bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychological Responses Among Korean Middle East Respiratory Syndrome Survivors and Bereaved Families
Authors: Lee Dayoung , Lee Junghyun H , Jeon Kyoungsun , Lee Nabin , Sim Minyoung
Published: May 2021

Objective:

In 2015, the outbreak of Middle East Respiratory Syndrome (MERS) in South Korea affected 186 patients and led to 38 bereaved families. This study aimed at investigating the nature and related factors of the psychological responses of MERS victims during the acute phase of disaster.

Methods:

The MERS Psychological Support Team under the Korean Ministry of Health and Welfare provided counseling services to MERS survivors and bereaved families for 4 weeks, based on crisis intervention. In this study, we reviewed the counseling records of 109 survivors and 80 bereaved family members, and analyzed their epidemiological and MERS-related information along with psychological responses.

Results:

Somatic symptoms and anxiety related to social stigmatization or disease transmission were common in MERS survivors, whereas grief reactions such as sadness, and anger were frequently observed in bereaved families. Bereaved MERS survivors showed more avoidance/isolation than non-bereaved MERS survivors. Females, those with an underlying physical or psychiatric health condition, and those having experienced longer duration of hospitalization and non-healthcare workers were more at risk of suffering from psychological problems.

Conclusions:

Survivors and bereaved families of epidemics can experience various psychological distresses depending on individual characteristics and the inherent features of the epidemic. Therefore, mental health in epidemics should be approached and considered more seriously.
Assessing Hospital Adaptive Resource Allocation Strategies in Responding to Mass Casualty Incidents
Authors: Trucco Paolo , Nocetti Claudio , Sannicandro Riccardo , Carlucci Michele , Weinstein Eric S. , Faccincani Roberto
Published: May 2021

Objectives:

Hospitals are expected to operate at a high-performance level even under exceptional conditions of peak demand and resource disruptions. This understanding is not mature yet, and there are wide areas of possible improvement. In particular, the fast mobilization and reconfiguration of resources frequently result into the severe disruption of elective activities, worsening the quality of care. More resilient resource allocation strategies, ie, which adapt to the dynamics of the prevailing circumstance, are needed to maximize the effectiveness of health-care delivery. In this study, a simulation approach was adopted to assess and compare different hospital’s adaptive resource allocation strategies in responding to a mass casualty incident (MCI).

Methods:

A specific set of performance metrics was developed to take into consideration multiple objectives and priorities and holistically assess the effectiveness of health-care delivery when coping with an MCI event. Discrete event simulation (DES) and system dynamics (SD) were used to model the key hospital processes and the MCI plan.

Results:

In the daytime scenario, during the recovery phase of the emergency, a gradual disengagement of resources from the emergency department (ED) to restart ordinary activities in operating rooms and wards, returned the best performance. In the night scenario, the absorption capacity of the ED was evaluated by identifying the current bottleneck and assessment of the benefit of different resource mobilization strategies.

Conclusions:

The present study offers a robust approach, effective strategies, and new insights to design more resilient plans to cope with MCIs. Future research is needed to widen the scope of the analysis and take into consideration additional resilience capacities, such as operational coordination mechanisms, among multiple hospitals in the same geographic area.
Evaluation of healthcare personnel exposures to patients with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) associated with personal protective equipment
Authors: Shah Vishal P. , Breeher Laura E. , Hainy Caitlin M. , Swift Melanie D.
Published: May 2021

Objective:

Personal protective equipment (PPE) is a critical aspect of preventing the transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in healthcare settings. We aimed to identify factors related to lapses in PPE use that may influence transmission of SARS-CoV-2 from patients to healthcare personnel (HCP).

Design:

Retrospective cohort study.

Setting:

Tertiary-care medical center in Minnesota.

Participants:

In total, 345 HCP who sustained a significant occupational exposure to a patient with coronavirus disease 2019 (COVID-19) from May 13, 2020, through November 30, 2020, were evaluated.

Results:

Overall, 8 HCP (2.3%) were found to have SARS-CoV-2 infection during their 14-day postexposure quarantine. A lack of eye protection during the care of a patient with COVID-19 was associated with HCP testing positive for SARS-CoV-2 by reverse-transcriptase polymerase chain reaction (RT-PCR) during the postexposure quarantine (relative risk [RR], 10.25; 95% confidence interval [CI], 1.28–82.39; P = .009). Overall, the most common reason for a significant exposure was the use of a surgical face mask instead of a respirator during an aerosol-generating procedure (55.9%). However, this was not associated with HCP testing positive for SARS-CoV-2 during the postexposure quarantine (RR, 0.99; 95% CI, 0.96–1; P = 1). Notably, transmission primarily occurred in units that did not regularly care for patients with COVID-19.

Conclusions:

The use of universal eye protection is a critical aspect of PPE to prevent patient-to-HCP transmission of SARS-CoV-2.
Transform the Land, Train the Youth: Water and Soil Conservation Teams and State-Induced Migration in mid-1960s China
Authors: Muscolino Micah S.
Published: May 2021

Beginning in 1964, the PRC party-state orchestrated the resettlement of thousands of young people from cities to erosion-prone areas in China's Loess Plateau to form “water and soil conservation teams” (shuitu baochi zhuanyedui). Although their ostensible mission was to limit erosion by building terraces and planting trees, documents related to conservation teams emphasized their capacity to thoroughly reform urban youth while mobilizing them to do the work of remaking the environment. Provincial and county archives, along with fieldwork conducted at the site of one water and soil conservation team in Shaanxi province's Baishui county, indicate that conservation teams did not realize either of these objectives. Due to urban youth's inexperience with agriculture and conservation, they did little to promote environmental management. At the same time, unruly teenagers who migrated to the countryside to join conservation teams, as well as the cadres who oversaw them, continued to engage in transgressive behavior.
Vitamin D status of children with paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS)
Authors: Darren Angeline , Osman Meissa , Masilamani Kavitha , Habib Ali Syed , Kanthimathinathan Hari Krishnan , Chikermane Ashish , Al-Abadi Eslam , Welch Steven B. , Hackett Scott , Scholefield Barnaby R. , Uday Suma , Jyothish Deepthi
Published: May 2021

Coronavirus disease 2019 (COVID-19) has caused mild illness in children, until the emergence of the novel hyperinflammatory condition paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS). PIMS-TS is thought to be a post-SARS-CoV-2 immune dysregulation with excessive inflammatory cytokine release. We studied 25 hydroxyvitamin D (25OHD) concentrations in children with PIMS-TS, admitted to a tertiary paediatric hospital in the UK, due to its postulated role in cytokine regulation and immune response. Eighteen children (median (range) age 8·9 (0·3-14·6) years, male = 10) met the case definition. The majority were of Black, Asian and Minority Ethnic (BAME) origin (89 %, 16/18). Positive SARS-CoV-2 IgG antibodies were present in 94 % (17/18) and RNA by PCR in 6 % (1/18). Seventy-eight percentage of the cohort were vitamin D deficient (< 30 nmol/l). The mean 25OHD concentration was significantly lower when compared with the population mean from the 2015/16 National Diet and Nutrition Survey (children aged 4–10 years) (24 v. 54 nmol/l (95 % CI −38·6, −19·7); P < 0·001). The paediatric intensive care unit (PICU) group had lower mean 25OHD concentrations compared with the non-PICU group, but this was not statistically significant (19·5 v. 31·9 nmol/l; P = 0·11). The higher susceptibility of BAME children to PIMS-TS and also vitamin D deficiency merits contemplation. Whilst any link between vitamin D deficiency and the severity of COVID-19 and related conditions including PIMS-TS requires further evidence, public health measures to improve vitamin D status of the UK BAME population have been long overdue.
Rethinking the Scopes Trial: Cultural Conflict, Media Spectacle, and Circus Politics
Authors: ARNOLD-FORSTER TOM
Published: May 2021

The Scopes trial has long been interpreted through claims about science and religion and about individual rights and liberties. This article recovers a different debate about the trial's political history that emerged in the later 1920s and resonated down the twentieth century. Here the trial figured as a fraught national circus, which raised difficult questions about the relationship between media spectacle and cultural conflict in the United States. The trial's circus dynamics intensified the conflicts it staged without ever actually resolving them; this trap was then perceived and negotiated in different ways by contemporary liberals, conservatives, socialists, and far-right activists.
Reflecting on task-based language teaching from an Instructed SLA perspective
Authors: Spada Nina
Published: May 2021

Task-based language teaching (TBLT) and instructed second language acquisition (ISLA) have much in common in terms of theory, research, and educational relevance. The distinguishing characteristic between the two is that TBLT adopts communicative tasks as the central unit for instruction and assessment, whereas ISLA comprises a broader range of instructional activities and assessment practices. In this presentation, I focus on two of the conference themes: Instruction and Outcomes. With respect to Instruction, I draw attention to the pedagogical timing of form-focused instruction (FFI) and corrective feedback. I discuss relevant studies within ISLA and TBLT and argue that TBLT is particularly well-suited to investigating questions about the timing of FFI. In discussing Outcomes, I consider differences in how outcomes are measured in TBLT (i.e. performance) and ISLA (i.e. development) and the different aspects of language examined within each, for example, accuracy, implicit/explicit knowledge in ISLA and complexity, accuracy and fluency in TBLT. I discuss underlying similarities between fluency and implicit knowledge, how they are measured, and propose research to investigate the pedagogical timing of FFI in relation to fluency development. I conclude with a brief discussion of the need for a balance between theoretically and pedagogically motivated research within ISLA and TBLT.
Be that as it may: The Unremarkable Trajectory of the English Subjunctive in North American Speech
Authors: Kastronic Laura , Poplack Shana
Published: May 2021

The English subjunctive has had a checkered history, ranging from extensive use in Old English to near extinction by Late Modern English. Since then, the mandative variant was reported to have revived, while the adverbial subjunctive continued to diminish. American English is heavily implicated in these developments; it is thought to be leading the revival of the former but lagging in the decline of the latter. Observing that most references to these changes are based on the written language, we examine the diachronic trajectory of the subjunctive in North American Englishspeech.Adopting a variationist perspective, we carried out systematic quantitative analyses of subjunctive use under hundreds of triggers. Results show that, despite the differences in their diachronic trajectories, today both types are not only extremely rare but heavily lexically constrained. We implicate violations of thePrinciple of Accountabilityin the disparities between the findings reported here and the consensus in the literature with respect to subjunctive use in North American English.
Transcatheter closure of patent vertical vein after repair of total anomalous pulmonary venous connection: a case series
Authors: Gumustas Mehmet , Donmez Yasemin N. , Aykan Hayrettin H. , Demircin Metin , Karagoz Tevfik
Published: May 2021

Background and objectives:

Total anomalous pulmonary venous connection is a rare cyanotic CHD that requires surgical repair. An unligated vertical vein after total anomalous pulmonary venous connection surgery may help to decrease the episodes of post-operative pulmonary hypertensive crises, low cardiac output syndrome, and mortality. The aim was to assess long-term outcome and our post-operative transcatheter vertical vein closure experiences in five patients with repaired total anomalous pulmonary venous connection patients.

Methods:

A retrospective study was conducted in five cases with an unligated vertical vein following repair of supra-cardiac total anomalous pulmonary venous connection at our hospital from 2011 through 2018. Patients characteristics, cardiac catheterisation findings, surgical, and transcatheter procedural details were retrospectively analysed.

Results:

Transcatheter closure of the unligated vertical vein was technically successful in all the patients. Procedure-related complications were not observed in any of the patients. No long-term complication was found.

Conclusions:

We suggest that transcatheter closure of the patent vertical vein is an effective and well-tolerated alternative to the surgical approach.
Between the city and the farm: food environments in artisanal mining communities in Upper Guinea
Authors: Nordhagen Stella , Fofana Mohamed L , Barry Alpha O , Diallo Sadio , Songbono Joseph L , Stokes-Walters Ronald , Zhang Laetitia X , Klemm Rolf , Winch Peter J
Published: May 2021

Objective:

Artisanal and small-scale mining (ASM) is a widespread livelihood in low- and middle-income countries; however, many in ASM communities face high levels of poverty and malnutrition. The food environments in ASM communities have non-agricultural rural characteristics that differ from those in urban and agricultural rural areas examined in much existing food environment literature.

Design:

We examine these complex external and personal food environments in ASM communities via a study using qualitative and quantitative methods. Market surveys and a cross-sectional household survey, plus qualitative mining site non-participant observations and in-depth structured interviews, were conducted in three waves.

Setting:

Eighteen study sites in ASM communities in northern Guinea.

Participants:

Surveys covered mothers in mining households with young children (n613); in-depth interviews engaged caregivers of young children (n45), food vendors (n40) and young single miners (n15); observations focused on mothers of young children (n25).

Results:

The external food environment in these ASM communities combines widespread availability of commercially processed and staple-heavy foods with lower availability and higher prices for more nutritious, non-staple foods. Within the personal food environment, miners are constrained in their food choices by considerable variability in daily cash income and limited time for acquisition and preparation.

Conclusions:

We demonstrate that ASM communities have characteristics of both urban and rural populations and argue for greater nuance and appreciation of complexity in food environment research and resultant policy and programming.
Is archaeology conceivable within the degrowth movement?
Authors: Zorzin Nicolas
Published: May 2021

Since the 1980s, archaeology has been further embedded in a reinforced and accelerating capitalist ideology, namely neo-liberalism. Most archaeologists had no alternative but to adapt to it through concessions to the free-market economy and to the so-called mitigations taking place within development. However, it is now apparent that the ongoing global socio-ecological disaster we are facing cannot be reversed with compromises but rather with a radical engagement against the injunctions of competition and growth. I suggest that we must anticipate the necessary transformations of archaeology in the coming decades, before archaeology becomes a technical avatar of the neo-liberal dogma, or before its complete annihilation for being deemed ‘superfluous’ (Wurst 2019, 171) by the capitalist regime. In this paper, I will use the idea of ‘degrowth’ to propose a new paradigm for archaeology by applying the concepts of civil disobedience, voluntary simplicity, redistribution of means and the ethics of no-growth.
Growth from birth to 6 months of infants with and without intrauterine preeclampsia exposure
Authors: Gow Megan L. , Roberts Lynne , Henry Amanda , Davis Gregory , Mangos George , Pettit Franziska , Khouri Joseph M. , Dosen Ana , Brown Mark A. , Craig Maria E.
Published: May 2021

Intrauterine preeclampsia exposure affects the lifelong cardiometabolic health of the child. Our study aimed to compare the growth (from birth to 6 months) of infants exposed to either a normotensive pregnancy or preeclampsia and explore the influence of being born small for gestational age (SGA). Participants were children of women participating in the Post-partum, Physiology, Psychology and Paediatric follow-up cohort study. Birth and 6-month weight and length z-scores were calculated for term and preterm (<37 weeks) babies, and change in weight z-score, rapid weight gain (≥0.67 increase in weight z-score) and conditional weight gain z-score were calculated. Compared with normotensive exposed infants (n = 298), preeclampsia exposed infants (n = 84) were more likely to be born SGA (7% versus 23%; P < 0.001), but weight gain from birth to 6 months, by any measure, did not differ between groups. Infants born SGA, irrespective of pregnancy exposure, were more likely to have rapid weight gain and had greater increases in weight z-score compared with those not born SGA. Preeclampsia exposed infants born SGA may benefit from interventions designed to prevent future cardiometabolic disease.
Maternal soy protein isolate diet during lactation programs deleterious effects on hepatic lipid metabolism, atherogenic indices, and function of adrenal in adult rat offspring
Authors: Ferreira Maíra Schuchter , Dutra Luquetti Sheila Cristina Potente , Brasiel Poliana Guiomar de Almeida , Mateus Kacia , Paulino Alice Helena de Souza , Carvalho Mayara Medeiros de Freitas , Andreazzi Ana Eliza , Aguiar Aline Silva de
Published: May 2021

The benefits of consuming soy and its protein have been reported in many studies. However, its phytoestrogen content raises concerns about consumption during lactation and gestation We therefore examined the effects of soybean or soy protein isolate on the parameters-related cardiovascular pathophysiology in lactating mothers and their offsprings at weaning and adulthood. Lactating rats were divided: casein control (C); soy protein isolate (SPI); and soybean (S). At weaning, half of the litter received commercial ration up to 150 days. The levels of 17-β-estradiol and superoxide dismutase were low in the S mothers. For the SPI mothers, we observed a reduction of thiobarbituric acid reactive substances (TBARS). At weaning, atherogenic indices [1 = total cholesterol (TC)/HDL; 2 = LDL/HDL; 3 = TC-HDL/HDL)] decreased in the S and SPI offsprings compared to the casein control group; TBARS and antioxidant enzymes increased in the S offspring, while reduced/oxidized glutathione ratio increased in the SPI offspring, indicating lower oxidative stress. In adulthood, the SPI offspring showed an increase in liver cholesterol and atherogenic index 1 and 3 (vs. C and S) and 2 (vs. S). In addition, we found a decrease in catecholamines in the adrenal medulla and an increase in caffeine-stimulated secretion, but tyrosine hydroxylase expression remained constant. Maternal consumption of SPI during lactation worsened atherogenic indices of the offsprings in adulthood, which was associated with increased liver cholesterol and decreased catecholamines in the adrenal medulla. Soy consumption had no consistent long-term effects on the evaluated parameters compared to casein consumption. The data suggest that the consumption of SPI during lactation should be done with caution.
Novel taxa of Acidobacteriota implicated in seafloor sulfur cycling
Authors: Flieder Mathias , Buongiorno Joy , Herbold Craig W , Hausmann Bela , Rattei Thomas , Lloyd Karen G , Loy Alexander , Wasmund Kenneth
Published: May 2021

Acidobacteriota are widespread and often abundant in marine sediments, yet their metabolic and ecological properties are poorly understood. Here, we examined metabolisms and distributions of Acidobacteriota in marine sediments of Svalbard by functional predictions from metagenome-assembled genomes (MAGs), amplicon sequencing of 16S rRNA and dissimilatory sulfite reductase (dsrB) genes and transcripts, and gene expression analyses of tetrathionate-amended microcosms. Acidobacteriota were the second most abundant dsrB-harboring (averaging 13%) phylum after Desulfobacterota in Svalbard sediments, and represented 4% of dsrB transcripts on average. Meta-analysis of dsrAB datasets also showed Acidobacteriota dsrAB sequences are prominent in marine sediments worldwide, averaging 15% of all sequences analysed, and represent most of the previously unclassified dsrAB in marine sediments. We propose two new Acidobacteriota genera, Candidatus Sulfomarinibacter (class Thermoanaerobaculia, “subdivision 23”) and Ca. Polarisedimenticola (“subdivision 22”), with distinct genetic properties that may explain their distributions in biogeochemically distinct sediments. Ca. Sulfomarinibacter encode flexible respiratory routes, with potential for oxygen, nitrous oxide, metal-oxide, tetrathionate, sulfur and sulfite/sulfate respiration, and possibly sulfur disproportionation. Potential nutrients and energy include cellulose, proteins, cyanophycin, hydrogen, and acetate. A Ca. Polarisedimenticola MAG encodes various enzymes to degrade proteins, and to reduce oxygen, nitrate, sulfur/polysulfide and metal-oxides. 16S rRNA gene and transcript profiling of Svalbard sediments showed Ca. Sulfomarinibacter members were relatively abundant and transcriptionally active in sulfidic fjord sediments, while Ca. Polarisedimenticola members were more relatively abundant in metal-rich fjord sediments. Overall, we reveal various physiological features of uncultured marine Acidobacteriota that indicate fundamental roles in seafloor biogeochemical cycling.
Fas/FasL mediates NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to drive liver fibrosis
Authors: Tan Siwei , Liu Xianzhi , Chen Lingjun , Wu Xiaoqin , Tao Li , Pan Xuemei , Tan Shuyan , Liu Huiling , Jiang Jie , Wu Bin
Published: May 2021

Fas/Fas ligand (FasL)-mediated cell apoptosis involves a variety of physiological and pathological processes including chronic hepatic diseases, and hepatocytes apoptosis contributes to the development of liver fibrosis following various causes. However, the mechanism of the Fas/FasL signaling and hepatocytes apoptosis in liver fibrogenesis remains unclear. The Fas/FasL signaling and hepatocytes apoptosis in liver samples from both human sections and mouse models were investigated. NF-κBp65 wild-type mice (p65f/f), hepatocytes specific NF-κBp65 deletion mice (p65Δhepa), p53-upregulated modulator of apoptosis (PUMA) wild-type (PUMA-WT) and PUMA knockout (PUMA-KO) littermate models, and primary hepatic stellate cells (HSCs) were also used. The mechanism underlying Fas/FasL-regulated hepatocytes apoptosis to drive HSCs activation in fibrosis was further analyzed. We found Fas/FasL promoted PUMA-mediated hepatocytes apoptosis via regulating autophagy signaling and NF-κBp65 phosphorylation, while inhibition of autophagy or PUMA deficiency attenuated Fas/FasL-modulated hepatocytes apoptosis and liver fibrosis. Furthermore, NF-κBp65 in hepatocytes repressed PUMA-mediated hepatocytes apoptosis via regulating the Bcl-2 family, while NF-κBp65 deficiency in hepatocytes promoted PUMA-mediated hepatocytes apoptosis and enhanced apoptosis-linked inflammatory response, which contributed to the activation of HSCs and liver fibrogenesis. These results suggest that Fas/FasL contributes to NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to enhance liver fibrogenesis, and this network could be a potential therapeutic target for liver fibrosis.
Distinct mutational backgrounds and clonal architectures implicated prognostic discrepancies in small-cell carcinomas of the esophagus and lung
Authors: Song Zhengbo , Liu Yueping , Cheng Guoping , Chang Lianpeng , Yu Zicheng , Chen Ming , Chen Gang
Published: May 2021

Small-cell carcinoma of the esophagus (SCCE) is a rare and aggressive cancer. Although several consistent genomic changes were observed previously between SCCE and small-cell lung cancer (SCLC), detailed mutational landscapes revealing discrepancies in genetic underpinnings of tumorigenesis between these two cancers are scarce, and little attention has been paid to answer whether these genetic alterations were related to the prognosis. Herein by performing whole-exome sequencing of 48 SCCE and 64 SCLC tumor samples, respectively we have shown that the number of driver mutations in SCCE was significantly lower than in SCLC (p = 0.0042). In SCCE, 46% of recurrent driver mutations were clonal, which occurred at an early stage during tumorigenesis, while 16 driver mutations were found clonal in SCLC. NOTCH1/3, PIK3CA, and ATM were specifically clonal in SCCE, while TP53 was clonal in SCLC. The total number of clonal mutations differed between two cancers and presented lower in SCCE compared to SCLC (p = 0.0036). Moreover, overall survival (OS) was shorter in patients with higher numbers of clonal mutations for both cancers. In summary, SCCE showed distinct mutational background and clonal architecture compared with SCLC. Organ-specific clonal events revealed different molecular mechanisms underlying tumorigenesis, tumor development, patients’ prognosis, and possible variations in therapeutic outcomes to candidate treatments.
CBP/p300 HAT maintains the gene network critical for β cell identity and functional maturity
Authors: Zhang Linlin , Sheng Chunxiang , Zhou Feiye , Zhu Kecheng , Wang Shushu , Liu Qianqian , Yuan Miaomiao , Xu Zhaoqian , Liu Yun , Lu Jieli , Liu Jianmin , Zhou Libin , Wang Xiao
Published: May 2021

Loss of β cell identity and functional immaturity are thought to be involved in β cell failure in type 2 diabetes. CREB-binding protein (CBP) and its paralogue p300 act as multifunctional transcriptional co-activators and histone acetyltransferases (HAT) with extensive biological functions. However, whether the regulatory role of CBP/p300 in islet β cell function depends on the HAT activity remains uncertain. In this current study, A-485, a selective inhibitor of CBP/p300 HAT activity, greatly impaired glucose-stimulated insulin secretion from rat islets in vitro and in vivo. RNA-sequencing analysis showed a comprehensive downregulation of β cell and α cell identity genes in A-485-treated islets, without upregulation of dedifferentiation markers and derepression of disallowed genes. A-485 treatment decreased the expressions of genes involved in glucose sensing, not in glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. In the islets of prediabetic db/db mice, CBP/p300 displayed a significant decrease with key genes for β cell function. The deacetylation of histone H3K27 as well as the transcription factors Hnf1α and Foxo1 was involved in CBP/p300 HAT inactivation-repressed expressions of β cell identity and functional genes. These findings highlight the dominant role of CBP/p300 HAT in the maintenance of β cell identity by governing transcription network.
INI1/SMARCB1 Rpt1 domain mimics TAR RNA in binding to integrase to facilitate HIV-1 replication
Authors: Dixit Updesh , Bhutoria Savita , Wu Xuhong , Qiu Liming , Spira Menachem , Mathew Sheeba , Harris Richard , Adams Lucas J. , Cahill Sean , Pathak Rajiv , Rajesh Kumar P. , Nguyen Minh , Acharya Seetharama A. , Brenowitz Michael , Almo Steven C. , Zou Xiaoqin , Steven Alasdair C. , Cowburn David , Girvin Mark , Kalpana Ganjam V.
Published: May 2021

INI1/SMARCB1 binds to HIV-1 integrase (IN) through its Rpt1 domain and exhibits multifaceted role in HIV-1 replication. Determining the NMR structure of INI1-Rpt1 and modeling its interaction with the IN-C-terminal domain (IN-CTD) reveal that INI1-Rpt1/IN-CTD interface residues overlap with those required for IN/RNA interaction. Mutational analyses validate our model and indicate that the same IN residues are involved in both INI1 and RNA binding. INI1-Rpt1 and TAR RNA compete with each other for IN binding with similar IC50 values. INI1-interaction-defective IN mutant viruses are impaired for incorporation of INI1 into virions and for particle morphogenesis. Computational modeling of IN-CTD/TAR complex indicates that the TAR interface phosphates overlap with negatively charged surface residues of INI1-Rpt1 in three-dimensional space, suggesting that INI1-Rpt1 domain structurally mimics TAR. This possible mimicry between INI1-Rpt1 and TAR explains the mechanism by which INI1/SMARCB1 influences HIV-1 late events and suggests additional strategies to inhibit HIV-1 replication.
Estimating COVID-19 mortality in Italy early in the COVID-19 pandemic
Authors: Modi Chirag , Böhm Vanessa , Ferraro Simone , Stein George , Seljak Uroš
Published: May 2021

Estimating rates of COVID-19 infection and associated mortality is challenging due to uncertainties in case ascertainment. We perform a counterfactual time series analysis on overall mortality data from towns in Italy, comparing the population mortality in 2020 with previous years, to estimate mortality from COVID-19. We find that the number of COVID-19 deaths in Italy in 2020 until September 9 was 59,000–62,000, compared to the official number of 36,000. The proportion of the population that died was 0.29% in the most affected region, Lombardia, and 0.57% in the most affected province, Bergamo. Combining reported test positive rates from Italy with estimates of infection fatality rates from the Diamond Princess cruise ship, we estimate the infection rate as 29% (95% confidence interval 15–52%) in Lombardy, and 72% (95% confidence interval 36–100%) in Bergamo.
Extensive introgression and mosaic genomes of Mediterranean endemic lizards
Authors: Yang Weizhao , Feiner Nathalie , Pinho Catarina , While Geoffrey M. , Kaliontzopoulou Antigoni , Harris D. James , Salvi Daniele , Uller Tobias
Published: May 2021

The Mediterranean basin is a hotspot of biodiversity, fuelled by climatic oscillation and geological change over the past 20 million years. Wall lizards of the genusPodarcisare among the most abundant, diverse, and conspicuous Mediterranean fauna. Here, we unravel the remarkably entangled evolutionary history of wall lizards by sequencing genomes of 34 major lineages covering 26 species. We demonstrate an early (>11 MYA) separation into two clades centred on the Iberian and Balkan Peninsulas, and two clades of Mediterranean island endemics. Diversification within these clades was pronounced between 6.5–4.0 MYA, a period spanning the Messinian Salinity Crisis, during which the Mediterranean Sea nearly dried up before rapidly refilling. However, genetic exchange between lineages has been a pervasive feature throughout the entire history of wall lizards. This has resulted in a highly reticulated pattern of evolution across the group, characterised by mosaic genomes with major contributions from two or more parental taxa. These hybrid lineages gave rise to several of the extant species that are endemic to Mediterranean islands. The mosaic genomes of island endemics may have promoted their extraordinary adaptability and striking diversity in body size, shape and colouration, which have puzzled biologists for centuries.
Colossal topological Hall effect at the transition between isolated and lattice-phase interfacial skyrmions
Authors: Raju M. , Petrović A. P. , Yagil A. , Denisov K. S. , Duong N. K. , Göbel B. , Şaşıoğlu E. , Auslaender O. M. , Mertig I. , Rozhansky I. V. , Panagopoulos C.
Published: May 2021

The topological Hall effect is used extensively to study chiral spin textures in various materials. However, the factors controlling its magnitude in technologically-relevant thin films remain uncertain. Using variable-temperature magnetotransport and real-space magnetic imaging in a series of Ir/Fe/Co/Pt heterostructures, here we report that the chiral spin fluctuations at the phase boundary between isolated skyrmions and a disordered skyrmion lattice result in a power-law enhancement of the topological Hall resistivity by up to three orders of magnitude. Our work reveals the dominant role of skyrmion stability and configuration in determining the magnitude of the topological Hall effect.
Landscape of allele-specific transcription factor binding in the human genome
Authors: Abramov Sergey , Boytsov Alexandr , Bykova Daria , Penzar Dmitry D. , Yevshin Ivan , Kolmykov Semyon K. , Fridman Marina V. , Favorov Alexander V. , Vorontsov Ilya E. , Baulin Eugene , Kolpakov Fedor , Makeev Vsevolod J. , Kulakovskiy Ivan V.
Published: May 2021

Sequence variants in gene regulatory regions alter gene expression and contribute to phenotypes of individual cells and the whole organism, including disease susceptibility and progression. Single-nucleotide variants in enhancers or promoters may affect gene transcription by altering transcription factor binding sites. Differential transcription factor binding in heterozygous genomic loci provides a natural source of information on such regulatory variants. We present a novel approach to call the allele-specific transcription factor binding events at single-nucleotide variants in ChIP-Seq data, taking into account the joint contribution of aneuploidy and local copy number variation, that is estimated directly from variant calls. We have conducted a meta-analysis of more than 7 thousand ChIP-Seq experiments and assembled the database of allele-specific binding events listing more than half a million entries at nearly 270 thousand single-nucleotide polymorphisms for several hundred human transcription factors and cell types. These polymorphisms are enriched for associations with phenotypes of medical relevance and often overlap eQTLs, making candidates for causality by linking variants with molecular mechanisms. Specifically, there is a special class of switching sites, where different transcription factors preferably bind alternative alleles, thus revealing allele-specific rewiring of molecular circuitry.
Spectroscopy of a tunable moiré system with a correlated and topological flat band
Authors: Liu Xiaomeng , Chiu Cheng-Li , Lee Jong Yeon , Farahi Gelareh , Watanabe Kenji , Taniguchi Takashi , Vishwanath Ashvin , Yazdani Ali
Published: May 2021

Moiré superlattices created by the twisted stacking of two-dimensional crystals can host electronic bands with flat energy dispersion in which enhanced interactions promote correlated electron states. The twisted double bilayer graphene (TDBG), where two Bernal bilayer graphene are stacked with a twist angle, is such a moiré system with tunable flat bands. Here, we use gate-tuned scanning tunneling spectroscopy to directly demonstrate the tunability of the band structure of TDBG with an electric field and to show spectroscopic signatures of electronic correlations and topology for its flat band. Our spectroscopic experiments are in agreement with a continuum model of TDBG band structure and reveal signatures of a correlated insulator gap at partial filling of its isolated flat band. The topological properties of this flat band are probed with the application of a magnetic field, which leads to valley polarization and the splitting of Chern bands with a large effective g-factor.
A stem cell population at the anorectal junction maintains homeostasis and participates in tissue regeneration
Authors: Mitoyan Louciné , Chevrier Véronique , Hernandez-Vargas Hector , Ollivier Alexane , Homayed Zeinab , Pannequin Julie , Poizat Flora , De Biasi-Cador Cécile , Charafe-Jauffret Emmanuelle , Ginestier Christophe , Guasch Géraldine
Published: May 2021

At numerous locations of the body, transition zones are localized at the crossroad between two types of epithelium and are frequently associated with neoplasia involving both type of tissues. These transition zones contain cells expressing markers of adult stem cells that can be the target of early transformation. The mere fact that transition zone cells can merge different architecture with separate functions implies for a unique plasticity that these cells must display in steady state. However, their roles during tissue regeneration in normal and injured state remain unknown. Here, by using in vivo lineage tracing, single-cell transcriptomics, computational modeling and a three-dimensional organoid culture system of transition zone cells, we identify a population of Krt17+ basal cells with multipotent properties at the squamo-columnar anorectal junction that maintain a squamous epithelium during normal homeostasis and can participate in the repair of a glandular epithelium following tissue injury.
Mitofusin-2 stabilizes adherens junctions and suppresses endothelial inflammation via modulation of β-catenin signaling
Authors: Kim Young-Mee , Krantz Sarah , Jambusaria Ankit , Toth Peter T. , Moon Hyung-Geun , Gunarathna Isuru , Park Gye Young , Rehman Jalees
Published: May 2021

Endothelial barrier integrity is ensured by the stability of the adherens junction (AJ) complexes comprised of vascular endothelial (VE)-cadherin as well as accessory proteins such as β-catenin and p120-catenin. Disruption of the endothelial barrier due to disassembly of AJs results in tissue edema and the influx of inflammatory cells. Using three-dimensional structured illumination microscopy, we observe that the mitochondrial protein Mitofusin-2 (Mfn2) co-localizes at the plasma membrane with VE-cadherin and β-catenin in endothelial cells during homeostasis. Upon inflammatory stimulation, Mfn2 is sulfenylated, the Mfn2/β-catenin complex disassociates from the AJs and Mfn2 accumulates in the nucleus where Mfn2 negatively regulates the transcriptional activity of β-catenin. Endothelial-specific deletion of Mfn2 results in inflammatory activation, indicating an anti-inflammatory role of Mfn2 in vivo. Our results suggest that Mfn2 acts in a non-canonical manner to suppress the inflammatory response by stabilizing cell–cell adherens junctions and by binding to the transcriptional activator β-catenin.
Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease
Authors: Chen Chun , McDonald David , Blain Alasdair , Sachdeva Ashwin , Bone Laura , Smith Anna L. M. , Warren Charlotte , Pickett Sarah J. , Hudson Gavin , Filby Andrew , Vincent Amy E. , Turnbull Doug M. , Reeve Amy K.
Published: May 2021

Here we report the application of a mass spectrometry-based technology, imaging mass cytometry, to perform in-depth proteomic profiling of mitochondrial complexes in single neurons, using metal-conjugated antibodies to label post-mortem human midbrain sections. Mitochondrial dysfunction, particularly deficiency in complex I has previously been associated with the degeneration of dopaminergic neurons in Parkinson’s disease. To further our understanding of the nature of this dysfunction, and to identify Parkinson’s disease specific changes, we validated a panel of antibodies targeting subunits of all five mitochondrial oxidative phosphorylation complexes in dopaminergic neurons from Parkinson’s disease, mitochondrial disease, and control cases. Detailed analysis of the expression profile of these proteins, highlighted heterogeneity between individuals. There is a widespread decrease in expression of all complexes in Parkinson’s neurons, although more severe in mitochondrial disease neurons, however, the combination of affected complexes varies between the two groups. We also provide evidence of a potential neuronal response to mitochondrial dysfunction through a compensatory increase in mitochondrial mass. This study highlights the use of imaging mass cytometry in the assessment and analysis of expression of oxidative phosphorylation proteins, revealing the complexity of deficiencies of these proteins within individual neurons which may contribute to and drive neurodegeneration in Parkinson’s disease.
Eye movements in patients in early psychosis with and without a history of cannabis use
Authors: Sami Musa Basseer , Annibale Luciano , O’Neill Aisling , Collier Tracy , Onyejiaka Chidimma , Eranti Savitha , Das Debasis , Kelbrick Marlene , McGuire Philip , Williams Steve C. R. , Rana Anas , Ettinger Ulrich , Bhattacharyya Sagnik
Published: May 2021

It is unclear whether early psychosis in the context of cannabis use is different from psychosis without cannabis. We investigated this issue by examining whether abnormalities in oculomotor control differ between patients with psychosis with and without a history of cannabis use. We studied four groups: patients in the early phase of psychosis with a history of cannabis use (EPC; n = 28); patients in the early phase of psychosis without (EPNC; n = 25); controls with a history of cannabis use (HCC; n = 16); and controls without (HCNC; n = 22). We studied smooth pursuit eye movements using a stimulus with sinusoidal waveform at three target frequencies (0.2, 0.4 and 0.6 Hz). Participants also performed 40 antisaccade trials. There were no differences between the EPC and EPNC groups in diagnosis, symptom severity or level of functioning. We found evidence for a cannabis effect (χ2 = 23.14, p < 0.001), patient effect (χ2 = 4.84, p = 0.028) and patient × cannabis effect (χ2 = 4.20, p = 0.04) for smooth pursuit velocity gain. There was a large difference between EPC and EPNC (g = 0.76–0.86) with impairment in the non cannabis using group. We found no significant effect for antisaccade error whereas patients had fewer valid trials compared to controls. These data indicate that impairment of smooth pursuit in psychosis is more severe in patients without a history of cannabis use. This is consistent with the notion that the severity of neurobiological alterations in psychosis is lower in patients whose illness developed in the context of cannabis use.
Superior haplotypes towards development of low glycemic index rice with preferred grain and cooking quality
Authors: Selvaraj Ramchander , Singh Arun Kumar , Singh Vikas Kumar , Abbai Ragavendran , Habde Sonali Vijay , Singh Uma Maheshwar , Kumar Arvind
Published: May 2021

Increasing trends in the occurrence of diabetes underline the need to develop low glycemic index (GI) rice with preferred grain quality. In the current study, a diverse set of 3 K sub-panel of rice consisting of 150 accessions was evaluated for resistant starch and predicted glycemic index, including nine other quality traits under transplanted situation. Significant variations were noticed among the accessions for the traits evaluated. Trait associations had shown that amylose content possess significant positive and negative association with resistant starch and predicted glycemic index. Genome-wide association studies with 500 K SNPs based on MLM model resulted in a total of 41 marker-trait associations (MTAs), which were further confirmed and validated with mrMLM multi-locus model. We have also determined the allelic effect of identified MTAs for 11 targeted traits and found favorable SNPs for 8 traits. A total of 11 genes were selected for haplo-pheno analysis to identify the superior haplotypes for the target traits where haplotypes ranges from 2 (Os10g0469000-GC) to 15 (Os06g18720-AC). Superior haplotypes for RS and PGI, the candidate gene Os06g11100 (H4-3.28% for high RS) and Os08g12590 (H13-62.52 as intermediate PGI). The identified superior donors possessing superior haplotype combinations may be utilized in Haplotype-based breeding to developing next-generation tailor-made high quality healthier rice varieties suiting consumer preference and market demand.
Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer’s disease mouse model
Authors: Fujita Yu , Kano Kuniyuki , Kishino Shigenobu , Nagao Toshihiro , Shen Xuefeng , Sato Chiharu , Hatakeyama Hatsune , Ota Yume , Niibori Sho , Nomura Ayako , Kikuchi Kota , Yasuno Wataru , Takatori Sho , Kikuchi Kazunori , Sano Yoshitake , Tomita Taisuke , Suzuki Toshiharu , Aoki Junken , Zou Kun , Natori Shunji , Komano Hiroto
Published: May 2021

Conjugated linoleic acid (CLA) is an isomer of linoleic acid (LA). The predominant dietary CLA is cis-9, trans-11-CLA (c-9, t-11-CLA), which constitutes up to ~ 90% of total CLA and is thought to be responsible for the positive health benefits associated with CLA. However, the effects of c-9, t-11-CLA on Alzheimer’s disease (AD) remain to be elucidated. In this study, we investigated the effect of dietary intake of c-9, t-11-CLA on the pathogenesis of an AD mouse model. We found that c-9, t-11-CLA diet-fed AD model mice significantly exhibited (1) a decrease in amyloid-β protein (Aβ) levels in the hippocampus, (2) an increase in the number of microglia, and (3) an increase in the number of astrocytes expressing the anti-inflammatory cytokines, interleukin-10 and 19 (IL-10, IL-19), with no change in the total number of astrocytes. In addition, liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatographic analysis revealed that the levels of lysophosphatidylcholine (LPC) containing c-9, t-11-CLA (CLA-LPC) and free c-9, t-11-CLA were significantly increased in the brain of c-9, t-11-CLA diet-fed mice. Thus, dietary c-9, t-11-CLA entered the brain and appeared to exhibit beneficial effects on AD, including a decrease in Aβ levels and suppression of inflammation.
Computer-aided autism diagnosis based on visual attention models using eye tracking
Authors: Oliveira Jessica S. , Franco Felipe O. , Revers Mirian C. , Silva Andréia F. , Portolese Joana , Brentani Helena , Machado-Lima Ariane , Nunes Fátima L. S.
Published: May 2021

An advantage of using eye tracking for diagnosis is that it is non-invasive and can be performed in individuals with different functional levels and ages. Computer/aided diagnosis using eye tracking data is commonly based on eye fixation points in some regions of interest (ROI) in an image. However, besides the need for every ROI demarcation in each image or video frame used in the experiment, the diversity of visual features contained in each ROI may compromise the characterization of visual attention in each group (case or control) and consequent diagnosis accuracy. Although some approaches use eye tracking signals for aiding diagnosis, it is still a challenge to identify frames of interest when videos are used as stimuli and to select relevant characteristics extracted from the videos. This is mainly observed in applications for autism spectrum disorder (ASD) diagnosis. To address these issues, the present paper proposes: (1) a computational method, integrating concepts of Visual Attention Model, Image Processing and Artificial Intelligence techniques for learning a model for each group (case and control) using eye tracking data, and (2) a supervised classifier that, using the learned models, performs the diagnosis. Although this approach is not disorder-specific, it was tested in the context of ASD diagnosis, obtaining an average of precision, recall and specificity of 90%, 69% and 93%, respectively.