bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between parental and offspring BMI: results from EPACI Portugal 2012
Authors: Nazareth Margarida , Pinto Elisabete , Severo Milton , Lopes Carla , Rêgo Carla
Published: April 2021

Objective:

To assess the longitudinal association between parental BMI and offspring’s BMI, in EPACI Portugal 2012.

Design:

Longitudinal study with retrospective collection of children’s anthropometry data since birth. Children’s anthropometric data were gathered from individual child health bulletins, and parents’ anthropometrics were self-reported. Children’s and parents’ BMI were classified according to WHO cut-offs. Linear mixed models with random intercept and slope for age were applied to quantify the association between parental BMI and children BMIZ-score (zBMI).

Setting:

EPACI Portugal 2012.

Participants:

Representative sample from the Portuguese population (n2230) aged from 12 to 36 months.

Results:

58·9 % of the fathers and 35·6 % of the mothers were overweight (OW) or obese. Prevalence of infants who were, at least, at risk of OW increased from 17·0 % to 30·3 % since birth to 12 months. About half of the mothers with pre-pregnancy OW and obesity (OB) gained gestational weight above the recommendations. The children from mothers with gestational weight gain (GWG) below the recommendations showed a −0·15SDlower zBMI (95 % CI −0·23, −0·06) in early life, comparing with mothers within GWG recommendations. Children of obese mothers were more likely to present a higher zBMI (0·24SD, 95 % CI 0·13, 0·35) throughout the first months of life.

Conclusions:

A high prevalence of OW and OB was observed in Portuguese young adults and toddlers. Mothers’ pre-pregnancy BMI and insufficient GWG had a direct effect on offspring BMI. Early effective interventions are needed in order to prevent the transgenerational transmission of OB.
Radiation-induced nausea and vomiting: a clinical audit of prophylactic antiemetic use
Authors: Alden-Bennett Verity , Ball Bev , Nightingale Hannah , Bridge Pete
Published: April 2021

Introduction:

Radiation-induced nausea and vomiting (RINV) is a common side effect of single fraction palliative radiotherapy. Patients experiencing RINV have significantly reduced quality of life and a prescription of prophylactic antiemetics, principally 5-HT3 antagonists, is recommended. There is a growing body of evidence relating to indications for this, but as yet there are no national guidelines.

Methods:

A retrospective audit aimed to determine the extent to which patients at high and moderate emetogenic risk receiving single fraction radiotherapy were prescribed prophylactic emetic medication in line with the current evidence base.

Results:

A total of 60 patients were included in the audit; of these patients, 50 were consented for the risk of nausea and/or vomiting. Prophylactic antiemetics were only prescribed to 28 (46·7%) of all audited patients. Out of the 50 patients who provided informed consent, only 24 (48%) were prescribed an antiemetic prior to their treatment.

Conclusion:

Antiemetic prescribing for single fraction patients at moderate to high emetogenic risk at a large regional centre is underutilised in relation to published evidence. Amended guidance and further audits are recommended to ensure that this patient group is best supported.
From converts to cooperation: Protestant internationalism, US missionaries and Indian Christians and ‘Professional’ social work between Boston and Bombay (c. 1920–1950)
Authors: Brunner Michael Phillipp
Published: April 2021

The 1920s and 30s were a high phase of liberal missionary internationalism driven especially by American-led visions of the Social Gospel. As the missionary consensus shifted from proselytization to social concerns, the indigenization of missions and the role of the ‘younger churches’ outside of Europe and North America was brought into focus. This article shows how Protestant internationalism pursued a ‘Christian Sociology’ in dialogue with the field’s academic and professional form.

Through the case study of settlement sociology and social work schemes by the American Marathi Mission (AMM) in Bombay, the article highlights the intricacies of applying internationalist visions in the field and asks how they were contested and shaped by local conditions and processes. Challenging a simplistic ‘secularization’ narrative, the article then argues that it was the liberal, anti-imperialist drive of the missionary discourse that eventually facilitated an American ‘professional imperialism’ in the development of secular social work in India. Adding local dynamics to the analysis of an internationalist discourse benefits the understanding of both Protestant internationalism and the genesis of Indian social work and shows the value of an integrated global micro-historical approach.
ESTAMOS DISTANCIADOS
Authors: Pattillo Mary , Rico Rosa Emilia Bermúdez , Guevara Ana María Mosquera
Published: April 2021

A Black middle class has emerged in many Latin American countries. Yet given the fluidity of Black identity, it is unclear if socioeconomic gains will result in the consolidation of a Black middle-class group identity with a sense of political responsibility or purpose. In this article, we use qualitative interviews with twenty-two Black professionals in Cali, Colombia, plus a small convenience survey, to explore the following research questions: Does the intersection of being Black and middle class cohere into a group identity? If so, does it translate into a Black political consciousness? And if not, what are the obstacles? We find that while respondents individually identify with a Black middle-class label, they do not experience it as a group that feels symbolic bonds of attachment or acts in a coordinated or mutually cognizant manner. It is a category without shape or coherence. It is amorphous. There are four primary explanations for Black middle class amorphism: the absence of shared or positive markers of collective Black identity; a lack of organizational infrastructure; taboos against organizing along racial lines in the workplace; and a strong individualist ethos towards protecting opportunities and enhancing personal status. We situate our findings within the field of Black politics to discuss what might be lost or gained by this amorphism.
Correlational Evidence for the Role of Spatial Perspective-Taking Ability in the Mental Rotation of Human-Like Objects
Authors: Muto Hiroyuki
Published: April 2021

Abstract. People can mentally rotate objects that resemble human bodies more efficiently than nonsense objects in the same/different judgment task. Previous studies proposed that this human-body advantage in mental rotation is mediated by one's projections of body axes onto a human-like object, implying that human-like objects elicit a strategy shift, from an object-based to an egocentric mental rotation. To test this idea, we investigated whether mental rotation performance involving a human-like object had a stronger association with spatial perspective-taking, which entails egocentric mental rotation, than a nonsense object. In the present study, female participants completed a chronometric mental rotation task with nonsense and human-like objects. Their spatial perspective-taking ability was then assessed using the Road Map Test and the Spatial Orientation Test. Mental rotation response times (RTs) were shorter for human-like than for nonsense objects, replicating previous research. More importantly, spatial perspective-taking had a stronger negative correlation with RTs for human-like than for nonsense objects. These findings suggest that human-like stimuli in the same/different mental rotation task induce a strategy shift toward efficient egocentric mental rotation.
Meaningful Versus Meaningless Sounds and Words
Authors: Olszewska Justyna , Hodel Amy , Falkowski Andrzej , Woldt Bernadette , Bednarek Hanna , Luttenberger Deanna
Published: April 2021

Abstract. The current study assessed memory performance for perceptually similar environmental sounds and speech-based material after short and long delays. In two studies, we demonstrated a similar pattern of memory performance for sounds and words in short-term memory, yet in long-term memory, the performance patterns differed. Experiment 1 examined the effects of two different types of sounds: meaningful (MFUL) and meaningless (MLESS), whereas Experiment 2 assessed memory performance for words and nonwords. We utilized a modified version of the classical Deese–Roediger–McDermott ( Deese, 1959 ; Roediger & McDermott, 1995 ) procedure and adjusted it to test the effects of acoustic similarities between auditorily presented stimuli. Our findings revealed no difference in memory performance between MFUL and MLESS sounds, and between words and nonwords after short delays. However, following long delays, greater reliance on meaning was noticed for MFUL sounds than MLESS sounds, while performance for linguistic material did not differ between words and nonwords. Importantly, participants' memory performance for words and nonwords was accompanied by a more lenient response strategy. The results are discussed in terms of perceptual and semantic similarities between MLESS and MFUL sounds, as well as between words and nonwords.
Fifty Year Trends in Global Ocean Heat Content Traced to Surface Heat Fluxes in the Sub‐Polar Ocean
Authors: Sohail Taimoor , Irving Damien B. , Zika Jan D. , Holmes Ryan M. , Church John A.
Published: April 2021

The ocean has absorbed approximately 90% of the accumulated heat in the climate system since 1970. As global warming accelerates, understanding ocean heat content changes and tracing these to surface heat input is increasingly important. We introduce a novel framework by organizing the ocean into temperature‐percentiles from warmest to coldest, allowing us to trace ocean temperature changes to changes in surface fluxes and mixing. Applying this framework to observations and historical CMIP6 simulations, we find that 50 ± 6% of surface heat uptake between 1970 and 2014 is confined to isotherms in the coldest 90% of the ocean volume. These isotherms outcrop over only 23% of the ocean's surface area in the sub‐polar regions, implying a disproportionately large heat input per unit area. Additionally, a cooling bias in the CMIP6 models is traced to inaccurate sea surface temperatures and surface heat fluxes into the warmest 5%–20% of the ocean volume.
Seismological Structures on Bimodal Distribution of Deep Tectonic Tremor
Authors: Sawaki Yasunori , Ito Yoshihiro , Ohta Kazuaki , Shibutani Takuo , Iwata Tomotaka
Published: April 2021

Deep tectonic tremors occur at the downdip extent of the seismogenic zone due to fluid processes. Beneath the northeastern Kii Peninsula, southwestern Japan, there is an along‐dip bimodal distribution of tremor. However, no constraint exists on the structures controlling that distribution. We extract detailed seismological structures from multi‐band receiver functions and evaluate conditional differences in the distribution. To achieve high resolution images along the plate interface, we utilize records of regional deep‐focus earthquakes from the Pacific slab. Cross‐section images show the subducting oceanic plate with depth‐dependent phases along the bimodal distribution, revealing a conspicuous plate interface at the updip portion and an inconspicuous interface below the mantle wedge at the downdip portion. This indicates that episodic tremors occur in the high pore‐fluid plate interface below the impermeable forearc crust, and that continual tremors occur at the permeable mantle wedge corner, owing to continuous fluid supply from the oceanic crust.
Modeling Interplanetary Expansion and Deformation of CMEs With ANTEATR‐PARADE: Relative Contribution of Different Forces
Authors: Kay C. , Nieves‐Chinchilla T.
Published: April 2021

Coronal Mass Ejections (CMEs) are key drivers of space weather activity but most predictions have been limited to the expected arrival time of a CME, rather than the internal properties that affect the severity of an impact. Many properties, such as the magnetic field density and mass density, follow conservation laws and vary systematically with changes in the size of a CME. We present ANTEATR‐PARADE, the newest version of the ANTEATR arrival time model, which now includes physics‐driven changes in the size and shape of both the CME's central axis and its cross section. Internal magnetic and thermal and external drag forces affect the acceleration of the CME in different directions, inducing asymmetries between the radial and perpendicular directions. These improvements should lead to more realistic CME velocities, both bulk and expansion, sizes and shapes, and internal properties. We present the model details, an initial illustration of the general behavior, and a study of the relative importance of the different forces. The model shows a pancaking of both the cross section and central axis of the CME so that their radial extent becomes smaller than their extent in the perpendicular direction. We find that the initial velocities, drag, any form of cross section expansion, and the precise form of thermal expansion have strong effects. The results are less sensitive to axial forces and the specific form of the cross section expansion.
Predicted Vulnerability of Carbon in Permafrost Peatlands With Future Climate Change and Permafrost Thaw in Western Canada
Authors: Treat Claire C. , Jones Miriam C. , Alder Jay , Sannel A. Britta K. , Camill Philip , Frolking Steve
Published: April 2021

Climate warming in high‐latitude regions is thawing carbon‐rich permafrost soils, which can release carbon to the atmosphere and enhance climate warming. Using a coupled model of long‐term peatland dynamics (Holocene Peat Model, HPM‐Arctic), we quantify the potential loss of carbon with future climate warming for six sites with differing climates and permafrost histories in Northwestern Canada. We compared the net carbon balance at 2100 CE resulting from new productivity and the decomposition of active layer and newly thawed permafrost peats under RCP8.5 as a high‐end constraint. Modeled net carbon losses ranged from −3.0 kg C m−2 (net loss) to +0.1 kg C m−2 (net gain) between 2015 and 2100. Losses of newly thawed permafrost peat comprised 0.2%–25% (median: 1.6%) of “old” C loss, which were related to the residence time of peat in the active layer before being incorporated into the permafrost, peat temperature, and presence of permafrost. The largest C loss was from the permafrost‐free site, not from permafrost sites. C losses were greatest from depths of 0.2–1.0 m. New C added to the profile through net primary productivity between 2015 and 2100 offset ∼40% to >100% of old C losses across the sites. Differences between modeled active layer deepening and flooding following permafrost thaw resulted in very small differences in net C loss by 2100, illustrating the important role of present‐day conditions and permafrost aggradation history in controlling net C loss.
Game Theoretic Countermeasure Analysis for Multistatic Radars and Multiple Jammers
Authors: He Bin , Su Hongtao
Published: April 2021

Radar and jammer can be considered as two players in the countermeasure game of electronic warfare (EW). A game framework for joint beamforming and power allocation is investigated for multistatic radars and multiple jammers in this paper. Under a certain target detection criterion, the major aim of every radar is to reduce its power consumption and suppress various jammings. Conversely, the multi‐agent jammers determine their transmitting power strategies to interfere with the multistatic radar network, which is based on the transmitting power of the radars. According to the countermeasure game, both existence and uniqueness are strictly confirmed about the Nash Equilibrium (NE) of the proposed game. Besides, the receive beamformer weight vector can be obtained by minimum variance distortionless response (MVDR). And the corresponding transmit beamformer weight vector is also obtained. An algorithm for joint beamforming and power allocation is proposed, which is iteratively convergent. Finally, the convergence and validity for the proposed algorithm and the interference rejection capability of the multistatic radars are supported by the numerical results.
Development of 3‐D Curved Fracture Swarms in Shale Rock Driven by Rapid Fluid Pressure Buildup: Insights From Numerical Modeling
Authors: Li Sanbai , Zhang Dongxiao
Published: April 2021

Despite the variety of studies that have investigated the development of fracture networks during kerogen maturation in organic‐rich shale, the fracture interaction modes and generation mechanisms in three‐dimensions are not yet fully understood. In this study, we introduce a novel numerical approach to model the evolution of fracture swarms with three‐dimensional nonplanar geometries. This model enables precise simulation of the propagation, interplay, and coalescence of the fracture swarms with variable apertures and geometries via solving fluid flow, fracture growth, and stress interference. Our results suggest five basic fracture interaction modes between neighboring fractures. The evolving fracture swarms exhibit simultaneous, alternant, and differential growth characteristics at different development phases. We also elucidate the mechanical mechanisms that determine the evolution of three‐dimensional curved fracture swarms. This work yields an improved understanding of fluid‐driven fracture swarms' development in organic‐rich shale due to rapid fluid generation.
PRDM4 inhibits cell proliferation and tumorigenesis by inactivating the PI3K/AKT signaling pathway through targeting of PTEN in cervical carcinoma
Authors: Yang Wen-Ting , Chen Mei , Xu Rui , Zheng Peng-Sheng
Published: April 2021

PR domain zinc finger protein 4 (PRDM4) is a transcription factor that plays key roles in stem cell self-renewal and tumorigenesis. However, its biological role and exact mechanism in cervical cancer remain unknown. Here, both immunohistochemistry (IHC) and Western blot assays demonstrated that the expression of PRDM4 in cervical cancer tissues was much lower than that in the normal cervix. A xenograft assay showed that PRDM4 overexpression in the cervical cancer cell lines SiHa and HeLa dramatically inhibited cell proliferation and tumorigenic potential in vivo. Conversely, the silencing of PRDM4 promoted cervical cancer cell proliferation and tumorigenic potential. Mechanistically, PRDM4 induced cell cycle arrest at the transition from G0/G1 phase to S phase by upregulating p27 and p21 expression and downregulating Cyclin D1 and CDK4 expression. Furthermore, the PI3K/AKT signaling pathway was inactivated in PRDM4-overexpressing cells, which decreased the levels of p-AKT and upregulated the expression of PTEN, an inhibitor of the PI3K/AKT signaling pathway, at both the transcriptional and translational levels. Dual-luciferase reporter assays and qChIP assays confirmed that PRDM4 transactivated the expression of PTEN by binding to two specific regions in thePTENpromoter. Furthermore, PTEN silencing or a PTEN inhibitor rescued the cell defects induced by PRDM4 overexpression. Therefore, our data suggest that PRDM4 inhibits cell proliferation and tumorigenesis by downregulating the activity of the PI3K/AKT signaling pathway by directly transactivating PTEN expression in cervical cancer.
Whole-exome sequencing with targeted analysis and epilepsy after acute symptomatic neonatal seizures
Authors: Numis Adam L. , da Gente Gilberto , Sherr Elliott H. , Glass Hannah C.
Published: April 2021

Background

The contribution of pathogenic gene variants with development of epilepsy after acute symptomatic neonatal seizures is not known.

Methods

Case–control study of 20 trios in children with a history of acute symptomatic neonatal seizures: 10 with and 10 without post-neonatal epilepsy. We performed whole-exome sequencing (WES) and identified pathogenic de novo, transmitted, and non-transmitted variants from established and candidate epilepsy association genes and correlated prevalence of these variants with epilepsy outcomes. We performed a sensitivity analysis with genes associated with coronary artery disease (CAD). We analyzed variants throughout the exome to evaluate for differential enrichment of functional properties using exploratory KEGG searches.

Results

Querying 200 established and candidate epilepsy genes, pathogenic variants were identified in 5 children with post-neonatal epilepsy yet in only 1 child without subsequent epilepsy. There was no difference in the number of trios with non-transmitted pathogenic variants in epilepsy or CAD genes. An exploratory KEGG analysis demonstrated a relative enrichment in cell death pathways in children without subsequent epilepsy.

Conclusions

In this pilot study, children with epilepsy after acute symptomatic neonatal seizures had a higher prevalence of coding variants with a targeted epilepsy gene sequencing analysis compared to those patients without subsequent epilepsy.

Impact

We performed whole-exome sequencing (WES) in 20 trios, including 10 children with epilepsy and 10 without epilepsy, both after acute symptomatic neonatal seizures.

Children with post-neonatal epilepsy had a higher burden of pathogenic variants in epilepsy-associated genes compared to those without post-neonatal epilepsy.

Future studies evaluating this association may lead to a better understanding of the risk of epilepsy after acute symptomatic neonatal seizures and elucidate molecular pathways that are dysregulated after brain injury and implicated in epileptogenesis.
The curious consistency of carbon biosignatures over billions of years of Earth-life coevolution
Authors: Garcia Amanda K , Cavanaugh Colleen M , Kacar Betul
Published: April 2021

The oldest and most wide-ranging signal of biological activity (biosignature) on our planet is the carbon isotope composition of organic materials preserved in rocks. These biosignatures preserve the long-term evolution of the microorganism-hosted metabolic machinery responsible for producing deviations in the isotopic compositions of inorganic and organic carbon. Despite billions of years of ecosystem turnover, evolutionary innovation, organismic complexification, and geological events, the organic carbon that is a residuum of the global marine biosphere in the rock record tells an essentially static story. The ~25‰ mean deviation between inorganic and organic 13C/12C values has remained remarkably unchanged over >3.5 billion years. The bulk of this record is conventionally attributed to early-evolved, RuBisCO-mediated CO2 fixation that, in extant oxygenic phototrophs, produces comparable isotopic effects and dominates modern primary production. However, billions of years of environmental transition, for example, in the progressive oxygenation of the Earth’s atmosphere, would be expected to have accompanied shifts in the predominant RuBisCO forms as well as enzyme-level adaptive responses in RuBisCO CO2-specificity. These factors would also be expected to result in preserved isotopic signatures deviating from those produced by extant RuBisCO in oxygenic phototrophs. Why does the bulk carbon isotope record not reflect these expected environmental transitions and evolutionary innovations? Here, we discuss this apparent discrepancy and highlight the need for greater quantitative understanding of carbon isotope fractionation behavior in extant metabolic pathways. We propose novel, laboratory-based approaches to reconstructing ancestral states of carbon metabolisms and associated enzymes that can constrain isotopic biosignature production in ancient biological systems. Together, these strategies are crucial for integrating the complementary toolsets of biological and geological sciences and for interpretation of the oldest record of life on Earth.
Correction to: Multimethod investigation of the neurobiological basis of ADHD symptomatology in children aged 9-10: baseline data from the ABCD study
Authors: Owens Max M. , Allgaier Nicholas , Hahn Sage , Yuan DeKang , Albaugh Matthew , Adise Shana , Chaarani Bader , Ortigara Joseph , Juliano Anthony , Potter Alexandra , Garavan Hugh
Published: April 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41398-021-01320-y
Attractor cortical neurodynamics, schizophrenia, and depression
Authors: Rolls Edmund T.
Published: April 2021

The local recurrent collateral connections between cortical neurons provide a basis for attractor neural networks for memory, attention, decision-making, and thereby for many aspects of human behavior. In schizophrenia, a reduction of the firing rates of cortical neurons, caused for example by reduced NMDA receptor function or reduced spines on neurons, can lead to instability of the high firing rate attractor states that normally implement short-term memory and attention in the prefrontal cortex, contributing to the cognitive symptoms. Reduced NMDA receptor function in the orbitofrontal cortex by reducing firing rates may produce negative symptoms, by reducing reward, motivation, and emotion. Reduced functional connectivity between some brain regions increases the temporal variability of the functional connectivity, contributing to the reduced stability and more loosely associative thoughts. Further, the forward projections have decreased functional connectivity relative to the back projections in schizophrenia, and this may reduce the effects of external bottom-up inputs from the world relative to internal top-down thought processes. Reduced cortical inhibition, caused by a reduction of GABA neurotransmission, can lead to instability of the spontaneous firing states of cortical networks, leading to a noise-induced jump to a high firing rate attractor state even in the absence of external inputs, contributing to the positive symptoms of schizophrenia. In depression, the lateral orbitofrontal cortex non-reward attractor network system is over-connected and has increased sensitivity to non-reward, providing a new approach to understanding depression. This is complemented by under-sensitivity and under-connectedness of the medial orbitofrontal cortex reward system in depression.
Impaired AGO2/miR-185-3p/NRP1 axis promotes colorectal cancer metastasis
Authors: Liu Xisheng , Meng Xiaole , Peng Xiao , Yao Qianlan , Zhu Fangming , Ding Zhongyi , Sun Hongze , Liu Xueni , Li Dan , Lu Ying , Tang Huamei , Li Bin , Peng Zhihai
Published: April 2021

Increasing evidence suggests that global downregulation of miRNA expression is a hallmark of human cancer, potentially due to defects in the miRNA processing machinery. In this study, we found that the protein expression of Argonaute 2 (AGO2), a key regulator of miRNA processing, was downregulated in colorectal cancer (CRC) tissues, which was also consistent with the findings of the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Furthermore, the correlation between the levels of AGO2 and epithelial-mesenchymal transition (EMT) markers (E-cadherin and vimentin) indicated that reduced levels of AGO2 promoted EMT in CRC. Low expression of AGO2 was an indicator of a poor prognosis among CRC patients. Knockdown of AGO2 in CRC cells promoted migration, invasion and metastasis formation in vitro and in vivo but had no influence on proliferation. To provide detailed insight into the regulatory roles of AGO2, we performed integrated transcriptomic, quantitative proteomic and microRNA sequencing (miRNA-seq) analyses of AGO2 knockdown cells and the corresponding wild-type cells and identified neuropilin 1 (NRP1) as a new substrate of AGO2 via miR-185-3p. Our data provided evidence that knockdown of AGO2 resulted in a reduction of miR-185-3p expression, leading to the upregulation of the expression of NRP1, which is a direct target of miR-185-3p, and elevated CRC cell metastatic capacity. Inhibition of NRP1 or treatment with a miR-185-3p mimic successfully rescued the phenotypes of impaired AGO2, which suggested that therapeutically targeting the AGO2/miR-185-3p/NRP1 axis may be a potential treatment approach for CRC.
Cellular fate of intersex differentiation
Authors: Wang Xin , Lai Fengling , Shang Dantong , Cheng Yibin , Lan Tian , Cheng Hanhua , Zhou Rongjia
Published: April 2021

Infertile ovotestis (mixture of ovary and testis) often occurs in intersex individuals under certain pathological and physiological conditions. However, how ovotestis is formed remains largely unknown. Here, we report the first comprehensive single-cell developmental atlas of the model ovotestis. We provide an overview of cell identities and a roadmap of germline, niche, and stem cell development in ovotestis by cell lineage reconstruction and a uniform manifold approximation and projection. We identify common progenitors of germline stem cells with two states, which reveal their bipotential nature to differentiate into both spermatogonial stem cells and female germline stem cells. Moreover, we found that ovotestis infertility was caused by degradation of female germline cells via liquid–liquid phase separation of the proteasomes in the nucleus, and impaired histone-to-protamine replacement in spermatid differentiation. Notably, signaling pathways in gonadal niche cells and their interaction with germlines synergistically determined distinct cell fate of both male and female germlines. Overall, we reveal a cellular fate map of germline and niche cell development that shapes cell differentiation direction of ovotestis, and provide novel insights into ovotestis development.
Inositol treatment inhibits medulloblastoma through suppression of epigenetic-driven metabolic adaptation
Authors: Badodi Sara , Pomella Nicola , Zhang Xinyu , Rosser Gabriel , Whittingham John , Niklison-Chirou Maria Victoria , Lim Yau Mun , Brandner Sebastian , Morrison Gillian , Pollard Steven M. , Bennett Christopher D. , Clifford Steven C. , Peet Andrew , Basson M. Albert , Marino Silvia
Published: April 2021

Deregulation of chromatin modifiers plays an essential role in the pathogenesis of medulloblastoma, the most common paediatric malignant brain tumour. Here, we identify a BMI1-dependent sensitivity to deregulation of inositol metabolism in a proportion of medulloblastoma. We demonstrate mTOR pathway activation and metabolic adaptation specifically in medulloblastoma of the molecular subgroup G4 characterised by a BMI1High;CHD7Low signature and show this can be counteracted by IP6 treatment. Finally, we demonstrate that IP6 synergises with cisplatin to enhance its cytotoxicity in vitro and extends survival in a pre-clinical BMI1High;CHD7Low xenograft model.
Role of Hakai in m6A modification pathway in Drosophila
Authors: Wang Yanhua , Zhang Lifeng , Ren Hang , Ma Lijuan , Guo Jian , Mao Decai , Lu Zhongwen , Lu Lijun , Yan Dong
Published: April 2021

N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNA, is installed by a multi-component writer complex; however, the exact roles of each component remain poorly understood. Here we show that a potential E3 ubiquitin ligase Hakai colocalizes and interacts with other m6A writer components, and Hakai mutants exhibit typical m6A pathway defects in Drosophila, such as lowered m6A levels in mRNA, aberrant Sxl alternative splicing, wing and behavior defects. Hakai, Vir, Fl(2)d and Flacc form a stable complex, and disruption of either Hakai, Vir or Fl(2)d led to the degradation of the other three components. Furthermore, MeRIP-seq indicates that the effective m6A modification is mostly distributed in 5’ UTRs in Drosophila, in contrast to the mammalian system. Interestingly, we demonstrate that m6A modification is deposited onto the Sxl mRNA in a sex-specific fashion, which depends on the m6A writer. Together, our work not only advances the understanding of mechanism and regulation of the m6A writer complex, but also provides insights into how Sxl cooperate with the m6A pathway to control its own splicing.
Poaceae-specific cell wall-derived oligosaccharides activate plant immunity via OsCERK1 during Magnaporthe oryzae infection in rice
Authors: Yang Chao , Liu Rui , Pang Jinhuan , Ren Bin , Zhou Huanbin , Wang Gang , Wang Ertao , Liu Jun
Published: April 2021

Many phytopathogens secrete cell wall degradation enzymes (CWDEs) to damage host cells and facilitate colonization. As the major components of the plant cell wall, cellulose and hemicellulose are the targets of CWDEs. Damaged plant cells often release damage-associated molecular patterns (DAMPs) to trigger plant immune responses. Here, we establish that the fungal pathogenMagnaporthe oryzaesecretes the endoglucanases MoCel12A and MoCel12B during infection of rice (Oryza sativa). These endoglucanases target hemicellulose of the rice cell wall and release two specific oligosaccharides, namely the trisaccharide 31-β-D-Cellobiosyl-glucose and the tetrasaccharide 31-β-D-Cellotriosyl-glucose. 31-β-D-Cellobiosyl-glucose and 31-β-D-Cellotriosyl-glucose bind the immune receptor OsCERK1 but not the chitin binding protein OsCEBiP. However, they induce the dimerization of OsCERK1 and OsCEBiP. In addition, these Poaceae cell wall-specific oligosaccharides trigger a burst of reactive oxygen species (ROS) that is largely compromised inoscerk1andoscebipmutants. We conclude that 31-β-D-Cellobiosyl-glucose and 31-β-D-Cellotriosyl-glucose are specific DAMPs released from the hemicellulose of rice cell wall, which are perceived by an OsCERK1 and OsCEBiP immune complex duringM. oryzaeinfection in rice.
Activation mechanism of a small prototypic Rec-GGDEF diguanylate cyclase
Authors: Teixeira Raphael D. , Holzschuh Fabian , Schirmer Tilman
Published: April 2021

Diguanylate cyclases synthesising the bacterial second messenger c-di-GMP are found to be regulated by a variety of sensory input domains that control the activity of their catalytical GGDEF domain, but how activation proceeds mechanistically is, apart from a few examples, still largely unknown. As part of two-component systems, they are activated by cognate histidine kinases that phosphorylate their Rec input domains. DgcR from Leptospira biflexa is a constitutively dimeric prototype of this class of diguanylate cyclases. Full-length crystal structures reveal that BeF3- pseudo-phosphorylation induces a relative rotation of two rigid halves in the Rec domain. This is coupled to a reorganisation of the dimeric structure with concomitant switching of the coiled-coil linker to an alternative heptad register. Finally, the activated register allows the two substrate-loaded GGDEF domains, which are linked to the end of the coiled-coil via a localised hinge, to move into a catalytically competent dimeric arrangement. Bioinformatic analyses suggest that the binary register switch mechanism is utilised by many diguanylate cyclases with N-terminal coiled-coil linkers.
RA3 is a reference-guided approach for epigenetic characterization of single cells
Authors: Chen Shengquan , Yan Guanao , Zhang Wenyu , Li Jinzhao , Jiang Rui , Lin Zhixiang
Published: April 2021

The recent advancements in single-cell technologies, including single-cell chromatin accessibility sequencing (scCAS), have enabled profiling the epigenetic landscapes for thousands of individual cells. However, the characteristics of scCAS data, including high dimensionality, high degree of sparsity and high technical variation, make the computational analysis challenging. Reference-guided approaches, which utilize the information in existing datasets, may facilitate the analysis of scCAS data. Here, we present RA3 (Reference-guided Approach for the Analysis of single-cell chromatin Accessibility data), which utilizes the information in massive existing bulk chromatin accessibility and annotated scCAS data. RA3 simultaneously models (1) the shared biological variation among scCAS data and the reference data, and (2) the unique biological variation in scCAS data that identifies distinct subpopulations. We show that RA3 achieves superior performance when used on several scCAS datasets, and on references constructed using various approaches. Altogether, these analyses demonstrate the wide applicability of RA3 in analyzing scCAS data.
Substitutional adsorptions of chloride at grain boundary sites on hydroxylated alumina surfaces initialize localized corrosion
Authors: Sundar Aditya , Chen Ganlin , Qi Liang
Published: April 2021

To understand the chloride (Cl)-induced initiation mechanism of localized corrosion of Aluminum (Al) alloys, we apply density functional theory (DFT) calculations and ab initio molecular dynamics (AIMD) simulations to investigate the interactions between Cl and hydroxylated α–Al2O3 surfaces, mainly (0001) orientation, under aqueous electrochemical conditions. Hydroxylated alumina surfaces thermodynamically stable in aqueous environments are constructed based on DFT calculations for both the single-crystal and bicrystal configurations. AIMD simulations suggest a Cl anion can only be stabilized on these surfaces by substituting a surface hydroxyl (OH) group. This substitution is thermodynamically favorable at sites on surface terminations of grain boundaries (GBs) in bicrystal configurations but not favorable at sites on single-crystal surfaces. Electronic structure analyses show that the different adsorption behaviors originate from the higher sensitivity of the Al–OH bond strength to the local coordination than its counterpart of the Al–Cl bond. The adsorbed Cl significantly increases the thermodynamic driving force for Al cation dissolution from alumina surfaces into the aqueous electrolyte, which can initiate localized corrosion.
Regenerative medicine meets mathematical modelling: developing symbiotic relationships
Authors: Waters S. L. , Schumacher L. J. , El Haj A. J.
Published: April 2021

Successful progression from bench to bedside for regenerative medicine products is challenging and requires a multidisciplinary approach. What has not yet been fully recognised is the potential for quantitative data analysis and mathematical modelling approaches to support this process. In this review, we highlight the wealth of opportunities for embedding mathematical and computational approaches within all stages of the regenerative medicine pipeline. We explore how exploiting quantitative mathematical and computational approaches, alongside state-of-the-art regenerative medicine research, can lead to therapies that potentially can be more rapidly translated into the clinic.
Author Correction: High-depth African genomes inform human migration and health
Authors:   TrypanoGEN Research Group, Choudhury Ananyo ,   H3Africa Consortium, Aron Shaun , Botigué Laura R. , Sengupta Dhriti , Botha Gerrit , Bensellak Taoufik , Wells Gordon , Kumuthini Judit , Shriner Daniel , Fakim Yasmina J. , Ghoorah Anisah W. , Dareng Eileen , Odia Trust , Falola Oluwadamilare , Adebiyi Ezekiel , Hazelhurst Scott , Mazandu Gaston , Nyangiri Oscar A. , Mbiyavanga Mamana , Benkahla Alia , Kassim Samar K. , Mulder Nicola , Adebamowo Sally N. , Chimusa Emile R. , Muzny Donna , Metcalf Ginger , Gibbs Richard A. , Rotimi Charles , Ramsay Michèle , Adeyemo Adebowale A. , Lombard Zané , Hanchard Neil A.
Published: April 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41586-021-03286-9.
Estimation of tuna population by the improved analytical pipeline of unique molecular identifier-assisted HaCeD-Seq (haplotype count from eDNA)
Authors: Yoshitake Kazutoshi , Fujiwara Atushi , Matsuura Aiko , Sekino Masashi , Yasuike Motoshige , Nakamura Yoji , Nakamichi Reiichiro , Kodama Masaaki , Takahama Yumiko , Takasuka Akinori , Asakawa Shuichi , Nishikiori Kazuomi , Kobayashi Takanori , Watabe Shugo
Published: April 2021

Many studies have investigated the ability to identify species from environmental DNA (eDNA). However, even when individual species are identified, the accurate estimation of their abundances by traditional eDNA analyses has been still difficult. We previously developed a novel analytical method called HaCeD-Seq (Haplotype Count from eDNA), which focuses on the mitochondrial D-loop sequence. The D-loop is a rapidly evolving sequence and has been used to estimate the abundance of eel species in breeding water. In the current study, we have further improved this method by applying unique molecular identifier (UMI) tags, which eliminate the PCR and sequencing errors and extend the detection range by an order of magnitude. Based on this improved HaCeD-Seq pipeline, we computed the abundance of Pacific bluefin tuna (Thunnus orientalis) in aquarium tanks at the Tokyo Sea Life Park (Kasai, Tokyo, Japan). This tuna species is commercially important but is at high risk of resource depletion. With the developed UMI tag method, 90 out of 96 haplotypes (94%) were successfully detected from Pacific bluefin tuna eDNA. By contrast, only 29 out of 96 haplotypes (30%) were detected when UMI tags were not used. Our findings indicate the potential for conducting non-invasive fish stock surveys by sampling eDNA.
Intake of food rich in saturated fat in relation to subclinical atherosclerosis and potential modulating effects from single genetic variants
Authors: Laguzzi Federica , Maitusong Buamina , Strawbridge Rona J. , Baldassarre Damiano , Veglia Fabrizio , Humphries Steve E. , Rauramaa Rainer , Kurl Sudhir , Smit Andries J. , Giral Philippe , Silveira Angela , Tremoli Elena , Hamsten Anders , de Faire Ulf , Gigante Bruna , Leander Karin ,   IMPROVE Study group, Sirtori C. R. , Calabresi L. , Amato M. , Frigerio B. , Ravani A. , Sansaro D. , Tedesco C. , Coggi D. , Capra N. , Bonomi A. , Eriksson P. , Cooper J. , Acharya J. , Savonen K. , Huttunen K. , Rauramaa E. , Penttila I. M. , Törrönen J. , van Gessel A. I. , van Roon A. M. , Nicolai A. , Mulder D. J. , Kontush A. , Carrié A. , Gallo A. , Karppi J. , Nurmi T. , Nyyssönen K. , Tuomainen T. P. , Tuomainen J. , Kauhanen J. , Sennblad B. , Pirro M. , Vaudo G. , Siepi D. , Lupattelli G. , Mannarino M. R. , Bianconi V.
Published: April 2021

The relationship between intake of saturated fats and subclinical atherosclerosis, as well as the possible influence of genetic variants, is poorly understood and investigated. We aimed to investigate this relationship, with a hypothesis that it would be positive, and to explore whether genetics may modulate it, using data from a European cohort including 3,407 participants aged 54–79 at high risk of cardiovascular disease. Subclinical atherosclerosis was assessed by carotid intima-media thickness (C-IMT), measured at baseline and after 30 months. Logistic regression (OR; 95% CI) was employed to assess the association between high intake of food rich in saturated fat (vs. low) and: (1) the mean and the maximum values of C-IMT in the whole carotid artery (C-IMTmean, C-IMTmax), in the bifurcation (Bif-), the common (CC-) and internal (ICA-) carotid arteries at baseline (binary, cut-point ≥ 75th), and (2) C-IMT progression (binary, cut-point > zero). For the genetic-diet interaction analyses, we considered 100,350 genetic variants. We defined interaction as departure from additivity of effects. After age- and sex-adjustment, high intake of saturated fat was associated with increased C-IMTmean (OR:1.27;1.06–1.47), CC-IMTmean (OR:1.22;1.04–1.44) and ICA-IMTmean (OR:1.26;1.07–1.48). However, in multivariate analysis results were no longer significant. No clear associations were observed between high intake of saturated fat and risk of atherosclerotic progression. There was no evidence of interactions between high intake of saturated fat and any of the genetic variants considered, after multiple testing corrections. High intake of saturated fats was not independently associated with subclinical atherosclerosis. Moreover, we did not identify any significant genetic-dietary fat interactions in relation to risk of subclinical atherosclerosis.
Predicting women with depressive symptoms postpartum with machine learning methods
Authors: Andersson Sam , Bathula Deepti R. , Iliadis Stavros I. , Walter Martin , Skalkidou Alkistis
Published: April 2021

Postpartum depression (PPD) is a detrimental health condition that affects 12% of new mothers. Despite negative effects on mothers’ and children’s health, many women do not receive adequate care. Preventive interventions are cost-efficient among high-risk women, but our ability to identify these is poor. We leveraged the power of clinical, demographic, and psychometric data to assess if machine learning methods can make accurate predictions of postpartum depression. Data were obtained from a population-based prospective cohort study in Uppsala, Sweden, collected between 2009 and 2018 (BASIC study, n = 4313). Sub-analyses among women without previous depression were performed. The extremely randomized trees method provided robust performance with highest accuracy and well-balanced sensitivity and specificity (accuracy 73%, sensitivity 72%, specificity 75%, positive predictive value 33%, negative predictive value 94%, area under the curve 81%). Among women without earlier mental health issues, the accuracy was 64%. The variables setting women at most risk for PPD were depression and anxiety during pregnancy, as well as variables related to resilience and personality. Future clinical models that could be implemented directly after delivery might consider including these variables in order to identify women at high risk for postpartum depression to facilitate individualized follow-up and cost-effectiveness.
Evaluating sediment and water sampling methods for the estimation of deep-sea biodiversity using environmental DNA
Authors: Brandt Miriam I. , Pradillon Florence , Trouche Blandine , Henry Nicolas , Liautard-Haag Cathy , Cambon-Bonavita Marie-Anne , Cueff-Gauchard Valérie , Wincker Patrick , Belser Caroline , Poulain Julie , Arnaud-Haond Sophie , Zeppilli Daniela
Published: April 2021

Despite representing one of the largest biomes on earth, biodiversity of the deep seafloor is still poorly known. Environmental DNA metabarcoding offers prospects for fast inventories and surveys, yet requires standardized sampling approaches and careful choice of environmental substrate. Here, we aimed to optimize the genetic assessment of prokaryote (16S), protistan (18S V4), and metazoan (18S V1–V2, COI) communities, by evaluating sampling strategies for sediment and aboveground water, deployed simultaneously at one deep-sea site. For sediment, while size-class sorting through sieving had no significant effect on total detected alpha diversity and resolved similar taxonomic compositions at the phylum level for all markers studied, it effectively increased the detection of meiofauna phyla. For water, large volumes obtained from an in situ pump (~ 6000 L) detected significantly more metazoan diversity than 7.5 L collected in sampling boxes. However, the pump being limited by larger mesh sizes (> 20 µm), only captured a fraction of microbial diversity, while sampling boxes allowed access to the pico- and nanoplankton. More importantly, communities characterized by aboveground water samples significantly differed from those characterized by sediment, whatever volume used, and both sample types only shared between 3 and 8% of molecular units. Together, these results underline that sediment sieving may be recommended when targeting metazoans, and aboveground water does not represent an alternative to sediment sampling for inventories of benthic diversity.