have been implicated in the pathogensis of several focal epilepsies. While there was little report on the electroencephalogram (EEG) feature of DEPDC5 related epilepsy, we decided to investigate the specific EEG pattern and the prognosis of DEPDC5 related epilepsy.

Methods
The records of 546 epilepsy patients with unknown causes who were admitted in Xijing Hospital and underwent whole exome sequencing (WES) from 2015 to 2019 were retrospectively reviewed. Finally, the clinical data of these 7 patients with DEPDC5 variants were collected in this study. We analyzed their clinical manifestations, EEG and magnetic resonance imaging (MRI).

Results
Seven DEPDC5 variants, including six novel mutations, were identified in seven individuals with focal epilepsy. Among these patients, one had family history. Four showed specific interictal EEG patterns, periodic-like sharp waves or spike waves, were found in four patients. Five out of seven patients (71.4%) were well-controlled by anti-epilepsy drugs while two patients with sleep-related hypermotor epilepsy had either drug resistance or relapse of epilepsy.

Conclusion
DEPDC5 variants were related to focal epilepsy in patients with or without family history. The EEG abnormalities of DEPDC5 related epilepsy were heterogeneous among different patients, while periodic-like sharp waves or spike waves might be the most characteristic interictal EEG pattern for DEPDC5 related epilepsies. In this study the prognosis of DEPDC5 related epilepsy was similar to other epilepsies. DEPDC5 variants may not predict the prognosis so far.
Epigenetic Conservation Is a Beacon of Function: An Analysis Using Methcon5 Software for Studying Gene Methylation
Authors: Hvitfeldt Emil , Xia Chao , Siegmund Kimberly D. , Shibata Darryl , Marjoram Paul 
Published: February 2020

PURPOSE Different epigenetic configurations allow one genome to develop into multiple cell types. Although the rules governing what epigenetic features confer gene expression are increasingly being understood, much remains uncertain. Here, we used a novel software package, Methcon5, to explore whether the principle of biologic conservation can be used to identify expressed genes. The hypothesis is that epigenetic configurations of important expressed genes will be conserved within a tissue. MATERIALS AND METHODS We compared the DNA methylation of approximately 850,000 CpG sites between multiple clonal crypts or glands of human colon, small intestine, and endometrium. We performed this analysis using the new software package, Methcon5, which enables detection of regions of high (or low) conservation. RESULTS We showed that DNA methylation is preferentially conserved at gene-associated CpG sites, particularly in gene promoters (eg, near the transcription start site) or the first exon. Furthermore, higher conservation correlated well with gene expression levels and performed better than promoter DNA methylation levels. Most conserved genes are in canonical housekeeping pathways. CONCLUSION This study introduces the new software package, Methcon5. In this example application, we showed that epigenetic conservation provides an alternative method for identifying functional genomic regions in human tissues.
GIP and GLP-1 Receptor Antagonism During a Meal in Healthy Individuals
Authors: Gasbjerg Lærke S , Helsted Mads M , Hartmann Bolette , Sparre-Ulrich Alexander H , Veedfald Simon , Stensen Signe , Lanng Amalie R , Bergmann Natasha C , Christensen Mikkel B , Vilsbøll Tina , Holst Jens J , Rosenkilde Mette M , Knop Filip K 
Published: February 2020

Abstract

Context
The actions of both endogenous incretin hormones during a meal have not previously been characterized.

Objective
Using specific receptor antagonists, we investigated the individual and combined contributions of endogenous glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism, energy expenditure, and gallbladder motility.

Design
Randomized, double-blinded, placebo-controlled, crossover design.

Setting
On four separate days, four liquid mixed meal tests (1894 kJ) over 270 minutes (min).

Patients or Other Participants
Twelve healthy male volunteers.

Interventions
Infusions of the GIP receptor antagonist GIP(3–30)NH2 (800 pmol/kg/min), the GLP-1 receptor antagonist exendin(9–39)NH2 (0–20 min: 1000 pmol/kg/min; 20–270 min: 450 pmol/kg/min), GIP(3–30)NH2+exendin(9–39)NH2, or placebo/saline.

Main Outcome Measure
Baseline-subtracted area under the curve (bsAUC) of C-peptide.

Results
Infusion of GIP(3–30)NH2+exendin(9–39)NH2 significantly increased plasma glucose excursions (bsAUC: 261 ± 142 mmol/L × min) during the liquid mixed meals compared with GIP(3–30)NH2 (180 ± 141 mmol/L × min; P = 0.048), exendin(9–39)NH2 (171 ± 114 mmol/L × min; P = 0.046), and placebo (116 ± 154 mmol/L × min; P = 0.015). Correspondingly, C-peptide:glucose ratios during GIP(3–30)NH2+exendin(9–39)NH2 infusion were significantly lower than during GIP(3–30)NH2 (P = 0.0057), exendin(9–39)NH2 (P = 0.0038), and placebo infusion (P = 0.014). GIP(3–30)NH2 resulted in significantly lower AUCs for glucagon than exendin(9–39)NH2 (P = 0.0417). Gallbladder ejection fraction was higher during GIP(3–30)NH2 compared with placebo (P = 0.004). For all interventions, energy expenditure and respiratory quotient were similar.

Conclusions
Endogenous GIP and GLP-1 lower postprandial plasma glucose excursions and stimulate insulin secretion but only endogenous GIP affects gallbladder motility. The two incretin hormones potentiate each other’s effects in the control of postprandial glycemia in healthy men.
The origin of animal body plans: a view from fossil evidence and the regulatory genome
Authors: Erwin Douglas H. 
Published: February 2020

ABSTRACT
The origins and the early evolution of multicellular animals required the exploitation of holozoan genomic regulatory elements and the acquisition of new regulatory tools. Comparative studies of metazoans and their relatives now allow reconstruction of the evolution of the metazoan regulatory genome, but the deep conservation of many genes has led to varied hypotheses about the morphology of early animals and the extent of developmental co-option. In this Review, I assess the emerging view that the early diversification of animals involved small organisms with diverse cell types, but largely lacking complex developmental patterning, which evolved independently in different bilaterian clades during the Cambrian Explosion.
Cell invasion by intracellular parasites – the many roads to infection
Authors: Horta Maria Fátima , Andrade Luciana Oliveira , Martins-Duarte Érica Santos , Castro-Gomes Thiago 
Published: February 2020

ABSTRACT
Intracellular parasites from the genera Toxoplasma, Plasmodium, Trypanosoma, Leishmania and from the phylum Microsporidia are, respectively, the causative agents of toxoplasmosis, malaria, Chagas disease, leishmaniasis and microsporidiosis, illnesses that kill millions of people around the globe. Crossing the host cell plasma membrane (PM) is an obstacle these parasites must overcome to establish themselves intracellularly and so cause diseases. The mechanisms of cell invasion are quite diverse and include (1) formation of moving junctions that drive parasites into host cells, as for the protozoans Toxoplasma gondii and Plasmodium spp., (2) subversion of endocytic pathways used by the host cell to repair PM, as for Trypanosoma cruzi and Leishmania, (3) induction of phagocytosis as for Leishmania or (4) endocytosis of parasites induced by specialized structures, such as the polar tubes present in microsporidian species. Understanding the early steps of cell entry is essential for the development of vaccines and drugs for the prevention or treatment of these diseases, and thus enormous research efforts have been made to unveil their underlying biological mechanisms. This Review will focus on these mechanisms and the factors involved, with an emphasis on the recent insights into the cell biology of invasion by these pathogens.
A DNA polymerization-independent role for mitochondrial DNA polymerase I-like protein C in African trypanosomes
Authors: Miller Jonathan C. , Delzell Stephanie B. , Concepción-Acevedo Jeniffer , Boucher Michael J. , Klingbeil Michele M. 
Published: February 2020

ABSTRACT
Mitochondrial DNA of Trypanosoma brucei and related parasites is a catenated network containing thousands of minicircles and tens of maxicircles, called kinetoplast DNA (kDNA). Replication of a single nucleoid requires at least three DNA polymerase I-like proteins (i.e. POLIB, POLIC and POLID), each showing discrete localizations near the kDNA during S phase. POLIB and POLID have roles in minicircle replication but the specific role of POLIC in kDNA maintenance is less clear. Here, we use an RNA interference (RNAi)-complementation system to dissect the functions of two distinct POLIC regions, i.e. the conserved family A DNA polymerase (POLA) domain and the uncharacterized N-terminal region (UCR). While RNAi complementation with wild-type POLIC restored kDNA content and cell cycle localization of kDNA, active site point mutations in the POLA domain impaired minicircle replication similar to that of POLIB and POLID depletions. Complementation with POLA domain alone abolished the formation of POLIC foci and partially rescued the RNAi phenotype. Furthermore, we provide evidence that the UCR is crucial in cell cycle-dependent protein localization and facilitates proper distribution of progeny networks. This is the first report of a DNA polymerase that impacts on mitochondrial nucleoid distribution.
This article has an associated First Person interview with the first author of the paper.
Distinct roles of two eIF4E isoforms in the germline of Caenorhabditis elegans
Authors: Huggins Hayden P. , Subash Jacob S. , Stoffel Hamilton , Henderson Melissa A. , Hoffman Jenna L. , Buckner David S. , Sengupta Madhu S. , Boag Peter R. , Lee Myon-Hee , Keiper Brett D. 
Published: February 2020

ABSTRACT
Germ cells use both positive and negative mRNA translational control to regulate gene expression that drives their differentiation into gametes. mRNA translational control is mediated by RNA-binding proteins, miRNAs and translation initiation factors. We have uncovered the discrete roles of two translation initiation factor eIF4E isoforms (IFE-1, IFE-3) that bind 7-methylguanosine (m7G) mRNA caps during Caenorhabditis elegans germline development. IFE-3 plays important roles in germline sex determination (GSD), where it promotes oocyte cell fate and is dispensable for spermatogenesis. IFE-3 is expressed throughout the germline and localizes to germ granules, but is distinct from IFE-1 and PGL-1, and facilitates oocyte growth and viability. This contrasts with the robust expression in spermatocytes of IFE-1, the isoform that resides within P granules in spermatocytes and oocytes, and promotes late spermatogenesis. Each eIF4E is localized by its cognate eIF4E-binding protein (IFE-1:PGL-1 and IFE-3:IFET-1). IFE-3 and IFET-1 regulate translation of several GSD mRNAs, but not those under control of IFE-1. Distinct mutant phenotypes, in vivo localization and differential mRNA translation suggest independent dormant and active periods for each eIF4E isoform in the germline.
Regulation of intrinsic polarity establishment by a differentiation-type MAPK pathway in S. cerevisiae
Authors: Prabhakar Aditi , Chow Jacky , Siegel Alan J. , Cullen Paul J. 
Published: February 2020

ABSTRACT
All cells establish and maintain an axis of polarity that is critical for cell shape and progression through the cell cycle. A well-studied example of polarity establishment is bud emergence in the yeast Saccharomyces cerevisiae, which is controlled by the Rho GTPase Cdc42p. The prevailing view of bud emergence does not account for regulation by extrinsic cues. Here, we show that the filamentous growth mitogen activated protein kinase (fMAPK) pathway regulates bud emergence under nutrient-limiting conditions. The fMAPK pathway regulated the expression of polarity targets including the gene encoding a direct effector of Cdc42p, Gic2p. The fMAPK pathway also stimulated GTP-Cdc42p levels, which is a critical determinant of polarity establishment. The fMAPK pathway activity was spatially restricted to bud sites and active during the period of the cell cycle leading up to bud emergence. Time-lapse fluorescence microscopy showed that the fMAPK pathway stimulated the rate of bud emergence during filamentous growth. Unregulated activation of the fMAPK pathway induced multiple rounds of symmetry breaking inside the growing bud. Collectively, our findings identify a new regulatory aspect of bud emergence that sensitizes this essential cellular process to external cues.
PTPN23 binds the dynein adaptor BICD1 and is required for endocytic sorting of neurotrophin receptors
Authors: Budzinska Marta I. , Villarroel-Campos David , Golding Matthew , Weston Anne , Collinson Lucy , Snijders Ambrosius P. , Schiavo Giampietro 
Published: February 2020

ABSTRACT
Signalling by target-derived neurotrophins is essential for the correct development of the nervous system and its maintenance throughout life. Several aspects concerning the lifecycle of neurotrophins and their receptors have been characterised over the years, including the formation, endocytosis and trafficking of signalling-competent ligand–receptor complexes. However, the molecular mechanisms directing the sorting of activated neurotrophin receptors are still elusive. Previously, our laboratory identified Bicaudal-D1 (BICD1), a dynein motor adaptor, as a key factor for lysosomal degradation of brain-derived neurotrophic factor (BDNF)-activated TrkB (also known as NTRK2) and p75NTR (also known as NGFR) in motor neurons. Here, using a proteomics approach, we identified protein tyrosine phosphatase, non-receptor type 23 (PTPN23), a member of the endosomal sorting complexes required for transport (ESCRT) machinery, in the BICD1 interactome. Molecular mapping revealed that PTPN23 is not a canonical BICD1 cargo; instead, PTPN23 binds the N-terminus of BICD1, which is also essential for the recruitment of cytoplasmic dynein. In line with the BICD1-knockdown phenotype, loss of PTPN23 leads to increased accumulation of BDNF-activated p75NTR and TrkB in swollen vacuole-like compartments, suggesting that neuronal PTPN23 is a novel regulator of the endocytic sorting of neurotrophin receptors.
What determines systemic blood flow in vertebrates?
Authors: Joyce William , Wang Tobias 
Published: February 2020

ABSTRACTIn the 1950s, Arthur C. Guyton removed the heart from its pedestal in cardiovascular physiology by arguing that cardiac output is primarily regulated by the peripheral vasculature. This is counterintuitive, as modulating heart rate would appear to be the most obvious means of regulating cardiac output. In this Review, we visit recent and classic advances in comparative physiology in light of this concept. Although most vertebrates increase heart rate when oxygen demands rise (e.g. during activity or warming), experimental evidence suggests that this tachycardia is neither necessary nor sufficient to drive a change in cardiac output (i.e. systemic blood flow, Q̇sys) under most circumstances. Instead, Q̇sys is determined by the interplay between vascular conductance (resistance) and capacitance (which is mainly determined by the venous circulation), with a limited and variable contribution from heart function (myocardial inotropy). This pattern prevails across vertebrates; however, we also highlight the unique adaptations that have evolved in certain vertebrate groups to regulate venous return during diving bradycardia (i.e. inferior caval sphincters in diving mammals and atrial smooth muscle in turtles). Going forward, future investigation of cardiovascular responses to altered metabolic rate should pay equal consideration to the factors influencing venous return and cardiac filling as to the factors dictating cardiac function and heart rate.
Higher DNA methylation of ABO gene promoter is associated with acute myocardial infarction in a hospital-based population in Karachi
Authors: Yousuf Farzana Abubakar , Kazmi Khawar , Iqbal Junaid , Ahmed Nikhat , Iqbal Mohammad Perwaiz 
Published: February 2020

Objective: To find out if there is any relationship of methylation status of ABO gene promoter with the risk of acute myocardial infarction (AMI) in a hospital-based Pakistani population in Karachi, Pakistan.
Methods: A case control study comprising of 39 adult AMI patients (both males and females; age range 30-70 years) and 39 normal healthy controls (both males and females and similar age range) nested in a large study (to see the relationship of ABO genotypes with AMI) was designed to investigate the methylation status of ABO gene promoter and its association with AMI. The study was carried out at the Aga Khan University, Karachi during July 2018 to June 2019. DNA isolated from samples of AMI patients and normal healthy controls were converted into bisulphite DNA using a kit method. Methylation specific polymerase chain reaction was carried out to determine the methylation status of ABO gene promoter in both cases and controls. Logistic regression was used to find out any association between increased methylation status of ABO gene promoter and risk of AMI.
Results: A significantly higher percentage of DNA methylation of the ABO gene promoter was observed in AMI patients as compared to normal healthy controls (82.1% vs. 35.9%; p value <0.001). This higher methylation status of ABO gene promoter was associated with AMI and the odds of AMI in this population were more than 6-fold in subjects with methylated gene promoter compared to those with unmethylated gene promoter after adjusting with age and waist circumference [AOR (95% CI) = 6.27 (1.76-22.3); p value = 0.005].
Conclusion: The ABO gene promoter’s hypermethylation appears to be increasing the risk of AMI in a hospital-based Pakistani population in Karachi, Pakistan.
doi: https://doi.org/10.12669/pjms.36.3.1406
How to cite this:Yousuf FA, Kazmi K, Iqbal J, Ahmed N, Iqbal MP. Higher DNA methylation of ABO gene promoter is associated with acute myocardial infarction in a hospital-based population in Karachi. Pak J Med Sci. 2020;36(3):505-510. doi: https://doi.org/10.12669/pjms.36.3.1406
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Anti-Mullerian hormone levels in female cancer patients of reproductive age in Indonesia: A cross-sectional study
Authors: Harzif Achmad Kemal , Wiweko Budi , Addina Putri , Iswaranti Kartika , Silvia Melisa , Mariana Ana , Mutia Kresna , Sumapraja Kanadi , Muharam R , Pratama Gita 
Published: February 2020

Background: Efforts in reproductive preservation for cancer patients have become one of the important aspects of cancer management. In fact, decline in reproductive function is known to occur after exposure to anti-cancer treatments. Measuring anti-Müllerian hormone (AMH) levels is known to be the best parameter in predicting ovarian reserves, which indicates reproductive function. In total, 68% of cancer survivors of reproductive age who underwent anti-cancer treatments suffer from infertility. Meanwhile, ovarian reserves also decrease with increasing age. There is ongoing debate on whether the ovarian reserves of cancer patients could be reduced long before exposure to anti-cancer therapy. Therefore, it is important to know whether ovarian reserves in cancer patients decrease before or after anti-cancer therapy. This can help predict the reproductive function in such cases and the effectiveness of ovarian preservation efforts. Methods: A cross-sectional study was conducted, comparing the AMH levels of 44 female cancer patients of reproductive age before cancer therapy, to 44 non-cancer patients of reproductive age (age matched). The AMH was determined from blood.The biological ages from both groups were adjusted using the Indonesian Kalkulator of Oocytes. Results: The median age in both groups was 28 years old. The AMH levels in the blood of the cancer group were found to be significantly lower in contrast to those in the non-cancer group (1.11 [0.08-4.65] ng/ml vs. 3.99 [1.19- 8.7]; p- value <0.001). Therefore, the biological age in the cancer group was 10 years older than that of the non-cancer group, indicating that ovarian aging occurs earlier in cancer patients. Conclusions: AMH levels of cancer patients of reproductive age were already reduced before cancer therapy, given an older biological age, in contrast to that of the non-cancer patients. Proper counseling and implementation of fertility-preserving methods is highly recommended in this group of patients.