bluuebunny/crossref_metadata_2025 huggingface dataset:
Heroic memory and contemporary war
Authors: Holleufer Gilbert
Published: October 2019

Inter-State wars seem to have come to an end in the late 1990s; ever since, the global reality of collective violence has come down to the chaos of contemporary civil wars and terrorist attacks. In this article, it will be argued that in today's civil wars, as well as in terrorist violence, the traditional warrior ethos is fading, giving way to types of violence governed by a new psychological and social paradigm. In other words, it is assumed that the very set of values that has universally determined the male gender role and the frame of hegemonic masculinity since time immemorial has also informed the waging of war according to a “heroic regime of violence”, and this phenomenon has made war a desirable option for countless generations of young men. On the other hand, the global changes entailed by modernity seem to have undermined this warrior ethos, giving way to a “post-heroic regime” in which extermination-oriented violence, rather than combat-oriented violence, is fostered. In this article, the author will scrutinize the founding psychological and social determinants that have so far upheld the cultural construct of the heroic model, in order to illuminate the ominous consequences of the deculturation of war in today's chaotic conflicts. In such contexts, the men who are fighting1 suffer from a loss of meaning and the impossibility of gaining dignity and social recognition in an ecosystem of humiliation and ubiquitous violence that has little to do with the expectations of pride and dignity conveyed by the past ideals of heroism associated with a certain vision of masculinity. The article will also discuss ways and means of getting the message of international humanitarian law through to men on the front lines caught up in such circumstances.
Changes in nutrient and calorie intake, adipose mass, triglycerides and TNF-α concentrations after non-caloric sweetener intake: A pilot study
Authors: Sánchez-Delgado Marcela , Estrada José Antonio , Paredes-Cervantes Vladimir , Kaufer-Horwitz Martha , Contreras Irazú
Published: October 2019

Abstract. Establishing the safety of non-caloric sweetener consumption in humans is a difficult task, since many contradictory results have been reported. The objective of this study was to compare the effect of frequent intake of sucrose, sucralose or steviol glycosides, on selected anthropometric, biochemical and immunological parameters in healthy, young adults. 38 individuals with normal body mass index were recruited and randomly divided into three experimental groups. After a washout week (where food with added sweeteners was restricted), each group was supplemented with sucrose (8 × 5 g packets/day), sucralose or steviol glycosides (4 × 1 g packets/day each) for 6 weeks. Selected variables were measured before and after treatment in each group and differences within and among groups were assessed. Our results showed that, compared to baseline, there was a modest but significant increase in weight (p = 0.0293) in the sucralose group, while the steviol glycosides group reduced their fat mass (p = 0.0390). No differences were observed in glycaemia; however, there was a significant increase in serum triglycerides (77.8–110.8 mg/dL) and cholesterol (162.0–172.3 mg/dL) in the sucrose group, whereas the steviol glycosides group presented lower triglycerides (104.7–92.8 mg/dL) and TNF-α concentrations (51.1–47.5 pg/mL). Comparison among groups showed differences in serum triglycerides (p = 0.0226), TNF-α (p = 0.0460) and IL-β (p = 0.0008). Our results suggest that, even in a short time span, frequent intake of steviol glycosides may have positive effects on metabolic parameters that may be relevant for human health.
Systematic Review of the Inclusion of People With Psychosis in Suicide-Specific Clinical Trials
Authors: Villa Jennifer , Ehret Blaire C. , Depp Colin A.
Published: October 2019

Abstract. Background: Psychosis is a significant, yet understudied, risk factor for suicide. There has yet to be a systematic investigation examining the rate and predictors of inclusion of psychotic disorders or symptoms in suicide-focused trials. Aim: Our aim was to conduct a systematic review of inclusion/exclusion of psychosis in studies with suicidal ideation or behavior as a primary endpoint, rate of inclusion across intervention type and other characteristics, and criteria used to exclude psychosis and accompanying rationale. Method: A literature search was conducted using PubMed, Cochrane Library, and PsycInfo to identify relevant articles published between 2000 and 2018. Statements regarding inclusion/exclusion were codified by authors. Results: Out of 122 studies selected, 75 (61.5%) excluded individuals with psychosis. This rate varied by intervention and sample size, but not by year of study or country of origin. Only 9% provided a rationale for psychosis exclusion. Limitations: Minimal reporting of participants' diagnosis in studies disallowed analysis of the rate of inclusion of psychosis in samples. Conclusion: Three out of five trials with suicide-related primary outcomes excluded psychosis; thus, people with psychosis are poorly represented in suicide-specific studies. This disparity could be remedied by either adapting protocols to include people with psychosis or developing new, tailored treatments.
Grief After Euthanasia and Physician-Assisted Suicide
Authors: Andriessen Karl , Krysinska Karolina , Castelli Dransart Dolores Angela , Dargis Luc , Mishara Brian L.
Published: October 2019

Abstract. Background: Several countries have regulated euthanasia and physician-assisted suicide (PAS). Research has looked at the experiences of patients, family, and professionals. However, little is known of the effects on bereaved individuals. Aims: We aimed to assess (a) what is known about the grief and mental health of people bereaved by euthanasia or PAS and (b) the quality of the research. Method: Systematic review according to PRISMA guidelines with searches in Cinahl, Embase, PsycINFO, Pubmed, and Scopus. Results: The searches identified 10 articles (eight studies), and the study quality was fair. People bereaved by euthanasia/PAS generally had similar or lower scores on measures of disordered grief, mental health, and posttraumatic stress compared with those who died naturally. Lack of social support and secrecy may compound their grief. Being involved in the decision-making process and having the feeling of honoring the deceased's will may facilitate their grief. Limitations: Studies used self-reports from non-random self-selected participants, were retrospective, and were conducted in only three countries. Conclusion: There is little evidence of increased risk of adverse grief or mental health outcomes in people bereaved by euthanasia/PAS. As more countries legalize assisted dying, high-quality studies of the factors that may hinder or facilitate the grief process are needed.
Suicide and Attempted Suicide in Jhenaidah District, Bangladesh, 2010–2018
Authors: Khan Anisur Rahman , Ratele Kopano , Arendse Najuwa , Islam Md. Zahidul , Dery Isaac
Published: October 2019

Abstract. Background: Suicide and attempted suicide are a serious but under-explored public health problem in Bangladesh. Survey estimates suggest that Jhenaidah District, one of the 64 districts that make up Bangladesh, is one of the highest suicide-prone regions in Bangladesh. Relatively little is known about the magnitude of suicide attempts in the district. Aims: This article describes the incidence of suicide and suicide attempts for Jhenaidah, Bangladesh for the period 2010–2018. Method: Primary descriptive analysis was performed on routine data collected by a Bangladesh-based nongovernment organization (NGO): Societies for Voluntary Activities (SOVA). Results: A total of 22,675 suicide attempts and 3,152 suicides occurred in the district. The rate of suicide attempts was found to be 136.35/100,000 and the suicide rate was found to be 20.6/100,000 in Jhenaidah. The subdistrict Sadar had the highest incidence of suicide attempt (38.09%) and suicide (33.47%). Poisoning was the most common method of suicide attempt for both males (77.07%) and females (77%). Limitations: Many cases of suicide attempts and suicide are unreported in Bangladesh owing to stigmatization; only reported cases form part of this investigation. Conclusion: Jhenaidah has very high rates of suicide and suicide attempts that surpass the global and Bangladesh averages. Although females demonstrate higher suicide rates, male suicide rates have gradually increased over the study period. Future studies are called for to better understand the local patterns and dynamics of fatal and nonfatal suicidal behaviors. Developing a sub-district-, district-, and national-level suicide prevention strategy ought to be considered a priority.
Dating Deep‐Sea Sediments With 230Th Excess Using a Constant Rate of Supply Model
Authors: Geibert W. , Stimac I. , Rutgers van der Loeff M. M. , Kuhn G.
Published: October 2019

We present a dating method for deep‐sea sediments that uses the natural radionuclide 230Th (half‐life 75,380 years) in analogy to 210Pb with the constant rate of supply (CRS) model. Using an example from the western Indian sector of the Southern Ocean, we demonstrate how sets of values of 230Th, 232Th, and U isotopes activities can supply absolute age information for the last ~450,000 years, given a sufficient precision, resolution, and depth coverage of the analytical data in a suitable core. An assessment of age uncertainties resulting from analytical errors using a Monte Carlo approach and an analytical solution for error propagation shows good agreement. We also investigate errors due to a violation of model assumptions by variable focusing of deep‐sea sediments by means of a simulated core. Finally, we use real examples from independently dated sediment cores containing carbonate, using previously existing 230Th data, to test the approach. The consideration of the systematic errors and the examples suggests that the uncertainties are smallest in the central part of the record and that the variability of focusing conditions controls the accuracy of the 230Th CRS dates. Our own example demonstrates an excellent agreement of the 230Th CRS method with independent age constraints, adding an important tool for dating marine records that does not depend on the presence of carbonate. The obtained values are also suitable to calculate 230Th‐normalized preserved vertical rain rates of various sedimentary compounds, permitting an improved quantitative comparison of marine paleorecords with other archives like ice cores.
Assessment and validation of spot urine in estimating the 24-h urinary sodium, potassium, and sodium/potassium ratio in Chinese adults
Authors: Xu Jianwei , Du Xiaofu , Bai Yamin , Fang Le , Liu Min , Ji Ning , Zhong Jieming , Yu Min , Wu Jing
Published: October 2019

The commonly used methods of estimating the 24-h urinary sodium (UNa) and urinary potassium (UK) from spot urine (SU) are the Kawasaki method (K-method), INTERSALT method (I-method), and Tanaka method (T-method), but the method that is suitable for use in the general Chinese population is still uncertain. We aimed to assess and validate these methods in estimating the 24-h UNa and UK using SU samples in Chinese adults. We studied 1428 individuals aged 18–69 years using SU and 24-h urine samples. For the K-method, I-method, and T-method, the Pearson correlation coefficients of the 24-h UNa were 0.35, 0.35, and 0.33 (all p < 0.01), and the intraclass correlation coefficients (ICC) were 0.34, 0.26, and 0.26 (all p < 0.01), respectively. The estimated 24-h UK using the K-method and T-method had correlation coefficients of 0.36 and 0.39 (all p < 0.01) and ICCs of 0.31 and 0.27 (all p < 0.01). The mean bias for the K-method in estimating the 24-h UNa and UK were the least biased among these methods. The bias between the 24-h urine Na/K ratio and the spot urinary Na/K ratio by the Bland–Altman method was −0.22. These methods for estimating the 24-h UNa and UK from SU were inadequate at the population level in Zhejiang Province, although the K-method showed the least bias among these methods. The spot urine Na/K ratio may be a useful and alternative method for 24-h urine collection for the estimation of the urinary Na/K ratio in the Chinese population.
The reciprocal interaction between tumor cells and activated fibroblasts mediated by TNF-α/IL-33/ST2L signaling promotes gastric cancer metastasis
Authors: Zhou Quan , Wu Xiongyan , Wang Xiaofeng , Yu Zhenjia , Pan Tao , Li Zhen , Chang Xinyu , Jin Zhijian , Li Jianfang , Zhu Zhenggang , Liu Bingya , Su Liping
Published: October 2019

Gastric cancer (GC) is characterized by extensive local invasion, distant metastasis and poor prognosis. In most cases, GC progression is associated with aberrant expression of cytokines or activation of signaling cascades mediated by tumor–stroma interactions. However, the mechanisms by which these interactions contribute to GC progression are poorly understood. In this study, we find that IL-33 and its receptor ST2L are upregulated in the human GC and served as prognostic markers for poor survival of GC patients. In a co-culture model with GC cells and cancer-associated fibroblasts (CAFs), we further demonstrate that CAFs-derived IL-33 enhances the migration and invasion of GC cells by inducing the epithelial–mesenchymal transition (EMT) through activation of the ERK1/2-SP1-ZEB2 pathway in a ST2L-dependent manner. Furthermore, the secretion of IL-33 by CAFs can be induced by the proinflammatory cytokines TNF-α that is released by GC cells via TNFR2-NF-κB-IRF-1 pathway. Additionally, silencing of IL-33 expression in CAFs or ST2L expression in GC cells inhibits the peritoneal dissemination and metastatic potential of GC cells in nude mice. Taken together, these results characterize a critical role of the interaction between epithelial-stroma mediated by the TNF-α/IL-33/ST2L signaling in GC progression, and provide a rationale for targeting this pathway to treat GC metastasis.
Tunneling nanotube-mediated intercellular vesicle and protein transfer in the stroma-provided imatinib resistance in chronic myeloid leukemia cells
Authors: Kolba Marta D. , Dudka Wioleta , Zaręba-Kozioł Monika , Kominek Agata , Ronchi Paolo , Turos Laura , Chroscicki Piotr , Wlodarczyk Jakub , Schwab Yannick , Klejman Agata , Cysewski Dominik , Srpan Katja , Davis Daniel M. , Piwocka Katarzyna
Published: October 2019

Intercellular communication within the bone marrow niche significantly promotes leukemogenesis and provides protection of leukemic cells from therapy. Secreted factors, intercellular transfer of mitochondria and the receptor–ligand interactions have been shown as mediators of this protection. Here we report that tunneling nanotubes (TNTs)—long, thin membranous structures, which have been identified as a novel mode of intercellular cross-talk—are formed in the presence of stroma and mediate transfer of cellular vesicles from stroma to leukemic cells. Importantly, transmission of vesicles via TNTs from stromal cells increases resistance of leukemic cells to the tyrosine kinase inhibitor, imatinib. Using correlative light-electron microscopy and electron tomography we show that stromal TNTs contain vesicles, provide membrane continuity with the cell bodies and can be open-ended. Moreover, trans-SILAC studies to reveal the non-autonomous proteome showed that specific sets of proteins are transferred together with cellular vesicles from stromal to leukemic cells, with a potential role in survival and adaptation. Altogether, our findings provide evidence for the biological role of the TNT-mediated vesicle exchange between stromal and leukemic cells, implicating the direct vesicle and protein transfer in the stroma-provided protection of leukemic cells.
Preparation of a new type 2 diabetic miniature pig model via the CRISPR/Cas9 system
Authors: Zou Xiaodong , Ouyang Hongsheng , Yu Tingting , Chen Xue , Pang Daxin , Tang Xiaochun , Chen Chengzhen
Published: October 2019

Diabetes has become one of the major noninfectious diseases that seriously endanger public health. The formation of islet amyloid polypeptide (IAPP) affects the normal physiological functions of the body, such as glucose metabolism and lipid metabolism. The mature human IAPP protein (hIAPP) has a strong tendency to misfold and is considered to be one of the major causes of amyloid changes in islets. Deposition of hIAPP is considered to be one of the leading causes of type 2 diabetes mellitus (T2DM). Miniature pigs are experimental animal models that are well suited for research on gene function and human diabetes. In our study, we obtained IAPP gene-humanized miniature pigs via the CRISPR/Cas9 system and somatic cell nuclear transfer (SCNT) technology. The hIAPP pigs can be used to further study the pathogenesis and related complications of T2DM and to lay a solid foundation for the prevention and treatment of T2DM.
Aspartate/asparagine-β-hydroxylase crystal structures reveal an unexpected epidermal growth factor-like domain substrate disulfide pattern
Authors: Pfeffer Inga , Brewitz Lennart , Krojer Tobias , Jensen Sacha A. , Kochan Grazyna T. , Kershaw Nadia J. , Hewitson Kirsty S. , McNeill Luke A. , Kramer Holger , Münzel Martin , Hopkinson Richard J. , Oppermann Udo , Handford Penny A. , McDonough Michael A. , Schofield Christopher J.
Published: October 2019

AspH is an endoplasmic reticulum (ER) membrane-anchored 2-oxoglutarate oxygenase whose C-terminal oxygenase and tetratricopeptide repeat (TPR) domains present in the ER lumen. AspH catalyses hydroxylation of asparaginyl- and aspartyl-residues in epidermal growth factor-like domains (EGFDs). Here we report crystal structures of human AspH, with and without substrate, that reveal substantial conformational changes of the oxygenase and TPR domains during substrate binding. Fe(II)-binding by AspH is unusual, employing only two Fe(II)-binding ligands (His679/His725). Most EGFD structures adopt an established fold with a conserved Cys1–3, 2–4, 5–6 disulfide bonding pattern; an unexpected Cys3–4 disulfide bonding pattern is observed in AspH-EGFD substrate complexes, the catalytic relevance of which is supported by studies involving stable cyclic peptide substrate analogues and by effects of Ca(II) ions on activity. The results have implications for EGFD disulfide pattern processing in the ER and will enable medicinal chemistry efforts targeting human 2OG oxygenases.
Randomized phase-II evaluation of letrozole plus dasatinib in hormone receptor positive metastatic breast cancer patients
Authors: Paul Devchand , Vukelja Svetislava J. , Ann Holmes Frankie , Blum Joanne L. , McIntyre Kristi J. , Lindquist Deborah L. , Osborne Cynthia R. , Sanchez Ines J. , Goldschmidt Jerome H. , Wang Yunfei , Asmar Lina , Strauss Lewis , O’Shaughnessy Joyce
Published: October 2019

The non-receptor tyrosine kinase Src activation plays a role in the malignant progression of breast cancer, including development of endocrine therapy resistance and survival of bone metastases. This study investigated whether adding Src kinase inhibitor dasatinib to aromatase inhibitor (AI) therapy improved outcomes in estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer (MBC). Postmenopausal patients with ER-positive, HER2-negative MBC (0–1 prior chemotherapies and no prior AI for MBC) were eligible for this non-comparative, parallel group, phase-II study. Patients were randomized to letrozole (2.5 mg/day PO) alone or with dasatinib (100 mg/day PO). Patients with disease progression on letrozole alone could crossover to dasatinib plus continued letrozole. The primary endpoint was clinical-benefit-rate (CBR; complete response + partial response + stable disease ≥6 months). A total of 120 patients were randomized. The CBR of 71% (95% CI 58–83%) was observed with letrozole + dasatinib versus the projected CBR of the combination of 56%. The CBR of 66% (95% CI 52–77%) with letrozole alone also exceeded the projected CBR of 39% with letrozole alone. The CBR was 23% in the crossover arm of letrozole plus dasatinib in patients progressing on letrozole alone. Median progression-free survival with the combination was 20.1 months and 9.9 months with letrozole alone. Letrozole plus dasatinib was well tolerated, although 26% of patients required dasatinib dose reductions. In this non-comparative phase-II trial, the CBR of 71% and the median PFS of 20.1 months with letrozole + dasatinib are encouraging and suggest that dasatinib may inhibit the emergence of acquired resistance to AI therapy.
Inhaled corticosteroids in COPD and onset of type 2 diabetes and osteoporosis: matched cohort study
Authors: Price David B. , Voorham Jaco , Brusselle Guy , Clemens Andreas , Kostikas Konstantinos , Stephens Jeffrey W. , Park Hye Yun , Roche Nicolas , Fogel Robert
Published: October 2019

Some studies suggest an association between onset and/or poor control of type 2 diabetes mellitus and inhaled corticosteroid (ICS) therapy for chronic obstructive pulmonary disease (COPD), and also between increased fracture risk and ICS therapy; however, study results are contradictory and these associations remain tentative and incompletely characterized. This matched cohort study used two large UK databases (1983–2016) to study patients (≥ 40 years old) initiating ICS or long-acting bronchodilator (LABD) for COPD from 1990–2015 in three study cohorts designed to assess the relation between ICS treatment and (1) diabetes onset (N = 17,970), (2) diabetes progression (N = 804), and (3) osteoporosis onset (N = 19,898). Patients had ≥ 1-year baseline and ≥ 2-year outcome data. Matching was via combined direct matching and propensity scores. Conditional proportional hazards regression, adjusting for residual confounding after matching, was used to compare ICS vs. LABD and to model ICS exposures. Median follow-up was 3.7–5.6 years/treatment group. For patients prescribed ICS, compared with LABD, the risk of diabetes onset was significantly increased (adjusted hazard ratio 1.27; 95% CI, 1.07–1.50), with overall no increase in risk of diabetes progression (adjusted hazard ratio 1.04; 0.87–1.25) or osteoporosis onset (adjusted hazard ratio 1.13; 0.93–1.39). However, the risks of diabetes onset, diabetes progression, and osteoporosis onset were all significantly increased, with evident dose–response relationships for all three outcomes, at mean ICS exposures of 500 µg/day or greater (vs. < 250 µg/day, fluticasone propionate–equivalent). Long-term ICS therapy for COPD at mean daily exposure of ≥ 500 µg is associated with an increased risk of diabetes, diabetes progression, and osteoporosis.
A public data set of spatio-temporal match events in soccer competitions
Authors: Pappalardo Luca , Cintia Paolo , Rossi Alessio , Massucco Emanuele , Ferragina Paolo , Pedreschi Dino , Giannotti Fosca
Published: October 2019

Soccer analytics is attracting increasing interest in academia and industry, thanks to the availability of sensing technologies that provide high-fidelity data streams for every match. Unfortunately, these detailed data are owned by specialized companies and hence are rarely publicly available for scientific research. To fill this gap, this paper describes the largest open collection of soccer-logs ever released, containing all the spatio-temporal events (passes, shots, fouls, etc.) that occured during each match for an entire season of seven prominent soccer competitions. Each match event contains information about its position, time, outcome, player and characteristics. The nature of team sports like soccer, halfway between the abstraction of a game and the reality of complex social systems, combined with the unique size and composition of this dataset, provide an ideal ground for tackling a wide range of data science problems, including the measurement and evaluation of performance, both at individual and at collective level, and the determinants of success and failure.
Population centroids of the world administrative units from nighttime lights 1992-2013
Authors: Hall Ola , Bustos Maria Francisca Archila , Olén Niklas Boke , Niedomysl Thomas
Published: October 2019

Knowledge about the past, current and future distribution of the human population is fundamental for tackling many global challenges. Censuses are used to collect information about population within a specified spatial unit. The spatial units are usually arbitrarily defined and their numbers, size and shape tend to change over time. These issues make comparisons between areas and countries difficult. We have in related work proposed that the shape of the lit area derived from nighttime lights, weighted by its intensity can be used to analyse characteristics of the population distribution, such as the mean centre of population. We have processed global nighttime lights data for the period 1992–2013 and derived centroids for administrative levels 0–2 of the Database of Global Administrative Areas, corresponding to nations and two levels of sub-divisions, that can be used to analyse patterns of global or local population changes. The consistency of the produced dataset was investigated and distance between true population centres and derived centres are compared using Swedish census data as a benchmark.
Decoupling a tandem-repeat protein: Impact of multiple loop insertions on a modular scaffold
Authors: Perez-Riba Albert , Komives Elizabeth , Main Ewan R. G. , Itzhaki Laura S.
Published: October 2019

The simple topology and modular architecture of tandem-repeat proteins such as tetratricopeptide repeats (TPRs) and ankyrin repeats makes them straightforward to dissect and redesign. Repeat-protein stability can be manipulated in a predictable way using site-specific mutations. Here we explore a different type of modification - loop insertion - that will enable a simple route to functionalisation of this versatile scaffold. We previously showed that a single loop insertion has a dramatically different effect on stability depending on its location in the repeat array. Here we dissect this effect by a combination of multiple and alternated loop insertions to understand the origins of the context-dependent loss in stability. We find that the scaffold is remarkably robust in that its overall structure is maintained. However, adjacent repeats are now only weakly coupled, and consequently the increase in solvent protection, and thus stability, with increasing repeat number that defines the tandem-repeat protein class is lost. Our results also provide us with a rulebook with which we can apply these principles to the design of artificial repeat proteins with precisely tuned folding landscapes and functional capabilities, thereby paving the way for their exploitation as a versatile and truly modular platform in synthetic biology.
Substrate composition directs slime molds behavior
Authors: Patino-Ramirez Fernando , Boussard Aurèle , Arson Chloé , Dussutour Audrey
Published: October 2019

Cells, including unicellulars, are highly sensitive to external constraints from their environment. Amoeboid cells change their cell shape during locomotion and in response to external stimuli. Physarum polycephalum is a large multinucleated amoeboid cell that extends and develops pseudopods. In this paper, changes in cell behavior and shape were measured during the exploration of homogenous and non-homogenous environments that presented neutral, and nutritive and/or adverse substances. In the first place, we developed a fully automated image analysis method to measure quantitatively changes in both migration and shape. Then we measured various metrics that describe the area covered, the exploration dynamics, the migration rate and the slime mold shape. Our results show that: (1) Not only the nature, but also the spatial distribution of chemical substances affect the exploration behavior of slime molds; (2) Nutritive and adverse substances both slow down the exploration and prevent the formation of pseudopods; and (3) Slime mold placed in an adverse environment preferentially occupies previously explored areas rather than unexplored areas using mucus secretion as a buffer. Our results also show that slime molds migrate at a rate governed by the substrate up until they get within a critical distance to chemical substances.
Morphology control of organic halide perovskites by adding BiFeO3 nanostructures for efficient solar cell
Authors: Xu Haowen , Zhang Heyi , Ma Yuhui , Jiang Mao , Zhang Yewei , Wu Yinan , Zhang Haoran , Xia Ruidong , Niu Qiaoli , Li Xing’ao , Huang Wei
Published: October 2019

The morphology of perovskite light-absorption layer plays an important role in the performance of perovskite solar cells (PSCs). In this work, BiFeO3 (BFO) nanostructures were used as additive for CH3NH3PbI3 (MAPbI3) via anti-solvent method. The addition of BFO nanostructures greatly enhanced the crystallinity, grain size and film uniformity of MAPbI3. As a result, the charge carrier mobility and electron diffusion length increased, leading to the increase of the short circuit current (JSC) of PSCs. This work provides a very simple but effective approach to improve the morphology of perovskite layer for efficient PSCs.
Antimalarial Quinoline Drugs Inhibit β-Hematin and Increase Free Hemin Catalyzing Peroxidative Reactions and Inhibition of Cysteine Proteases
Authors: Herraiz Tomás , Guillén Hugo , González-Peña Diana , Arán Vicente J.
Published: October 2019

Malaria caused by Plasmodium affects millions people worldwide. Plasmodium consumes hemoglobin during its intraerythrocytic stage leaving toxic heme. Parasite detoxifies free heme through formation of hemozoin (β-hematin) pigment. Proteolysis of hemoglobin and formation of hemozoin are two main targets for antimalarial drugs. Quinoline antimarial drugs and analogs (β-carbolines or nitroindazoles) were studied as inhibitors of β-hematin formation. The most potent inhibitors were quinacrine, chloroquine, and amodiaquine followed by quinidine, mefloquine and quinine whereas 8-hydroxyquinoline and β-carbolines had no effect. Compounds that inhibited β-hematin increased free hemin that promoted peroxidative reactions as determined with TMB and ABTS substrates. Hemin-catalyzed peroxidative reactions were potentiated in presence of proteins (i.e. globin or BSA) while antioxidants and peroxidase inhibitors decreased peroxidation. Free hemin increased by chloroquine action promoted oxidative reactions resulting in inhibition of proteolysis by three cysteine proteases: papain, ficin and cathepsin B. Glutathione reversed inhibition of proteolysis. These results show that active quinolines inhibit hemozoin and increase free hemin which in presence of H2O2 that abounds in parasite digestive vacuole catalyzes peroxidative reactions and inhibition of cysteine proteases. This work suggests a link between the action of quinoline drugs with biochemical processes of peroxidation and inhibition of proteolysis.
Time and rate dependent synaptic learning in neuro-mimicking resistive memories
Authors: Ahmed Taimur , Walia Sumeet , Mayes Edwin L. H. , Ramanathan Rajesh , Bansal Vipul , Bhaskaran Madhu , Sriram Sharath , Kavehei Omid
Published: October 2019

Memristors have demonstrated immense potential as building blocks in future adaptive neuromorphic architectures. Recently, there has been focus on emulating specific synaptic functions of the mammalian nervous system by either tailoring the functional oxides or engineering the external programming hardware. However, high device-to-device variability in memristors induced by the electroforming process and complicated programming hardware are among the key challenges that hinder achieving biomimetic neuromorphic networks. Here, a simple hybrid complementary metal oxide semiconductor (CMOS)-memristor approach is reported to implement different synaptic learning rules by utilizing a CMOS-compatible memristor based on oxygen-deficient SrTiO3-x (STOx). The potential of such hybrid CMOS-memristor approach is demonstrated by successfully imitating time-dependent (pair and triplet spike-time-dependent-plasticity) and rate-dependent (Bienenstosk-Cooper-Munro) synaptic learning rules. Experimental results are benchmarked against in-vitro measurements from hippocampal and visual cortices with good agreement. The scalability of synaptic devices and their programming through a CMOS drive circuitry elaborates the potential of such an approach in realizing adaptive neuromorphic computation and networks.
Large nearshore storm waves off the Irish coast
Authors: Fedele Francesco , Herterich James , Tayfun Aziz , Dias Frederic
Published: October 2019

We present a statistical analysis of nearshore waves observed during two major North–East Atlantic storms in 2015 and 2017. Surface elevations were measured with a 5-beam acoustic Doppler current profiler (ADCP) at relatively shallow waters off the west coast of Ireland. To compensate for the significant variability of both sea states in time, we consider a novel approach for analyzing the non-stationary surface-elevation series and compare the distributions of crest and wave heights observed with theoretical predictions based on the Forristall, Tayfun and Boccotti models. In particular, the latter two models have been largely applied to and validated for deep-water waves. We show here that they also describe well the characteristics of waves observed in relatively shallow waters. The largest nearshore waves observed during the two storms do not exceed the rogue thresholds as the Draupner, Andrea, Killard or El Faro rogue waves do in intermediate or deep-water depths. Nevertheless, our analysis reveals that modulational instabilities are ineffective, third-order resonances negligible and the largest waves observed here have characteristics quite similar to those displayed by rogue waves for which second order bound nonlinearities are the principal factor that enhances the linear dispersive focusing of extreme waves.
Ribosomal protein uL3 targets E2F1 and Cyclin D1 in cancer cell response to nucleolar stress
Authors: Pecoraro Annalisa , Carotenuto Pietro , Russo Giulia , Russo Annapina
Published: October 2019

Several experimental strategies in the treatment of cancer include drug alteration of cell cycle regulatory pathways as a useful strategy. Extra-ribosomal functions of human ribosomal protein L3 (uL3) may affect DNA repair, cell cycle arrest and apoptosis. In the present study, we demonstrated that uL3 is required for the activation of G1/S transition genes. Luciferase assays established that uL3 negatively regulates the activity of E2F1 promoter. Induced ribosome-free uL3 reduces Cyclin D1 mRNA and protein levels. Using protein/protein immunoprecipitation methods, we demonstrated that uL3 physically interacts with PARP-1 affecting E2F1 transcriptional activity. Our findings led to the identification of a new pathway mediated by uL3 involving E2F1 and Cyclin D1 in the regulation of cell cycle progression.
Intralesional EBV-DNA load as marker of prognosis for nasopharyngeal cancer
Authors: Nilsson Johan S. , Forslund Ola , Andersson Fredrik C. , Lindstedt Malin , Greiff Lennart
Published: October 2019

Nasopharyngeal cancer (NPC) is associated with the Epstein-Barr virus (EBV). The clinical presentation and prognosis of NPC is well described, but not in relation to intralesional EBV-DNA load. In a retrospective design, 48 patients with NPC were examined. Patient history was re-evaluated, and diagnostic biopsies were re-examined. Furthermore, intralesional EBV-DNA was quantitated and HPV status determined. Cancer stage, disease-free survival (DFS), and overall survival (OS) were assessed. Of the 48 patients, 36 (75%) patients featured lesions that were positive for EBER (Epstein–Barr virus-encoded small RNA) and 40 (83%) were positive for EBV-DNA. Seven patients (15%) were HPV positive. The levels of EBV-DNA ranged from 0.0005 to 94617 copies/cell. An EBV-DNA load of more than 70 copies/cell was associated with a prolonged DFS for EBV-DNA positive patients treated with curative intent (p = 0.046). In conclusion, the EBV-DNA load in NPC lesions appears to vary greatly. For patients with EBV-DNA positive NPC treated with curative intent, an EBV-DNA load of more than 70 copies/cell is associated with a better outcome in terms of 7-year DFS.
Proteome and Secretome Dynamics of Human Retinal Pigment Epithelium in Response to Reactive Oxygen Species
Authors: Meyer Jesse G. , Garcia Thelma Y. , Schilling Birgit , Gibson Bradford W. , Lamba Deepak A.
Published: October 2019

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries, and is characterized by slow retinal degeneration linked to chronic reactive oxygen species (ROS) in the retinal pigmented epithelium (RPE). The molecular mechanisms leading to RPE dysfunction in response to ROS are unclear. Here, human stem cell-derived RPE samples were stressed with ROS for 1 or 3 weeks, and both intracellular and secreted proteomes were quantified by mass spectrometry. ROS increased glycolytic proteins but decreased mitochondrial complex I subunits, as well as membrane proteins required for endocytosis. RPE secreted over 1,000 proteins, many of which changed significantly due to ROS. Notably, secreted APOE is decreased 4-fold, and urotensin-II, the strongest known vasoconstrictor, doubled. Furthermore, secreted TGF-beta is increased, and its cognate signaler BMP1 decreased in the secretome. Together, our results paint a detailed molecular picture of the retinal stress response in space and time.
Arctic seabirds and shrinking sea ice: egg analyses reveal the importance of ice-derived resources
Authors: Cusset Fanny , Fort Jérôme , Mallory Mark , Braune Birgit , Massicotte Philippe , Massé Guillaume
Published: October 2019

In the Arctic, sea-ice plays a central role in the functioning of marine food webs and its rapid shrinking has large effects on the biota. It is thus crucial to assess the importance of sea-ice and ice-derived resources to Arctic marine species. Here, we used a multi-biomarker approach combining Highly Branched Isoprenoids (HBIs) with δ13C and δ15N to evaluate how much Arctic seabirds rely on sea-ice derived resources during the pre-laying period, and if changes in sea-ice extent and duration affect their investment in reproduction. Eggs of thick-billed murres (Uria lomvia) and northern fulmars (Fulmarus glacialis) were collected in the Canadian Arctic during four years of highly contrasting ice conditions, and analysed for HBIs, isotopic (carbon and nitrogen) and energetic composition. Murres heavily relied on ice-associated prey, and sea-ice was beneficial for this species which produced larger and more energy-dense eggs during icier years. In contrast, fulmars did not exhibit any clear association with sympagic communities and were not impacted by changes in sea ice. Murres, like other species more constrained in their response to sea-ice variations, therefore appear more sensitive to changes and may become the losers of future climate shifts in the Arctic, unlike more resilient species such as fulmars.
The microphthalmia-associated transcription factor (Mitf) gene and its role in regulating eye function
Authors: García-Llorca Andrea , Aspelund Snaefridur Gudmundsdottir , Ogmundsdottir Margret Helga , Steingrimsson Eiríkur , Eysteinsson Thor
Published: October 2019

Mutations in the microphthalmia-associated transcription factor (Mitf) gene can cause retinal pigment epithelium (RPE) and retinal dysfunction and degeneration. We examined retinal and RPE structure and function in 3 month old mice homo- or heterozygous or compound heterozygous for different Mitf mutations (Mitfmi-vga9/+, Mitfmi-enu22(398)/Mitfmi-enu22(398), MitfMi-Wh/+ and MitfMi-Wh/Mitfmi) which all have normal eye size with apparently normal eye pigmentation. Here we show that their vision and retinal structures are differentially affected. Hypopigmentation was evident in all the mutants while bright-field fundus images showed yellow spots with non-pigmented areas in the Mitfmi-vga9/+ mice. MitfMi-Wh/+ and MitfMi-Wh/Mitfmi mice showed large non-pigmented areas. Fluorescent angiography (FA) of all mutants except Mitfmi-vga9/+ mice showed hyperfluorescent areas, whereas FA from both Mitf-Mi-Wh/+ and MitfMi-Wh/Mitfmi mice showed reduced capillary network as well as hyperfluorescent areas. Electroretinogram (ERG) recordings show that MitfMi-Wh/+ and MitfMi-Wh/Mitfmi mice are severely impaired functionally whereas the scotopic and photopic ERG responses of Mitfmi-vga9/+ and Mitfmi-enu22(398)/Mitfmi-enu22(398) mice were not significantly different from wild type mice. Histological sections demonstrated that the outer retinal layers were absent from the MitfMi-Wh/+ and MitfMi-Wh/Mitfmi blind mutants. Our results show that Mitf mutations affect eye function, even in the heterozygous condition and that the alleles studied can be arranged in an allelic series in this respect.
Structure of Turnip mosaic virus and its viral-like particles
Authors: Cuesta Rebeca , Yuste-Calvo Carmen , Gil-Cartón David , Sánchez Flora , Ponz Fernando , Valle Mikel
Published: October 2019

Turnip mosaic virus (TuMV), a potyvirus, is a flexible filamentous plant virus that displays a helical arrangement of coat protein copies (CPs) bound to the ssRNA genome. TuMV is a bona fide representative of the Potyvirus genus, one of most abundant groups of plant viruses, which displays a very wide host range. We have studied by cryoEM the structure of TuMV virions and its viral-like particles (VLPs) to explore the role of the interactions between proteins and RNA in the assembly of the virions. The results show that the CP-RNA interaction is needed for the correct orientation of the CP N-terminal arm, a region that plays as a molecular staple between CP subunits in the fully assembled virion.
A highly sensitive safrole sensor based on polyvinyl acetate (PVAc) nanofiber-coated QCM
Authors: Triyana Kuwat , Rianjanu Aditya , Nugroho Doni Bowo , As’ari Ahmad Hasan , Kusumaatmaja Ahmad , Roto Roto , Suryana Risa , Wasisto Hutomo Suryo
Published: October 2019

A novel, highly sensitive and selective safrole sensor has been developed using quartz crystal microbalance (QCM) coated with polyvinyl acetate (PVAc) nanofibers. The nanofibers were collected on the QCM sensing surface using an electrospinning method with an average diameter ranging from 612 nm to 698 nm and relatively high Q–factors (rigid coating). Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to analyze the PVAc nanofiber surface morphology, confirming its high surface area and roughness, which are beneficial in improving the sensor sensitivity compared to its thin-film counterpart. The as-spun PVAc nanofiber sensor could demonstrate a safrole limit of detection (LOD) of down to 0.7 ppm with a response time of 171 s and a sensitivity of 1.866 Hz/ppm. It also showed good reproducibility, rapid response time, and excellent recovery. Moreover, cross-interference of the QCM sensor response to non-target gases was investigated, yielding very low cross-sensitivity and high selectivity of the safrole sensor. Owing to its high robustness and low fabrication cost, this proposed sensing device is expected to be a promising alternative to classical instrumental analytical methods for monitoring safrole-based drug precursors.
Use of reliable contraceptives and its correlates among women participating in Simulated HIV vaccine efficacy trials in key-populations in Uganda
Authors: Abaasa Andrew , Todd Jim , Mayanja Yunia , Price Matt , Fast Patricia E. , Kaleebu Pontiano , Nash Stephen
Published: October 2019

To prevent pregnancy in trials, reliable contraceptive use is key. We investigated reliable contraceptive use at baseline and six months in key-populations in Uganda, during two Simulated HIV Vaccine Efficacy trials (SiVETs). SiVETs were nested within observational cohorts of Fisherfolk (2012–2014) and Female sex workers (2014–2017). Women in the observational cohorts were screened and enrolled into the SiVET. The trial administered a licensed Hepatitis B vaccine at 0, 1 and 6 months. Contraceptive use data were recorded at baseline and follow-up clinic visits. Reliable contraceptives (injectable Depot Medroxyprogesterone Acetate (DMPA), implant, pills, and intrauterine device (IUD)) were promoted and provided to women not using a reliable method at enrolment. Overall, 367 women were enrolled. At baseline 203 (55%) reported use of reliable contraceptive. Of the 164 women not using a reliable method at enrolment, 131 (80%) started using them during follow-up bringing the overall number to 334 (91%) at the end of follow-up. Young age (≤35 years) was an independent predictor of reliable contraceptive use at both time points while other factors varied. Promotion and provision of reliable contraceptives increased the proportion using them and could help reduce the risk of pregnancy in future HIV prevention trials.
Identification of novel targets for host-directed therapeutics against intracellular Staphylococcus aureus
Authors: Bravo-Santano Natalia , Capilla-Lasheras Pablo , Mateos Luis M. , Calle Yolanda , Behrends Volker , Letek Michal
Published: October 2019

During patient colonization,Staphylococcus aureusis able to invade and proliferate within human cells to evade the immune system and last resort drugs such as vancomycin. Hijacking specific host molecular factors and/or pathways is necessary for pathogens to successfully establish an intracellular infection. In this study, we employed an unbiased shRNA screening coupled with ultra-fast sequencing to screen 16,000 human genes duringS. aureusinfection and we identified several host genes important for this intracellular pathogen. In addition, we interrogated our screening results to find novel host-targeted therapeutics against intracellularS. aureus. We found that silencing the human geneTRAM2resulted in a significant reduction of intracellular bacterial load while host cell viability was restored, showing its importance during intracellular infection. Furthermore, TRAM2 is an interactive partner of the endoplasmic reticulum SERCA pumps and treatment with the SERCA-inhibitor Thapsigargin halted intracellular MRSA survival. Our results suggest that Thapsigargin could be repurposed to tackleS. aureushost cell infection in combination with conventional antibiotics.
Biochemical and Structural Insights Concerning Triclosan Resistance in a Novel YX7K Type Enoyl-Acyl Carrier Protein Reductase from Soil Metagenome
Authors: Khan Raees , Zeb Amir , Choi Kihyuck , Lee Gihwan , Lee Keun Woo , Lee Seon-Woo
Published: October 2019

Enoyl-acyl carrier protein reductase (ENR) catalyzes the last reduction step in the bacterial type II fatty acid biosynthesis cycle. ENRs include FabI, FabL, FabL2, FabK, and FabV. Previously, we reported a unique triclosan (TCL) resistant ENR homolog that was predominant in obligate intracellular pathogenic bacteria and Apicomplexa. Herein, we report the biochemical and structural basis of TCL resistance in this novel ENR. The purified protein revealed NADH-dependent ENR activity and shared similarity to prototypic FabI. Thus, this metagenome-derived ENR was designated FabI2. Unlike other prototypic bacterial ENRs with the YX6K type catalytic domain, FabI2 possessed a unique YX7K type catalytic domain. Computational modeling followed by site-directed mutagenesis revealed that mild resistance (20 µg/ml of minimum inhibitory concentration) of FabI2 to TCL was confined to the relatively less bulky side chain of A128. Substitution of A128 in FabI2 with bulky valine (V128) elevated TCL resistance. Phylogenetic analysis further suggested that the novel FabI2 and prototypical FabI evolved from a common short-chain dehydrogenase reductase family. To our best knowledge, FabI2 is the only known ENR shared by intracellular pathogenic prokaryotes, intracellular pathogenic lower eukaryotes, and a few higher eukaryotes. This suggests that the ENRs of prokaryotes and eukaryotes diverged from a common ancestral ENR of FabI2.