bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of ethnic/racial discrimination with internalizing symptoms and externalizing behaviors among juvenile justice‐involved youth of color
Authors: Loyd Aerika Brittian , Hotton Anna L. , Walden Angela L. , Kendall Ashley D. , Emerson Erin , Donenberg Geri R.
Published: August 2019

Introduction

Youth of color (e.g., Black/African American and Latinx/Hispanic) are overrepresented in the juvenile justice system and experience greater health disparities compared to non‐Hispanic White youth. Ethnic/racial discrimination (ERD) is a risk marker for poor mental health and behavioral outcomes among youth of color, and traumatic stress and emotion dysregulation have been implicated in these pathways. Despite the relevance of these factors for justice‐involved youth of color, understanding of their interrelations within this demographic is lacking.

Methods

Participants were 173 recently arrested adolescents (86% African American; 45% girls; ages 13–18) on probation in a large Midwest city in the United States. Participants completed surveys assessing ERD, traumatic stress, emotion dysregulation, internalizing symptoms, and externalizing behaviors. Using linear regression and path analysis, this study tested the cross‐sectional links among two types of ERD (i.e., interpersonal experiences and perceptions of group experiences), traumatic stress symptoms, emotion dysregulation, and internalizing symptoms and externalizing behaviors.

Results

Interpersonal ERD (e.g., hearing racial insults) was associated with increased internalizing symptoms and externalizing behaviors; for internalizing symptoms, the relation was stronger for girls than boys. Gender differences were partially accounted for by traumatic stress symptoms and emotion dysregulation.

Conclusions

This study offers new insights into ERD experiences among juvenile justice‐involved youth of color, gender differences in ethnic/racial discrimination experiences, and the potential value of gender‐sensitive and culturally responsive programming in strengthening youths’ ability to cope with ERD.
Adherence to post colorectal cancer surveillance colonoscopy guidelines at a tertiary care center
Authors: Mohy-ud-din Nabeeha , Umar Shifa , Syed Aslam , Monga Dulabh
Published: August 2019

Background Surveillance colonoscopy 1 year after resection of colorectal cancer is recommended by all major societies, including National Comprehensive Cancer Network and United States Multi Society Task Force.

Study objectives Our study assesses adherence to post colorectal cancer resection surveillance colonoscopy guidelines at a large tertiary care center and aims to identify reasons for non-adherence.

Methods A retrospective study was conducted for patients who underwent curative resection for colorectal cancer between January 2016 and June 2017. Adherence to surveillance colonoscopy for non-obstructed or partially obstructed colon and rectal cancers was defined as performance of colonoscopy 11–14 months and 11–15 months after surgery, respectively.

Results A total of 80 patients were identified. Mean age was 66 ± 13 years and 58% (n = 46) were males. 60% (n = 48) had colon cancer and 40% (n = 32) had rectal cancer. 69% (n = 24) of patients with colon cancer and 42% (n = 8) of patients with rectal cancer adhered to surveillance colonoscopy guidelines and the mean time to colonoscopy was 315 ± 44 days and 369 ± 103 days, respectively. The most commonly identified reasons for non-adherence to surveillance colonoscopy included metastases (10.9%) and patients’ refusal to undergo surveillance (6.5%).

Conclusion Overall, post colorectal cancer resection to follow up surveillance is inadequate. There is a need to identify barriers to surveillance post colorectal cancer resection and address them.
Healthcare of the Eritrean People’s Liberation Front and its Politicization, 1970–1991: Treating the Body Politic
Authors: Hjalmarsson Clarissa Charlotte
Published: August 2019

This article explores the health service provided by the Eritrean People’s Liberation Front (EPLF) during the Eritrean Liberation War, and its political dimensions and implications. The EPLF used healthcare to define itself politically against its rivals and to penetrate communities. It aimed to incorporate population groups into the struggle, to inculcate EPLF ideology, and to transform the national community. EPLF practitioners were most successful when they cooperated with existing structures of power. The progressive, dynamic, and transformative nature of the healthcare system is inextricable from the coercion sometimes used to achieve the ideals of the EPLF, and the way in which healthcare became an instrument of biopolitical control.
Normal and oblique drop impact of yield stress fluids with thixotropic effects
Authors: Oishi Cassio M. , Thompson Roney L. , Martins Fernando P.
Published: August 2019

Normal and oblique drop impact on a solid surface is numerically analysed for yield stress fluids. A rich diversity of results are generated as a consequence of the exploration of the inertial, elastic, plastic and thixotropic features of the process, as well as the inclination of the solid surface. We show that drops of more thixotropic fluids have a higher tendency to bounce in the normal impact, and to roll or to bounce in the case of an oblique drop impact. Concerning elasticity, we found a critical value for the elastic Ohnesorge number above which no bouncing takes place. Experimental findings such as the fact that the stored energy due to the elasticity of the fluid drop plays a role similar to the stored energy of an interfacial nature in inelastic fluid drops are corroborated in the present study.
Glycaemic, gastrointestinal, hormonal and appetitive responses to pearl millet or oats porridge breakfasts: a randomised, crossover trial in healthy humans
Authors: Alyami Jaber , Whitehouse Ella , Yakubov Gleb E. , Pritchard Susan E. , Hoad Caroline L. , Blackshaw Elaine , Heissam Khaled , Cordon Sally M. , Bligh H. Frances J. , Spiller Robin C. , Macdonald Ian A. , Aithal Guruprasad P. , Gowland Penny A. , Taylor Moira A. , Marciani Luca
Published: August 2019

Whole-grain cereal breakfast consumption has been associated with beneficial effects on glucose and insulin metabolism as well as satiety. Pearl millet is a popular ancient grain variety that can be grown in hot, dry regions. However, little is known about its health effects. The present study investigated the effect of a pearl millet porridge (PMP) compared with a well-known Scottish oats porridge (SOP) on glycaemic, gastrointestinal, hormonal and appetitive responses. In a randomised, two-way crossover trial, twenty-six healthy participants consumed two isoenergetic/isovolumetric PMP or SOP breakfast meals, served with a drink of water. Blood samples for glucose, insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide (GIP), peptide YY, gastric volumes and appetite ratings were collected 2 h postprandially, followed by an ad libitum meal and food intake records for the remainder of the day. The incremental AUC (iAUC2h) for blood glucose was not significantly different between the porridges (P > 0·05). The iAUC2h for gastric volume was larger for PMP compared with SOP (P = 0·045). The iAUC2h for GIP concentration was significantly lower for PMP compared with SOP (P = 0·001). Other hormones and appetite responses were similar between meals. In conclusion, the present study reports, for the first time, data on glycaemic and physiological responses to a pearl millet breakfast, showing that this ancient grain could represent a sustainable alternative with health-promoting characteristics comparable with oats. GIP is an incretin hormone linked to TAG absorption in adipose tissue; therefore, the lower GIP response for PMP may be an added health benefit.
Street food in Dushanbe, Tajikistan: availability and nutritional value
Authors: Albuquerque Gabriela , Morais Inês , Gelormini Marcello , Casal Susana , Damasceno Albertino , Pinho Olívia , Moreira Pedro , Jewell Jo , Breda João , Lunet Nuno , Padrão Patrícia
Published: August 2019

Street food is part of the culture in central Asia. Although nourishing food can be found, unhealthier options are becoming increasingly popular – a marker of nutrition transition. The nutritional composition of street food in urban settings is, however, unknown. The objective of the present study was, thus, to characterise the street food availability in Dushanbe, Tajikistan. A total of 800 street food vending sites in public markets were selected through random and systematic procedures. Trained interviewers collected data on vending sites’ characteristics, location and food available. Samples of the most commonly available food were collected (ninety-nine homemade and thirty-five industrial). Macronutrients were quantified through proximate analysis. Fruit, drinks and food other than fruits were available, respectively, in 4·5, 40·5 and 87·4 %, of the vending sites. Among the latter, 63·6 % sold only homemade (e.g. bread, traditional dishes, snacks, pastries, sandwiches and cakes), 19·3 % only industrial (e.g. bread, snacks, pastries and cookies) and 17·1 % both types of food. Homemade food presented higher energy per serving compared with industrial food (median 452 v. 276 kcal/serving (1891 v. 1155 kJ/serving); P < 0·001). A high content of SFA (soup: 10·9 g/serving) and trans-fatty acids (cakes: 1·8 g/serving) was also found in homemade food. However, industrial wafers showed the highest content of these fatty acids (12·9 g/serving and 2·5 g/serving, respectively). Soft drinks were available in 68·5 % of the vending sites selling beverages. Homemade and industrial street food, with heterogeneous nutritional value, were widely available in Dushanbe. Hence, policies promoting the availability of healthy food should be encouraged.
Genetic variation among biparental Robusta coffee families and implications for variety development
Authors: Akpertey Abraham , Anim-Kwapong Esther , Adu-Gyamfi Paul Kwasi Krah , Ofori Atta
Published: August 2019

Understanding the genetic variability, heritability and genetic advance (GA) of traits in any plant population is an important pre-requisite for variety development. The objectives of the study were to assess the level of genetic variability among vegetative growth traits and yield, assess the relationship among the growth traits and yield and predict GA for the most heritable traits among Robusta coffee full-sib families. The trial was established in June 2009 at the experimental fields of the Cocoa Research Institute of Ghana with 62 full-sib families planted in a randomized complete block design with six replications. Significant (p< 0.05) variation was observed among the full-sib families evaluated for all traits, except for span (canopy diameter). Span and number of laterals were genetically correlated (p< 0.001) with cumulative yield (2013–2017), with span being the vegetative growth trait most strongly related to cumulative yield (rg= 0.60,p< 0.001). The most heritable vegetative growth and yield traits were, respectively, number of laterals (H2= 0.59) and cumulative yield (H2= 0.41). The top 10 families (BP40, BP41, BP9, BP36, BP34, BP28, BP37, BP14, BP4 and BP10) in terms of cumulative yield are proposed for multi-location evaluation and possible release as hybrids for coffee farmers in Ghana.
Do Informal Contracts Matter for Corporate Innovation? Evidence from Social Capital
Authors: Gupta Atul , Raman Kartik , Shang Chenguang
Published: August 2019

We examine the relevance of informal contracting mechanisms for corporate innovation. Using social capital to capture the social costs imposed on opportunistic behavior by management, we report evidence that firms headquartered in states with higher levels of social capital are associated with more innovation. This result is more pronounced when employees are more susceptible to holdup (e.g., firms with low labor union coverage, firms located in states with weak legal protections for employees, and firms surrounded by few external employment opportunities) and when employees face higher levels of information asymmetry. Our study highlights the importance of informal contracts for innovation.
Kurt Hirschfeld and the Visionary Internationalism of the Schauspielhaus Zürich
Authors: Arons Wendy
Published: August 2019

Outside Switzerland, the Schauspielhaus Zürich (Zürich Playhouse) is best known among theatre historians for the role it played in supporting and advancing the career of German playwright Bertolt Brecht during and just after World War II. We learn, from our studies of Brecht, that while he was living in exile in Finland and the United States his plays Mother Courage and Her Children, The Good Person of Szechwan, and Galileo all received their first productions in Zürich, and that when he returned to Europe from exile the city was also his initial destination. Brecht was not the only exiled playwright to find a producing home at the Schauspielhaus; the theatre has additionally long been recognized, particularly among German and Swiss theatre historians, for the important role it played in producing the work of many other exiled German and Austrian playwrights during World War II. Some American theatre historians have also made note of the quality of the work produced at the Schauspielhaus: for example, Oscar Brockett mentions the Zürich theatre in passing as “one of the best in Europe during the Nazi regime because so many refugees settled in Switzerland.” But what remains underrecognized among historians outside Switzerland is the pivotal role that both the Schauspielhaus and its dramaturg (and later artistic director) Kurt Hirschfeld played in keeping an international repertoire on life support in Europe when most of the Continent was under Nazi occupation (Fig. 1). A look at the list of wartime and postwar productions at the Schauspielhaus reveals a veritable who's who of the modern Western dramatic canon: productions of works by playwrights like Karel Čapek, Thornton Wilder, Jean Giraudoux, Jean-Paul Sartre, Paul Claudel, Federico García Lorca, T. S. Eliot, Arthur Miller, Tennessee Williams, Luigi Pirandello, and many, many—in fact, many dozens—of others.
“A Glimpse of ‘Another Russia’”: Elisaveta Fen's Chekhov Translations
Authors: Warden Claire
Published: August 2019

Since the first British production of Anton Chekhov's play The Seagull in 1909, audiences have found the Russian's plays both beguiling and frustrating in seemingly equal measure. After living in Britain some years, Russian translator Elisaveta Fen began to recognize the problem:

These plays are tragi-comedies: they are the stuff life is made of. They do not fit into any conventional category. Awkwardly presented, they can disappoint, baffle, irritate, or they can cast their spell over the spectator and make him feel he is watching real people, living real lives—on the stage.
ARE LICHEN GROWTH FORM CATEGORIES SUPPORTED BY CONTINUOUS FUNCTIONAL TRAITS: WATER-HOLDING CAPACITY AND SPECIFIC THALLUS MASS?
Authors: Wan S. , Ellis C. J.
Published: August 2019

The focus of community ecology has shifted from the description of taxonomic composition towards an understanding of community assembly based on species’ ‘functional traits’. The functional trait approach is well developed for vascular plants, utilising variability of continuous phenotypic characters that affect ecological fitness, such as specific leaf area, tissue nitrogen concentration or seed mass, to explain community structure. In contrast, community assembly studies for poikilohydric cryptogamic plants and fungi, such as lichens, remain focused on broad categorical traits such as growth form difference: fruticose, foliose or crustose. This study examined intra- and interspecific variability for two highly promising continuous phenotypic measurements that affect lichen physiology and ecological fitness: water-holding capacity (WHC) and specific thallus mass (STM). Values for WHC and STM were compared within and among species, and within and among key macrolichen growth forms (fruticose and green-algal and cyanolichen foliose species), asking whether these widely used categories adequately differentiate the continuous variables (WHC and STM). We show large intra- and interspecific variability that does not map satisfactorily onto growth form categories, and on this basis provide recommendations and caveats in the future use of lichen functional traits.
Repeated Sport-Related Concussion Shows Only Minimal White Matter Differences Many Years After Playing High School Football
Authors: Terry Douglas P. , Mewborn Catherine M. , Miller L. Stephen
Published: August 2019

Objective: Multiple concussions sustained in youth sport may be associated with later-life brain changes and worse cognitive outcomes. We examined the association between two or more concussions during high school football and later-life white matter (WM) microstructure (i.e., 22–47 years following football retirement) using diffusion tensor imaging (DTI). Method: Forty former high school football players aged 40–65 who received 2+ concussions during high school football (N = 20), or denied concussive events (N = 20) were recruited. Participants underwent neurocognitive testing and DTI scanning. Results: Groups did not statistically differ on age, education, or estimated pre-morbid intelligence. Tract-based Spatial Statistics (TBSS) correcting for Family-Wise Error (FWE)(p < .05) did not yield differences between groups at the whole-brain level. Region of interest analyses showed higher mean diffusivity (MD) in the anterior limb of the internal capsule (ALIC) in the concussed group compared to the non-concussed former players. More liberal analyses (i.e., p < .001, uncorrected for multiple comparisons, ≥8 voxels) also revealed that former players endorsing 2+ concussions had higher MD in the ALIC. Analyses that covaried for age did not reveal differences at either threshold. Concussive histories were not associated with worse cognitive functioning, nor did it impact the relationship between neuropsychological scores and DTI metrics. Discussion: Results suggest only minimal neuroanatomical brain differences in former athletes many years following original concussive injuries compared to controls.
Analysing the policy space for the promotion of healthy, sustainable edible oil consumption in India
Authors: Cuevas Soledad , Downs Shauna M , Ghosh-Jerath Suparna , Aafrin  , Shankar Bhavani
Published: August 2019

Objective:

To identify opportunities and challenges for the promotion of healthy, sustainable oil consumption in India.

Design:

We use a framework for policy space analysis which distinguishes between policy context, process and characteristics.

Setting:

We focus on the Indian edible oils sector and on factors shaping the policy space at a national level.

Participants:

The study is based on the analysis of policy documents and semi-structured interviews with key experts and stakeholders in the edible oils sector.

Results:

We find opportunities associated with the emergence of multisectoral policy frameworks for climate adaptation and non-communicable disease (NCD) prevention at a national level which explicitly include the oils sector, the existence of structures for sectoral policy coordination, some supportive factors for the translation of nutrition evidence into practice, and the possibility of integrating nutrition-sensitive approaches within current state-led agricultural interventions. However, the trade-offs perceived across sustainability, NCD prevention and food security objectives in the vegetable oils sector are considered a barrier for policy influence and implementation. Sustainability and nutrition advocates tend to focus on different segments of the value chain, missing potential synergies. Moreover, policy priorities are dominated by historical concerns for food security, understood as energy provision, as well as economic and strategic priorities.

Conclusions:

Systematic efforts towards identifying synergistic approaches, from agricultural production to distribution of edible oils, as well as increased involvement of nutrition advocates with upstream policies in the oils sector, could increase policy influence for advocates of both nutrition and sustainability.
Functional Validation of DownRegulated MicroRNAs in HeLa Cells Treated with Polyalthia longifolia Leaf Extract Using Different Microscopic Approaches: A Morphological Alteration-Based Validation
Authors: Shanmugapriya  , Vijayarathna Soundararajan , Sasidharan Sreenivasan
Published: August 2019

Several microscopy methods have been developed to assess the morphological changes in cells in the investigations of the mode of cell death in response to a stimulus. Our recent finding on the treatment of the IC50concentration (26.67μg/mL) ofPolyalthia longifolialeaf extract indicated the induction of apoptotic cell death via the regulation of miRNA in HeLa cells. Hence, the current study was conducted to validate the function of these downregulated microRNAs inP. longifolia-treated HeLa cells using microscopic approaches. These include scanning electron microscope (SEM), transmission electron microscope (TEM), and acridine orange/propidium iodide (AO/PI)-based fluorescent microscopy techniques by observing the morphological alterations to cells after transfection with mimic miRNA. Interestingly, the morphological changes observed in this study demonstrated the apoptotic hallmarks, for instance, cell blebbing, cell shrinkage, cytoplasmic and nuclear condensation, vacuolization, cytoplasmic extrusion, and the formation of apoptotic bodies, which proved the role of dysregulated miRNAs in apoptotic HeLa cell death after treatment with theP. longifolialeaf extract. Conclusively, the current study proved the crucial role of downregulated miR-484 and miR-221-5p in the induction of apoptotic cell death inP. longifolia-treated HeLa cells using three approaches—SEM, TEM, and AO/PI-based fluorescent microscope.
Jürgen Wirtgen & others v. The Czech Republic, PCA Case No.2014-03
Authors: Lewis Carla
Published: August 2019

On 11 October 2017, an ad hoc tribunal seated in Geneva and chaired by Professor Gabrielle Kaufmann-Kohler, with co-arbitrators Gary Born (Claimants' appointee, dissenting) and Judge Peter Tomka (Respondent's appointee), issued its award in Jürgen Wirtgen & others v. The Czech Republic (the Award). The Tribunal dismissed the Claimants' claims in full and ordered the Parties to bear their own legal costs and expenses.
Estimation of the Dust Aerosol Shortwave Direct Forcing Over Land Based on an Equi‐albedo Method From Satellite Measurements
Authors: Tian Lin , Zhang Peng , Chen Lin
Published: August 2019

It is important but difficult to measure the shortwave radiative forcing of the dust aerosols over land from satellite‐observed radiance because the inhomogeneous surface albedo varies in a large dynamic range. In this study, we proposed a satellite‐based equi‐albedo method to derive the dust aerosol shortwave direct forcing over land. In the method, an equal radiance at the top of atmosphere was assumed for the region with the similar surface albedo and the similar solar zenith angle. The aerosol optical depth (AOD) from Moderate Resolution Imaging Spectroradiometer and the shortwave radiance product from Clouds and Earth's Radiant Energy System were used to derive the dust aerosol radiative forcing. The dust storm events outbroken on 9 and 24 April 2010 in Taklimakan desert were selected as study cases. The mean dust shortwave direct forcing efficiency is −35.08 W/m2 per unit of dust AOD during the dust storm events. The results were validated with the calculated radiative forcing from Moderate Resolution Imaging Spectroradiometer AOD product by the radiative transfer model. It shows that the derived radiative forcing is well correlated with the simulated one. The mean difference is 10.57 and the standard deviation is 1.35. Moreover, uncertainty has been estimated. The regional mean‐directed radiative forcing due to dust are −28.98 ± 7.99 and −35.76 ± 10.61 W/m2 of these two cases directly from satellite observations. This research indicates that the proposed method is reliable and effective, which can be used to estimate the shortwave direct radiative forcing of the dust storm event.
Flexural Rigidity and Shoot Reconfiguration Determine Wake Length Behind Saltmarsh Vegetation Patches
Authors: Marjoribanks T. I. , Lague D. , Hardy R. J. , Boothroyd R. J. , Leroux J. , Mony C. , Puijalon S.
Published: August 2019

Vegetation patches play an important role in controlling sediment deposition in shallow aquatic environments such as coastal saltmarshes and fluvial systems. However, predicting deposition around vegetation patches is difficult due to the complexity of patch morphology and their dynamic interaction with the flow. Here we incorporate a biomechanical model, parameterized using field data, within a 3‐D computational fluid dynamics model which allows prediction of individual shoot reconfiguration within patches due to flow forcing. The model predicts velocity attenuation and bed shear stresses within the wake of the patch which agree spatially with accretion patterns measured in the field using terrestrial lidar. The model is applied to sparse patches of Suaeda maritima, located in saltmarshes of coastal habitats, to explore the role of (I) shoot distribution, (II) patch geometry, (III) shoot flexural rigidity, and (IV) bulk flow velocity in determining the length of the predicted wake region. We demonstrate that for Suaeda maritima, with intermediate rigidity, the vertical shear layer over the vegetation controls the length of the predicted wake region. Consequently, reconfiguration due to flexural rigidity strongly impacts on wake length, confounding the relationship between patch height and wake length. A simplified model for predicting wake length based on shoot reconfiguration is applied to the simulation data and shows good agreement. The results demonstrate that the observed wake characteristics can be well explained by intraspecific variability in flexural rigidity, thus demonstrating the importance of biomechanical traits in determining flow‐vegetation‐sediment interactions.
Circulating microbiota-derived metabolites: a “liquid biopsy?
Authors: Aragonès Gemma , Colom-Pellicer Marina , Aguilar Carmen , Guiu-Jurado Esther , Martínez Salomé , Sabench Fàtima , Antonio Porras José , Riesco David , Del Castillo Daniel , Richart Cristóbal , Auguet Teresa
Published: August 2019

Background/Objectives

Non-alcoholic fatty liver disease (NAFLD) causes a wide spectrum of liver damage, from simple steatosis (SS) to cirrhosis. SS and non-alcoholic steatohepatitis (NASH) cannot be distinguished by clinical or laboratory features. Dysregulation of the gut microbiota is involved in NASH pathogenesis. The aim of this study was to assess the relationship between microbiota-derived metabolites and the degrees of NAFLD; also, to investigate whether these metabolites could be included in a panel of NASH biomarkers.

Subjects/Methods

We used liquid chromatography coupled to triple-quadrupole-mass spectrometry (LC-QqQ) analysis to quantify choline and its derivatives, betaine, endogenous ethanol, bile acids, short-chain fatty acids and soluble TLR4 in serum from women with normal weight (n = 29) and women with morbid obesity (MO) (n = 82) with or without NAFLD. We used real-time polymerase chain reaction (RT-PCR) analysis to evaluate the hepatic and intestinal expression level of all genes studied (TLR2, TLR4, TLR9, LXRα, SREBP1C, ACC1, FAS, PPARα, CPT1α, CROT, SREBP2, ABCA1, ABCG1 and FXR in the liver; TLR2, TLR4, TLR5, TLR9, GLP-1R, DPP-4, FXR and PPARɣ in the jejunum) in 82 women with MO with normal liver histology (NL, n = 29), SS (n = 32), and NASH (n = 21).

Results

Hepatic FAS, TLR2, and TLR4 expression were overexpressed in NAFLD patients. TLR2 was overexpressed in NASH patients. In women with MO with NAFLD, we found upregulation of intestinal TLR9 expression and downregulation of intestinal FXR expression in women with NASH. Circulating TMAO, glycocholic acid and deoxycholic acid levels were significantly increased in NAFLD patients. Endogenous circulating ethanol levels were increased in NASH patients in comparison to those in SS patients.

Conclusions

These findings suggest that the intestine participates in the progression of NAFLD. Moreover, levels of certain circulating microbiota-related metabolites are associated with NAFLD severity and could be used as a “liquid biopsy” in the noninvasive diagnosis of NASH.
Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function
Authors: Guo Daji , Peng Yinghui , Wang Laijian , Sun Xiaoyu , Wang Xiaojun , Liang Chunmei , Yang Xiaoman , Li Shengnan , Xu Junyu , Ye Wen-Cai , Jiang Bin , Shi Lei
Published: August 2019

Genetic studies of autism spectrum disorder (ASD) have revealed multigene variations that converge on synaptic dysfunction. DOCK4, a gene at 7q31.1 that encodes the Rac1 guanine nucleotide exchange factor Dock4, has been identified as a risk gene for ASD and other neuropsychiatric disorders. However, whether and how Dock4 disruption leads to ASD features through a synaptic mechanism remain unexplored. We generated and characterized a line of Dock4 knockout (KO) mice, which intriguingly displayed a series of ASD-like behaviors, including impaired social novelty preference, abnormal isolation-induced pup vocalizations, elevated anxiety, and perturbed object and spatial learning. Mice with conditional deletion of Dock4 in hippocampal CA1 recapitulated social preference deficit in KO mice. Examination in CA1 pyramidal neurons revealed that excitatory synaptic transmission was drastically attenuated in KO mice, accompanied by decreased spine density and synaptic content of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)- and NMDA (N-methyl-D-aspartate)-type glutamate receptors. Moreover, Dock4 deficiency markedly reduced Rac1 activity in the hippocampus, which resulted in downregulation of global protein synthesis and diminished expression of AMPA and NMDA receptor subunits. Notably, Rac1 replenishment in the hippocampal CA1 of Dock4 KO mice restored excitatory synaptic transmission and corrected impaired social deficits in these mice, and pharmacological activation of NMDA receptors also restored social novelty preference in Dock4 KO mice. Together, our findings uncover a previously unrecognized Dock4-Rac1-dependent mechanism involved in regulating hippocampal excitatory synaptic transmission and social behavior.
Hydrogen peroxide inducible clone-5 sustains NADPH oxidase-dependent reactive oxygen species-c-jun N-terminal kinase signaling in hepatocellular carcinoma
Authors: Wu Jia-Ru , You Ren-In , Hu Chi-Tan , Cheng Chuan-Chu , Rudy Rudy , Wu Wen-Sheng
Published: August 2019

Target therapy aiming at critical molecules within the metastatic signal pathways is essential for prevention of hepatocellular carcinoma (HCC) progression. Hic-5 (hydrogen peroxide inducible clone-5) which belongs to the paxillin superfamily, can be stimulated by a lot of metastatic factors, such as transforming growth factor (TGF-β), hepatocyte growth factor (HGF), and reactive oxygen species (ROS). Previous studies implicated Hic-5 cross-talks with the ROS-c-jun N-terminal kinase (JNK) signal cascade in a positive feedback manner. In this report, we addressed this issue in a comprehensive manner. By RNA interference and ectopic Hic-5 expression, we demonstrated Hic-5 was essential for activation of NADPH oxidase and ROS generation leading to activation of downstream JNK and c-jun transcription factor. This was initiated by interaction of Hic-5 with the regulator and adaptor of NADPH oxidase, Rac1 and Traf4, respectively, which may further phosphorylate the nonreceptor tyrosine kinase Pyk2 at Tyr881. On the other hand, promoter activity assay coupled with deletion mapping and site directed mutagenesis strategies demonstrated the distal c-jun and AP4 putative binding regions (943–1126 bp upstream of translational start site) were required for transcriptional activation of Hic-5. Thus Hic-5 was both downstream and upstream of NADPH oxidase-ROS-JNK-c-jun cascade. This signal circuit was essential for regulating the expression of epithelial mesenchymal transition (EMT) factors, such as Snail, Zeb1, E-cadherin, and matrix metalloproteinase 9, involved in HCC cell migration and metastasis. Due to the limited expression of Hic-5 in normal tissue, it can be a promising therapeutic target for preventing HCC metastasis.
TonEBP/NFAT5 promotes obesity and insulin resistance by epigenetic suppression of white adipose tissue beiging
Authors: Lee Hwan Hee , An Seung Min , Ye Byeong Jin , Lee Jun Ho , Yoo Eun Jin , Jeong Gyu Won , Kang Hyun Je , Alfadda Assim A. , Lim Sun Woo , Park Jiyoung , Lee-Kwon Whaseon , Kim Jae Bum , Choi Soo Youn , Kwon Hyug Moo
Published: August 2019

Tonicity-responsive enhancer binding protein (TonEBP or NFAT5) is a regulator of cellular adaptation to hypertonicity, macrophage activation and T-cell development. Here we report that TonEBP is an epigenetic regulator of thermogenesis and obesity. In mouse subcutaneous adipocytes, TonEBP expression increases > 50-fold in response to high-fat diet (HFD) feeding. Mice with TonEBP haplo-deficiency or adipocyte-specific TonEBP deficiency are resistant to HFD-induced obesity and metabolic defects (hyperglycemia, hyperlipidemia, and hyperinsulinemia). They also display increased oxygen consumption, resistance to hypothermia, and beiging of subcutaneous fat tissues. TonEBP suppresses the promoter of β3-adrenoreceptor gene, a critical regulator of lipolysis and thermogenesis, in ex vivo and cultured adipocytes. This involves recruitment of DNMT1 DNA methylase and methylation of the promoter. In human subcutaneous adipocytes TonEBP expression displays a correlation with body mass index but an inverse correlation with β3-adrenoreceptor expression. Thus, TonEBP is an attractive therapeutic target for obesity, insulin resistance, and hyperlipidemia.
Synaptotagmin 17 controls neurite outgrowth and synaptic physiology via distinct cellular pathways
Authors: Ruhl David A. , Bomba-Warczak Ewa , Watson Emma T. , Bradberry Mazdak M. , Peterson Tabitha A. , Basu Trina , Frelka Alyssa , Evans Chantell S. , Briguglio Joseph S. , Basta Tamara , Stowell Michael H. B. , Savas Jeffrey N. , Roopra Avtar , Pearce Robert A. , Piper Robert C. , Chapman Edwin R.
Published: August 2019

The synaptotagmin (syt) proteins have been widely studied for their role in regulating fusion of intracellular vesicles with the plasma membrane. Here we report that syt-17, an unusual isoform of unknown function, plays no role in exocytosis, and instead plays multiple roles in intracellular membrane trafficking. Syt-17 is localized to the Golgi complex in hippocampal neurons, where it coordinates import of vesicles from the endoplasmic reticulum to support neurite outgrowth and facilitate axon regrowth after injury. Further, we discovered a second pool of syt-17 on early endosomes in neurites. Loss of syt-17 disrupts endocytic trafficking, resulting in the accumulation of excess postsynaptic AMPA receptors and defective synaptic plasticity. Two distinct pools of syt-17 thus control two crucial, independent membrane trafficking pathways in neurons. Function of syt-17 appears to be one mechanism by which neurons have specialized their secretory and endosomal systems to support the demands of synaptic communication over sprawling neurite arbors.
Cytokinin functions as an asymmetric and anti-gravitropic signal in lateral roots
Authors: Waidmann Sascha , Ruiz Rosquete Michel , Schöller Maria , Sarkel Elizabeth , Lindner Heike , LaRue Therese , Petřík Ivan , Dünser Kai , Martopawiro Shanice , Sasidharan Rashmi , Novak Ondrej , Wabnik Krzysztof , Dinneny José R. , Kleine-Vehn Jürgen
Published: August 2019

Directional organ growth allows the plant root system to strategically cover its surroundings. Intercellular auxin transport is aligned with the gravity vector in the primary root tips, facilitating downward organ bending at the lower root flank. Here we show that cytokinin signaling functions as a lateral root specific anti-gravitropic component, promoting the radial distribution of the root system. We performed a genome-wide association study and reveal that signal peptide processing of Cytokinin Oxidase 2 (CKX2) affects its enzymatic activity and, thereby, determines the degradation of cytokinins in natural Arabidopsis thaliana accessions. Cytokinin signaling interferes with growth at the upper lateral root flank and thereby prevents downward bending. Our interdisciplinary approach proposes that two phytohormonal cues at opposite organ flanks counterbalance each other’s negative impact on growth, suppressing organ growth towards gravity and allow for radial expansion of the root system.
A single shot coherent Ising machine based on a network of injection-locked multicore fiber lasers
Authors: Babaeian Masoud , Nguyen Dan T. , Demir Veysi , Akbulut Mehmetcan , Blanche Pierre-A , Kaneda Yushi , Guha Saikat , Neifeld Mark A. , Peyghambarian N.
Published: August 2019

Combinatorial optimization problems over large and complex systems have many applications in social networks, image processing, artificial intelligence, computational biology and a variety of other areas. Finding the optimized solution for such problems in general are usually in non-deterministic polynomial time (NP)-hard complexity class. Some NP-hard problems can be easily mapped to minimizing an Ising energy function. Here, we present an analog all-optical implementation of a coherent Ising machine (CIM) based on a network of injection-locked multicore fiber (MCF) lasers. The Zeeman terms and the mutual couplings appearing in the Ising Hamiltonians are implemented using spatial light modulators (SLMs). As a proof-of-principle, we demonstrate the use of optics to solve several Ising Hamiltonians for up to thirteen nodes. Overall, the average accuracy of the CIM to find the ground state energy was ~90% for 120 trials. The fundamental bottlenecks for the scalability and programmability of the presented CIM are discussed as well.
Wine aging: a bottleneck story
Authors: Karbowiak Thomas , Crouvisier-Urion Kevin , Lagorce Aurélie , Ballester Jordi , Geoffroy André , Roullier-Gall Chloé , Chanut Julie , Gougeon Régis D. , Schmitt-Kopplin Philippe , Bellat Jean-Pierre
Published: August 2019

The sporadic oxidation of white wines remains an open question, making wine shelf life a subjective debate. Through a multidisciplinary synoptic approach performed as a remarkable case study on aged bottles of white wine, this work unraveled a yet unexplored route for uncontrolled oxidation. By combining sensory evaluation, chemical and metabolomics analyses of the wine, and investigating oxygen transfer through the bottleneck/stopper, this work elucidates the importance of the glass/cork interface. It shows unambiguously that the transfer of oxygen at the interface between the cork stopper and the glass bottleneck must be considered a potentially significant contributor to oxidation state during the bottle aging, leading to a notable modification of a wine’s chemical signature.
Bifurcation analysis of the dynamics of interacting subnetworks of a spiking network
Authors: Lagzi Fereshteh , Atay Fatihcan M. , Rotter Stefan
Published: August 2019

We analyze the collective dynamics of hierarchically structured networks of densely connected spiking neurons. These networks of sub-networks may represent interactions between cell assemblies or different nuclei in the brain. The dynamical activity pattern that results from these interactions depends on the strength of synaptic coupling between them. Importantly, the overall dynamics of a brain region in the absence of external input, so called ongoing brain activity, has been attributed to the dynamics of such interactions. In our study, two different network scenarios are considered: a system with one inhibitory and two excitatory subnetworks, and a network representation with three inhibitory subnetworks. To study the effect of synaptic strength on the global dynamics of the network, two parameters for relative couplings between these subnetworks are considered. For each case, a bifurcation analysis is performed and the results have been compared to large-scale network simulations. Our analysis shows that Generalized Lotka-Volterra (GLV) equations, well-known in predator-prey studies, yield a meaningful population-level description for the collective behavior of spiking neuronal interaction, which have a hierarchical structure. In particular, we observed a striking equivalence between the bifurcation diagrams of spiking neuronal networks and their corresponding GLV equations. This study gives new insight on the behavior of neuronal assemblies, and can potentially suggest new mechanisms for altering the dynamical patterns of spiking networks based on changing the synaptic strength between some groups of neurons.
Convolutional Neural Networks for Spectroscopic Analysis in Retinal Oximetry
Authors: DePaoli Damon T. , Tossou Prudencio , Parent Martin , Sauvageau Dominic , Côté Daniel C.
Published: August 2019

Retinal oximetry is a non-invasive technique to investigate the hemodynamics, vasculature and health of the eye. Current techniques for retinal oximetry have been plagued by quantitatively inconsistent measurements and this has greatly limited their adoption in clinical environments. To become clinically relevant oximetry measurements must become reliable and reproducible across studies and locations. To this end, we have developed a convolutional neural network algorithm for multi-wavelength oximetry, showing a greatly improved calculation performance in comparison to previously reported techniques. The algorithm is calibration free, performs sensing of the four main hemoglobin conformations with no prior knowledge of their characteristic absorption spectra and, due to the convolution-based calculation, is invariable to spectral shifting. We show, herein, the dramatic performance improvements in using this algorithm to deduce effective oxygenation (SO2), as well as the added functionality to accurately measure fractional oxygenation ($${{\bf{SO}}}_{{\bf{2}}}^{{\boldsymbol{f}}{\boldsymbol{r}}}$$

SO

2

f
r

). Furthermore, this report compares, for the first time, the relative performance of several previously reported multi-wavelength oximetry algorithms in the face of controlled spectral variations. The improved ability of the algorithm to accurately and independently measure hemoglobin concentrations offers a high potential tool for disease diagnosis and monitoring when applied to retinal spectroscopy.
An efficacy evaluation method for non-normal outcomes in randomized controlled trials
Authors: Li Yang , Zhang Zhang , Feng Qian , Yi Danhui , Lu Fang
Published: August 2019

Randomized controlled trials (RCT) are widely used in clinical efficacy evaluation studies. Linear regression is a general method to evaluate treatment efficacy considering the existence of confounding variables. However, when residuals are not normally distributed, parameter estimation based on ordinary least squares (OLS) is inefficient. This study introduces an exponential squared loss (ESL) model to evaluate treatment effect. The proposed method provides robust estimation for non-normal data. Simulation results show that it outperforms ordinary least squares regression with contaminated data. In the mild cognitive impairment (MCI) efficacy evaluation study with traditional Chinese medicine, our method is applied to construct a linear efficacy evaluation model for the difference in Alzheimer’s disease assessment scale-cognitive (ADAS-cog) scores between the final and baseline records (ADASFA), with the existence of confounding factors and non- normal residuals. The results coincide with existing medical literatures. This proposed method overcomes the limitation of confounding variables and non-normal residuals in RCT efficacy studies. It outperforms OLS on estimation efficiency in situations where the percentage of non-normal contamination reaches 30%. These advantages make it a good method for real-world clinical studies.
Proteolysis of the low density lipoprotein receptor by bone morphogenetic protein-1 regulates cellular cholesterol uptake
Authors: Banerjee Sreemoti , Andrew Robert J. , Duff Christopher J. , Fisher Kate , Jackson Carolyn D. , Lawrence Catherine B. , Maeda Nobuyo , Greenspan Daniel S. , Kellett Katherine A. B. , Hooper Nigel M.
Published: August 2019

The development of cardiovascular disease is intimately linked to elevated levels of low-density lipoprotein (LDL) cholesterol in the blood. Hepatic LDL receptor (LDLR) levels regulate the amount of plasma LDL. We identified the secreted zinc metalloproteinase, bone morphogenetic protein 1 (BMP1), as responsible for the cleavage of human LDLR within its extracellular ligand-binding repeats at Gly171↓Asp172. The resulting 120 kDa membrane-bound C-terminal fragment (CTF) of LDLR had reduced capacity to bind LDL and when expressed in LDLR null cells had compromised LDL uptake as compared to the full length receptor. Pharmacological inhibition of BMP1 or siRNA-mediated knockdown prevented the generation of the 120 kDa CTF and resulted in an increase in LDL uptake into cells. The 120 kDa CTF was detected in the livers from humans and mice expressing human LDLR. Collectively, these results identify that BMP1 regulates cellular LDL uptake and may provide a target to modulate plasma LDL cholesterol.
Maternal transmission of an Igf2r domain 11: IGF2 binding mutant allele (Igf2rI1565A) results in partial lethality, overgrowth and intestinal adenoma progression
Authors: Hughes Jennifer , Surakhy Mirvat , Can Sermet , Ducker Martin , Davies Nick , Szele Francis , Bühnemann Claudia , Carter Emma , Trikin Roman , Crump Matthew P. , Frago Susana , Hassan A. Bassim
Published: August 2019

The cation-independent mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R or IGF2R) traffics IGF2 and M6P ligands between pre-lysosomal and extra-cellular compartments. Specific IGF2 and M6P high-affinity binding occurs via domain-11 and domains-3-5-9, respectively. Mammalian maternal Igf2r allele expression exceeds the paternal allele due to imprinting (silencing). Igf2r null-allele maternal transmission results in placenta and heart over-growth and perinatal lethality (>90%) due to raised extra-cellular IGF2 secondary to impaired ligand clearance. It remains unknown if the phenotype is due to either ligand alone, or to both ligands. Here, we evaluate Igf2r specific loss-of-function of the domain-11 IGF2 binding site by replacing isoleucine with alanine in the CD loop (exon 34, I1565A), a mutation also detected in cancers. Igf2rI1565A/+p maternal transmission (heterozygote), resulted in placental and embryonic over-growth with reduced neonatal lethality (<60%), and long-term survival. The perinatal mortality (>80%) observed in homozygotes (Igf2rI1565A/I1565A) suggested that wild-type paternal allele expression attenuates the heterozygote phenotype. To evaluate Igf2r tumour suppressor function, we utilised intestinal adenoma models known to be Igf2 dependent. Bi-allelic Igf2r expression suppressed intestinal adenoma (ApcMin). Igf2rI1565A/+p in a conditional model (Lgr5-Cre, Apcloxp/loxp) resulted in worse survival and increased adenoma proliferation. Growth, survival and intestinal adenoma appear dependent on IGF2R-domain-11 IGF2 binding.