bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic Aspects of Anthracycline Cardiotoxicity
Authors: Russo Michele , Della Sala Angela , Tocchetti Carlo Gabriele , Porporato Paolo Ettore , Ghigo Alessandra
Published: February 2021

Opinion statement

Heart failure (HF) is increasingly recognized as the major complication of chemotherapy regimens. Despite the development of modern targeted therapies such as monoclonal antibodies, doxorubicin (DOXO), one of the most cardiotoxic anticancer agents, still remains the treatment of choice for several solid and hematological tumors. The insurgence of cardiotoxicity represents the major limitation to the clinical use of this potent anticancer drug. At the molecular level, cardiac side effects of DOXO have been associated to mitochondrial dysfunction, DNA damage, impairment of iron metabolism, apoptosis, and autophagy dysregulation. On these bases, the antioxidant and iron chelator molecule, dexrazoxane, currently represents the unique FDA-approved cardioprotectant for patients treated with anthracyclines.

A less explored area of research concerns the impact of DOXO on cardiac metabolism. Recent metabolomic studies highlight the possibility that cardiac metabolic alterations may critically contribute to the development of DOXO cardiotoxicity. Among these, the impairment of oxidative phosphorylation and the persistent activation of glycolysis, which are commonly observed in response to DOXO treatment, may undermine the ability of cardiomyocytes to meet the energy demand, eventually leading to energetic failure. Moreover, increasing evidence links DOXO cardiotoxicity to imbalanced insulin signaling and to cardiac insulin resistance. Although anti-diabetic drugs, such as empagliflozin and metformin, have shown interesting cardioprotective effects in vitro and in vivo in different models of heart failure, their mechanism of action is unclear, and their use for the treatment of DOXO cardiotoxicity is still unexplored.

This review article aims at summarizing current evidence of the metabolic derangements induced by DOXO and at providing speculations on how key players of cardiac metabolism could be pharmacologically targeted to prevent or cure DOXO cardiomyopathy.
Truss-type maintenance devices and corresponding pipeline lifting control strategies
Authors: Zhao Tian-Feng , Zhang Qing-Yuan , Chu Gui
Published: February 2021

For new submarine pipeline maintenance lifting equipment, a specialized analysis model is constructed in this study. A pipeline can be divided into the lifted portion and the touch-down portion that lies on the seabed, and each of these portions can be analyzed separately by converting the continuity conditions at the touch-down points to boundary conditions. The typical two-point sequence secant iterative technique is used to obtain the unknown lifted length and determine pipeline lifting configurations. The BVP4C module in MATLAB software is used to solve this multiple-point boundary value problem issued from first-order differential equations. Also, the triple-point lifting mode of truncated maintenance and the two-point lifting mode of online maintenance are discussed. When the lifted heights at truss positions are shown, the lifting deformation, lifting forces, bending moment distribution, and axial force distribution can be analyzed using a dedicated analysis program. Numerical results can then be used to design a lifting strategy to protect the pipeline.
Two Kinds of Imaginative Vividness
Authors: Langkau Julia
Published: February 2021

This paper argues that we should distinguish two different kinds of imaginative vividness: vividness of mental images and vividness of imaginative experiences. Philosophy has focussed on mental images, but distinguishing more complex vivid imaginative experiences from vivid mental images can help us understand our intuitions concerning the notion as well as the explanatory power of vividness. In particular, it can help us understand the epistemic role imagination can play on the one hand and our emotional engagement with literary fiction on the other hand.
Teaching I-O psychology to undergraduate students: Do we practice what we preach?
Authors: Kath Lisa M. , Salter Nicholas P. , Bachiochi Peter , Brown Kenneth G. , Hebl Mikki
Published: February 2021

As industrial-organizational (I-O) psychologists, we have expertise in applying psychological and/or organizational science to the workplace. However, many of us haven’t taken the time to think about how our I-O psychology knowledge can apply to our teaching practice. We walk through some examples of how I-O psychology research can help us be better teachers, and the goal of our paper is to encourage readers to make evidence-based changes to their teaching based on I-O psychology research. We organize our discussion around four areas: training and development, diversity and inclusion, groups and teams, and leadership. Within each, we offer small, medium, and large changes that could be incorporated into classrooms. We hope that readers will be inspired to build on what they do in their classrooms to help students learn about (and be inspired by) our field.
Association betweenSalmonellainfection and colon cancer: a nationwide registry-based cohort study
Authors: Duijster Janneke W. , Hansen Jørgen V. , Franz Eelco , Neefjes Jacques J. C. , Frisch Morten , Mughini-Gras Lapo , Ethelberg Steen
Published: February 2021

Laboratory data increasingly suggest thatSalmonellainfection may contribute to colon cancer (CC) development. Here, we examined epidemiologically the potential risk of CC associated with salmonellosis in the human population. We conducted a population-based cohort study using four health registries in Denmark. Person-level demographic data of all residents were linked to laboratory-confirmed non-typhoidal salmonellosis and to CC diagnoses in 1994–2016. Hazard ratios (HRs) for CC (overall/proximal/distal) associated with reported salmonellosis were estimated using Cox proportional hazard models. Potential effects of serovar, age, sex, inflammatory bowel disease and follow-up time post-infection were also assessed. We found no increased risk of CC ≥1 year post-infection (HR 0.99; 95% confidence interval (CI) 0.88–1.13). When stratifying by serovar, there was a significantly increased risk of proximal CC ≥1 year post-infection with serovars other than Enteritidis and Typhimurium (HR 1.40; 95% CI 1.03–1.90). CC risk was significantly increased in the first year post-infection (HR 2.08; 95% CI 1.48–2.93). The association between salmonellosis and CC in the first year post-infection can be explained by increased stool testing around the time of CC diagnosis. The association between proximal CC and non-Enteritidis/non-Typhimurium serovars is unclear and warrants further investigation. Overall, this study provides epidemiological evidence that notifiedSalmonellainfections do not contribute significantly to CC risk in the studied population.
Analysing how changes in the health status of healthcare workers affects epidemic outcomes
Authors: Phadke I. , McKee A. , Conway J.M. , Shea K.
Published: February 2021

During a disease outbreak, healthcare workers (HCWs) are essential to treat infected individuals. However, these HCWs are themselves susceptible to contracting the disease. As more HCWs get infected, fewer are available to provide care for others, and the overall quality of care available to infected individuals declines. This depletion of HCWs may contribute to the epidemic's severity. To examine this issue, we explicitly model declining quality of care in four differential equation-based susceptible, infected and recovered-type models with vaccination. We assume that vaccination, recovery and survival rates are affected by quality of care delivered. We show that explicitly modelling HCWs and accounting for declining quality of care significantly alters model-predicted disease outcomes, specifically case counts and mortality. Models neglecting the decline of quality of care resulting from infection of HCWs may significantly under-estimate cases and mortality. These models may be useful to inform health policy that may differ for HCWs and the general population. Models accounting for declining quality of care may therefore improve the management interventions considered to mitigate the effects of a future outbreak.
Zigler's conceptualization of diversity: Implications for the early childhood development workforce
Authors: García Coll Cynthia , Ferrer Kia L.
Published: February 2021

The United States is entering a pivotal period in history, led by extraordinary shifts in the demographic makeup of children who are in need of medical, educational, and developmental services. For the first time in this country's history, the majority of children are being born to non-white populations. Simultaneously, racism (personal, institutional, and systemic) is now being recognized as a powerful social determinant of children's mental and physical health by the time they enter kindergarten. It is crucial to evaluate how early childhood development (ECD) settings are prepared to authentically engage racially diverse children. In this paper, we critically analyze the narratives of the architect of Head Start, Dr. Edward Zigler, and investigate his evolving contributions to early childhood programming. We propose that Zigler's conceptualization of culture and its impact on children's development, although advanced for his time, had historical limitations that have perpetuated the personal, institutional, and systemic racism that children of color experience in early childhood settings. This paper concludes with suggestions to include topics covering implicit bias, white privilege, and the impact of slavery, colonization, and oppression as core principles in professional training. Only then will we be able to eliminate racism across early childhood settings in the United States.
Recovery priorities of people with psychosis in acute mental health in-patient settings: a Q-methodology study
Authors: Douglas Catherine , Wood Lisa , Taggart Danny
Published: February 2021

Background:

Personal recovery from psychosis has been explored extensively in community samples but there has been little exploration with people currently receiving care from an acute mental health in-patient setting.

Aims:

The aim of this study was to explore the personal recovery priorities of people experiencing psychosis who are currently receiving care from an acute mental health in-patient ward.

Method:

A Q-methodology mixed-methods approach was adopted. Thirty-eight participants were recruited from an outer London acute mental health hospital. They were required to sort 54 statements regarding personal recovery from most important to least important to reflect their recovery priorities. Thirty-six were included in the final analysis.

Results:

Analysis revealed four distinct viewpoints relating to factors that promote recovery in the acute mental health in-patient setting. These were: stability, independence and ‘keeping a roof over your head’; hope, optimism and enhancing well-being; personal change, self-management and social support; and symptom reduction through mental health support.

Conclusions:

Acute mental health in-patient wards need to ensure that they are considering the personal recovery needs of in-patients. Symptom reduction was valued by some, but broad psychosocial factors were also of priority.
Expanding health care coverage in Canada: a dramatic shift in the debate
Authors: Marchildon Gregory P. , Tuohy Carolyn H.
Published: February 2021

The coronavirus disease 2019 (COVID-19) pandemic has shifted the health policy debate in Canada. While the pre-pandemic focus of policy experts and government reports was on the question of whether to add outpatient pharmaceuticals to universal health coverage, the clustering of pandemic deaths in long-term care facilities has spurred calls for federal standards in long-term care (LTC) and its possible inclusion in universal health coverage. This has led to the probability that the federal government will attempt to expand medicare as Canadians have known it for the first time in over a half century. However, these efforts are likely to fail if the federal government relies on the shared-cost federalism that marked the earlier introduction of medicare. Two alternative pathways are suggested, one for LTC and one for pharmaceuticals, that are more likely to succeed given the state of the Canadian federation in the early 21st century.
Review of the Precise Orbit Determination for Chinese Lunar Exploration Projects
Authors: Liu Shanhong , Yan Jianguo , Cao Jianfeng , Ye Mao , Li Xie , Li Fei , Barriot Jean‐Pierre
Published: February 2021

China's lunar exploration program has developed and progressed for more than 13 years. Over this time, Precise Orbit Determination (POD) has guaranteed successful execution of the Chang’e missions, and is the basis for further scientific investigations using radio science data; for example, recovering the lunar gravity field to explore the inner structure and detect craters to study the evolutionary history of the moon. This study briefly reviews the Chang’e series mission orbit and radio tracking measurements. We reprocessed the tracking data and comprehensively summarized the evolution of the POD accuracy and the tracking system precision from the Chang’e 1 to Chang’e 4 missions using in‐house software. Our results show a progression of the tracking station, as the first Chang’e 1 mission only reached several millimeters per second level accuracy in the Doppler measurements and several meters level accuracy for the two‐way range measurements. Later on the accuracy of Chang’e 5T1 Doppler measurements reached about 0.35 mm/s and the accuracy of the Chang’e 3 two‐way range measurements below 0.7 m. Moreover, the newest Chang’e 4 relay satellite achieved POD residuals Root Mean Square for the two‐way range less than a meter and orbital accuracy at 200 m level, in contrast to meters level residual and the half‐kilometer level accuracy achieved during the Chang’e 1 mission. We can clearly see that the POD performance of the Chang’e spacecraft continuously improved. This research study is a reference for future Chinese Lunar exploration missions, as well as Chinese Mars and asteroid explorations.
Crust and Upper Mantle Structure of the South China Sea and Adjacent Areas From the Joint Inversion of Ambient Noise and Earthquake Surface Wave Dispersions
Authors: Chen Haopeng , Li Zhiwei , Luo Zhicai , Ojo Adebayo Oluwaseun , Xie Jun , Bao Feng , Wang Liaoliang , Tu Guanghong
Published: February 2021

In this study, we built a high‐resolution 3D S‐wave velocity model of the South China Sea (SCS) and adjacent areas by the joint inversion of surface wave dispersions retrieved from ambient noise and earthquake data. We first measured Rayleigh wave phase velocity dispersions from the waveforms recorded by 94 broadband seismic stations. Subsequently, we used a generalized least squares inversion scheme with spatially varying resolution to perform 2D tomographic inversion at different periods. Lastly, we performed 1D inversion at different grid points and obtained the 3D S‐wave velocity model in the depth range of 15–250 km. Our model reveals a prominent high velocity (high‐V) anomaly beneath the SCS basin and shows that the lithosphere beneath the SCS basin is about 70–80 km thick. We observe a prominent low velocity (low‐V) anomaly in the asthenosphere beneath the SCS basin, and we interpret this as evidence for the ongoing partial melting of the asthenosphere. An obvious high‐V anomaly is also revealed beneath the Khorat Plateau (KP) in the depth range of 80–150 km, suggesting that the KP has a cold and thick lithosphere and has suffered limited destruction in the Cenozoic era. In the northern part of Kalimantan Island (KI), a prominent low‐V anomaly is shown in the upper 60 km of the lithosphere revealing the upwelling of the asthenosphere. Our findings shed lights on the tectonic evolution of the SCS and adjacent areas.
Sensitive Dependence of Ultrarelativistic Electron Precipitation on EMIC Wave Frequency
Authors: Lee Dae‐Young
Published: February 2021

Electromagnetic ion cyclotron (EMIC) waves have long been considered to cause atmospheric precipitation loss of relativistic electrons, the quantitative evaluation of which is critical for understanding the radiation belt electron flux dropouts. In this study, we report test particle calculation results on precipitation loss rates of 5 MeV electrons with initial pitch angles of 4–10° at the equator by He+ band EMIC waves. We find a sensitive dependence of the precipitation loss rates on the wave frequency in that a preferred wave frequency (maximum loss frequency) exists at which the loss rate peaks predominantly and away from which it declines substantially. According to a cold plasma dispersion relation, a small difference in wave frequency just below the He+ gyrofrequency corresponds to a significant difference in wavenumber. Different frequencies lead to phase trapping of different extents, which determines the significance of loss cone scattering at the exit latitude from the wave zone. At frequencies below the maximum loss frequency, phase trapping causes large advective pitch angle changes, prohibiting loss cone scattering. At the maximum loss frequency, the phase‐trapping effect is optimized such that diffusion is dominant over advection and large enough to allow effective loss cone scattering. At frequencies above the maximum loss frequency, the phase‐trapping effect disappears, and the resulting (both diffusive and advective) scattering is too weak to drive loss cone scattering unless the initial pitch angle is close enough to the loss cone angle.
Two Years of Observations of the Io Plasma Torus by Juno Radio Occultations: Results From Perijoves 1 to 15
Authors: Phipps Phillip H. , Withers Paul , Buccino Dustin R. , Yang Yu‐Ming , Parisi Marzia
Published: February 2021

The Io plasma torus is the primary source for plasma in Jupiter’s magnetosphere. Observations of fundamental properties of the torus place valuable constraints on how the Io plasma torus behaves. Yet measurements of the density structure of the torus that precisely determine its location, total electron content, and scale height are rare. Here, we report measurements of four profiles of the total electron content through the torus by the Juno spacecraft. These profiles were acquired by radio occultation observations during Juno Perijoves 10, 11, 14, and 15. They complement previously reported profiles from Perijoves 1, 3, 6, and 8, for which an initial ad hoc correction has been verified by improved calibration at the ground station. Fits to each profile determined the location, peak total electron content, and scale height of two torus regions: the cold torus and the torus beyond 5.5 RJ. Measurements show the torus locations depend on longitude, but not time. The peak total electron content values vary with time but do not exhibit any clear dependence on longitude. The scale heights may depend on longitude and/or time. There is no apparent dependence of these properties on the Io phase angle. Future analysis of more observations by the Juno spacecraft will clarify the respective roles of longitude, time, and the Io phase angle in shaping the density structure of the Io plasma torus. Observations at previously sampled longitudes will be particularly valuable, as demonstrated here by Perijoves 8 and 15, which sampled the same longitude 1 year apart.
A High‐Resolution Paleosecular Variation Record for Marine Isotope Stage 6 From Southeastern Black Sea Sediments
Authors: Nowaczyk Norbert R. , Liu Jiabo , Plessen Birgit , Wegwerth Antje , Arz Helge W.
Published: February 2021

A full‐vector paleosecular variation (PSV) record (inclination, declination, and relative paleointensity) from the pen‐ultimate glacial (130–180 ka) could be constructed from a total of 12 sediment cores recovered from the Arkhangelsky Ridge in the SE Black Sea. Stacking of the individual partly fragmented records was achieved by a detailed correlation using high‐resolution data records from X‐ray fluorescence scanning, Ca/Ti and K/Ti log‐ratios, as well as magnetic susceptibility. Age constraints are provided by a detailed composite oxygen isotope stratigraphy from three of the cores, correlated to U‐Th‐dated speleothem oxygen isotope records from Hungary and Turkey. The temporal resolution of the stacked paleomagnetic data records is 200 years. Practically, this data set is the first high‐resolution PSV record for SE Europe/SW Asia from marine isotope stage 6, comprising inclination, declination and relative paleointensity. Besides an easterly swing in declination at ∼159 ka and a pronounced intensity low together with low inclinations at ∼148 ka, both not reaching an excursional PSV index of >0.5, the obtained directional variations reflect only normal PSVs, with a PSV index of <0.3.
Continuous Dynamics of Dissolved Methane Over 2 Years and its Carbon Isotopes (δ13C, Δ14C) in a Small Arctic Lake in the Mackenzie Delta
Authors: McIntosh Marcek Hadley A. , Lesack Lance F. W. , Orcutt Beth N. , Wheat C. Geoff , Dallimore Scott R. , Geeves Kimberley , Lapham Laura L.
Published: February 2021

Seasonally ice‐covered permafrost lakes in the Arctic emit methane to the atmosphere during periods of open‐water. However, processes contributing to methane cycling under‐ice have not been thoroughly addressed despite the potential for significant methane emission to the atmosphere at ice‐out. We studied annual dissolved methane dynamics within a small (0.2 ha) Mackenzie River Delta lake using sensor and water sampling packages that autonomously and continuously collected lake water samples, respectively, for two years at multiple water column depths. Lake physical and biogeochemical properties (temperature; light; concentrations of dissolved oxygen, manganese, iron, and dissolved methane, including stable carbon, and radiocarbon isotopes) revealed annual patterns. Dissolved methane concentrations increase under‐ice after electron acceptors (oxygen, manganese, and iron oxides) are depleted or inaccessible from the water column. The radiocarbon age of dissolved methane suggests a source from recently decomposed carbon as opposed to thawed ancient permafrost. Sources of dissolved methane under‐ice include a diffusive flux from the sediments and may include water column methanogenesis and/or under‐ice hydrodynamic controls. Following ice‐out, the water column only partially mixes allowing half of the winter‐derived dissolved methane to be microbially oxidized. Despite oxidation at depth, surface water was a source of methane to the atmosphere. The greatest diffusive fluxes to the atmosphere occurred following ice‐out (75 mmol CH4 m−2 d−1) and during a mixing episode in mid‐July, likely driven by a storm event. This study demonstrates the importance of fine‐scale temporal sampling to understand dissolved methane processes in seasonally ice‐covered lakes.
Effective Chemical Delivery Through Multi‐Screen Wells to Enhance Mixing and Reaction of Solute Plumes in Porous Media
Authors: Ye Yu , Zhang Yu , Lu Chunhui , Xie Yifan , Luo Jian
Published: February 2021

In‐situ groundwater remediation is usually limited by the incomplete mixing of reactive species due to creeping flow characteristics and limited dispersion in porous media. In this study, we propose a novel approach to deliver chemicals through a multi‐screen well (MSW) to enhance the in‐situ remediation efficiency without extra energy or labor costs. The basic idea is to separate the injected solution into several plumes to enlarge the contact area between injected chemical compounds and ambient contaminants and enhance the mass exchange flux and reactive mixing. We perform laboratory experiments and numerical simulations of steady‐state instantaneous reactive transport in two‐dimensional porous media. We consider three separate screens in an MSW for the injection of treatment solutions and compare its plume distributions with a classical single‐screen well system. The experimental results confirm our conjecture and demonstrate the reliability of the numerical model. Furthermore, we derive an optimal injection interval of the MSW system by comparing analytical and numerical methods and demonstrate its capability to achieve effective transverse mixing and reaction enhancement. An interval that is smaller than the optimal injection interval leads to the exhaustion of contaminants between the injected plumes and the coalescence of the separate injected plumes at the downgradient portion along the travel distance, which reduces the effectiveness of the MSW system. We also investigate the sensitivity of the injected concentration, individual screen length, transverse dispersivity, and seepage rate on the determination of the optimal injection interval and provide suggestions about the design of an MSW system.
Morphodynamics of Boulder‐Bed Semi‐Alluvial Streams in Northern Fennoscandia: A Flume Experiment to Determine Sediment Self‐Organization
Authors: Polvi L. E.
Published: February 2021

In northern Fennoscandia, semi‐alluvial boulder‐bed channels with coarse glacial legacy sediment are abundant, and due to widespread anthropogenic manipulation during timber‐floating, unimpacted reference reaches are rare. The landscape context of these semi‐alluvial rapids—with numerous mainstem lakes that buffer high flows and sediment connectivity in addition to a regional low sediment yield—contribute to low amounts of fine sediment and incompetent flows to transport boulders. To determine the morphodynamics of semi‐alluvial rapids and potential self‐organization of sediment with multiple high flows, a flume experiment was designed and carried out to mimic conditions in semi‐alluvial rapids in northern Fennoscandia. Two slope setups (2% and 5%) were used to model a range of flows (Q1 (summer high flow), Q2, Q10, and Q50) in a 8 × 1.1 m flume with a sediment distribution analogous to field conditions; bed topography was measured using structure‐from‐motion photogrammetry after each flow to obtain DEMs. No classic steep coarse‐bed channel bedforms (e.g., step‐pools) developed. However, similarly to boulder‐bed channels with low relative submergence, at Q10 and Q50 flows, sediment deposited upstream of boulders and scoured downstream. Because the Q50 flow was not able to rework the channel by disrupting grain‐interlocking from preceding lower flows, transporting boulders, or forming channel‐spanning boulders, the channel‐forming discharge is larger than the Q50. These results have implications for restoration of gravel spawning beds in northern Fennoscandia and highlight the importance of large grains in understanding channel morphodynamics.
Viral vector platforms within the gene therapy landscape
Authors: Bulcha Jote T. , Wang Yi , Ma Hong , Tai Phillip W. L. , Gao Guangping
Published: February 2021

Throughout its 40-year history, the field of gene therapy has been marked by many transitions. It has seen great strides in combating human disease, has given hope to patients and families with limited treatment options, but has also been subject to many setbacks. Treatment of patients with this class of investigational drugs has resulted in severe adverse effects and, even in rare cases, death. At the heart of this dichotomous field are the viral-based vectors, the delivery vehicles that have allowed researchers and clinicians to develop powerful drug platforms, and have radically changed the face of medicine. Within the past 5 years, the gene therapy field has seen a wave of drugs based on viral vectors that have gained regulatory approval that come in a variety of designs and purposes. These modalities range from vector-based cancer therapies, to treating monogenic diseases with life-altering outcomes. At present, the three key vector strategies are based on adenoviruses, adeno-associated viruses, and lentiviruses. They have led the way in preclinical and clinical successes in the past two decades. However, despite these successes, many challenges still limit these approaches from attaining their full potential. To review the viral vector-based gene therapy landscape, we focus on these three highly regarded vector platforms and describe mechanisms of action and their roles in treating human disease.
Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation
Authors: Zhang Jin-dong , Liu Jiao , Zhu Shi-wei , Fang Yuan , Wang Ben , Jia Qiong , Hao Hui-feng , Kao John Y. , He Qi-hua , Song Li-jin , Liu Fei , Zhu Bao-li , Owyang Chung , Duan Li-ping
Published: February 2021

Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS). However, the potential mechanisms remain unclear. In this study we investigated the effects of berberine on the microbiota-gut-brain axis in two rat models of visceral hypersensitivity, i.e., specific pathogen-free SD rats subjected to chronic water avoidance stress (WAS) and treated with berberine (200 mg· kg−1 ·d−1, ig, for 10 days) as well as germ-free (GF) rats subjected to fecal microbiota transplantation (FMT) from a patient with IBS (designated IBS-FMT) and treated with berberine (200 mg· kg−1 ·d−1, ig, for 2 weeks). Before the rats were sacrificed, visceral sensation and depressive behaviors were evaluated. Then colonic tryptase was measured and microglial activation in the dorsal lumbar spinal cord was assessed. The fecal microbiota was profiled using 16S rRNA sequencing, and short chain fatty acids (SCFAs) were measured. We showed that berberine treatment significantly alleviated chronic WAS-induced visceral hypersensitivity and activation of colonic mast cells and microglia in the dorsal lumbar spinal cord. Transfer of fecal samples from berberine-treated stressed donors to GF rats protected against acute WAS. FMT from a patient with IBS induced visceral hypersensitivity and pro-inflammatory phenotype in microglia, while berberine treatment reversed the microglial activation and altered microbial composition and function and SCFA profiles in stools of IBS-FMT rats. We demonstrated that berberine did not directly influence LPS-induced microglial activation in vitro. In both models, several SCFA-producing genera were enriched by berberine treatment, and positively correlated to the morphological parameters of microglia. In conclusion, activation of microglia in the dorsal lumbar spinal cord was involved in the pathogenesis of IBS caused by dysregulation of the microbiota–gut–brain axis, and the berberine-altered gut microbiome mediated the modulatory effects of the agent on microglial activation and visceral hypersensitivity, providing a potential option for the treatment of IBS.
Tetraarsenic hexoxide enhances generation of mitochondrial ROS to promote pyroptosis by inducing the activation of caspase-3/GSDME in triple-negative breast cancer cells
Authors: An Haein , Heo Jin Sun , Kim Pyunggang , Lian Zenglin , Lee Siyoung , Park Jinah , Hong Eunji , Pang Kyoungwha , Park Yuna , Ooshima Akira , Lee Jihee , Son Minjung , Park Hyeyeon , Wu Zhaoyan , Park Kyung-Soon , Kim Seong-Jin , Bae Illju , Yang Kyung-Min
Published: February 2021

Although tetraarsenic hexoxide is known to exert an anti-tumor effect by inducing apoptosis in various cancer cells, its effect on other forms of regulated cell death remains unclear. Here, we show that tetraarsenic hexoxide induces the pyroptotic cell death through activation of mitochondrial reactive oxygen species (ROS)-mediated caspase-3/gasdermin E (GSDME) pathway, thereby suppressing tumor growth and metastasis of triple-negative breast cancer (TNBC) cells. Interestingly, tetraarsenic hexoxide-treated TNBC cells exhibited specific pyroptotic characteristics, including cell swelling, balloon-like bubbling, and LDH releases through pore formation in the plasma membrane, eventually suppressing tumor formation and lung metastasis of TNBC cells. Mechanistically, tetraarsenic hexoxide markedly enhanced the production of mitochondrial ROS by inhibiting phosphorylation of mitochondrial STAT3, subsequently inducing caspase-3-dependent cleavage of GSDME, which consequently promoted pyroptotic cell death in TNBC cells. Collectively, our findings highlight tetraarsenic hexoxide-induced pyroptosis as a new therapeutic strategy that may inhibit cancer progression of TNBC cells.
Darwinian properties and their trade-offs in autocatalytic RNA reaction networks
Authors: Ameta Sandeep , Arsène Simon , Foulon Sophie , Saudemont Baptiste , Clifton Bryce E. , Griffiths Andrew D. , Nghe Philippe
Published: February 2021

Discovering autocatalytic chemistries that can evolve is a major goal in systems chemistry and a critical step towards understanding the origin of life. Autocatalytic networks have been discovered in various chemistries, but we lack a general understanding of how network topology controls the Darwinian properties of variation, differential reproduction, and heredity, which are mediated by the chemical composition. Using barcoded sequencing and droplet microfluidics, we establish a landscape of thousands of networks of RNAs that catalyze their own formation from fragments, and derive relationships between network topology and chemical composition. We find that strong variations arise from catalytic innovations perturbing weakly connected networks, and that growth increases with global connectivity. These rules imply trade-offs between reproduction and variation, and between compositional persistence and variation along trajectories of network complexification. Overall, connectivity in reaction networks provides a lever to balance variation (to explore chemical states) with reproduction and heredity (persistence being necessary for selection to act), as required for chemical evolution.
Alloying–realloying enabled high durability for Pt–Pd-3d-transition metal nanoparticle fuel cell catalysts
Authors: Wu Zhi-Peng , Caracciolo Dominic T. , Maswadeh Yazan , Wen Jianguo , Kong Zhijie , Shan Shiyao , Vargas Jorge A. , Yan Shan , Hopkins Emma , Park Keonwoo , Sharma Anju , Ren Yang , Petkov Valeri , Wang Lichang , Zhong Chuan-Jian
Published: February 2021

Alloying noble metals with non-noble metals enables high activity while reducing the cost of electrocatalysts in fuel cells. However, under fuel cell operating conditions, state-of-the-art oxygen reduction reaction alloy catalysts either feature high atomic percentages of noble metals (>70%) with limited durability or show poor durability when lower percentages of noble metals (<50%) are used. Here, we demonstrate a highly-durable alloy catalyst derived by alloying PtPd (<50%) with 3d-transition metals (Cu, Ni or Co) in ternary compositions. The origin of the high durability is probed by in-situ/operando high-energy synchrotron X-ray diffraction coupled with pair distribution function analysis of atomic phase structures and strains, revealing an important role of realloying in the compressively-strained single-phase alloy state despite the occurrence of dealloying. The implication of the finding, a striking departure from previous perceptions of phase-segregated noble metal skin or complete dealloying of non-noble metals, is the fulfilling of the promise of alloy catalysts for mass commercialization of fuel cells.
Cross-linking mass spectrometry uncovers protein interactions and functional assemblies in synaptic vesicle membranes
Authors: Wittig Sabine , Ganzella Marcelo , Barth Marie , Kostmann Susann , Riedel Dietmar , Pérez-Lara Ángel , Jahn Reinhard , Schmidt Carla
Published: February 2021

Synaptic vesicles are storage organelles for neurotransmitters. They pass through a trafficking cycle and fuse with the pre-synaptic membrane when an action potential arrives at the nerve terminal. While molecular components and biophysical parameters of synaptic vesicles have been determined, our knowledge on the protein interactions in their membranes is limited. Here, we apply cross-linking mass spectrometry to study interactions of synaptic vesicle proteins in an unbiased approach without the need for specific antibodies or detergent-solubilisation. Our large-scale analysis delivers a protein network of vesicle sub-populations and functional assemblies including an active and an inactive conformation of the vesicular ATPase complex as well as non-conventional arrangements of the luminal loops of SV2A, Synaptophysin and structurally related proteins. Based on this network, we specifically target Synaptobrevin-2, which connects with many proteins, in different approaches. Our results allow distinction of interactions caused by ‘crowding’ in the vesicle membrane from stable interaction modules.
Carbon dioxide utilization in concrete curing or mixing might not produce a net climate benefit
Authors: Ravikumar Dwarakanath , Zhang Duo , Keoleian Gregory , Miller Shelie , Sick Volker , Li Victor
Published: February 2021

Carbon capture and utilization for concrete production (CCU concrete) is estimated to sequester 0.1 to 1.4 gigatons of carbon dioxide (CO2) by 2050. However, existing estimates do not account for the CO2 impact from the capture, transport and utilization of CO2, change in compressive strength in CCU concrete and uncertainty and variability in CCU concrete production processes. By accounting for these factors, we determine the net CO2 benefit when CCU concrete produced from CO2 curing and mixing substitutes for conventional concrete. The results demonstrate a higher likelihood of the net CO2 benefit of CCU concrete being negative i.e. there is a net increase in CO2 in 56 to 68 of 99 published experimental datasets depending on the CO2 source. Ensuring an increase in compressive strength from CO2 curing and mixing and decreasing the electricity used in CO2 curing are promising strategies to increase the net CO2 benefit from CCU concrete.
The singularity response reveals entrainment properties of the plant circadian clock
Authors: Masuda Kosaku , Tokuda Isao T. , Nakamichi Norihito , Fukuda Hirokazu
Published: February 2021

Circadian clocks allow organisms to synchronize their physiological processes to diurnal variations. A phase response curve allows researchers to understand clock entrainment by revealing how signals adjust clock genes differently according to the phase in which they are applied. Comprehensively investigating these curves is difficult, however, because of the cost of measuring them experimentally. Here we demonstrate that fundamental properties of the curve are recoverable from the singularity response, which is easily measured by applying a single stimulus to a cellular network in a desynchronized state (i.e. singularity). We show that the singularity response of Arabidopsis to light/dark and temperature stimuli depends on the properties of the phase response curve for these stimuli. The measured singularity responses not only allow the curves to be precisely reconstructed but also reveal organ-specific properties of the plant circadian clock. The method is not only simple and accurate, but also general and applicable to other coupled oscillator systems as long as the oscillators can be desynchronized. This simplified method may allow the entrainment properties of the circadian clock of both plants and other species in nature.
Monitoring the microbiome for food safety and quality using deep shotgun sequencing
Authors: Beck Kristen L. , Haiminen Niina , Chambliss David , Edlund Stefan , Kunitomi Mark , Huang B. Carol , Kong Nguyet , Ganesan Balasubramanian , Baker Robert , Markwell Peter , Kawas Ban , Davis Matthew , Prill Robert J. , Krishnareddy Harsha , Seabolt Ed , Marlowe Carl H. , Pierre Sophie , Quintanar André , Parida Laxmi , Dubois Geraud , Kaufman James , Weimer Bart C.
Published: February 2021

In this work, we hypothesized that shifts in the food microbiome can be used as an indicator of unexpected contaminants or environmental changes. To test this hypothesis, we sequenced the total RNA of 31 high protein powder (HPP) samples of poultry meal pet food ingredients. We developed a microbiome analysis pipeline employing a key eukaryotic matrix filtering step that improved microbe detection specificity to >99.96% during in silico validation. The pipeline identified 119 microbial genera per HPP sample on average with 65 genera present in all samples. The most abundant of these were Bacteroides, Clostridium, Lactococcus, Aeromonas, and Citrobacter. We also observed shifts in the microbial community corresponding to ingredient composition differences. When comparing culture-based results for Salmonella with total RNA sequencing, we found that Salmonella growth did not correlate with multiple sequence analyses. We conclude that microbiome sequencing is useful to characterize complex food microbial communities, while additional work is required for predicting specific species’ viability from total RNA sequencing.
Structural aspects of lesional and non-lesional skin microbiota reveal key community changes in leprosy patients from India
Authors: Bayal Nitin , Nagpal Sunil , Haque Mohammed Monzoorul , Patole Milind S. , Shouche Yogesh , Mande Shekhar C. , Mande Sharmila S.
Published: February 2021

Although skin is the primary affected organ in Leprosy, the role of the skin microbiome in its pathogenesis is not well understood. Recent reports have shown that skin of leprosy patients (LP) harbours perturbed microbiota which grants inflammation and disease progression. Herein, we present the results of nested Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE) which was initially performed for investigating the diversity of bacterial communities from lesional skin (LS) and non-lesional skin (NLS) sites of LP (n = 11). Further, we performed comprehensive analysis of 16S rRNA profiles corresponding to skin samples from participants (n = 90) located in two geographical locations i.e. Hyderabad and Miraj in India. The genusStaphylococcuswas observed to be one of the representative bacteria characterizing healthy controls (HC; n = 30), which in contrast was underrepresented in skin microbiota of LP. Taxa affiliated to phyla Firmicutes and Proteobacteria were found to be signatures of HC and LS, respectively. Observed diversity level changes, shifts in core microbiota, and community network structure support the evident dysbiosis in normal skin microbiota due to leprosy. Insights obtained indicate the need for exploring skin microbiota modulation as a potential therapeutic option for leprosy.
Electro-Quasistatic Animal Body Communication for Untethered Rodent Biopotential Recording
Authors: Sriram Shreeya , Avlani Shitij , Ward Matthew P. , Sen Shreyas
Published: February 2021

Continuous multi-channel monitoring of biopotential signals is vital in understanding the body as a whole, facilitating accurate models and predictions in neural research. The current state of the art in wireless technologies for untethered biopotential recordings rely on radiative electromagnetic (EM) fields. In such transmissions, only a small fraction of this energy is received since the EM fields are widely radiated resulting in lossy inefficient systems. Using the body as a communication medium (similar to a ’wire’) allows for the containment of the energy within the body, yielding order(s) of magnitude lower energy than radiative EM communication. In this work, we introduce Animal Body Communication (ABC), which utilizes the concept of using the body as a medium into the domain of untethered animal biopotential recording. This work, for the first time, develops the theory and models for animal body communication circuitry and channel loss. Using this theoretical model, a sub-inch$$^3$$

3

[1″ × 1″ × 0.4″], custom-designed sensor node is built using off the shelf components which is capable of sensing and transmitting biopotential signals, through the body of the rat at significantly lower powers compared to traditional wireless transmissions. In-vivo experimental analysis proves that ABC successfully transmits acquired electrocardiogram (EKG) signals through the body with correlation $$>99\%$$

>
99
%

when compared to traditional wireless communication modalities, with a 50$$\times$$
×
reduction in power consumption.
Improving prediction and assessment of global fires using multilayer neural networks
Authors: Joshi Jaideep , Sukumar Raman
Published: February 2021

Fires determine vegetation patterns, impact human societies, and are a part of complex feedbacks into the global climate system. Empirical and process-based models differ in their scale and mechanistic assumptions, giving divergent predictions of fire drivers and extent. Although humans have historically used and managed fires, the current role of anthropogenic drivers of fires remains less quantified. Whereas patterns in fire–climate interactions are consistent across the globe, fire–human–vegetation relationships vary strongly by region. Taking a data-driven approach, we use an artificial neural network to learn region-specific relationships between fire and its socio-environmental drivers across the globe. As a result, our models achieve higher predictability as compared to many state-of-the-art fire models, with global spatial correlation of 0.92, monthly temporal correlation of 0.76, interannual correlation of 0.69, and grid-cell level correlation of 0.60, between predicted and observed burned area. Given the current socio-anthropogenic conditions, Equatorial Asia, southern Africa, and Australia show a strong sensitivity of burned area to temperature whereas northern Africa shows a strong negative sensitivity. Overall, forests and shrublands show a stronger sensitivity of burned area to temperature compared to savannas, potentially weakening their status as carbon sinks under future climate-change scenarios.
The prevalence and related factors of metabolic syndrome in outpatients with first-episode drug-naive major depression comorbid with anxiety
Authors: Zhong Yinghua , Hu Manji , Wang Qiang , Yang Zhendong , Zhu Na , Wang Fei , Zhang Xiyan , Zhang Chengfang , Min Jie , Wang Hao , Chen Fazhan , Zhao Xudong , Zhang Xiangyang
Published: February 2021

Metabolic syndrome (MetS) is associated with depression, but its role in major depressive disorder comorbid with anxiety (AMD) is unclear. This study aimed to investigate the prevalence and clinical correlates of MetS in first-episode drug-naive (FEDN) patients with AMD in a Chinese Han population. In total, 1380 FEDN outpatients with AMD were recruited in this cross-sectional study. The sociodemographic features, clinical characteristics, history of suicide attempts, thyroid-stimulating hormone (TSH) levels, and MetS parameters of each subject were evaluated. All subjects were rated on the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and the Positive and Negative Syndrome Scale positive symptom subscale. The prevalence of MetS among AMD patients was 8.04%. Compared to the non-MetS group, age, age of onset, TSH level, HAM-A and HAM-D scores, history of attempted suicide, and comorbid psychiatric symptoms were higher in the MetS group. Those in this group were also more likely to be married, and they had a lower educational level. Furthermore, age, psychiatric symptoms, suicide attempts, and higher TSH levels were independently associated with MetS in AMD patients. This study suggests a lower prevalence of MetS in FEDN patients with AMD in a Chinese Han population. Older age, comorbid psychiatric symptoms, history of attempted suicide, and higher TSH levels are related factors for MetS in AMD patients.