bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico study of the effects of anti-arrhythmic drug treatment on sinoatrial node function for patients with atrial fibrillation
Authors: Bai Jieyun , Lu Yaosheng , Zhang Henggui 
Published: January 2020

AbstractSinus node dysfunction (SND) is often associated with atrial fibrillation (AF). Amiodarone is the most frequently used agent for maintaining sinus rhythm in patients with AF, but it impairs the sinoatrial node (SAN) function in one-third of AF patients. This study aims to gain mechanistic insights into the effects of the antiarrhythmic agents in the setting of AF-induced SND. We have adapted a human SAN model to characterize the SND conditions by incorporating experimental data on AF-induced electrical remodelling, and then integrated actions of drugs into the modified model to assess their efficacy. Reductions in pacing rate upon the implementation of AF-induced electrical remodelling associated with SND agreed with the clinical observations. And the simulated results showed the reduced funny current (If) in these remodelled targets mainly contributed to the heart rate reduction. Computational drug treatment simulations predicted a further reduction in heart rate during amiodarone administration, indicating that the reduction was the result of actions of amiodarone on INa, IKur, ICaL, ICaT, If and beta-adrenergic receptors. However, the heart rate was increased in the presence of disopyramide. We concluded that disopyramide may be a desirable choice in reversing the AF-induced SND phenotype.
Postprandial Metabolism is Impaired in Overweight Normoglycemic Young Adults without Family History of Diabetes
Authors: Kumar A. Aneesh , Satheesh Gopika , Vijayakumar Gadadharan , Chandran Mahesh , Prabhu Priya R. , Simon Leena , Kutty Vellappillil Raman , Kartha Chandrasekharan C. , Jaleel Abdul 
Published: January 2020

AbstractWhile the risk factors for Type 2 diabetes (T2DM) are known, early predictive markers of transition from normal to a prediabetes state are unidentified. We studied the basal metabolism and metabolic response to a mixed-meal challenge in 110 healthy subjects in the age group of 18 to 40 years (Male:Female = 1:1); grouped into first degree relatives of patients with T2DM (n = 30), those with a body mass index >23 kg/m2 but <30 kg/m2 (n = 30), those with prediabetes (n = 20) and normal controls (n = 30). We performed an untargeted metabolomics analysis of plasma and related that with clinical and biochemical parameters, markers of inflammation, and insulin sensitivity. Similar to prediabetes subjects, overweight subjects had insulin resistance and significantly elevated levels of C-peptide, adiponectin and glucagon and lower level of ghrelin. Metabolites such as MG(22:2(13Z, 16Z)/0:0/0:0) and LysoPC (15:0) were reduced in overweight and prediabetes subjects. Insulin sensitivity was significantly lower in men. Fasting levels of uric acid, xanthine, and glycochenodeoxycholic-3-glucuronide were elevated in men. However, both lysophospholipids and antioxidant defense metabolites were higher in women. Impaired postprandial metabolism and insulin sensitivity in overweight normoglycemic young adults indicates a risk of developing hyperglycemia. Our results also indicate a higher risk of diabetes in young men.
The Male Warrior Hypothesis: Testosterone-related Cooperation and Aggression in the Context of Intergroup Conflict
Authors: Muñoz-Reyes J. A. , Polo P. , Valenzuela N. , Pavez P. , Ramírez-Herrera O. , Figueroa O. , Rodriguez-Sickert C. , Díaz D. , Pita M. 
Published: January 2020

AbstractThe Male Warrior Hypothesis (MWH) establishes that men’s psychology has been shaped by inter-group competition to acquire and protect reproductive resources. In this context, sex-specific selective pressures would have favored cooperation with the members of one’s group in combination with hostility towards outsiders. We investigate the role of developmental testosterone, as measured indirectly through static markers of prenatal testosterone (2D:4D digit ratio) and pubertal testosterone (body musculature and facial masculinity), on both cooperation and aggressive behavior in the context of intergroup conflict among men. Supporting the MWH, our results show that the intergroup conflict scenario promotes cooperation within group members and aggression toward outgroup members. Regarding the hormonal underpinnings of this phenomenon, we find that body musculature is positively associated with aggression and cooperation, but only for cooperation when context (inter-group competition) is taken into account. Finally, we did not find evidence that the formidability of the group affected individual rates of aggression or cooperation, controlling for individual characteristics.
Real-time monitoring of bacterial growth kinetics in suspensions using laser speckle imaging
Authors: Loutfi Hadi , Pellen Fabrice , Le Jeune Bernard , Lteif Roger , Kallassy Mireille , Le Brun Guy , Abboud Marie 
Published: January 2020

AbstractIn microbiology, monitoring the growth of any microorganism in culture is important for studying and optimizing the growth kinetics, the biomass and the metabolite production. In this work, we show that laser speckle imaging is a reliable technique that can be used to perform real-time monitoring of bacteria growth kinetic in liquid culture media. Speckle parameters, specifically speckle grain size and the spatial contrast of the speckle images, and standard analytical parameters (optical density, pH and colony forming units) were measured during the culture of different strains ofBacillus thuringiensis. Our results show that both speckle grain size and spatial contrast decrease with bacterial growth. Furthermore, speckle parameters are sensitive to the fermentation conditions. Statistical analysis revealed a relatively high correlation between speckle and analytical parameters.
BAD sensitizes breast cancer cells to docetaxel with increased mitotic arrest and necroptosis
Authors: Mann Jasdeep , Yang Ning , Montpetit Rachel , Kirschenman Raven , Lemieux Hélène , Goping Ing Swie 
Published: January 2020

AbstractBreast cancer patients are commonly treated with taxane (e.g. docetaxel) chemotherapy, despite poor outcomes and eventual disease relapse. We previously identified the Bcl-2-associated death promoter (BAD) as a prognostic indicator of good outcome in taxane-treated breast cancer patients. We also demonstrated that BAD expression in human breast carcinoma cells generated larger tumors in mouse xenograft models. These paradoxical results suggest that BAD-expressing tumors are differentially sensitive to taxane treatment. We validated this here and show that docetaxel therapy preferentially reduced growth of BAD-expressing xenograft tumors. We next explored the cellular mechanism whereby BAD sensitizes cells to docetaxel. Taxanes are microtubule inhibiting agents that cause cell cycle arrest in mitosis whereupon the cells either die in mitosis or aberrantly exit (mitotic slippage) and survive as polyploid cells. In response to docetaxel, BAD-expressing cells had lengthened mitotic arrest with a higher proportion of cells undergoing death in mitosis with decreased mitotic slippage. Death in mitosis was non-apoptotic and not dependent on Bcl-XL interaction or caspase activation. Instead, cell death was necroptotic, and dependent on ROS. These results suggest that BAD is prognostic for favourable outcome in response to taxane chemotherapy by enhancing necroptotic cell death and inhibiting the production of potentially chemoresistant polyploid cells.
Polycystin 2 is increased in disease to protect against stress-induced cell death
Authors: Brill Allison L. , Fischer Tom T. , Walters Jennifer M. , Marlier Arnaud , Sewanan Lorenzo R. , Wilson Parker C. , Johnson Eric K. , Moeckel Gilbert , Cantley Lloyd G. , Campbell Stuart G. , Nerbonne Jeanne M. , Chung Hee Jung , Robert Marie E. , Ehrlich Barbara E. 
Published: January 2020

AbstractPolycystin 2 (PC2 or TRPP1, formerly TRPP2) is a calcium-permeant Transient Receptor Potential (TRP) cation channel expressed primarily on the endoplasmic reticulum (ER) membrane and primary cilia of all cell and tissue types. Despite its ubiquitous expression throughout the body, studies of PC2 have focused primarily on its role in the kidney, as mutations in PC2 lead to the development of autosomal dominant polycystic kidney disease (ADPKD), a debilitating condition for which there is no cure. However, the endogenous role that PC2 plays in the regulation of general cellular homeostasis remains unclear. In this study, we measure how PC2 expression changes in different pathological states, determine that its abundance is increased under conditions of cellular stress in multiple tissues including human disease, and conclude that PC2-deficient cells have increased susceptibility to cell death induced by stress. Our results offer new insight into the normal function of PC2 as a ubiquitous stress-sensitive protein whose expression is up-regulated in response to cell stress to protect against pathological cell death in multiple diseases.
Vitamin D/VDR signaling induces miR-27a/b expression in oral lichen planus
Authors: Ge Xuejun , Yuan Lu , Wei Jizhen , Nguyen Tivoli , Tang Chenwei , Liao Wang , Li Ran , Yang Fang , Zhang Fang , Zhao Bin , Du Jie 
Published: January 2020

AbstractMicroRNA-27a/b are small non-coding RNAs which are reported to regulate inflammatory response and cell proliferation. Although some studies have demonstrated that miR-27b is down-regulated in the oral specimens of patients suffering with oral lichen planus (OLP), the molecular mechanism of miR-27b decrease remains a large mystery, and the expression of miR-27a in OLP is not well explored. Here, we demonstrated both miR-27a and miR-27b, compared with healthy controls, were reduced in the oral biopsies, serum and saliva samples derived from OLP patients. The reductions of miR-27a/b were also confirmed in the lipopolysaccharide (LPS)- or activated CD4+ T cell-treated human oral keratinocytes (HOKs). Furthermore, we found vitamin D receptor (VDR) binding sites in the promoters of miR-27a/b genes and verified this finding. We also tested miR-27a/b levels in the oral epithelium from paricalcitol-treated, vitamin D deficient or VDR knockout mice. In the rescue experiments, we confirmed vitamin D and VDR inhibited LPS- or activated CD4+ T cell-induced miR-27a/b reductions in HOKs. In sum, our results show that vitamin D/VDR signaling induces miR-27a/b in oral lichen planus.
Tuning mitochondrial structure and function to criticality by fluctuation-driven mechanotransduction
Authors: Bartolák-Suki Erzsébet , Suki Béla 
Published: January 2020

AbstractCells in vascular walls are exposed to blood pressure variability (BPV)-induced cycle-by-cycle fluctuations in mechanical forces which vary considerably with pathology. For example, BPV is elevated in hypertension but reduced under anesthesia. We hypothesized that the extent of mechanical fluctuations applied to vascular smooth muscle cells (VSMCs) regulates mitochondrial network structure near the percolation transition, which also influences ATP and reactive oxygen species (ROS) production. We stretched VSMCs in culture with cycle-by-cycle variability in area strain ranging from no variability (0%), as in standard laboratory conditions, through abnormally small (6%) and physiological (25%) to pathologically high (50%) variability mimicking hypertension, superimposed on 0.1 mean area strain. To explore how oxidative stress and ATP-dependent metabolism affect mitochondria, experiments were repeated in the presence of hydrogen peroxide and AMP-PNP, an ATP analog and competitive inhibitor of ATPases. Physiological 25% variability maintained activated mitochondrial cluster structure at percolation with a power law distribution and exponent matching the theoretical value in 2 dimensions. The 25% variability also maximized ATP and minimized cellular and mitochondrial ROS production via selective control of fission and fusion proteins (mitofusins, OPA1 and DRP1) as well as through stretch-sensitive regulation of the ATP synthase and VDAC1, the channel that releases ATP into the cytosol. Furthermore, pathologically low or high variability moved mitochondria away from percolation which reduced the effectiveness of the electron transport chain by lowering ATP and increasing ROS productions. We conclude that normal BPV is required for maintaining optimal mitochondrial structure and function in VSMCs.
Encapsulation boosts islet-cell signature in differentiating human induced pluripotent stem cells via integrin signalling
Authors: Legøy Thomas Aga , Vethe Heidrun , Abadpour Shadab , Strand Berit L. , Scholz Hanne , Paulo Joao A. , Ræder Helge , Ghila Luiza , Chera Simona 
Published: January 2020

AbstractCell replacement therapies hold great therapeutic potential. Nevertheless, our knowledge of the mechanisms governing the developmental processes is limited, impeding the quality of differentiation protocols. Generating insulin-expressing cells in vitro is no exception, with the guided series of differentiation events producing heterogeneous cell populations that display mixed pancreatic islet phenotypes and immaturity. The achievement of terminal differentiation ultimately requires the in vivo transplantation of, usually, encapsulated cells. Here we show the impact of cell confinement on the pancreatic islet signature during the guided differentiation of alginate encapsulated human induced pluripotent stem cells (hiPSCs). Our results show that encapsulation improves differentiation by significantly reshaping the proteome landscape of the cells towards an islet-like signature. Pathway analysis is suggestive of integrins transducing the encapsulation effect into intracellular signalling cascades promoting differentiation. These analyses provide a molecular framework for understanding the confinement effects on hiPSCs differentiation while confirming its importance for this process.
Enhanced production of sucrose in the fast-growing cyanobacterium Synechococcus elongatus UTEX 2973
Authors: Lin Po-Cheng , Zhang Fuzhong , Pakrasi Himadri B. 
Published: January 2020

AbstractCyanobacteria are attractive microbial hosts for production of chemicals using light and CO2. However, their low productivity of chemicals is a major challenge for commercial applications. This is mostly due to their relatively slow growth rate and carbon partitioning toward biomass rather than products. Many cyanobacterial strains synthesize sucrose as an osmoprotectant to cope with salt stress environments. In this study, we harnessed the photosynthetic machinery of the fast-growing cyanobacterium Synechococcus elongatus UTEX 2973 to produce sucrose under salt stress conditions and investigated if the high efficiency of photosynthesis can enhance the productivity of sucrose. By expressing the sucrose transporter CscB, Synechococcus 2973 produced 8 g L−1 of sucrose with a highest productivity of 1.9 g L−1 day−1 under salt stress conditions. The salt stress activated the sucrose biosynthetic pathway mostly via upregulating the sps gene, which encodes the rate-limiting sucrose-phosphate synthase enzyme. To alleviate the demand on high concentrations of salt for sucrose production, we further overexpressed the sucrose synthesis genes in Synechococcus 2973. The engineered strain produced sucrose with a productivity of 1.1 g L−1 day−1 without the need of salt induction. The engineered Synechococcus 2973 in this study demonstrated the highest productivity of sucrose in cyanobacteria.
Diversity and seasonality of horse flies (Diptera: Tabanidae) in Uruguay
Authors: Lucas Martín , Krolow Tiago K. , Riet-Correa Franklin , Barros Antonio Thadeu M. , Krüger Rodrigo F. , Saravia Anderson , Miraballes Cecilia 
Published: January 2020

AbstractHorse flies (Diptera: Tabanidae) cause direct and indirect losses in livestock production and are important vectors of pathogens. The aim of this study was to determine the diversity and seasonality of horse fly species at an experimental farm in Tacuarembó and the diversity of species in different departments of Uruguay. For 20 months, systematic collections were performed in two different environments at the experimental farm using Nzi and Malaise traps. In addition, nonsystematic collections were performed at farms located in the departments of Paysandú, Tacuarembó and Colonia. A total of 3,666 horse flies were collected, and 16 species were identified. These species included three species that had not been previously recorded in Uruguay, namely,Dasybasis ornatissima(Brèthes),Dasybasis missionum(Macquart), andTabanus aff.platensisBrèthes, and a species that had not been previously taxonomically described (Tabanussp.1). Among the systematically captured samples, the most abundant species wereTabanus campestrisBrèthes,T.aff.platensisandD.missionum, representing 77.6% of the collected specimens. The horse fly season in Tacuarembó started in September and ended in May. No horse flies were caught during winter. Variations in the prevalences of species in the different departments were observed, which indicates the need for new sampling efforts.
A CBL-interacting protein kinase AdCIPK5 confers salt and osmotic stress tolerance in transgenic tobacco
Authors: Singh Naveen Kumar , Shukla Pawan , Kirti P. B. 
Published: January 2020

AbstractCBL interacting protein kinases play important roles in adaptation to stress conditions. In the present study, we isolated a CBL-interacting protein kinase homolog(AdCIPK5)from a wild peanut (Arachis diogoi) with similarity toAtCIPK5of Arabidopsis. Expression analyses in leaves of the wild peanut showedAdCIPK5induction by exogenous signaling molecules including salicylic acid, abscisic acid and ethylene or abiotic stress factors like salt, PEG and sorbitol. The recombinant AdCIPK5-GFP protein was found to be localized to the nucleus, plasma membrane and cytoplasm. We overexpressedAdCIPK5in tobacco plants and checked their level of tolerance to biotic and abiotic stresses. While wild type and transgenic plants displayed no significant differences to the treatment with the phytopathogen,Phytophthora parasiticapvnicotianae, the expression ofAdCIPK5increased salt and osmotic tolerance in transgenic plants. Analysis of different physiological parameters revealed that the transgenic plants maintained higher chlorophyll content and catalase activity with lower levels of H2O2and MDA content during the abiotic stress conditions.AdCIPK5overexpression also contributed to the maintenance of a higher the K+/Na+ratio under salt stress. The enhanced tolerance of transgenic plants was associated with elevated expression of stress-related marker genes;NtERD10C,NtERD10D,NtNCED1,NtSus1,NtCATandNtSOS1. Taken together, these results indicate that AdCIPK5 is a positive regulator of salt and osmotic stress tolerance.
Dicarbonyl derived post-translational modifications: chemistry bridging biology and aging-related disease
Authors: Sibbersen Christian , Johannsen Mogens 
Published: January 2020

AbstractIn living systems, nucleophilic amino acid residues are prone to non-enzymatic post-translational modification by electrophiles. α-Dicarbonyl compounds are a special type of electrophiles that can react irreversibly with lysine, arginine, and cysteine residues via complex mechanisms to form post-translational modifications known as advanced glycation end-products (AGEs). Glyoxal, methylglyoxal, and 3-deoxyglucosone are the major endogenous dicarbonyls, with methylglyoxal being the most well-studied. There are several routes that lead to the formation of dicarbonyl compounds, most originating from glucose and glucose metabolism, such as the non-enzymatic decomposition of glycolytic intermediates and fructosyl amines. Although dicarbonyls are removed continuously mainly via the glyoxalase system, several conditions lead to an increase in dicarbonyl concentration and thereby AGE formation. AGEs have been implicated in diabetes and aging-related diseases, and for this reason the elucidation of their structure as well as protein targets is of great interest. Though the dicarbonyls and reactive protein side chains are of relatively simple nature, the structures of the adducts as well as their mechanism of formation are not that trivial. Furthermore, detection of sites of modification can be demanding and current best practices rely on either direct mass spectrometry or various methods of enrichment based on antibodies or click chemistry followed by mass spectrometry. Future research into the structure of these adducts and protein targets of dicarbonyl compounds may improve the understanding of how the mechanisms of diabetes and aging-related physiological damage occur.
Associations Between Parenting Stress, Language Comprehension, and Inhibitory Control in Children With Hearing Loss
Authors: Blank Andrew , Frush Holt Rachael , Pisoni David B. , Kronenberger William G. 
Published: January 2020

Purpose
Parenting stress has been studied as a potential predictor of developmental outcomes in children with normal hearing and children who are deaf and hard of hearing. However, it is unclear how parenting stress might underlie at-risk spoken language and neurocognitive outcomes in this clinical pediatric population. We investigated parenting stress levels and the shared relations between parenting stress, language comprehension, and inhibitory control skills in children with and without hearing loss (HL) using a cross-sectional design.

Method

Families of children with HL (
n =
39) and with normal hearing (
n =
41) were tested. Children completed an age-appropriate version of the Concepts & Following Directions subtest of the Clinical Evaluation of Language Fundamentals and the NIH Toolbox Flanker Test of Attention and Inhibitory control. Caregivers completed the Parenting Stress Index–Short Form 4.

Results
Parenting stress levels were not significantly different between parents of children with and without HL. A significant negative association was observed between parenting stress and our measure of language comprehension in children with HL. A negative association between parenting stress and inhibitory control skills was also found in families of children with HL, but not hearing children. The parenting stress–inhibitory control relationship was indirectly accounted for by delayed language comprehension skills in children with HL.

Conclusion
Even at moderate levels of parenting stress similar to parents of children with normal hearing, increases in parenting stress were associated with lower scores on our measures of language comprehension and inhibitory control in children with HL. Thus, parenting stress may underlie some of the variability in at-risk pediatric HL outcomes.
Slot antenna excited by novel substrate integrated coaxial line cavity for millimetre wave application
Authors: Baghel N. , Mukherjee S. 
Published: January 2020

In this Letter, a novel compact slot antenna has been realised using substrate integrated coaxial line (SICL) cavity. SICL technology helps to achieve cavity size of while maintaining its inherent advantage of self shielded and low loss transmission line at millimetre frequencies. A SICL cavity is designed by shorting the middle conductor at the two edges and keeping the other two edges separated from the sidewall. The eigenmode analysis affirms the presence of a dominant TEM mode at 28 GHz along with the presence of SICL even and odd modes. A half wavelength diagonal slot is etched on the bottom plate of the cavity to disturb the TEM mode surface current at 28 GHz. Measurement results show the SICL cavity backed slot antenna exhibits a gain of 5.6 dBi at 28.6 GHz and high front‐to‐back ratio better than 17 dB. The SICL‐based cavity exhibits millimetre wave resonance with much smaller size, which helps to improve the compactness of the design. The proposed antenna can be used for millimetre wave applications like handheld mobile devices at millimetre‐wave frequencies.