bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequential programming for replicated data stores
Authors: Lewchenko Nicholas V. , Radhakrishna Arjun , Gaonkar Akash , Černý Pavol
Published: July 2019

We introduce Carol, a refinement-typed programming language for replicated data stores. The salient feature of Carol is that it allows programming and verifying replicated store operations
modularly
, without consideration of other operations that might interleave, and
sequentially
, without requiring reference to or knowledge of the concurrent execution model. This is in stark contrast with existing systems, which require understanding the concurrent interactions of all pairs of operations when developing or verifying them.

The key enabling idea is the
consistency guard
, a two-state predicate relating the locally-viewed store and the hypothetical remote store that an operation’s updates may eventually be applied to, which is used by the Carol programmer to declare their precise consistency requirements. Guards appear to the programmer and refinement typechecker as simple data pre-conditions, enabling sequential reasoning, while appearing to the distributed runtime as consistency control instructions.

We implement and evaluate the Carol system in two parts: (1) the algorithm used to statically translate guards into the runtime coordination actions required to enforce them, and (2) the networked-replica runtime which executes arbitrary operations, written in a Haskell DSL, according to the Carol language semantics.
Call-by-need is clairvoyant call-by-value
Authors: Hackett Jennifer , Hutton Graham
Published: July 2019

Call-by-need evaluation, also known as lazy evaluation, provides two key benefits: compositional programming and infinite data. The standard semantics for laziness is Launchbury’s natural semantics DBLP:conf/popl/Launchbury93, which uses a heap to memoise the results of delayed evaluations. However, the stateful nature of this heap greatly complicates reasoning about the operational behaviour of lazy programs. In this article, we propose an alternative semantics for laziness,
clairvoyant evaluation
, that replaces the state effect with nondeterminism, and prove this semantics equivalent in a strong sense to the standard semantics. We show how this new semantics greatly simplifies operational reasoning, admitting much simpler proofs of a number of results from the literature, and how it leads to the first
denotational cost semantics
for lazy evaluation.
Repairnator patches programs automatically
Authors: Monperrus Martin , Urli Simon , Durieux Thomas , Martinez Matias , Baudry Benoit , Seinturier Lionel
Published: July 2019

Repairnator is a bot. It constantly monitors software bugs discovered during continuous integration of open-source software and tries to fix them automatically. If it succeeds in synthesizing a valid patch, Repairnator proposes the patch to the human developers, disguised under a fake human identity. To date, Repairnator has been able to produce patches that were accepted by the human developers and permanently merged into the code base. This is a milestone for human-competitiveness in software engineering research on automatic program repair.
Human Lung Microbiome on the Way to Cancer
Authors: Kovaleva Olga V. , Romashin Daniil , Zborovskaya Irina B. , Davydov Mikhail M. , Shogenov Murat S. , Gratchev Alexei
Published: July 2019

Recent research on cancer-associated microbial communities led to the accumulation of data on the interplay between bacteria, immune and tumor cells, the pathways of bacterial induction of carcinogenesis, and its meaningfulness for medicine. Microbial communities that have any kind of impact on tumor progression and microorganisms associated with tumors have been defined as oncobiome. Over the last decades, a number of studies were dedicated toHelicobacter pyloriand its role in the progression of stomach tumors, so this correlation can be regarded as proven. Involvement of bacteria in the induction of lung cancer has been largely ignored for a long time, though some correlations between this type of cancer and lung microbiome were established. Despite the fact that in the present the microbial impact on lung cancer progression has many confirmations, the underlying mechanisms are poorly understood. Microorganisms can contribute to tumor initiation and progression through production of bacteriotoxins and other proinflammatory factors. The purpose of this review is to organize the available data on lung cancer microbiome and its role in malignant tumor progression.
Autophagy: A Player in response to Oxidative Stress and DNA Damage
Authors: Galati Serena , Boni Christian , Gerra Maria Carla , Lazzaretti Mirca , Buschini Annamaria
Published: July 2019

Autophagy is a catabolic pathway activated in response to different cellular stressors, such as damaged organelles, accumulation of misfolded or unfolded proteins, ER stress, accumulation of reactive oxygen species, and DNA damage. Some DNA damage sensors like FOXO3a, ATM, ATR, and p53 are known to be important autophagy regulators, and autophagy seems therefore to have a role in DNA damage response (DDR). Recent studies have partly clarified the pathways that induce autophagy during DDR, but its precise role is still not well known. Previous studies have shown that autophagy alterations induce an increase in DNA damage and in the occurrence of tumor and neurodegenerative diseases, highlighting its fundamental role in the maintenance of genomic stability. During DDR, autophagy could act as a source of energy to maintain cell cycle arrest and to sustain DNA repair activities. In addition, autophagy seems to play a role in the degradation of components involved in the repair machinery. In this paper, molecules which are able to induce oxidative stress and/or DNA damage have been selected and their toxic and genotoxic effects on the U937 cell line have been assessed in the presence of the single compounds and in concurrence with an inhibitor (chloroquine) or an inducer (rapamycin) of autophagy. Our data seem to corroborate the fundamental role of this pathway in response to direct and indirect DNA-damaging agents. The inhibition of autophagy through chloroquine had no effect on the genotoxicity induced by the tested compounds, but it led to a high increase of cytotoxicity. The induction of autophagy, through cotreatment with rapamycin, reduced the genotoxic activity of the compounds. The present study confirms the cytoprotective role of autophagy during DDR; its inhibition can sensitize cancer cells to DNA-damaging agents. The modulation of this pathway could therefore be an innovative approach able to reduce the toxicity of many compounds and to enhance the activity of others, including anticancer drugs.
Analysis of the UGT1A1 Genotype in Hyperbilirubinemia Patients: Differences in Allele Frequency and Distribution
Authors: Mi Xiao-xiao , Yan Jian , Ma Xiao-jie , Zhu Ge-li , Gao Yi-dan , Yang Wen-jun , Kong Xiao-wen , Chen Gong-ying , Shi Jun-ping , Gong Ling
Published: July 2019

Objective. The spectrum of UDP-glucuronyl transferase A1 (UGT1A1) variants in hereditary unconjugated hyperbilirubinemia varies markedly between different ethnic populations. This study evaluated the UGT1A1 genotypes in hyperbilirubinemia patients from southeastern China. Methods. We enrolled 60 patients from southeastern China (44 men and 16 women; age range: 3–76 years) with unconjugated hyperbilirubinemia and performed genetic analysis of the UGT1A1 gene by direct sequencing. Results. For patients with Gilbert syndrome, 85% (47/55) harbored pathogenic variants of UGT1A1⁎60. Both UGT1A1⁎28 and UGT1A1⁎81 were detected in the promoter region of UGT1A1. Additionally, 83% (20/24) of patients with Gilbert syndrome heterozygous for UGT1A1⁎60 had an association with heterozygous variation of UGT1A1⁎28 or UGT1A1⁎81, while 91% (21/23) of Gilbert syndrome patients homozygous for UGT1A1⁎60 had biallelic variations of UGT1A1⁎28 and UGT1A1⁎81. We detected 213 UGT1A1 allelic variants, including six novel variations, with the most frequent allele being the UGT1A1⁎60, followed by UGT1A1⁎28 and UGT1A1⁎6. All of the patients showed multiple sites of variants in UGT1A1; however, variation number was not associated with bilirubin levels (P>0.05). Conclusions. The spectrum of UGT1A1 variants in southeastern Chinese patients was distinct from other ethnic populations. Our findings broaden the knowledge concerning traits associated with UGT1A1 variants and help profile genotype–phenotype correlations in hyperbilirubinemia patients.
Persistent Left Superior Vena Cava and Absent Right Superior Vena Cava with Left Subclavian Vein Stenosis: Technical Challenges with Pacemaker Implantation
Authors: Kanjwal Khalil , Soos Michael , Gonzalez-Morales Daniel , Shah Ibrahim , Madala Mohan , Mughal Majid , Kang Muhammad Awais
Published: July 2019

We present a challenging case of a 75-year-old female with a history of paroxysmal atrial fibrillation (PAF) and symptomatic sick sinus syndrome (SSS) who presented for a dual chamber pacemaker implantation and was found to have persistent left superior vena cava and absent right superior vena cava with stenosis of the left subclavian vein. In this report, we discuss the implant technique in this group of patients.
C-Phycocyanin Alleviates Bladder Inflammation and Dysfunction in Cyclophosphamide-Induced Cystitis in a Mouse Model by Inhibiting COX-2 and EP4
Authors: Bao Xing-qi , Huang Yi-chen , Chen Fang
Published: July 2019

Objective. To explore the effect of C-phycocyanin (C-PC) on voiding behavior and histological changes in cyclophosphamide- (CYP-) induced cystitis in mice. Methods. Sixty female mice were included. The mice in the C-PC group received C-PC (25 mg/kg, twice, i.p.) and then CYP (200 mg/kg, i.p.) two hours later, while the mice in the CYP group only received the equivalent CYP. Saline was injected in the mice in the control group. A voided stain on paper (VSOP) test was conducted to analyze the micturition. The bladders were harvested for histological evaluation and measurements of inflammatory factors. Results. C-PC reduced the micturition frequency in the mice with CYP-induced cystitis. The bladder/body weight ratio and edema were remarkably higher in the CYP group compared to the C-PC group. C-PC suppressed the expressions of COX-2, PGE2, and EP4 (prostaglandin E receptor 4) according to the ELISA assay. Immunohistochemical staining also indicated that C-PC reduced the expressions of COX-2 in urothelium and EP4 in smooth muscles. Conclusions. C-PC relieved symptoms associated with CYP-induced cystitis in mice by inhibiting bladder inflammation through COX-2 and EP4 expression.
Intratumoral Fusobacterium Nucleatum Levels Predict Therapeutic Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma
Authors: Yamamura Kensuke , Izumi Daisuke , Kandimalla Raju , Sonohara Fuminori , Baba Yoshifumi , Yoshida Naoya , Kodera Yasuhiro , Baba Hideo , Goel Ajay
Published: July 2019

Purpose:

Emerging evidence indicates that gut microbiome plays a crucial role in the cancer pathogenesis. Although Fusobacterium nucleatum (F. nucleatum) is associated with poor prognosis in multiple cancers, its clinical significance in predicting response to chemotherapy in patients with esophageal squamous cell carcinoma (ESCC) remains unclear.

Experimental Design:

The F. nucleatum levels were quantified by qPCR assays in tumor tissues from 551 patients with ESCC from two independent cohorts, including 101 patients who received neoadjuvant chemotherapy prior to curative resection. Associations between F. nucleatum burden and recurrence-free survival (RFS), as well with chemotherapeutic response were evaluated using response evaluation criteria in solid tumors (RECISTs), primary tumor metabolic response defined by maximum standardized uptake value (SUVmax) changes in positron emission tomography-CT (PET/CT), and pathologic tumor regression grade (TRG).

Results:

High burden of F. nucleatum in patients with ESCC associated with poor RFS in both training [log-rank P = 0.02; HR = 1.61; P = 0.03] and validation cohorts (log-rank P = 0.003; HR = 1.96; P = 0.004). Importantly, patients with ESCC with high levels of F. nucleatum displayed poor chemotherapeutic response for all three evaluation methods: RECIST (P = 0.04), SUVmax change in PET/CT (P = 0.0004), and TRG (P = 0.003).

Conclusions:

We conclude that high levels of intratumoral F. nucleatum have a prognostic significance for predicting poor RFS in patients with ESCC. More importantly, our data indicates that higher F. nucleatum burden correlates with poor response to neoadjuvant chemotherapy, suggesting the possibility that an antibiotic intervention against this bacterium may significantly improve therapeutic response in patients with ESCC.
ESM1 as a Marker of Macrotrabecular-Massive Hepatocellular Carcinoma
Authors: Calderaro Julien , Meunier Léa , Nguyen Cong Trung , Boubaya Marouane , Caruso Stefano , Luciani Alain , Amaddeo Giuliana , Regnault Hélène , Nault Jean-Charles , Cohen Justine , Oberti Frédéric , Michalak Sophie , Bouattour Mohamed , Vilgrain Valérie , Pageaux Georges Philippe , Ramos Jeanne , Barget Nathalie , Guiu Boris , Paradis Valérie , Aubé Christophe , Laurent Alexis , Pawlotsky Jean-Michel , Ganne-Carrié Nathalie , Zucman-Rossi Jessica , Seror Olivier , Ziol Marianne
Published: July 2019

Purpose:

Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a novel morphological subtype of HCC associated with early relapse after resection or percutaneous ablation, independently of classical clinical and radiological prognostic factors. The aim of the present study was to identify immunohistochemical markers of MTM-HCC, to ease its diagnosis and implementation into clinical practice.

Experimental Design:

To identify potential biomarkers of MTM-HCC, we first analyzed gene expression profiling data from The Cancer Genome Atlas study and further selected two candidate biomarkers. Performance of both biomarkers for diagnosis of MTM-HCC was further tested by immunohistochemistry in two independent series of 67 and 132 HCC biopsy samples.

Results:

Analysis of RNA sequencing data showed that MTM-HCC was characterized by a high expression of neoangiogenesis-related genes. Two candidate biomarkers, Endothelial-Specific Molecule 1 (ESM1) and Carbonic Anhydrase IX (CAIX), were selected. In the discovery series, sensitivity and specificity of ESM1 expression by stromal endothelial cells for the detection of MTM-HCC were 97% (28/29), and 92% (35/38), respectively. Sensitivity and specificity of CAIX were 48% (14/29) and 89% (34/38). In the validation set, sensitivity and specificity of ESM1 for the identification of MTM-HCC were 93% (14/15) and 91% (107/117), respectively. Interobserver agreement for ESM1 assessment was good in both series (Cohen Kappa 0.77 and 0.76).

Conclusions:

Using a molecular-driven selection of biomarkers, we identified ESM1 as a reliable microenvironment immunohistochemical marker of MTM-HCC. The results represent a step toward the implementation of HCC morpho-molecular subtyping into clinical practice.
Influence of the pH Value of Refluxate and Proximal Extent on Heartburn Perception in Patients with Proton Pump Inhibitor-Refractory Non-Erosive Reflux Disease
Authors: Abe Yasuaki , Koike Tomoyuki , Saito Masahiro , Okata Tomoki , Norita Kazuaki , Kikuchi Hiroki , Nakagawa Kenichiro , Hatta Waku , Asanuma Kiyotaka , Uno Kaname , Asano Naoki , Imatani Akira , Shimosegawa Tooru , Masamune Atsushi
Published: July 2019

Background and Objectives: Weakly acidic reflux has been reported as the major cause of symptom occurrence in patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD). This study is aimed at clarifying whether the pH value of weakly acidic reflux affects the induction of symptoms. Methods: We retrospectively evaluated the records of combined multichannel intraluminal impedance and pH monitoring in 57 patients with PPI-refractory NERD. Weakly acidic refluxes were divided into 3 categories based on the pH value of the refluxate: pH 4–5, 5–6, and 6–7. Results: A total of 29 patients were positive in the symptom index. The symptom provocation rate in reflux of pH 4–5 (19%) was much higher than in that of pH 5–6 (11%) and pH 6–7 (12%). In the reflux at pH 4–5, the symptom provocation rate in the proximal reflux was higher than that in the distal reflux (p < 0.05), whereas the reflux at pH 5–6 and pH 6–7 was not significantly different in the symptom provocation rate between the proximal and distal refluxes. Conclusion: Reflux at pH <5 reaching the proximal esophagus was the main factor in the induced symptoms of patients with PPI-refractory NERD.
Early-Pregnancy Circulating Antioxidant Capacity and Hemodynamic Adaptation in Recurrent Placental Syndrome: An Exploratory Study
Authors: Severens-Rijvers Carmen A.H. , Al-Nasiry Salwan , Vincken Annemiek , Haenen Guido , Winkens Bjorn , Ghossein-Doha Chahinda , Spaanderman Marc A.E. , Peeters Louis L.H.
Published: July 2019

Background/Aims: Placental syndromes (PS) refer to pregnancy complications that include gestational hypertension, (pre)eclampsia, HELLP syndrome, and/or placental insufficiency-induced fetal growth restriction. These disorders are characterized by increased oxidative stress. This study aims to test the hypothesis that the abnormal hemodynamic adaptation to pregnancy, typical for early PS pregnancy, is accompanied by abnormal maternal levels of antioxidants relative to those in normal pregnancy. Methods: Before, and at 12, 16, and 20 weeks pregnancy, we measured trolox equivalent antioxidant capacity (TEAC), uric acid (UA), and TEACC (TEAC corrected for UA) in maternal serum of former PS patients, who either developed recurrent PS (rPS; n = 16) or had a normal next pregnancy (non-rPS; n = 23). Concomitantly, we also measured various hemodynamic variables. Results: rPS differed from non-rPS by higher TEACC levels before pregnancy (178 vs. 152 µM; p = 0.02) and at 20 weeks pregnancy (180 vs. 160 µM; p = 0.04). Only non-rPS responded to pregnancy by significant rises in hemodynamic measures. Conclusion: These data indicate that rPS pregnancies are preceded by an increase in antioxidant capacity, presumably induced by subclinical vascular injury and low-grade chronic inflammation.
Clinical Presentation and Mortality Determinants of Alcohol-Related Liver Disease: A Single-Center Experience of the Rising Menace from Eastern India
Authors: Ray Gautam , Manjubhargav P.
Published: July 2019

Objectives: Recently,the incidenceof alcohol-related liver disease has been rising alarmingly in India with late presentation and short survival. Better delineation of factors affecting mortality is needed for optimal utilization of constrained resources like liver transplantation. Methods: Baseline data of 395 patients with alcohol-related liver disease including age, clinical presentation, alcohol parameters (amount, duration, type), laboratory parameters for detecting organ failure, and prognostic scores were compared between survivor and deceased groups. Further subgroup analysis of deceased patients was done to identify factors associated with early mortality in acute-on-chronic liver failure (ACLF) and cirrhosis groups by multivariate analysis and receiver operating characteristic (ROC) curves. Only best supportive medical therapy was offered to all. Results: 80 (20.3%) patients had alcoholic hepatitis (without cirrhosis) and recovered completely with abstinence. 315 (79.7%) had evidence of either cirrhosis (n = 182, 46.1%) or ACLF (n = 133, 33.6%) at presentation and all died within the next 2 years of follow-up, earlier in the ACLF cases. All deceased patients had been heavy drinkers for long periods (>85 g/day for >17 years). Higher age, amount of alcohol consumption, number of organ failures and discriminant function score predicted severe disease and early mortality, the latter being the best predictor. The European Foundation for the study of chronic liver failure consortium (CLIF-C) score has good applicability in Indian ACLF cohorts. Serum glutamic pyruvic transaminase was normal in 73.8% of deceased patients compared to only 12.5% of survivors. Abstinence did not result in complete normalization of deranged laboratory parameters in those who died. Conclusion: Alcohol-related liver disease is serious with high short-term mortality, which has early identifiable but mostly irreversible factors. Urgent measures need to be taken to curb this rising menace.
Leptin Is Not Essential for Obesity-Associated Hypertension
Authors: von Schnurbein Julia , Manzoor Jaida , Brandt Stephanie , Denzer Friederike , Kohlsdorf Katja , Fischer-Posovszky Pamela , Weißenberger Mario , Frank-Podlech Sabine , Mahmood Saqib , Wabitsch Martin
Published: July 2019

Background and Objective: Hyperleptinemia is supposed to play a causal role in the development of obesity-associated hypertension, possibly via increased sympathetic tone. Hence patients with congenital leptin deficiency should be hypotensive and their low blood pressure should increase under leptin substitution. Subjects and Methods: To test this assumption, we examined ambulatory blood pressure, resting heart rate, Schellong test results, cold pressor test results, heart rate variability, catecholamine metabolites, and aldosterone levels in 6 patients with congenital leptin deficiency before as well as 2–7 days and 7–14 months after the start of leptin substitution. Ambulatory blood pressure was also examined in 3 patients with biallelic disease-causing variants in the leptin receptor gene. Results: Contrary to our expectations, even before leptin substitution, 1 patient with biallelic leptin receptor gene variants and 4 patients with leptin deficiency had been suffering from hypertension. Short-term substitution with leptin increased blood pressure further in 3 out of 4 patients (from 127.0 ± 11.7 to 133.8 ± 10.6 mm Hg), concomitant with an increase in resting heart rate as well as in heart rate during the Schellong test in all patients (from 87.6 ± 7.7 to 99.9 ± 11.0 bpm, p = 0.031, and from 102.9 ± 13.5 to 115.6 ± 11.3 bpm, p = 0.031, respectively). Furthermore, the systolic blood pressure response during the cold pressor test increased in 4 out of 6 patients. Unexpectedly, catecholamine metabolites and aldosterone levels did not increase. After long-term leptin substitution and weight loss, the resting heart rate decreased in 4 out of 6 patients compared to baseline, and in all patients below the heart rate seen immediately after the start of therapy (from 99.9 ± 11.0 to 81.7 ± 5.4 bpm; p = 0.031). Conclusions: These results show that obesity-associated hypertension does not depend on the presence of leptin. However, short-term leptin substitution can increase the blood pressure and heart rate in obese humans with leptin deficiency, indicating that leptin plays at least an additive role in obesity-associated hypertension. The mechanisms behind this are not clear but might include an increase in regional sympathetic tone.
Preventing Diabetes Mellitus in Nigeria: Effect of Physical Exercise, Appropriate Diet, and Lifestyle Modification
Authors: Adeleke Olasunkanmi R. , Ayenigbara George O. 
Published: July 2019

In this systematic review, we explored the effects of physical activity, diet, and lifestyle on the prevention of diabetes mellitus in Nigeria. Diabetes is an autoimmune disease which occurs when the body does not produce or respond properly to insulin, a hormone essential for daily life. Diabetes is an incurable disease, which has no racial, social, or sex barrier. The risk factors include a poor diet, lack of physical activity, obesity, and an unhealthy lifestyle. About 100 million people in the United States have diabetes mellitus, and the total economic costs of diabetes exceed USD 132 billion a year. Diabetes accounts for 1 of every 10th USD spent on health care in the United States, and an estimated 48 million Americans may develop diabetes by 2050. However, it is estimated that in 90% of the patients with type 2 diabetes the disease could be prevented if people adopted a healthy lifestyle, including regular physical activity, a moderate-good diet, and modest weight. Because of the deleterious health consequences which include blindness; kidney damage; cardiovascular disease; and reduced life span, as well as high treatment costs, prevention of the disease in Nigeria, where you are confronted with a poor health care system, poverty, and ignorance, but also have ample opportunities for physical activity and rich local nutrients to supply an ideal diet, is a viable option. Consequent upon this, the paper recommends, among others, that available local resources be used for this purpose.
Gut Microbiota and Fecal Levels of Short-Chain Fatty Acids Differ Upon 24-Hour Blood Pressure Levels in Men
Authors: Huart Justine , Leenders Justine , Taminiau Bernard , Descy Julie , Saint-Remy Annie , Daube Georges , Krzesinski Jean-Marie , Melin Pierrette , de Tullio Pascal , Jouret François
Published: July 2019

Gut microbiota may influence blood pressure (BP), namely via end products of carbohydrate fermentation. After informed consent, male volunteers were prospectively categorized into 3 groups upon European Society of Hypertension criteria based on 24-hour ambulatory BP measurements: (1) hypertension, (2) borderline hypertension, and (3) normotension. Stool, urine and serum samples were collected in fasting conditions. Gut microbiota was characterized by 16S amplicon sequencing. Metabolomics, including quantification of short-chain fatty acids, was conducted using nuclear magnetic resonance. Two-way ANOVA combined with Tukey post hoc test, as well as multiple permutation test and Benjamini-Hochberg-Yekutieli false discovery rate procedure, was used. The cohort included 54 males: 38 hypertensive (including 21 under treatment), 7 borderline, and 9 normotensive. No significant difference was observed between groups concerning age, body mass index, smoking habits, and weekly alcohol consumption. The genus
Clostridium sensu stricto 1
positively correlated with BP levels in nontreated patients (n=33). This correlation was significant after multiple permutation tests but was not substantiated following false discovery rate adjustment. Short-chain fatty acid levels were significantly different among groups, with higher stool levels of acetate, butyrate, and propionate in hypertensive versus normotensive individuals. No difference was observed in serum and urine metabolomes. Correlation between stool metabolome and 24-hour BP levels was evidenced, with R
2
reaching 0.9. Our pilot study based on 24-hour ambulatory BP measurements, 16S amplicon sequencing, and metabolomics supports an association between gut microbiota and BP homeostasis, with changes in stool abundance of short-chain fatty acids.
Proximal Tubule-Specific Deletion of the NHE3 (Na
+
/H
+
Exchanger 3) in the Kidney Attenuates Ang II (Angiotensin II)-Induced Hypertension in Mice
Authors: Li Xiao C. , Zhu Dongmin , Chen Xu , Zheng Xiaowen , Zhao Chunling , Zhang Jianfeng , Soleimani Manoocher , Rubera Isabelle , Tauc Michel , Zhou Xinchun , Zhuo Jia L.
Published: July 2019

The present study directly tested the hypothesis that the NHE3 (Na
+
/H
+
exchanger 3) in the proximal tubules of the kidney is required for the development of Ang II (angiotensin II)-induced hypertension using PT-
Nhe3
−/−
(proximal tubule-specific NHE3 knockout) mice. Specifically, PT-
Nhe3
−/−
mice were generated using the
SGLT2-Cre
/
Nhe3

loxlox

approach, whereas Ang II-induced hypertension was studied in 12 groups (n=5–12 per group) of adult male and female wild-type (WT) and PT-
Nhe3
−/−
mice. Under basal conditions, systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were significantly lower in male and female PT-
Nhe3
−/−
than WT mice (
P
<0.01). A high pressor, 1.5 mg/kg per day, intraperitoneal or a slow pressor dose of Ang II, 0.5 mg/kg per day, intraperitoneal for 2 weeks significantly increased systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure in male and female WT mice (
P
<0.01), but the hypertensive response to Ang II was markedly attenuated in male and female PT-
Nhe3
−/−
mice (
P
<0.01). Ang II impaired the pressure-natriuresis response in WT mice, whereas proximal tubule-specific deletion of NHE3 improved the pressure-natriuresis response in Ang II-infused PT-
Nhe3
−/−
mice (
P
<0.01). AT
1
receptor blocker losartan completely blocked Ang II-induced hypertension in both WT and PT-
Nhe3
−/−
mice (
P
<0.01). However, inhibition of nitric oxide synthase with L-N
G
-Nitroarginine methyl ester had no effect on Ang II-induced hypertension in WT or PT-
Nhe3
−/−
mice (not significant). Furthermore, Ang II-induced hypertension was significantly attenuated by an orally absorbable NHE3 inhibitor AVE0657. In conclusion, NHE3 in the proximal tubules of the kidney may be a therapeutical target in hypertension induced by Ang II or with increased NHE3 expression in the proximal tubules.
How to Enlarge NATO: The Debate inside the Clinton Administration, 1993–95
Authors: Sarotte M.E.
Published: July 2019

Newly available sources show how the 1993–95 debate over the best means of expanding the North Atlantic Treaty Organization unfolded inside the Clinton administration. This evidence comes from documents recently declassified by the Clinton Presidential Library, the Defense Department, and the State Department because of appeals by the author. As President Bill Clinton repeatedly remarked, the two key questions about enlargement were when and how. The sources make apparent that, during a critical decisionmaking period twenty-five years ago, supporters of a relatively swift conferral of full membership to a narrow range of countries outmaneuvered proponents of a slower, phased conferral of limited membership to a wide range of states. Pleas from Central and Eastern European leaders, missteps by Russian President Boris Yeltsin, and victory by the pro-expansion Republican Party in the 1994 U.S. congressional election all helped advocates of full-membership enlargement to win. The documents also reveal the surprising impact of Ukrainian politics on this debate and the complex roles played by both Strobe Talbott, a U.S. ambassador and later deputy secretary of state, and Andrei Kozyrev, the Russian foreign minister. Finally, the sources suggest ways in which the debate's outcome remains significant for transatlantic and U.S.-Russian relations today.
A new species of Aconitum (Ranunculaceae) from Eastern Himalaya
Authors: TIWARY RAGHUVAR , SINGH HARSH , ADHIKARI DIBYENDU , SINGH PREM PRAKASH , BARIK SAROJ KANTA
Published: July 2019

Aconitum tawangense, a new species from Tawang, Eastern Himalaya is described and illustrated here. This newly described species differ in the shape, size and vestiture of the sepals from its allied taxa A. assamicum and A. orochryseum. Other distinguishing characters include the colour of the petals and number of the carpels. The species was also assessed for its threat status.
Liparis popaensis (Orchidaceae), a new species from Myanmar
Authors: MU AYE THIN , AUNG YE LWIN , JIN XIAOHUA
Published: July 2019

Liparis popaensis, a new species of Orchidaceae, is described from Popa Mountain National Park, central Myanmar. Liparis popaensis is morphologically similar to L. odorata but it differs from the latter by having oblong-lanceolate dorsal sepal, column with two triangular wings and lip with a pair of subconical and basally adjoining calli at its base. Identification key and colour photographs are provided. A preliminary conservation assessment according to the IUCN Red List Categories and Criteria is given for the new species.
A new genus and species of larval Erythraeinae (Acari: Prostigmata: Erythraeidae) from Ukraine and the taxonomic state of Zhangiella
Authors: SABOORI ALIREZA , KHAUSTOV ALEXANDR A. , HAKIMITABAR MASOUD , HAJIQANBAR HAMIDREZA
Published: July 2019

Makolia crimeaensis Saboori, Khaustov & Hakimitabar gen. et sp. nov. (Acari: Erythraeidae) is described and illustrated from larvae ectoparasitic on Lasius sp. (Hymenoptera: Formicidae) from Ukraine. A key to world genera of Erythraeinae (larva) is presented and the genus Zhangiella Saboori, Cobanoglu & Bayram is synonymised with Curteria Southcott.
A conspectus of the flower fly genus Allograpta (Diptera: Syrphidae) with description of a new subgenus and species
Authors: MENGUAL XIMO , RUIZ CARLOS , ROJO SANTOS , STÅHLS GUNILLA , THOMPSON F. CHRISTIAN
Published: July 2019

A new subgenus [Allograpta (Costarica Mengual & Thompson), type Allograpta zumbadoi Thompson], and one new species [Allograpta (Costarica) nishida Mengual & Thompson; type-locality: Costa Rica, type-depository: Instituto Nacional de Biodiversidad de Costa Rica] of flower flies (Diptera: Syrphidae) are described from the Neotropical biotic region. A checklist of the world species of Allograpta including synonyms is provided, and a key to and diagnoses of the subgenera are also supplied. The phylogenetic relationships among Allograpta species, representing all hitherto detected morphological diversity of the genus, and related genera were studied under parsimony based on morphological characters.
Phylogenetic revision and the origin of Polyphrix Townes (Hymenoptera, Ichneumonidae, Cryptinae), with description of a new species
Authors: SANTOS BERNARDO F. , AGUIAR ALEXANDRE P. , TEDESCO ANAZÉLIA M.
Published: July 2019

Polyphrix stellata sp. nov., from the Brazilian Amazon Forest, is described and illustrated. The validity of the genus is cladistically tested using implied weighting, in a matrix with 26 species and 75 morphological characters. Concavity constants (K) from 1 to 6 were tested. All analyses recovered all known Polyphrix species as a monophyletic group. The preferred results, with K2–6, suggest (Prosthoporus nigrifemur Gupta + Lagarosoma assitum Gupta) + Messatoporus sp. as the sister group of the genus; with K1, this group also included two species of Gabuniina. The results with K1–5 suggest an Amazonian origin of the genus, with species from northern Brazil appearing basally in the clade, while both Atlantic Forest species appear as sister groups. A redescription of Polyphrix is presented, combining the original definition with recently published additions and original information. An updated key to species is presented, and new morphometric data is provided for P. varians and P. cristata. Prosthoporus mexicanus comb. nov. is proposed as a new combination for Polyphrix mexicanus Kasparyan & Ruíz, representing the first record of Prosthoporus from North America. Seven new distribution records are provided for Polyphrix, expanding its known range to 29º51' of latitude, from Guyana to Paraná (southern Brazil).
Biogeography and divergence time estimation of the relict Cape dragonfly genus Syncordulia: global significance and implications for conservation
Authors: WARE JESSICA L. , SIMAIKA JOHN P. , SAMWAYS MICHAEL J.
Published: July 2019

Syncordulia (Odonata: Anisoptera: Libelluloidea) inhabits mostly cool mountainous streams in the Cape Floristic Region of South Africa. It is found at low densities in geographically restricted areas. Syncordulia is endemic to South Africa and, until recently, only two species were known, S. venator (Barnard, 1933) and S. gracilis (Burmeister 1839), both considered Vulnerable by the World Conservation Union (IUCN). Two new species, S. serendipator Dijsktra, Samways & Simaika 2007 and S. legator Dijsktra, Samways & Simaika 2007, were described from previously unrecognized museum specimens and new field collections. Here we corroborate the validity of these two new species using multiple genes and propose intergeneric relationships within Syncordulia. Molecular data from two independent gene fragments (nuclear 28S and ribosomal and cytochrome oxidase subunit I mitochondrial data) were sequenced and/or downloaded from GenBank for 7 libelluloid families, including 12 Syncordulia specimens (2 Syncordulia gracilis, 4 S. serendipator, 2 S. legator and 4 S. venator). The lower libelluloid group GSI (sensu Ware et al. 2007), a diverse group of non– corduliine taxa, is strongly supported as monophyletic. Syncordulia is well supported by both methods of phylogenetic analyses as a monophyletic group deeply nested within the GSI clade. A DIVA biogeographical analysis suggests that the ancestor to the genus Syncordulia may have arisen consequent to the break–up of Gondwana (>120 Mya). Divergence time estimates suggest that Syncordulia diverged well after the breakup of Gondwana, approximately 60 million years ago (Mya), which coincides with the divergence of several Cape fynbos taxa, between 86 – 60 Mya. DIVA analyses suggest that the present distributions of Syncordulia may be the result of dispersal events. We relate these phylogenetic data to the historical biogeography of the genus and to the importance of conservation action.
Dual Sympathetic Input into Developing Salivary Glands
Authors: Teshima T.H.N. , Tucker A.S. , Lourenço S.V.
Published: July 2019

Neuronal signaling is known to be required for salivary gland development, with parasympathetic nerves interacting with the surrounding tissues from early stages to maintain a progenitor cell population and control morphogenesis. In contrast, postganglionic sympathetic nerves arrive late in salivary gland development to perform a secretory function; however, no previous report has shown their role during development. Here, we show that a subset of neuronal cells within the parasympathetic submandibular ganglion (PSG) express the catecholaminergic marker tyrosine hydroxylase (TH) in developing murine and human submandibular glands. This sympathetic phenotype coincided with the expression of transcription factor Hand2 within the PSG from the bud stage (E12.5) of mouse embryonic salivary gland development. Hand2 was previously associated with the decision of neural crest cells to become sympathetic in other systems, suggesting a role in controlling neuronal fate in the salivary gland. The PSG therefore provides a population of TH-expressing neurons prior to the arrival of the postganglionic sympathetic axons from the superior cervical ganglion at E15.5. In culture, in the absence of nerves from the superior cervical ganglion, these PSG-derived TH neurons were clearly evident forming a network around the gland. Chemical ablation of dopamine receptors in explant culture with the neurotoxin 6-hydroxydopamine at early stages of gland development resulted in specific loss of the TH-positive neurons from the PSG, and subsequent branching was inhibited. Taken altogether, these results highlight for the first time the detailed developmental time course of TH-expressing neurons during murine salivary gland development and suggest a role for these neurons in branching morphogenesis.
Subjective Age and Memory Performance Among Older Chinese Adults
Authors: Shao Jingjin , Zhang Li , Xiao Luxia , Li Xiying , Li Jiamei
Published: July 2019

This study aims to examine the mediating role of learning self-efficacy in the relationship between subjective age and memory performance as well as the moderating role of education in these indirect and direct relationships. A study was conducted with 200 older adults aged 60 to 81 years who completed measures of subjective age, learning self-efficacy, education, and memory performance. Analysis revealed that learning self-efficacy partially mediated the association between subjective age and memory performance. Further analysis found that the indirect associations between subjective age and memory through learning self-efficacy vary as a function of education. Implications and suggestions for future research are discussed.
Pro-market governance, migration status and worker vulnerability: The case of Australian horticulture
Authors: van den Broek Diane , Wright Chris F , Howe Joanna , Reilly Alexander
Published: July 2019

The migration status of temporary migrant workers is often presented as a major determinant of labour rights and worker vulnerabilities. Using a sequential mixed method approach this article interrogates this proposition to examine the factors exacerbating temporary migrant worker exploitation within the Australian horticulture industry. The article finds that temporary migrants’ access to labour rights are shaped by their migration status. However, in contrast to prevalent assumptions, visa conditions play a preliminary, rather than a deterministic, role in this vulnerability. The article argues that notwithstanding the considerable links between vulnerability and migration status, changes in the political economy of Australian horticulture towards neoliberal or ‘pro-market governance’ arrangements have been central drivers of worker vulnerability. It focuses on three manifestations of these arrangements – the intensification of supply chain pressures, the emergence of labour market intermediaries, and the reduced presence of trade unions – as critical actors shaping temporary migrant worker agency.
The importance of engaging students on public assistance: New insights and recommendations for practice
Authors: Elias Nicole M , Marrin Madeleine
Published: July 2019

Student engagement in institutions of higher education has become a central priority for educators and administrators. What “student engagement” means for a diverse student body is an important question for public institutions with justice-related missions. As social welfare policy shifts to allow more recipients of public assistance access to higher education, research regarding their engagement experiences remains scarce. To support a socioeconomically diverse student body, consistent with the Network of Schools of Public Policy, Affairs, and Administration (NASPAA) standards, this project explores the nature of engagement among student recipients of public assistance by asking the following research questions: what forms of engagement with students on public assistance take place? Why is engaging students on public assistance important? How can we foster greater engagement with students on public assistance? To answer these questions, student and faculty focus groups are conducted. From this analysis, we highlight normative implications of engaging a socioeconomically diverse student population and present recommendations for fostering greater engagement.
Age-group differences in beginning-state comfort reveal an increase in motor planning capabilities
Authors: Scharoun Benson Sara M. , Bryden Pamela J. , Roy Eric A.
Published: July 2019

Objects can be grasped in different ways to ensure a movement plan is aligned with the intended action. The current study assessed grasp posture in joint action object manipulation in children (ages 6–11, n = 68), young adults ( n = 21), and older adults ( n = 23). Participants performed two actions (pickup and pass; pickup and pass for use) within two movement contexts (using a dowel as if it were the actual object; actual object use), using two objects (glass and hammer) that differed in use-dependent experience. Beginning-state comfort (prioritizing a comfortable initial hand posture for an object recipient) was assessed. Taken together, findings support the notion that the ability to anticipate the intended action, and thus consider an action partner in one’s action plan, increases with age. With age and use-dependent experience, it can be argued that there is a shift from stimulus-driven, familiar responses, to considering affordances and task demands. Together, findings add to our understanding of changes in motor planning capabilities across the life span.
Implications of we-talk for relationships and health among patients with type 1 diabetes and their spouses
Authors: Lee Juwon , Helgeson Vicki S. , Van Vleet Meredith , Tracy Eunjin L. , de Grey Robert G. Kent , Zajdel Melissa , Berg Cynthia A.
Published: July 2019

We-talk (first-person plural pronoun usage) is frequently used to represent the degree to which a person views an illness as shared within a couple. There is evidence that we-talk is related to good relationship and health. However, research has failed to examine the implications of we-talk for spouses and the interpersonal mechanisms that underlie relational and health benefits. To address these limitations, we investigated the association of we-talk to relationship and health among 199 couples in which one person had type 1 diabetes. We-talk was assessed in the context of a brief coping interview with patients and spouses separately. Patients reported their perceptions of their spouse’s behavior over the past month. Actor–partner interdependence, regression, and bootstrap models showed that patient we-talk was unrelated to patient and spouse well-being, but greater spouse we-talk was associated with higher patient relationship satisfaction, higher patient self-efficacy, and better patient self-care behavior. For spouses, greater spouse we-talk also was associated with higher relationship satisfaction, lower stress, and fewer depressive symptoms. Mediational analyses showed that patients’ perceptions of spouses’ greater emotional support and fewer critical behaviors partially accounted for these associations. Spouse we-talk may be more important than patient we-talk because it signifies that spouses are involved in helping with diabetes management, namely by providing emotional support and refraining from criticizing the patient.
Enhancing Public Health Messaging: Discrete-Choice Experiment Evidence on the Design of HIV Testing Messages in China
Authors: Durvasula Maya , Pan Stephen W. , Ong Jason J. , Tang Weiming , Cao Bolin , Liu Chuncheng , Terris-Prestholt Fern , Tucker Joseph D.
Published: July 2019

Introduction. While a growing literature documents the effectiveness of public health messaging on social media, our understanding of the factors that encourage individuals to engage with and share messages is limited. In the context of human immunodeficiency virus (HIV) among men who have sex with men (MSM) in China, rising incidence and low testing rates despite decades of interventions suggest the need for effective, targeted messaging to reach underserved populations. Social media platforms and sex-seeking apps present a promising avenue, as web-based strategies can take advantage of existing trust within dense social networks. Methods. We conducted an online discrete-choice experiment in January 2017 with MSM from across China. Participants were presented with 6 choice tasks, each composed of 2 messages about HIV testing, and were asked in which scenario they were more likely to share the content. Participants were given information about the source of the HIV testing message, the social media sharing platform, and the recipients with whom they would share the message. They were given the option of sharing 1 message or neither. Multinomial and mixed logit models were used to model preferences within 4 subgroups. Results. In total, 885 MSM joined the survey, completing 4387 choice tasks. The most important attribute for 3 of the 4 subgroups was social media sharing platform. Men were more willing to share messages on sex-seeking mobile applications and less willing to share materials on generic (non-MSM) social media platforms. We found that men with more active online presences were less willing to share HIV testing messages on generic social media platforms. Conclusions. Our findings suggest that sex-seeking platforms represent a targeted, efficient method of actively engaging MSM in public health interventions.