bluuebunny/crossref_metadata_2025 huggingface dataset:
The Reformers as fathers of the church: Luther and Calvin in the thought of Karl Barth
Authors: Bender Kimlyn J.
Published: November 2019

Karl Barth's understanding of Luther and Calvin is not best illumined by an examination of his direct citation of their work, but by a consideration of his description of their vocation as church fathers as outlined in Church Dogmatics, I/2, a position held with remarkable consistency over the course of his career. Barth's discussion of Luther and Calvin there not only sets forth his understanding of the Reformers in a historical genealogy of revelation and its witnesses, but places them in an ordering of church authorities. Moreover, his description of their unique vocation sheds important light upon his understanding of the modern discipline of church history itself. His treatment of the Reformers thus both exemplifies and follows from his conviction that church history is not an independent theological discipline but can only accompany the central disciplines of exegetical, dogmatic and practical theology.
Understanding the severity of depression: do nondepressive symptoms influence global ratings of depression severity?
Authors: Zimmerman Mark , Balling Caroline , Chelminski Iwona , Dalrymple Kristy
Published: November 2019

Objective.

Almost all depression measures have been developed without discussing how to best conceptualize and assess the severity of depression. It is therefore not surprising that measures differ in both how items are rated and item content. The question that we address in the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project is whether a measure of depression severity should include symptoms that are frequent in depressed patients but are defining features of other disorders (eg, anxiety, irritability)

Methods.

Patients were evaluated with a semi-structured interview and severity ratings were made of each symptom of major depressive disorder (MDD) as well as anxiety, irritability, and somatization. Patients were also rated on the Clinical Global Index of severity (CGI).

Results.

Three of the 5 nondepressive symptoms (psychic anxiety, somatic anxiety, and subjective anger) were significantly correlated with the CGI. The correlation between the sum of all 5 nondepressive symptoms and the CGI was significantly lower than the correlation between the sum of the depressive symptom severity ratings (0.12 vs 0.52, z = 11.0, p < .001). The partial correlation between the CGI and the nondepressive symptom severity ratings (after controlling for the total depressive symptom ratings) was nonsignificant.

Discussion.

After accounting for the severity of depressive symptoms, the severity of the nondepressive symptoms was not associated with global ratings of depressive severity. These findings raise questions regarding the appropriateness of including ratings of anxiety, irritability, and somatization on a measure that purportedly assesses the severity of depression.
Ingestion of magnesium was not associated with coronary calcium score	in a cross-sectional study
Authors: Levy Jéssica , Miranda Andreia Alexandra Machado , De Carli Eduardo , Bittencourt Marcio Sommer , Benseñor Isabela Judith , Lotufo Paulo Andrade , Marchioni Dirce Maria
Published: November 2019

Abstract. Background and aims: Magnesium plays a key role in glucose metabolism, vascular tone, and inflammation. Therefore, it might be a dietary risk factor for cardiovascular diseases. In vitro and animal studies have suggested a decrease in vascular calcification with an increase in the magnesium intake. The objective of the present study was to investigate the association between magnesium intake and coronary artery calcium (CAC) score among participants of the ELSA-Brasil. Methods: This is an observational, cross-sectional study undertaken with a sub-sample from the ELSA-Brasil baseline data. In this sub-sample, only participants with CAC examination data were included (n = 4,306). Dietary intake was assessed by a validated food frequency questionnaire. The association between magnesium intake and presence of CAC (0 versus > 0) was investigated using multiple logistic regression models. Results: The participants were predominantly female (54.4 %), with self-reported white skin color (59.1 %), no smoking habit (53.7 %) and undergraduate or postgraduate education (44.4 %). The range of magnesium consumption was 37.24 – 1266.31 mg/day. CAC prevalence was 28.4 %. No significant association was found between magnesium intake and CAC after adjustments for diet, lifestyle, and clinical characteristics. In a first univariate model, the fifth quintile of magnesium intake, in comparison to the first quintile (lowest intake), resulted in an OR = 1.25, 95 % CI: 1.01 – 1.54 ( P-linear trend = 0.005). However, in the last fully adjusted model, the fifth quintile of magnesium intake resulted in OR = 0.86, 95 % CI: 0.64 – 1.17 ( P-linear trend = 0.239). Conclusions: In ELSA-Brasil, the intake of magnesium was not associated with the presence of coronary artery calcification.
Delayed Weakening and Reactivation of Rate‐and‐State Faults Driven by Pressure Changes Due to Fluid Injection
Authors: Andrés Sandro , Santillán David , Mosquera Juan Carlos , Cueto‐Felgueroso Luis
Published: November 2019

Fault reactivation induced by pore pressure changes involves complex frictional phenomena because effective normal stresses vary in space and time due to fluid flow and rock deformation. The impact of time‐varying normal stresses on fault friction has been characterized in stress‐step laboratory experiments and modeled through extended rate‐and‐state laws that incorporate a stressing‐rate dependence of the state variable. Building on these rate‐and‐state models, we use 2‐D poroelastic simulations to understand how the evolution of pore pressures due to fluid injection affects fault strength and reactivation. A sharp increase in pore pressure, associated with fluid injection, leads to an increase in friction coefficient and to a delayed weakening of the fault. Conversely, a sharp pressure decrease during extraction leads to a delayed strengthening. Stressing‐rate effects emerge as a purely frictional mechanism that delays or accelerates the onset of fault slip, suggesting that reactivation under fluid injection may occur long after flow rates have decreased and pore pressures have stabilized at the fault. Hence, earthquakes induced by injection may ensue as a deferred process triggered several days later than predicted by simple estimates based on constant friction. The duration of the delay depends on the type of rate‐and‐state law used in calculations and on a characteristic relaxation time: The memory time over which the state variable evolves under stationary contact. Our results help understand the connection between injection protocols and frictional weakening mechanisms, suggesting that injection processes can be engineered to minimize the risk of induced seismicity for a given injected volume.
Earthquake Initiation From Laboratory Observations and Implications for Foreshocks
Authors: McLaskey Gregory C.
Published: November 2019

This paper reviews laboratory observations of earthquake initiation and describes new experiments on a 3‐m rock sample where the nucleation process is imaged in detail. Many of the laboratory observations are consistent with previous work that showed a slow and smoothly accelerating earthquake nucleation process that expands to a critical nucleation length scale Lc, before it rapidly accelerates to dynamic fault rupture. The experiments also highlight complexities not currently considered by most theoretical and numerical models. This includes a loading rate dependency where a “kick” above steady state produces smaller and more abrupt initiation. Heterogeneity of fault strength also causes abrupt initiation when creep fronts coalesce on a stuck patch that is somewhat stronger than the surrounding fault. Taken together, these two mechanisms suggest a rate‐dependent “cascade up” model for earthquake initiation. This model simultaneously accounts for foreshocks that are a by‐product of a larger nucleation process and similarities between initial P wave signatures of small and large earthquakes. A diversity of nucleation conditions are expected in the Earth's crust, ranging from slip limited environments with Lc < 1 m, to ignition‐limited environments with Lc > 10 km. In the latter case, Lc fails to fully characterize the initiation process since earthquakes nucleate not because a slipping patch reaches a critical length but because fault slip rate exceeds a critical power density needed to ignite dynamic rupture.
Seismic Tomography Using Variational Inference Methods
Authors: Zhang Xin , Curtis Andrew
Published: November 2019

Seismic tomography is a methodology to image the interior of solid or fluid media and is often used to map properties in the subsurface of the Earth. In order to better interpret the resulting images, it is important to assess imaging uncertainties. Since tomography is significantly nonlinear, Monte Carlo sampling methods are often used for this purpose, but they are generally computationally intractable for large data sets and high‐dimensional parameter spaces. To extend uncertainty analysis to larger systems, we use variational inference methods to conduct seismic tomography. In contrast to Monte Carlo sampling, variational methods solve the Bayesian inference problem as an optimization problem yet still provide fully nonlinear, probabilistic results. In this study, we applied two variational methods, automatic differential variational inference and Stein variational gradient descent, to 2‐D seismic tomography problems using both synthetic and real data, and we compare the results to those from two different Monte Carlo sampling methods. The results show that automatic differential variational inference provides a biased approximation because of its implicit transformed‐Gaussian approximation, and it cannot be used to find generally multimodal posteriors; Stein variational gradient descent produces more accurate approximations to the results of Monte Carlo sampling methods. Both methods estimate the posterior distribution at significantly lower computational cost, provided that gradients of parameters with respect to data can be calculated efficiently. We expect that the methods can be applied fruitfully to many other types of geophysical inverse problems.
Electron Temperature Response to Solar Forcing in the Low‐Latitude Martian Ionosphere
Authors: Pilinski M. , Andersson L. , Fowler C. , Peterson W. K. , Thiemann E. , Elrod M. K.
Published: November 2019

Electron temperatures are a key parameter for understanding the ionosphere‐thermosphere system. This study uses in situ data from the MAVEN mission to investigate the level of coupling between the Martian ionospheric electrons and the neutral thermosphere below the altitude of 190 km. Such coupling is responsible for significant diurnal variations and dawn/dusk asymmetries in both the neutral and plasma portions of the ionosphere‐thermosphere system. Earlier theoretical studies suggested that neutral species controlled the electron temperature by collisional cooling thus implying a diurnal trend in electron temperatures due to the diurnal variability of the neutrals. This hypothesis is evaluated across the dayside ionosphere in the present work. Observations of neutral densities confirm that neutral‐electron collisions are the primary process controlling the cooling of electrons in the Martian ionosphere below ~190 km. The consequence of this is that electron temperatures can be anticorrelated with the extreme ultraviolet (EUV) irradiance due to enhanced electron cooling brought about by an expansion of neutral densities. The results also indicate that in the afternoon sector, neutral densities are less responsive to changes in EUV. This might be associated with enhanced winds leading to dynamic cooling that mitigates the thermal expansion of the thermosphere in the afternoon region. Subsequently, the electron temperature as a function of EUV is relatively uncorrelated in the afternoon sector.
Representing Intrahillslope Lateral Subsurface Flow in the Community Land Model
Authors: Swenson Sean C. , Clark Martyn , Fan Ying , Lawrence David M. , Perket Justin
Published: November 2019

The concept of using representative hillslopes to simulate hydrologically similar areas of a catchment has been incorporated in many hydrologic models but few Earth system models. Here we describe a configuration of the Community Land Model version 5 in which each grid cell is decomposed into one or more multicolumn hillslopes. Within each hillslope, the intercolumn connectivity is specified, and the lateral saturated subsurface flow from each column is passed to its downslope neighbor. We first apply the model to simulate a headwater catchment and assess the results against runoff and evapotranspiration flux measurements. By redistributing soil water within the catchment, the model is able to reproduce the observed difference between evapotranspiration in the upland and lowland portions of the catchment. Next, global simulations based on hypothetical hillslope geomorphic parameters are used to show the model's sensitivity to differences in hillslope shape and discretization. Differences in evapotranspiration between upland and lowland hillslope columns are found to be largest in arid and semiarid regions, while humid tropical and high‐latitude regions show limited evapotranspiration increases in lowlands relative to uplands.
Efficient treatment of murine acute GvHD by in vitro expanded donor regulatory T cells
Authors: Riegel Christin , Boeld Tina J. , Doser Kristina , Huber Elisabeth , Hoffmann Petra , Edinger Matthias
Published: November 2019

Acute graft-versus-host disease (aGvHD) is a frequent complication after allogeneic bone marrow/stem cell transplantation (BMT/SCT) induced by co-transplanted alloreactive conventional donor T cells. We previously demonstrated that the adoptive transfer of donor CD4+CD25+Foxp3+ regulatory T cells (Treg) at the time of BMT prevents aGvHD in murine models. Yet, the therapeutic potential of donor Treg for the treatment of established aGvHD has not yet been studied in detail. We now used in vitro expanded phenotypically and functionally stable murine Treg to explore their therapeutic efficacy in haploidentical aGvHD models. Upon transfer donor Treg ameliorate clinical and histologic signs of aGvHD and significantly improve survival. They migrate to lymphoid as well as aGvHD target organs, predominantly the gastrointestinal tract, where they inhibit the proliferation of conventional T cells, reduce the influx of myeloid cells, and the accumulation of inflammatory cytokines. Successfully treated animals restore aGvHD-induced tissue damage in target organs and lymphoid tissues, thereby supporting lymphocyte reconstitution. The therapeutically applied Treg population survives long term without conversion into pathogenic effector T cells. These results demonstrate that donor Treg not only prevent aGvHD, but are also efficacious for the treatment of this life-threatening BMT complication.
Inhibiting lysine 353 oxidation of GRP78 by a hypochlorous probe targeting endoplasmic reticulum promotes autophagy in cancer cells
Authors: Ning Junya , Lin Zhaomin , Zhao Xuan , Zhao Baoxiang , Miao Junying
Published: November 2019

The level of hypochlorous acid (HOCl) in cancer cells is higher than that in non-cancer cells. HOCl is an essential signal for the regulation of cell fate and works mainly through the protein post-translational modifications in cancer cells. However, the mechanism of HOCl regulating autophagy has not been clarified. Here we reported that a HOCl probe named ZBM-H targeted endoplasmic reticulum and induced an intact autophagy flux in lung cancer cells. Furthermore, ZBM-H promoted the binding of GRP78 to AMPK and increased the phosphorylation of AMPK in a dose- and time-dependent manner. GRP78 knockdown inhibited ZBM-H-induced AMPK phosphorylation and ZBM-H-stimulated autophagy. In addition, mass spectrometry combined with point mutation experiments revealed that ZBM-H increased GRP78 activity by inhibiting HOCl-induced lysine 353 oxidation of GRP78. Following ZBM-H treatment in vitro and in vivo, cell growth was significantly inhibited while apoptosis was induced. Nevertheless, exogenous HOCl partially reversed ZBM-H-inhibited cell growth and ZBM-H-induced GRP78 activation. In brief, we found that an endoplasmic reticulum-targeted HOCl probe named ZBM-H, acting through attenuating HOCl-induced GRP78 oxidation, inhibited tumor cell survival by promoting autophagy and apoptosis. Overall, these data demonstrated a novel mechanism of hypochlorous acid regulating autophagy by promoting the oxidation modification of GRP78.
Endogenous alpha-synuclein monomers, oligomers and resulting pathology: let’s talk about the lipids in the room
Authors: Killinger Bryan A. , Melki Ronald , Brundin Patrik , Kordower Jeffrey H.
Published: November 2019

Alpha-synuclein is an intrinsically disordered, highly dynamic protein that pathogenically aggregates into inclusion structures called Lewy bodies, in several neurogenerative diseases termed synucleinopathies. Despite its importance for understanding disease, the oligomerization status of alpha-synuclein in healthy cells remains unclear. Alpha-synuclein may exist predominantly as either a monomer or a variety of oligomers of different molecular weights. There is solid evidence to support both theories. Detection of apparent endogenous oligomers are intimately dependent on vesicle and lipid interactions. Here we consider the possibility that apparent endogenous alpha-synuclein oligomers are in fact conformations of membrane-bound alpha-synuclein and not a bona fide stable soluble species. This perspective posits that the formation of any alpha-synuclein oligomers within the cell is likely toxic and interconversion between monomer and oligomer is tightly controlled. This differs from the hypothesis that there is a continuum of endogenous non-toxic oligomers and they convert, through unclear mechanisms, to toxic oligomers. The distinction is important, because it clarifies the biological origin of synucleinopathy. We suggest that a monomer-only, lipid-centric view of endogenous alpha-synuclein aggregation can explain how alpha-synuclein pathology is triggered, and that the interactions between alpha-synuclein and lipids can represent a target for therapeutic intervention. This discussion is well-timed due to recent studies that show lipids are a significant component of Lewy pathology.
Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification
Authors: La Merrill Michele A. , Vandenberg Laura N. , Smith Martyn T. , Goodson William , Browne Patience , Patisaul Heather B. , Guyton Kathryn Z. , Kortenkamp Andreas , Cogliano Vincent J. , Woodruff Tracey J. , Rieswijk Linda , Sone Hideko , Korach Kenneth S. , Gore Andrea C. , Zeise Lauren , Zoeller R. Thomas
Published: November 2019

Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with hormone action, thereby increasing the risk of adverse health outcomes, including cancer, reproductive impairment, cognitive deficits and obesity. A complex literature of mechanistic studies provides evidence on the hazards of EDC exposure, yet there is no widely accepted systematic method to integrate these data to help identify EDC hazards. Inspired by work to improve hazard identification of carcinogens using key characteristics (KCs), we have developed ten KCs of EDCs based on our knowledge of hormone actions and EDC effects. In this Expert Consensus Statement, we describe the logic by which these KCs are identified and the assays that could be used to assess several of these KCs. We reflect on how these ten KCs can be used to identify, organize and utilize mechanistic data when evaluating chemicals as EDCs, and we use diethylstilbestrol, bisphenol A and perchlorate as examples to illustrate this approach.
Clinical and genetic variability in children with partial albinism
Authors: Campbell Patrick , Ellingford Jamie M. , Parry Neil R. A. , Fletcher Tracy , Ramsden Simon C. , Gale Theodora , Hall Georgina , Smith Katherine , Kasperaviciute Dalia , Thomas Ellen , Lloyd I. Chris , Douzgou Sofia , Clayton-Smith Jill , Biswas Susmito , Ashworth Jane L. , Black Graeme C. M. , Sergouniotis Panagiotis I.
Published: November 2019

Individuals who have ocular features of albinism and skin pigmentation in keeping with their familial background present a considerable diagnostic challenge. Timely diagnosis through genomic testing can help avert diagnostic odysseys and facilitates accurate genetic counselling and tailored specialist management. Here, we report the clinical and gene panel testing findings in 12 children with presumed ocular albinism. A definitive molecular diagnosis was made in 8/12 probands (67%) and a possible molecular diagnosis was identified in a further 3/12 probands (25%).TYRwas the most commonly mutated gene in this cohort (75% of patients, 9/12). A disease-causingTYRhaplotype comprised of two common, functional polymorphisms,TYRc.[575 C > A;1205 G > A] p.[(Ser192Tyr);(Arg402Gln)], was found to be particularly prevalent. One participant hadGPR143-associated X-linked ocular albinism and another proband had biallelic variants inSLC38A8, a glutamine transporter gene associated with foveal hypoplasia and optic nerve misrouting without pigmentation defects. Intriguingly, 2/12 individuals had a single, rare, likely pathogenic variant in each ofTYRandOCA2– a significant enrichment compared to a control cohort of 4046 individuals from the 100,000 genomes project pilot dataset. Overall, our findings highlight that panel-based genetic testing is a clinically useful test with a high diagnostic yield in children with partial/ocular albinism.
Determinants of Childhood Anemia in India
Authors: Onyeneho Nkechi G. , Ozumba Benjamin C. , Subramanian S. V.
Published: November 2019

We analyzed a sample of 112714 children from the 2015–2016 Indian National Fertility and Health Survey with available data on hemoglobin. Multinomial logistic regression models were used to establish associations between parent anemia, household characteristics and nutritional intake of children. Linear regression analysis was also conducted to see the link between the household characteristic and childhood nutritional intake on one hand and hemoglobin levels on the other hand. A number of socio-demographic factors, namely maternal age, type of residence and maternal education, as well as wealth index, among others correlate with incidence of childhood anemia. For instance, whereas 52.9% of children in the richest households were anemic, 63.2% of children in the poorest household were anemic (p < 0.001). Mean Vitamin A intake in the last six months was 0.63 (0.626–0.634) which was 0.18% of the recommended intake. Mean iron intake, from sources other than breast milk, in the last 24 hours was 0.29 (0.286–0.294) and 2.42% of the recommended daily intake. Fifty-nine percent (58.5%) of the children surveyed were anemic (Hb level: 9.75 g/dL [9.59–9.91]). Children with anemia were more prone to being iron deficient (odds ratio [OR]: 0.981 (0.961–1.001), Vitamin A deficient (OR: 0.813 (0.794–0.833)), and have lower maternal hemoglobin level (OR: 1.992 (1.957–2.027)). Combining nutritional supplementation and food-fortification programmes with reduction in maternal anemia and family poverty may yield optimal improvement of childhood anemia in India.
Anthropogenic aerosol drives uncertainty in future climate mitigation efforts
Authors: Larson E. J. L. , Portmann R. W.
Published: November 2019

The 2016 Paris agreement set a global mean surface temperature (GMST) goal of not more than 2 degrees Celsius above preindustrial. This is an ambitious goal that will require substantial decreases in emission rates of long-lived greenhouse gasses (GHG). This work provides a mathematical framework, based on current state of the art climate models, to calculate the GHG emissions consistent with prescribed GMST pathways that meet the Paris agreement goal. The unique capability of this framework, to start from a GMST timeseries and efficiently calculate the emissions required to meet that temperature pathway, makes it a powerful resource for policymakers. Our results indicate that aerosol emissions play a large role in determining the near-term allowable greenhouse gas emissions that will limit future warming to 2 °C, however in the long term, drastic GHG emissions reductions are required under any reasonable aerosol scenario. With large future aerosol emissions, similar to present day amounts, GHG emissions need to be reduced 8% by 2040 and 74% by 2100 to limit warming to 2 °C. Under a more likely low aerosol scenario, GHG emissions need to be reduced 36% and 80% by 2040 and 2100, respectively. The Paris agreement Intended Nationally Determined Contributions are insufficient to meet this goal.
Coexistence with Pseudomonas aeruginosa alters Staphylococcus aureus transcriptome, antibiotic resistance and internalization into epithelial cells
Authors: Briaud Paul , Camus Laura , Bastien Sylvère , Doléans-Jordheim Anne , Vandenesch François , Moreau Karen
Published: November 2019

Cystic fibrosis (CF) is the most common life-threatening genetic disease among Caucasians. CF patients suffer from chronic lung infections due to the presence of thick mucus, caused by cftr gene dysfunction. The two most commonly found bacteria in the mucus of CF patients are Staphylococcus aureus and Pseudomonas aeruginosa. It is well known that early-infecting P. aeruginosa strains produce anti-staphylococcal compounds and inhibit S. aureus growth. More recently, it has been shown that late-infecting P. aeruginosa strains develop commensal-like/coexistence interaction with S. aureus. The aim of this study was to decipher the impact of P. aeruginosa strains on S. aureus. RNA sequencing analysis showed 77 genes were specifically dysregulated in the context of competition and 140 genes in the context of coexistence in the presence of P. aeruginosa. In coexistence, genes encoding virulence factors and proteins involved in carbohydrates, lipids, nucleotides and amino acids metabolism were downregulated. On the contrary, several transporter family encoding genes were upregulated. In particular, several antibiotic pumps belonging to the Nor family were upregulated: tet38, norA and norC, leading to an increase in antibiotic resistance of S. aureus when exposed to tetracycline and ciprofloxacin and an enhanced internalization rate within epithelial pulmonary cells. This study shows that coexistence with P. aeruginosa affects the S. aureus transcriptome and virulence.
Comparison of targeted next-generation sequencing for whole-genome sequencing of Hantaan orthohantavirus in Apodemus agrarius lung tissues
Authors: No Jin Sun , Kim Won-Keun , Cho Seungchan , Lee Seung-Ho , Kim Jeong-Ah , Lee Daesang , Song Dong Hyun , Gu Se Hun , Jeong Seong Tae , Wiley Michael R. , Palacios Gustavo , Song Jin-Won
Published: November 2019

Orthohantaviruses, negative-sense single-strand tripartite RNA viruses, are a global public health threat. In humans, orthohantavirus infection causes hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. Whole-genome sequencing of the virus helps in identification and characterization of emerging or re-emerging viruses. Next-generation sequencing (NGS) is a potent method to sequence the viral genome, using molecular enrichment methods, from clinical specimens containing low virus titers. Hence, a comparative study on the target enrichment NGS methods is required for whole-genome sequencing of orthohantavirus in clinical samples. In this study, we used the sequence-independent, single-primer amplification, target capture, and amplicon NGS for whole-genome sequencing of Hantaan orthohantavirus (HTNV) from rodent specimens. We analyzed the coverage of the HTNV genome based on the viral RNA copy number, which is quantified by real-time quantitative PCR. Target capture and amplicon NGS demonstrated a high coverage rate of HTNV in Apodemus agrarius lung tissues containing up to 103–104 copies/μL of HTNV RNA. Furthermore, the amplicon NGS showed a 10-fold (102 copies/μL) higher sensitivity than the target capture NGS. This report provides useful insights into target enrichment NGS for whole-genome sequencing of orthohantaviruses without cultivating the viruses.
Completion of BAX recruitment correlates with mitochondrial fission during apoptosis
Authors: Maes M. E. , Grosser J. A. , Fehrman R. L. , Schlamp C. L. , Nickells R. W.
Published: November 2019

BAX, a member of the BCL2 gene family, controls the committed step of the intrinsic apoptotic program. Mitochondrial fragmentation is a commonly observed feature of apoptosis, which occurs through the process of mitochondrial fission. BAX has consistently been associated with mitochondrial fission, yet how BAX participates in the process of mitochondrial fragmentation during apoptosis remains to be tested. Time-lapse imaging of BAX recruitment and mitochondrial fragmentation demonstrates that rapid mitochondrial fragmentation during apoptosis occurs after the complete recruitment of BAX to the mitochondrial outer membrane (MOM). The requirement of a fully functioning BAX protein for the fission process was demonstrated further in BAX/BAK-deficient HCT116 cells expressing a P168A mutant of BAX. The mutant performed fusion to restore the mitochondrial network. but was not demonstrably recruited to the MOM after apoptosis induction. Under these conditions, mitochondrial fragmentation was blocked. Additionally, we show that loss of the fission protein, dynamin-like protein 1 (DRP1), does not temporally affect the initiation time or rate of BAX recruitment, but does reduce the final level of BAX recruited to the MOM during the late phase of BAX recruitment. These correlative observations suggest a model where late-stage BAX oligomers play a functional part of the mitochondrial fragmentation machinery in apoptotic cells.
Effect of different types of statins on kidney function decline and proteinuria: a network meta-analysis
Authors: Esmeijer K. , Dekkers Olaf M. , de Fijter Johan W. , Dekker Friedo W. , Hoogeveen Ellen K.
Published: November 2019

Previous studies showed that statins reduce the progression of kidney function decline and proteinuria, but whether specific types of statins are more beneficial than others remains unclear. We performed a network meta-analysis of randomized controlled trials (RCT) to investigate which statin most effectively reduces kidney function decline and proteinuria. We searched MEDLINE, Embase, Web of Science, and the Cochrane database until July 13, 2018, and included 43 RCTs (>110,000 patients). We performed a pairwise random-effects meta-analysis and a network meta-analysis according to a frequentist approach. We assessed network inconsistency, publication bias, and estimated for each statin the probability of being the best treatment. Considerable heterogeneity was present among the included studies. In pairwise meta-analyses, 1-year use of statins versus control reduced kidney function decline by 0.61 (95%-CI: 0.27; 0.95) mL/min/1.73 m2and proteinuria with a standardized mean difference of −0.58 (95%-CI:−0.88; −0.29). The network meta-analysis for the separate endpoints showed broad confidence intervals due to the small number available RCTs for each individual comparison. In conclusion, 1-year statin use versus control attenuated the progression of kidney function decline and proteinuria. Due to the imprecision of individual comparisons, results were inconclusive as to which statin performs best with regard to renal outcome.
Encapsulation of ovarian allograft precludes immune rejection and promotes restoration of endocrine function in immune-competent ovariectomized mice
Authors: Day James Ronald , David Anu , Barbosa Mayara Garcia de Mattos , Brunette Margaret Ann , Cascalho Marilia , Shikanov Ariella
Published: November 2019

Premature ovarian insufficiency (POI) is a significant complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. POI is particularly devastating for young girls reaching puberty, because it irreversibly affects their physical and cognitive development. Changes occurring during puberty determine their height, bone health, insulin responsiveness, lipid metabolism, cardiovascular health and cognition. The only available treatment for POI during puberty is hormone replacement therapy (HRT), which delivers non-physiological levels of estrogen, lacks other ovarian hormones and pulsatility, and is not responsive to feedback regulation. Here we report that ovarian allografts encapsulated in a hydrogel-based capsule and implanted in ovariectomized mice restore ovarian endocrine function in immune competent mice. Ovarian tissue from BALB/c mice was encapsulated in poly(ethylene-glycol) (PEG) hydrogels, with a proteolytically degradable core and a non-degradable shell. The dual capsules were implanted subcutaneously in immune competent ovariectomized C57BL/6 mice for a period of 60 days. As expected, non-encapsulated ovarian allografts implanted in a control group sensitized the recipients as confirmed with donor-specific IgG in the serum, which increased 26-fold in the 3 weeks following transplantation (p = 0.02) and infiltration of the graft with CD8 T cells consistent with allo-immunity. In contrast, encapsulation in the Dual PEG capsules prevented sensitization to the allograft in all the recipients with no evidence of lymphocytic infiltration. In summary, the approach of hydrogel-based immunoisolation presents a minimally invasive and robust cell-therapy to restore hormonal balance in ovarian insufficiency. This report is the first to demonstrate the application of a tunable PEG-based hydrogel as an immunoisolator of allogeneic ovarian tissue to restore endocrine function in ovariectomized mice and prevent cell-mediated immune rejection in immune competent mice.
Soil carbon and nitrogen fraction dynamics affected by tillage erosion
Authors: Nie Xiao-Jun , Zhang He-Bing , Su Yan-Yan
Published: November 2019

Understanding the impact of tillage erosion on soil organic carbon (SOC) and nitrogen (N) fractions is essential for targeted soil conservation in mountainous and hilly areas. However, little is known about this issue. In this study, we selected a tillage erosion-dominated hillslope from the Sichuan Basin, China, to determine the effect of tillage erosion on particulate OC (POC), dissolved OC (DOC), light fraction OC (LFOC), ammonium N (NH4+-N), nitrate N (NO3−-N) and alkali-hydrolysable N (AN). Additionally, we investigated the microbial activities in relation to soil C and N dynamics, including soil microbial biomass, β-glucosidase and urease activities. Tillage erosion induced serious soil loss in upper slope positions and soil deposition in lower slope positions. The observations of the various labile OC fraction distributions across the hillslope suggest that tillage erosion exerts less impact on DOC and LFOC dynamics but a notable effect on POC. The distribution pattern in total organic carbon under tillage erosion mainly depends on POC redistribution. The POC redistribution is a major factor affecting microbial activities. The AN is more prone to the tillage erosion impact than NH4+-N and NO3−-N. Effective soil conservation measures should be taken to weaken the adverse impacts of tillage erosion on POC and AN redistribution in sloping farmlands.
Mucoadhesive effect of Curcuma longa extract and curcumin decreases the ranitidine effect, but not bismuth subsalicylate on ethanol-induced ulcer model
Authors: Orona-Ortiz Alejandra , Medina-Torres Luis , Velázquez-Moyado Josué A. , Pineda-Peña Elizabeth A. , Balderas-López José Luis , Bernad-Bernad María Josefa , Tavares Carvalho José Carlos , Navarrete Andrés
Published: November 2019

The study of pharmacological interactions between herbal remedies and conventional drugs is important because consuming traditional herbal remedies as supplements or alternative medicine is fairly common and their concomitant administration with prescribed drugs could either have a favorable or unfavorable effect. Therefore, this work aims to determine the pharmacological interactions of a turmeric acetone extract (TAE) and its main metabolite (curcumin) with common anti-ulcer drugs (ranitidine and bismuth subsalicylate), using an ethanol-induced ulcer model in Wistar rats. The analysis of the interactions was carried out via the Combination Index-Isobologram Equation method. The combination index (CI) calculated at 0.5 of the affected fraction (fa) indicated that the TAE or curcumin in combination with ranitidine had a subadditive interaction. The results suggest that this antagonistic mechanism is associated to the mucoadhesion of curcumin and the TAE, determined by rheological measurements. Contrastingly, both the TAE and curcumin combined with bismuth subsalicylate had an additive relationship, which means that there is no pharmacological interaction. This agrees with the normalized isobolograms obtained for each combination. The results of this study suggest that mucoadhesion of curcumin and the TAE could interfere in the effectiveness of ranitidine, and even other drugs.
Sangivamycin and its derivatives inhibit Haspin-Histone H3-survivin signaling and induce pancreatic cancer cell death
Authors: Bastea Ligia I. , Hollant Laeticia M. A. , Döppler Heike R. , Reid Elizabeth M. , Storz Peter
Published: November 2019

Current treatment options for patients with pancreatic cancer are suboptimal, resulting in a five year survival rate of about 9%. Difficulties with treatment are due to an immunosuppressive, fibrotic tumor microenvironment that prevents drugs from reaching tumor cells, but also to the limited efficacy of existing FDA-approved chemotherapeutic compounds. We here show that the nucleoside analog Sangivamycin and its closely-related compound Toyocamycin target PDA cell lines, and are significantly more efficient than Gemcitabine. Using KINOMEscan screening, we identified the kinase Haspin, which is overexpressed in PDA cell lines and human PDA samples, as a main target for both compounds. Inhibition of Haspin leads to a decrease in Histone H3 phosphorylation and prevents Histone H3 binding to survivin, thus providing mechanistic insight of how Sangivamycin targets cell proliferation, mitosis and induces apoptotic cell death. In orthotopically implanted tumors in mice, Sangivamycin was efficient in decreasing the growth of established tumors. In summary, we show that Sangivamycin and derivatives can be an efficient new option for treatment of PDA.
The effect of material defects on resonant spin wave modes in a nanomagnet
Authors: Abeed Md Ahsanul , Sahoo Sourav , Winters David , Barman Anjan , Bandyopadhyay Supriyo
Published: November 2019

We have theoretically studied how resonant spin wave modes in an elliptical nanomagnet are affected by fabrication defects, such as small local thickness variations. Our results indicate that defects of this nature, which can easily result from the fabrication process, or are sometimes deliberately introduced during the fabrication process, will significantly alter the frequencies, magnetic field dependence of the frequencies, and the power and phase profiles of the resonant spin wave modes. They can also spawn new resonant modes and quench existing ones. All this has important ramifications for multi-device circuits based on spin waves, such as phase locked oscillators for neuromorphic computing, where the device-to-device variability caused by defects can be inhibitory.
The effects of simulated +Gz and microgravity on intervertebral disc degeneration in rabbits
Authors: Wu Di , Zhou Xi , Zheng Chao , He Yu , Yu Lingjia , Qiu Guixing , Wu Zhihong , Wu Ji , Liu Yong
Published: November 2019

The overall objective of this study was to test the hypothesis that +Gz (hypergravity/positive acceleration) and microgravity can both aggravate intervertebral disc degeneration (IVDD). Due to +Gz and microgravity, many pilots develop IVDD. However, the lack of animal models of IVDD under conditions of simulated +Gz and microgravity has hampered research on the onset and prevention of IVDD. Rabbits were randomly allotted to a control group, microgravity group, +Gz group, or mixed (+Gz + microgravity) group. A tail-suspension model was utilized to simulate a microgravity environment and an animal centrifuge to mimic +Gz conditions. After exposure to the above conditions for 4, 8, and 24 weeks, the body weights (BW) of animals in the control group gradually increased over time, while those of animals in the microgravity and mixed groups both decreased (p < 0.001). As compared with the control group, the proteoglycan content of animals in the other three groups was significantly reduced (F = 192.83, p < 0.001). The imageological, histopathological, and immunohistochemical changes to the L6–S1 intervertebral disc samples suggests that the effects of +Gz and microgravity can aggravate IVDD over time. The mixed effects of +Gz and microgravity had the greatest effect on degeneration and +Gz had a particularly greater effect than microgravity.
Acoustic Manipulation of Droplets under Reduced Gravity
Authors: Hasegawa Koji , Watanabe Ayumu , Abe Yutaka
Published: November 2019

Contactless manipulation of matter is essential for studying physical phenomena. Acoustic manipulation of liquid samples using ultrasonic phased arrays provides a novel and attractive solution for mid-air manipulation, such as levitation, transportation, coalescence, mixing, separation, evaporation, and extraction, with a simple and single sequence. Despite the importance of gravity in droplet dynamics, its effect on a levitated droplet with an ultrasonic phased array remains unclear. To disseminate acoustic manipulation, better understanding of the fundamental physics of a droplet manipulated by ultrasonic phased arrays is required. Here, we show contactless levitation, transportation, and coalescence of multiple droplets under both ground and reduced gravity. Under ground gravity, the possible levitation size of the sample is limited to below the half wavelength of sound. Under reduced gravity, however, droplets that are larger than the limit can be successfully levitated, transported, and coalesced. Furthermore, the threshold of sound pressure for droplet levitation and manipulation could be minimised with the suppression of nonlinear acoustic phenomena under reduced gravity. These insights promote the development of contactless manipulation techniques of droplets for future space experiment and inhabitancy.
Retraction Note: Inhibition of airway inflammation in a cockroach allergen model of asthma by agonists of miRNA-33b
Authors: Niu Ruichao , Xiao Xuping , Liu Bin , Li Yunqiu , zhong Yu , Ma Lijuan
Published: November 2019

This article has been retracted.
A single-particle enumeration method for the detection of Fe2+ based on a near-infrared core–shell upconversion nanoparticle and IR-808 dye composite nanoprobe
Authors: Zhao Mingying , Xu Fagong , Wang Lun , Chen Hongqi
Published: November 2019

A single particle enumeration method was developed for the detection of Fe2+ based on an upconversion nanoparticle and IR-808 dye composite nanoprobe.
Nickel-catalyzed electrochemical reductive decarboxylative coupling of N-hydroxyphthalimide esters with quinoxalinones
Authors: Lian Fei , Xu Kun , Meng Wei , Zhang Haonan , Tan Zhoumei , Zeng Chengchu
Published: November 2019

The first example of electrochemically enabled, NiCl2-catalyzed reductive decarboxylative coupling of N-hydroxyphthalimide esters with quinoxalinones was developed.
Organoaluminum cations for carbonyl activation
Authors: Kannan Ramkumar , Chambenahalli Raju , Kumar Sandeep , Krishna Athul , Andrews Alex P. , Jemmis Eluvathingal D. , Venugopal Ajay
Published: November 2019

A Lewis acidic cationic organoaluminum catalyst is demonstrated to perform aldehyde dimerization and ketone hydrosilylation via a carbonyl activation pathway.
Seed-assisted synthesis of fcc Ru–Cu bimetallic nanostructures and their catalytic properties for the hydrogen evolution reaction
Authors: Zhang Kai , Ji Muwei , Zhang Wenming , Zhu Caizhen , Deng Qian , Li Bo , Wang Jin
Published: November 2019

Adjusting the chemical composition and/or crystal structures is an important approach to tune the activity of catalysts.
Size-controlled excitonic effects on electronic and optical properties of Sb2S3 nanowires
Authors: Peng Yuting , Xia Congxin , Tan Zhi , An Jiao , Zhang Qiming
Published: November 2019

In this work, the electronic and optical properties of one-dimensional (1D) Sb2S3 nanowires (NWs) with different sizes are investigated using first-principles calculations.
Karst landform-featured monolithic electrode for water electrolysis in neutral media
Authors: Gao Xueqing , Chen Yingdong , Sun Tong , Huang Jianmei , Zhang Wei , Wang Qiang , Cao Rui
Published: November 2019

The development of cheap and efficient electrodes for water splitting is an ongoing challenge.
Progress, challenges, and opportunities in enhancing NOM flocculation using chemically modified chitosan: a review towards future development
Authors: Loganathan Paripurnanda , Gradzielski Michael , Bustamante Heriberto , Vigneswaran Saravanamuthu
Published: November 2019

Natural organic matter (NOM) occurs ubiquitously in water bodies and this can greatly affect feed or raw water quality (taste, colour, odour, bacterial growth). Chemically modified chitosan can effectively remove NOM by the flocculation process.
Removing scale-forming cations from produced waters
Authors: Shafer-Peltier Karen , Kenner Colton , Albertson Eric , Chen Ming , Randtke Stephen , Peltier Edward
Published: November 2019

The formation of precipitates (scales) during reinjection limits the reuse of oil and gas production water (produced water) for additional oil recovery.
Fungi characteristics of biofilms from sewage and greywater in small diameter gravity sewers
Authors: Li Wenkai , Zheng Tianlong , Ma Yingqun , Liu Junxin
Published: November 2019

Fungi characteristics of small diameter gravity sewer (SDGS) biofilms were investigated and influences of wastewater type (rural sewage and greywater) on fungi number, communities and pathogen were analyzed.
Transition metal-free construction of trinuclear N-fused hybrid scaffolds by double nucleophilic aromatic substitution under microwave irradiation
Authors: Dao Pham Duy Quang , Lim Ho-Jin , Cho Chan Sik
Published: November 2019

A green construction of trinuclear N-fused hybrid scaffolds by transition metal-free double C(sp2)–N coupling of 2-(2-bromoaryl)- and 2-(2-bromovinyl)benzimidazoles with 2-aminoazoles under microwave irradiation has been developed.
One-step synthesis of an antimicrobial framework based on covalently cross-linked chitosan/lignosulfonate (CS@LS) nanospheres
Authors: Pandey Ravi P. , Rasool Kashif , Rasheed P. Abdul , Gomez Tricia , Pasha Mujaheed , Mansour Said A. , Lee One-Sun , Mahmoud Khaled A.
Published: November 2019

Herein, renewable and uniform nanospheres based on chitosan (CS) and lignosulfonate (LS): (CS@LS) were designed for the first time through a simple one-step covalent cross-linking protocol.
Injection molded open microfluidic well plate inserts for user-friendly coculture and microscopy
Authors: Day John H. , Nicholson Tristan M. , Su Xiaojing , van Neel Tammi L. , Clinton Ivor , Kothandapani Anbarasi , Lee Jinwoo , Greenberg Max H. , Amory John K. , Walsh Thomas J. , Muller Charles H. , Franco Omar E. , Jefcoate Colin R. , Crawford Susan E. , Jorgensen Joan S. , Theberge Ashleigh B.
Published: November 2019

An injection molded coculture platform is presented with use cases that highlight the accessibility and enabling facets of our platform.
Application of organic–graphene hybrids in high performance photodetectors
Authors: Liu Jie , Liang Qiu , Zhao Ruoyu , Lei Shengbin , Hu Wenping
Published: November 2019

High performance photodetectors play important roles in the improvement of innovative technologies in many fields, for instance, medicine, military, optical communication, environment monitoring, etc.