bluuebunny/crossref_metadata_2025 huggingface dataset:
Water Group Exospheres and Surface Interactions on the Moon, Mercury, and Ceres
Authors: Schörghofer Norbert , Benna Mehdi , Berezhnoy Alexey A. , Greenhagen Benjamin , Jones Brant M. , Li Shuai , Orlando Thomas M. , Prem Parvathy , Tucker Orenthal J. , Wöhler Christian
Published: September 2021

Water ice, abundant in the outer solar system, is volatile in the inner solar system. On the largest airless bodies of the inner solar system (Mercury, the Moon, Ceres), water can be an exospheric species but also occurs in its condensed form. Mercury hosts water ice deposits in permanently shadowed regions near its poles that act as cold traps. Water ice is also present on the Moon, where these polar deposits are of great interest in the context of future lunar exploration. The lunar surface releases either OH or H2O during meteoroid showers, and both of these species are generated by reaction of implanted solar wind protons with metal oxides in the regolith. A consequence of the ongoing interaction between the solar wind and the surface is a surficial hydroxyl population that has been observed on the Moon. Dwarf planet Ceres has enough gravity to have a gravitationally-bound water exosphere, and also has permanently shadowed regions near its poles, with bright ice deposits found in the most long-lived of its cold traps. Tantalizing evidence for cold trapped water ice and exospheres of molecular water has emerged, but even basic questions remain open. The relative and absolute magnitudes of sources of water on Mercury and the Moon remain largely unknown. Exospheres can transport water to cold traps, but the efficiency of this process remains uncertain. Here, the status of observations, theory, and laboratory measurements is reviewed.
Spatiotemporal blocking of the bouncy particle sampler for efficient inference in state-space models
Authors: Goldman Jacob Vorstrup , Singh Sumeetpal S.
Published: September 2021

We propose a novel blocked version of the continuous-time bouncy particle sampler of Bouchard-Côté et al. (J Am Stat Assoc 113(522):855–867, 2018) which is applicable to any differentiable probability density. This alternative implementation is motivated by blocked Gibbs sampling for state-space models (Singh et al. in Biometrika 104(4):953–969, 2017) and leads to significant improvement in terms of effective sample size per second, and furthermore, allows for significant parallelization of the resulting algorithm. The new algorithms are particularly efficient for latent state inference in high-dimensional state-space models, where blocking in both space and time is necessary to avoid degeneracy of MCMC. The efficiency of our blocked bouncy particle sampler, in comparison with both the standard implementation of the bouncy particle sampler and the particle Gibbs algorithm of Andrieu et al. (J R Stat Soc Ser B Stat Methodol 72(3):269–342, 2010), is illustrated numerically for both simulated data and a challenging real-world financial dataset.
Serological and viral genetic features of patients with COVID-19 in a selected German patient cohort—correlation with disease characteristics
Authors: Schmidt Jonas , Berghaus Sandro , Blessing Frithjof , Wenzel Folker , Herbeck Holger , Blessing Josef , Schierack Peter , Rödiger Stefan , Roggenbuck Dirk
Published: September 2021

To study host-virus interactions after SARS coronavirus-2 (SARS-CoV-2) infection, genetic virus characteristics and the ensued humoral immune response were investigated for the first time. Fifty-five SARS-CoV-2-infected patients from the early pandemic phase were followed up including serological testing and whole genome sequencing. Anti-spike and nucleocapsid protein (S/N) IgG and IgM levels were determined by screening ELISA and IgG was further characterized by reactivity to S-subunit 1 (anti-S1), S-subunit 2 (anti-S2) and anti-N. In 55 patients, 90 genetic SARS-CoV-2 changes including 48 non-synonymous single nucleotide variants were identified. Phylogenetic analysis of the sequencing data showed a cluster representing a local outbreak and various family clusters. Anti-S/N and anti-N IgG were detected in 49 patients at an average of 83 days after blood collection. Anti-S/N IgM occurred significantly less frequently than IgG whereas anti-S2 was the least prevalent IgG reactivity (P < 0.05, respectively). Age and overweight were significantly associated with higher anti-S/N and anti-S1 IgG levels while age only with anti-N IgG (multiple regression, P < 0.05, respectively). Anti-S/N IgG/IgM levels, blood group A + , cardiovascular and tumour disease, NSP12 Q444H and ORF3a S177I were independent predictors of clinical characteristics with anti-S/N IgM being associated with the need for hospitalization (multivariate regression, P < 0.05, respectively). Anti-SARS-CoV-2 antibody generation was mainly affected by higher age and overweight in the present cohort. COVID-19 traits were associated with genetic SARS-CoV-2 variants, anti-S/N IgG/IgM levels, blood group A + and concomitant disease. Anti-S/N IgM was the only antibody associated with the need for hospitalization.
Prediction of risk factors and outcomes of neonatal acute kidney injury
Authors: AlGadeeb Kumail , Qaraqei Mostafa , Algadeeb Rahma , Faqeehi Hassan , Al-Matary Abdulrahman
Published: September 2021

Introduction

Neonatal Acute kidney injury (AKI) is an underestimated morbidity in the neonatal intensive care unit (ICU). However, there is a paucity of information about risk factors, outcomes, and possible preventive measures to limit its occurrence.

Aim

This study aimed to determine the prevalence of neonatal AKI in a neonatal ICU. Data obtained from this study will help to better understand current local practices and investigate possible preventive strategies.

Materials and methods

Charts from January 2011 to December 2018 were reviewed. Neonates less than 2 weeks old who depended on intravenous fluid as a nutrition source for at least two days were included.

Results

Overall, the eight-year prevalence of neonatal AKI in the neonatal ICU was 19.6%, and severity was distributed as follows: stage 1 (46.2%), stage 2 (26.5%), and stage 3 (27.3%). Caffeine administration before 29 weeks’ gestational age significantly decreased the incidence of neonatal AKI. The incidence of neonatal AKI was independently associated with death (odds ratios (OR) = 7.11, P < 0.001) and extended length of hospital stay (OR = 2.47, P < 0.001). In the multivariate regression model, vancomycin (AOR = 1.637, P < 0.004), loop diuretics (AOR = 2.203, P < 0.001), intraventricular hemorrhage (AOR = 2.605, P < 0.001), surgical intervention (AOR = 1.566, P < 0.008), mechanical ventilation (AOR = 1.463, P < 0.015), and dopamine administration (AOR = 2.399, P < 0.001) were independently associated with neonatal AKI.

Conclusion

Neonatal AKI occurred in one-fifth of the study population in a neonatal ICU. Outcomes can be improved by identifying high-risk infants and cautiously monitoring kidney function.
The 3-D Skills Model: a Randomised Controlled Pilot Study Comparing a Novel 1–1 Near-Peer Teaching Model to a Formative OSCE with Self-regulated Practice
Authors: Robertson C. , Al-Moasseb Z. , Noonan Z. , Boyle J. G.
Published: September 2021

Introduction

Near-peer teaching is a popular pedagogical teaching tool, with well-recognised benefits for students and tutors. There are multiple existing models to structure these interventions, but it is often unclear how they translate to academic attainment. We designed a novel near-peer teaching model that expands on previous research.

Methods

Our model was piloted in a formative Objective Structured Clinical Examination (OSCE) setting, trialled on 22 pre-clinical medical students to establish feasibility, acceptability and descriptive outcomes that could inform the design of a larger study. Students were randomly assigned to intervention or control cohorts. Each cohort undertook 5 min formative OSCE assessments with either 3 additional minutes of structured teaching or 3 min of self-regulated practice before reattempting the first OSCE station. Checklist marking sheets for 1st and 2nd sittings were collected by independent external markers, in addition to a global assessment rating in which we used the Borderline Regression Method to establish the station pass mark.

Results

A quantitative and qualitative result analysis was performed, demonstrating that students gained on average 3 additional marks after teaching with this model. Students and student-tutors reported increased confidence, high course satisfaction and evidence of reflective practice.

Discussion

We established acceptability and feasibility outcomes. The descriptive outcomes will support the design of a larger, adequately powered study required to demonstrate translation to summative exam performance.
Viral social media videos can raise pro-social behaviours when an epidemic arises
Authors: Guo Yiting , Shachat Jason , Walker Matthew J. , Wei Lijia
Published: September 2021

Access to information via social media is one of the biggest differentiators of public health crises today. During the early stages of the Covid-19 outbreak in January 2020, we conducted an experiment in Wuhan, China to assess the impact of viral social media content on pro-social and trust behaviours and preferences towards risk taking with known and unknown probabilities. Prior to the experiment, participants viewed one of two videos that had been widely and anonymously shared on Chinese social media: a central government leader visiting a local hospital and supermarket, or health care volunteers transiting to Wuhan. In a control condition, participants watched a Neutral video, unrelated to the crisis. Viewing one of the leadership or volunteer videos leads to higher levels of pro-sociality and lesser willingness to take risks in an ambiguous situation relative to the control condition. The leadership video, however, induces lower levels of trust. We provide evidence from two post-experiment surveys that the video’s impact on pro-sociality is modulated by influencing the viewer’s affective emotional state.
Gestationsdiabetes und polyzystisches Ovarialsyndrom
Authors: Kollmann Martina
Published: September 2021

Das polyzystische Ovarialsyndrom (PCOS) ist die häufigste endokrine Störung bei Frauen im reproduktiven Alter. Schwangerschaftskomplikationen kommen bei Frauen mit PCOS signifikant häufiger vor. Die häufigste Komplikation während der Schwangerschaft ist der Gestationsdiabetes mellitus (GDM). Neben dem PCOS spielen genetische Prädispositionen, Übergewicht, das mütterliche Alter und der Lebensstil der Frauen eine Rolle bei der Entstehung eines GDM. Eine frühe Diagnosestellung und eine damit verbundene Therapie sind essenziell, um mütterliche und kindliche Komplikationen zu reduzieren. Lifestyle-Interventionen spielen die wichtigste Rolle. Bei ca. 30 % der Frauen ist zusätzlich eine medikamentöse Therapie notwendig. Epidemiologische Studien haben gezeigt, dass die postpartale Betreuung und das Beibehalten der Lifestyle Änderungen essenziell ist. Regelmäßige physische Aktivität, eine gesunde Ernährung, das Vermeiden von Übergewicht wie auch eine verlängerte Stilldauer wirken sich positiv aus und minimieren das Risiko später an einem Typ-2-Diabtes zu erkranken.
Overcome Death Anxiety: The Development of an Online Cognitive Behaviour Therapy Programme for Fears of Death
Authors: Menzies Rachel E. , Sharpe Louise , Helgadóttir Fjóla Dögg , Dar-Nimrod Ilan
Published: September 2021

Emerging research suggests that death anxiety is a transdiagnostic construct, which may underpin a number of mental illnesses. Although cognitive behaviour therapy (CBT) has been found to be the most effective treatment for death anxiety, no self-guided treatments for this construct exist at present. Furthermore, there is a growing need for accessible, scalable and cost-effective psychological treatments. To address these gaps, we createdOvercome Death Anxiety(ODA), an online CBT-based programme which specifically targets fears of death. ODA was designed to be a fully automated, standalone, yet individualised online treatment. The present study outlines the development and structure of this programme using responses from four users to illustrate feasibility. Research is needed to examine the efficacy and usability of ODA with a larger clinical sample.
The curious case of miR-155 in SLE
Authors: Ibrahim S. A. , Afify A. Y. , Fawzy I. O. , El-Ekiaby N. , Abdelaziz A. I.
Published: September 2021

Epigenetic modifications have been well documented in autoimmune diseases. MicroRNAs (miRNAs), in particular, have long intrigued scientists in the field of autoimmunity. Owing to its central role in the development of the immune system, microRNA-155 (miR-155) is deeply involved in systemic lupus erythematosus (SLE). Despite the advancements made in treating SLE, the disease still remains incurable. Therefore, recent attention has been drawn to the manipulation of epigenetics in the development of curative treatments. In fact, it is a widely held view that miRNA-targeted therapy is a new glimmer of hope in the treatment of autoimmune diseases. However, the duplicity of miRNAs should not be overlooked. A single miRNA can target several mRNAs, and some mRNAs may possess opposing functions. In this review, we highlight the role of miR-155 as a biomarker and review its functions in SLE patients and animal models while discussing possible reasons behind inconsistencies across studies.
Impact of polydispersity and confinement on diffusion in hydrodynamically interacting colloidal suspensions
Authors: Gonzalez Emma , Aponte-Rivera Christian , Zia Roseanna N.
Published: September 2021

We present a computational study of the equilibrium dynamics of a polydisperse hard-sphere colloidal dispersion confined in a spherical cavity. We account for many-body hydrodynamic and lubrication interactions between particles and with the confining cavity utilizing our confined Stokesian dynamics model, expanded here for size polydispersity. We find that, even though the tendency of polydispersity to homogenize structure in a suspension is still present in confinement, strong correlations induced by the cavity resist homogenization. Although seemingly opposite, these two effects have a common driver, which is to maximize configurational entropy of particles in the cavity interior. These structural effects couple with the hydrodynamics to change the particle dynamics: polydispersity weakens lubrication effects near the cavity wall, allowing small (large) particles to diffuse faster (slower) than in a monodisperse suspension. As a small (large) particle gets farther from the wall, polydispersity weakens many-body hydrodynamic couplings, driving diffusivity up (down). While the local cage dynamics dominates short-time self-diffusion, long-time dynamics is also affected. In the concentrated regime, polydispersity and confinement combine to induce radial de-mixing into size-segregated populations. The cavity becomes the most influential ‘nearest neighbour’, setting the length scale of and dynamics within these radial domains. This intermediate length-scale caging makes the angular dynamics insensitive to polydispersity but leads to radial long-time mean-square displacement that changes qualitatively with volume composition. These results hold promise for explaining colloidal-scale physics implicated in the functioning of biological cells, and the engineering of non-living confined colloids where size de-mixing could be useful in the design of encapsulated micro-reactors and therapeutic vesicles.
Access denied: understanding the relationship between women and sacred forests in Western India
Authors: Mokashi Shruti , Diemont Stewart A. W.
Published: September 2021

Sacred forests or groves are patches of forest vegetation that are traditionally protected by local communities because of their religious or cultural significance. The ecological aspects of sacred forests have been the focus of most of the scholarly discourse; little scholarship has examined how local people perceive their sacred areas. This scholarly lacuna is especially pronounced with respect to women, as the majority of sacred forests have traditionally been the domain of the men. Until recently, the sacred forests tradition in most regions endured with minimal participation of women, but with changing socio-economic and cultural conditions, sacred forests are declining. By examining women's perspectives regarding their relationship with their sacred forests, this research informs the scholarship on gender and sacred forests, and explores the role women can play in forest conservation. In 2015–2017, we conducted village meetings and in-depth interviews in four villages located in and around the Bhimashankar Wildlife Sanctuary in the Western Ghats region of Maharashtra state, India. We found that apart from rules and taboos governing the protection of these sacred forests, taboos also revolve around the access and interaction of women with the sacred forests, with women having less control and decision-making power than men. Nevertheless, women expressed interest in continuation of the tradition of sacred forests, and the younger generation wants some of the gendered rules to change. We recommend including women in management and decision-making processes to strengthen the institution of sacred forests.
Justice as Checks and Balances
Authors: Franco-Vivanco Edgar
Published: September 2021

The centralization of conflict resolution and the administration of justice, two crucial elements of state formation, are often ignored by the state-building literature. This article studies the monopolization of justice administration, using the historical example of the General Indian Court (gic) of colonial Mexico. The author argues that this court’s development and decision-making process can show us how the rule of law develops in highly authoritarian contexts. Centralized courts could be used strategically to solve an agency problem, limiting local elites’ power and monitoring state agents. To curb these actors’ power, the Spanish Crown allowed the indigenous population to raise claims and access property rights. But this access remained limited and subject to the Crown’s strategic considerations. The author’s theory predicts that a favorable ruling for the indigenous population was more likely in cases that threatened to increase local elites’ power. This article shows the conditions under which the rule of law can emerge in a context where a powerful ruler is interested in imposing limits on local powers—and on their potential predation of the general population. It also highlights the endogenous factors behind the creation of colonial institutions and the importance of judicial systems in colonial governance.
Access to administrative justice and the role of outreach measures: empirical findings on the Austrian Ombudsman Board
Authors: Dahlvik Julia , Pohn-Weidinger Axel
Published: September 2021

While access to civil-law institutions has been a traditional area of socio-legal research, access to administrative justice still constitutes an underresearched field. In the field of administrative law, public ombuds institutions represent an important pathway to resolve disputes without invoking a court. To date, we have little knowledge about who uses these ombuds institutions and which factors facilitate access to the ombuds. In this paper, on the basis of our survey among users of the Austrian Ombudsman Board (n= 8,274), we explore the effects of institutional design on the user population. The findings suggest that the two outreach measures – regular consultation days and a weekly TV broadcast – contribute to reducing existing inequalities with regard to users’ sociodemographic characteristics.
Soil Moisture Responses to Rainfall: Implications for Runoff Generation
Authors: Singh Nitin K. , Emanuel Ryan E. , McGlynn Brian L. , Miniat Chelcy F.
Published: September 2021

Soil moisture is a key control on runoff generation and biogeochemical processes on hillslopes. Precipitation events can evoke different soil moisture responses with depth through the soil profile, and responses can differ among landscape positions along a hillslope. We sought to elucidate the nature of these responses by estimating changes in water content, response time between peak precipitation and peak soil moisture, and wetting front velocities for 43 storms at 45 locations on three adjacent hillslopes within a headwater catchment of the southern Appalachian Mountains (NC, USA). We used a multivariate modeling approach to quantify the relative influences and the predictability of soil moisture responses by a combination of landscape and storm characteristics. We quantified the lag correlations between hillslope mean soil moisture and catchment runoff to demonstrate how storm properties and hillslope‐scale characteristics may influence runoff at the catchment outlet. Soil moisture responses varied widely, and no consistent patterns were observed among response metrics laterally or vertically along hillslopes. In contrast to other studies, we found that the relative influence of hillslope properties and storm characteristics varied with soil moisture responses and during storms. Antecedent conditions and storm depths influenced the strength of lag correlations between soil moisture and runoff, whereas storm mean intensity was correlated with the lag times. These results highlight the utility of intensive observations for characterizing heterogeneity in soil moisture responses, suggesting, among other things, a need for better representation of the subsurface processes in rainfall‐runoff models. Identifying the relative importance of drivers can be beneficial in building parsimonious hydrological models.
Formation of East Asian Stagnant Slabs Due To a Pressure‐Driven Cenozoic Mantle Wind Following Mesozoic Subduction
Authors: Peng Diandian , Liu Lijun , Hu Jiashun , Li Sanzhong , Liu Yiming
Published: September 2021

The extensive fast seismic anomalies in the mantle transition zone beneath East Asia are often interpreted as stagnant Pacific slabs, and a reason for the widespread tectonics since the Mesozoic. Previous hypotheses for their formation mostly emphasize vertical resistances to slab penetration or trench retreat. In this study, we investigate the origin of these stagnant slabs using global‐scale thermal‐chemical models with data‐assimilation. We find that subduction of the Izanagi‐Pacific mid‐ocean ridge marked the transition of mantle flow beneath western Pacific from being surface‐driven Couette‐type flow to pressure‐driven Poiseuille‐type flow, a result previously unrealized. This Cenozoic westward mantle wind driven by the pressure gradient independently explains seismic anisotropy in the region. We conclude that the mantle wind is the dominant mechanism for the formation of stagnant slabs by advecting them westward while the pressure gradient holds them in the transition zone.
Gestational body weight gain and risk of low birth weight or macrosomia in women of Japan: a nationwide cohort study
Authors: Uchinuma Hiroyuki , Tsuchiya Kyoichiro , Sekine Tetsuo , Horiuchi Sayaka , Kushima Megumi , Otawa Sanae , Yokomichi Hiroshi , Miyake Kunio , Akiyama Yuka , Ooka Tadao , Kojima Reiji , Shinohara Ryoji , Hirata Shuji , Yamagata Zentaro ,   Japan Environment and Children’s Study Group, Kamijima Michihiro , Yamazaki Shin , Ohya Yukihiro , Kishi Reiko , Yaegashi Nobuo , Hashimoto Koichi , Mori Chisato , Ito Shuichi , Yamagata Zentaro , Inadera Hidekuni , Nsakayama Takeo , Iso Hiroyasu , Shima Masayuki , Kurozawa Youichi , Suganuma Narufumi , Kusuhara Koichi , Katoh Takahiko
Published: September 2021

Objective

Both maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) influence maternal and pediatric outcomes. We sought to clarify the impact of prepregnancy BMI-specific GWG and its patterns on the risk of low birth weight (LBW) or macrosomia using data from a large nationwide study in Japan.

Methods

This cohort study (n = 98,052) used data from the Japan Environment and Children’s Study (JECS). The outcome variables in this study were LBW and macrosomia. We stratified the subjects into groups according to prepregnancy BMI.

Results

GWG from pre-pregnancy to the first trimester had a small effect on the risk of LBW and macrosomia. From the first to second trimesters, insufficient GWG was associated with the risk of LBW, and from the second trimester to delivery, a GWG of less than 2 kg was associated with the risk of LBW. These associations were commonly observed in all prepregnancy BMI categories. Irrespective of the GWG from pre-pregnancy to the first trimester, GWG from the first to second trimesters affects LBW and/or macrosomia. Irrespective of the GWG from the first to second trimesters, GWG from the second trimester to delivery affects LBW and/or macrosomia. LBW or macrosomia was associated with the prevalence of a sustained low or high BMI percentile until three years of age, respectively.

Conclusions

The present large national cohort study indicates that the risk of LBW or macrosomia is associated with GWG in women in Japan; the significance of this risk depends on the GWG patterns.
Obesity status and obesity-associated gut dysbiosis effects on hypothalamic structural covariance
Authors: Contreras-Rodriguez O. , Arnoriaga-Rodríguez M. , Miranda-Olivos R. , Blasco G. , Biarnés C. , Puig J. , Rivera-Pinto J. , Calle M. L. , Pérez-Brocal V. , Moya A. , Coll C. , Ramió-Torrentà L. , Soriano-Mas C. , Fernandez-Real J. M.
Published: September 2021

Background

Functional connectivity alterations in the lateral and medial hypothalamic networks have been associated with the development and maintenance of obesity, but the possible impact on the structural properties of these networks remains largely unexplored. Also, obesity-related gut dysbiosis may delineate specific hypothalamic alterations within obese conditions. We aim to assess the effects of obesity, and obesity and gut-dysbiosis on the structural covariance differences in hypothalamic networks, executive functioning, and depressive symptoms.

Methods

Medial (MH) and lateral (LH) hypothalamic structural covariance alterations were identified in 57 subjects with obesity compared to 47 subjects without obesity. Gut dysbiosis in the subjects with obesity was defined by the presence of high (n = 28) and low (n = 29) values in a BMI-associated microbial signature, and posthoc comparisons between these groups were used as a proxy to explore the role of obesity-related gut dysbiosis on the hypothalamic measurements, executive function, and depressive symptoms.

Results

Structural covariance alterations between the MH and the striatum, lateral prefrontal, cingulate, insula, and temporal cortices are congruent with previously functional connectivity disruptions in obesity conditions. MH structural covariance decreases encompassed postcentral parietal cortices in the subjects with obesity and gut-dysbiosis, but increases with subcortical nuclei involved in the coding food-related hedonic information in the subjects with obesity without gut-dysbiosis. Alterations for the structural covariance of the LH in the subjects with obesity and gut-dysbiosis encompassed increases with frontolimbic networks, but decreases with the lateral orbitofrontal cortex in the subjects with obesity without gut-dysbiosis. Subjects with obesity and gut dysbiosis showed higher executive dysfunction and depressive symptoms.

Conclusions

Obesity-related gut dysbiosis is linked to specific structural covariance alterations in hypothalamic networks relevant to the integration of somatic-visceral information, and emotion regulation.
Abnormal levels of mitochondrial proteins in plasma neuronal extracellular vesicles in major depressive disorder
Authors: Goetzl Edward J. , Wolkowitz Owen M. , Srihari Vinod H. , Reus Victor I. , Goetzl Laura , Kapogiannis Dimitrios , Heninger George R. , Mellon Synthia H.
Published: September 2021

To characterize neuronal mitochondrial abnormalities in major depressive disorder (MDD), functional mitochondrial proteins (MPs) extracted from enriched plasma neuron-derived extracellular vesicles (NDEVs) of MDD participants (n = 20) were quantified before and after eight weeks of treatment with a selective serotonin reuptake inhibitor (SSRI). Pretreatment baseline NDEV levels of the transcriptional type 2 nuclear respiratory factor (NRF2) which controls mitochondrial biogenesis and many anti-oxidant gene responses, regulators of diverse neuronal mitochondrial functions cyclophilin D (CYPD) and mitofusin-2 (MFN2), leucine zipper EF-hand containing transmembrane 1 protein (LETM1) component of a calcium channel/calcium channel enhancer, mitochondrial tethering proteins syntaphilin (SNPH) and myosin VI (MY06), inner membrane electron transport complexes I (subunit 6) and III (subunit 10), the penultimate enzyme of nicotinamide adenine dinucleotide (NAD) generation nicotinamide mononucleotide adenylytransferase 2 (NMNAT2), and neuronal mitochondrial metabolic regulatory and protective factors humanin and mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c) all were significantly lower than those of NDEVs from matched controls (n = 10), whereas those of pro-neurodegenerative NADase Sterile Alpha and TIR motif-containing protein 1 (SARM1) were higher. The baseline NDEV levels of transcription factor A mitochondrial (TFAM) and the transcriptional master-regulator of mitochondrial biogenesis PPAR γ coactivator-1α (PGC-1α) showed no differences between MDD participants and controls. Several of these potential biomarker proteins showed substantially different changes in untreated MDD than those we reported in untreated first-episode psychosis. NDEV levels of MPs of all functional classes, except complex I-6, NRF2 and PGC-1α were normalized in MDD participants who responded to SSRI therapy (n = 10) but not in those who failed to respond (n = 10) by psychiatric evaluation. If larger studies validate NDEV MP abnormalities, they may become useful biomarkers and identify new drug targets.
Whole-genome sequencing facilitates patient-specific quantitative PCR-based minimal residual disease monitoring in acute lymphoblastic leukaemia, neuroblastoma and Ewing sarcoma
Authors: Subhash Vinod Vijay , Huang Libby , Kamili Alvin , Wong Marie , Chen Dan , Venn Nicola C. , Atkinson Caroline , Mayoh Chelsea , Venkat Pooja , Tyrrell Vanessa , Marshall Glenn M. , Cowley Mark J. , Ekert Paul G. , Norris Murray D. , Haber Michelle , Henderson Michelle J. , Sutton Rosemary , Fletcher Jamie I. , Trahair Toby N.
Published: September 2021

Background

Minimal residual disease (MRD) measurement is a cornerstone of contemporary acute lymphoblastic leukaemia (ALL) treatment. The presence of immunoglobulin (Ig) and T cell receptor (TCR) gene recombinations in leukaemic clones allows widespread use of patient-specific, DNA-based MRD assays. In contrast, paediatric solid tumour MRD remains experimental and has focussed on generic assays targeting tumour-specific messenger RNA, methylated DNA or microRNA.

Methods

We examined the feasibility of using whole-genome sequencing (WGS) data to design tumour-specific polymerase chain reaction (PCR)-based MRD tests (WGS-MRD) in 18 children with high-risk relapsed cancer, including ALL, high-risk neuroblastoma (HR-NB) and Ewing sarcoma (EWS) (n = 6 each).

Results

Sensitive WGS-MRD assays were generated for each patient and allowed quantitation of 1 tumour cell per 10−4 (0.01%)–10–5 (0.001%) mononuclear cells. In ALL, WGS-MRD and Ig/TCR-MRD were highly concordant. WGS-MRD assays also showed good concordance between quantitative PCR and droplet digital PCR formats. In serial clinical samples, WGS-MRD correlated with disease course. In solid tumours, WGS-MRD assays were more sensitive than RNA-MRD assays.

Conclusions

WGS facilitated the development of patient-specific MRD tests in ALL, HR-NB and EWS with potential clinical utility in monitoring treatment response. WGS data could be used to design patient-specific MRD assays in a broad range of tumours.
Multiomics: unraveling the panoramic landscapes of SARS-CoV-2 infection
Authors: Wang Xin , Xu Gang , Liu Xiaoju , Liu Yang , Zhang Shuye , Zhang Zheng
Published: September 2021

In response to emerging infectious diseases, such as the recent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is critical to quickly identify and understand responsible pathogens, risk factors, host immune responses, and pathogenic mechanisms at both the molecular and cellular levels. The recent development of multiomic technologies, including genomics, proteomics, metabolomics, and single-cell transcriptomics, has enabled a fast and panoramic grasp of the pathogen and the disease. Here, we systematically reviewed the major advances in the virology, immunology, and pathogenic mechanisms of SARS-CoV-2 infection that have been achieved via multiomic technologies. Based on well-established cohorts, omics-based methods can greatly enhance the mechanistic understanding of diseases, contributing to the development of new diagnostics, drugs, and vaccines for emerging infectious diseases, such as COVID-19.
Chromosome-scale assembly and evolution of the tetraploid Salvia splendens (Lamiaceae) genome
Authors: Jia Kai-Hua , Liu Hui , Zhang Ren-Gang , Xu Jie , Zhou Shan-Shan , Jiao Si-Qian , Yan Xue-Mei , Tian Xue-Chan , Shi Tian-Le , Luo Hang , Li Zhi-Chao , Bao Yu-Tao , Nie Shuai , Guo Jing-Fang , Porth Ilga , El-Kassaby Yousry A. , Wang Xiao-Ru , Chen Charles , Van de Peer Yves , Zhao Wei , Mao Jian-Feng
Published: September 2021

Polyploidization plays a key role in plant evolution, but the forces driving the fate of homoeologs in polyploid genomes, i.e., paralogs resulting from a whole-genome duplication (WGD) event, remain to be elucidated. Here, we present a chromosome-scale genome assembly of tetraploid scarlet sage (Salvia splendens), one of the most diverse ornamental plants. We found evidence for three WGD events following an older WGD event shared by most eudicots (the γ event). A comprehensive, spatiotemporal, genome-wide analysis of homoeologs from the most recent WGD unveiled expression asymmetries, which could be associated with genomic rearrangements, transposable element proximity discrepancies, coding sequence variation, selection pressure, and transcription factor binding site differences. The observed differences between homoeologs may reflect the first step toward sub- and/or neofunctionalization. This assembly provides a powerful tool for understanding WGD and gene and genome evolution and is useful in developing functional genomics and genetic engineering strategies for scarlet sage and other Lamiaceae species.
Effects of ozone water irrigation and spraying on physiological characteristics and gene expression of tomato seedlings
Authors: Xu Jin-Peng , Yu Yan-Chong , Zhang Tao , Ma Qian , Yang Hong-Bing
Published: September 2021

Tomato seedlings were used as experimental materials and treated with 1.0, 2.0, 3.0, and 4.0 mg/L ozone water irrigation and 0.2, 0.4, 0.6, and 0.8 mg/L ozone water spray treatments. Indexes including the malondialdehyde (MDA) content, superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), activities, soil and plant analysis development (SPAD) value, and nitrogen content of leaves were measured. Furthermore, the expression of antioxidant enzyme, chlorophyll synthesis and nitrogen absorption genes was analyzed after optimal ozone water treatment. The results showed that the activities of antioxidant enzymes in tomato leaves were significantly increased, and the MDA content in tomato leaves was significantly reduced by ozone water irrigation and spray treatment, which indicated that ozone water treatment can significantly improve the stress tolerance of tomato seedlings. Ozone water irrigation and spraying could also significantly increase the leaf SPAD value and nitrogen content of tomato seedlings, and the optimal concentrations of ozone water irrigation and spraying were 3.0 mg/L and 0.6 mg/L, respectively. The effect of ozone water irrigation on improving the physiological characteristics of tomato seedlings was better than that of spraying. After treatment with the optimal concentration of ozone water, the relative expression of antioxidant enzyme, chlorophyll synthesis, and nitrogen absorption genes was significantly increased, and the maximum expression level was reached at 12 h. In addition, ozone water irrigation could promote the expression of genes more than ozone water spraying, which was consistent with the improvements in the physiological characteristics of the tomato seedlings.
Transcripts switched off at the stop of phloem unloading highlight the energy efficiency of sugar import in the ripening V. vinifera fruit
Authors: Savoi Stefania , Torregrosa Laurent , Romieu Charles
Published: September 2021

Transcriptomic changes at the cessation of sugar accumulation in the pericarp ofVitis viniferawere addressed on single berries re-synchronised according to their individual growth patterns. The net rates of water, sugars and K+accumulation inferred from individual growth and solute concentration confirmed that these inflows stopped simultaneously in the ripe berry, while the small amount of malic acid remaining at this stage was still being oxidised at low rate. Re-synchronised individual berries displayed negligible variations in gene expression among triplicates. RNA-seq studies revealed sharp reprogramming of cell-wall enzymes and structural proteins at the stop of phloem unloading, associated with an 80% repression of multiple sugar transporters and aquaporins on the plasma or tonoplast membranes, with the noticeable exception of H+/sugar symporters, which were rather weakly and constitutively expressed. This was verified in three genotypes placed in contrasted thermo-hydric conditions. The prevalence of SWEET suggests that electrogenic transporters would play a minor role on the plasma membranes of SE/CC complex and the one of the flesh, while sucrose/H+exchangers dominate on its tonoplast.Cis-regulatory elements present in their promoters allowed to sort these transporters in different groups, also including specific TIPs and PIPs paralogs, and cohorts of cell wall-related genes. Together with simple thermodynamic considerations, these results lead to propose that H+/sugar exchangers at the tonoplast, associated with a considerably acidic vacuolar pH, may exhaust cytosolic sugars in the flesh and alleviate the need for supplementary energisation of sugar transport at the plasma membrane.
The basic helix-loop-helix transcription factor TabHLH1 increases chlorogenic acid and luteolin biosynthesis in Taraxacum antungense Kitag
Authors: Liu Qun , Li Li , Cheng Haitao , Yao Lixiang , Wu Jie , Huang Hui , Ning Wei , Kai Guoyin
Published: September 2021

Polyphenols are the main active components of the anti-inflammatory compounds in dandelion, and chlorogenic acid (CGA) is one of the primary polyphenols. However, the molecular mechanism underlying the transcriptional regulation of CGA biosynthesis remains unclear. Hydroxycinnamoyl-CoA:quinate hydroxycinnamoyl transferase (HQT2) is the last rate-limiting enzyme in chlorogenic acid biosynthesis in Taraxacum antungense. Therefore, using the TaHQT2 gene promoter as a probe, a yeast one-hybrid library was performed, and a basic helix-loop-helix (bHLH) transcription factor, TabHLH1, was identified that shared substantial homology with Gynura bicolor DC bHLH1. The TabHLH1 transcript was highly induced by salt stress, and the TabHLH1 protein was localized in the nucleus. CGA and luteolin concentrations in TabHLH1-overexpression transgenic lines were significantly higher than those in the wild type, while CGA and luteolin concentrations in TabHLH1-RNA interference (RNAi) transgenic lines were significantly lower. Quantitative real-time polymerase chain reaction demonstrated that overexpression and RNAi of TabHLH1 in T. antungense significantly affected CGA and luteolin concentrations by upregulating or downregulating CGA and luteolin biosynthesis pathway genes, especially TaHQT2, 4-coumarate-CoA ligase (Ta4CL), chalcone isomerase (TaCHI), and flavonoid-3′-hydroxylase (TaF3′H). Dual-luciferase, yeast one-hybrid, and electrophoretic mobility shift assays indicated that TabHLH1 directly bound to the bHLH-binding motifs of proTaHQT2 and proTa4CL. This study suggests that TabHLH1 participates in the regulatory network of CGA and luteolin biosynthesis in T. antungense and might be useful for metabolic engineering to promote plant polyphenol biosynthesis.
The grapevine (Vitis vinifera L.) floral transcriptome in Pinot noir variety: identification of tissue-related gene networks and whorl-specific markers in pre- and post-anthesis phases
Authors: Vannozzi Alessandro , Palumbo Fabio , Magon Gabriele , Lucchin Margherita , Barcaccia Gianni
Published: September 2021

The comprehension of molecular processes underlying the development and progression of flowering in plants is a hot topic, not only because that often the products of interest for human and animal nutrition are linked to the development of fruits or seeds, but also because the processes of gametes formation occurring in sexual organs are at the basis of recombination and genetic variability which constitutes the matter on which evolution acts, whether understood as natural or human driven. In the present study, we used an NGS approach to produce a grapevine flower transcriptome snapshot in different whorls and tissues including calyx, calyptra, filament, anther, stigma, ovary, and embryo in both pre- and post-anthesis phases. Our investigation aimed at identifying hub genes that unequivocally distinguish the different tissues providing insights into the molecular mechanisms that are at the basis of floral whorls and tissue development. To this end we have used different analytical approaches, some now consolidated in transcriptomic studies on plants, such as pairwise comparison and weighted-gene coexpression network analysis, others used mainly in studies on animals or human’s genomics, such as the tau (τ) analysis aimed at isolating highly and absolutely tissue-specific genes. The intersection of data obtained by these analyses allowed us to gradually narrow the field, providing evidence about the molecular mechanisms occurring in those whorls directly involved in reproductive processes, such as anther and stigma, and giving insights into the role of other whorls not directly related to reproduction, such as calyptra and calyx. We believe this work could represent an important genomic resource for functional analyses of grapevine floral organ growth and fruit development shading light on molecular networks underlying grapevine reproductive organ determination.
Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques
Authors: Marlin Romain , Godot Veronique , Cardinaud Sylvain , Galhaut Mathilde , Coleon Severin , Zurawski Sandra , Dereuddre-Bosquet Nathalie , Cavarelli Mariangela , Gallouët Anne-Sophie , Maisonnasse Pauline , Dupaty Léa , Fenwick Craig , Naninck Thibaut , Lemaitre Julien , Gomez-Pacheco Mario , Kahlaoui Nidhal , Contreras Vanessa , Relouzat Francis , Fang Raphaël Ho Tsong , Wang Zhiqing , Ellis Jerome , Chapon Catherine , Centlivre Mireille , Wiedemann Aurelie , Lacabaratz Christine , Surenaud Mathieu , Szurgot Inga , Liljeström Peter , Planas Delphine , Bruel Timothée , Schwartz Olivier , Werf Sylvie van der , Pantaleo Giuseppe , Prague Mélanie , Thiébaut Rodolphe , Zurawski Gerard , Lévy Yves , Grand Roger Le
Published: September 2021

Achieving sufficient worldwide vaccination coverage against SARS-CoV-2 will require additional approaches to currently approved viral vector and mRNA vaccines. Subunit vaccines may have distinct advantages when immunizing vulnerable individuals, children and pregnant women. Here, we present a new generation of subunit vaccines targeting viral antigens to CD40-expressing antigen-presenting cells. We demonstrate that targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to CD40 (αCD40.RBD) induces significant levels of specific T and B cells, with long-term memory phenotypes, in a humanized mouse model. Additionally, we demonstrate that a single dose of the αCD40.RBD vaccine, injected without adjuvant, is sufficient to boost a rapid increase in neutralizing antibodies in convalescent non-human primates (NHPs) exposed six months previously to SARS-CoV-2. Vaccine-elicited antibodies cross-neutralize different SARS-CoV-2 variants, including D614G, B1.1.7 and to a lesser extent B1.351. Such vaccination significantly improves protection against a new high-dose virulent challenge versus that in non-vaccinated convalescent animals.
Quantum enhanced multiple-phase estimation with multi-mode N00N states
Authors: Hong Seongjin , ur Rehman Junaid , Kim Yong-Su , Cho Young-Wook , Lee Seung-Woo , Jung Hojoong , Moon Sung , Han Sang-Wook , Lim Hyang-Tag
Published: September 2021

Quantum metrology can achieve enhanced sensitivity for estimating unknown parameters beyond the standard quantum limit. Recently, multiple-phase estimation exploiting quantum resources has attracted intensive interest for its applications in quantum imaging and sensor networks. For multiple-phase estimation, the amount of enhanced sensitivity is dependent on quantum probe states, and multi-mode N00N states are known to be a key resource for this. However, its experimental demonstration has been missing so far since generating such states is highly challenging. Here, we report generation of multi-mode N00N states and experimental demonstration of quantum enhanced multiple-phase estimation using the multi-mode N00N states. In particular, we show that the quantum Cramer-Rao bound can be saturated using our two-photon four-mode N00N state and measurement scheme using a 4 × 4 multi-mode beam splitter. Our multiple-phase estimation strategy provides a faithful platform to investigate multiple parameter estimation scenarios.
Loss of SNORA73 reprograms cellular metabolism and protects against steatohepatitis
Authors: Sletten Arthur C. , Davidson Jessica W. , Yagabasan Busra , Moores Samantha , Schwaiger-Haber Michaela , Fujiwara Hideji , Gale Sarah , Jiang Xuntian , Sidhu Rohini , Gelman Susan J. , Zhao Shuang , Patti Gary J. , Ory Daniel S. , Schaffer Jean E.
Published: September 2021

Dyslipidemia and resulting lipotoxicity are pathologic signatures of metabolic syndrome and type 2 diabetes. Excess lipid causes cell dysfunction and induces cell death through pleiotropic mechanisms that link to oxidative stress. However, pathways that regulate the response to metabolic stress are not well understood. Herein, we show that disruption of the box H/ACA SNORA73 small nucleolar RNAs encoded within the small nucleolar RNA hosting gene 3 (Snhg3) causes resistance to lipid-induced cell death and general oxidative stress in cultured cells. This protection from metabolic stress is associated with broad reprogramming of oxidative metabolism that is dependent on the mammalian target of rapamycin signaling axis. Furthermore, we show that knockdown of SNORA73 in vivo protects against hepatic steatosis and lipid-induced oxidative stress and inflammation. Our findings demonstrate a role for SNORA73 in the regulation of metabolism and lipotoxicity.