bluuebunny/crossref_metadata_2025 huggingface dataset:
Distributed genetic effects of the corpus callosum subregions suggest links to neuropsychiatric disorders and related traits
Authors: Campbell Megan L. , Dalvie Shareefa , Shadrin Alexey , van der Meer Dennis , O’Connell Kevin , Frei Oleksander , Andreassen Ole A. , Stein Dan J. , Rokicki Jaroslav
Published: August 2023

Background:

The corpus callosum (CC) is a brain structure with a high heritability and potential role in psychiatric disorders. However, the genetic architecture of the CC and the genetic link with psychiatric disorders remain largely unclear. We investigated the genetic architectures of the volume of the CC and its subregions and the genetic overlap with psychiatric disorders.

Methods:

We applied multivariate genome-wide association study (GWAS) to genetic and T1-weighted magnetic resonance imaging (MRI) data of 40,894 individuals from the UK Biobank, aiming to boost genetic discovery and to assess the pleiotropic effects across volumes of the five subregions of the CC (posterior, mid-posterior, central, mid-anterior and anterior) obtained by FreeSurfer 7.1. Multivariate GWAS was run combining all subregions, co-varying for relevant variables. Gene-set enrichment analyses were performed using MAGMA. Linkage disequilibrium score regression (LDSC) was used to determine Single nucleotide polymorphism (SNP)-based heritability of total CC volume and volumes of its subregions as well as their genetic correlations with relevant psychiatric traits.

Results:

We identified 70 independent loci with distributed effects across the five subregions of the CC (p < 5 × 10−8). Additionally, we identified 33 significant loci in the anterior subregion, 23 in the mid-anterior, 29 in the central, 7 in the mid-posterior and 56 in the posterior subregion. Gene-set analysis revealed 156 significant genes contributing to volume of the CC subregions (p < 2.6 × 10−6). LDSC estimated the heritability of CC to (h2SNP = 0.38, SE = 0.03) and subregions ranging from 0.22 (SE = 0.02) to 0.37 (SE = 0.03). We found significant genetic correlations of total CC volume with bipolar disorder (BD, rg = −0.09, SE = 0.03; p = 5.9 × 10−3) and drinks consumed per week (rg = −0.09, SE = 0.02; p = 4.8 × 10−4), and volume of the mid-anterior subregion with BD (rg = −0.12, SE = 0.02; p = 2.5 × 10−4), major depressive disorder (MDD) (rg = −0.12, SE = 0.04; p = 3.6 × 10−3), drinks consumed per week (rg = −0.13, SE = 0.04; p = 1.8 × 10−3) and cannabis use (rg = −0.09, SE = 0.03; p = 8.4 × 10−3).

Conclusions:

Our results demonstrate that the CC has a polygenic architecture implicating multiple genes and show that CC subregion volumes are heritable. We found that distinct genetic factors are involved in the development of anterior and posterior subregions, consistent with their divergent functional specialisation. Significant genetic correlation between volumes of the CC and BD, drinks per week, MDD and cannabis consumption subregion volumes with psychiatric traits is noteworthy and deserving of further investigation.
Was there a nonglacial episode in the western Hudson Bay Lowland during Marine Isotope Stage 3?
Authors: Hodder Tyler J. , Gauthier Michelle S. , Ross Martin , Lian Olav B.
Published: August 2023

Establishing the timing of glacial and nonglacial intervals in the core regions of the Laurentide Ice Sheet (LIS) is essential to constrain ice-sheet configuration at times of globally reduced ice volume, such as during Marine Isotope Stage (MIS) 3 (~57–29 ka). Hudson Bay Lowland (HBL) deglaciation, at the centre of the LIS, has been inferred at MIS 3 based on near-infinite wood radiocarbon ages and limited luminescence ages. To better constrain the age of the penultimate deglaciation of the western HBL, this study initially identified the youngest intertill nonglacial sediments, based on extensive fieldwork and till characterization. Next, vetted radiocarbon ages were combined with revised stratigraphy to show that five previously identified “MIS 3” sites were likely deposited during an earlier ice-free period. Finally, new optical ages targeting the youngest intertill nonglacial bed at three localities yielded ages ranging from 166 to 146 ka; all older than MIS 3. These ages indicate that the penultimate deglaciation of the western HBL likely occurred during MIS 5e. This interpretation better explains accompanying paleobotanic data sets that indicate vegetation similar to vegetation existing under present interglacial conditions. Currently no firm evidence exists in the terrestrial stratigraphic record for the deglaciation of the western HBL during MIS 3.
Who Intervenes in Supreme Court Cases in Canada?
Authors: McNabb Danielle
Published: August 2023

With the patriation of the Constitution in 1982, the Supreme Court of Canada (SCC) inherited extraordinary political powers. In response to the Court's expanded power of judicial review, there was a sizeable increase in the number of political actors “intervening” in SCC cases. Scholars of Canadian law and politics are deeply divided on whether civil society participation in the courts—particularly as intervenors—is democratically legitimate. This important debate cannot be settled without an empirical evaluation of who intervenes. This research note provides an analysis of all the Charter cases heard by the SCC between 2013 and 2021. In contrast to the field's dominant theory on interest-group legal mobilization—the Court Party thesis—the findings reveal that equity-deserving interest groups, such as those representing women, have an irregular presence in Court. Instead, powerful actors such as governments and legal associations make up a majority of the “repeat player” intervenors. While further research is warranted, the research note concludes that without the maintenance of sufficient support structures, intervention may be unable to perform a democratizing function.
Child-related Social Policies in Europe during the COVID-19 Pandemic
Authors: Daly Mary , Ryu Sunwoo
Published: August 2023

Looking at core features of child and family related spending and policy design, and covering five domains of policy, the paper offers new empirical evidence and an original perspective for better understanding how EU countries and the UK responded to the needs of children and families during the pandemic and how to classify responses in terms of child-centredness. The paper is driven by a concept of child-centredness to examine developments from March to December 2020 in five policy fields: income support, food assistance, early childcare and education services, school opening and support for parental care-giving. The analysis shows strong variation across countries in terms of how active they were and what fields they were active in. One very striking commonality, though, is that the most popular field of policy action was in resourcing parental care of children at home, through paid leaves usually. A related finding is that there was little prioritising of children for most kinds of actions. Thirdly, in terms of national patterning those countries that were generous spenders on this field of policy prior to the pandemic were most child-centred in their response and there are few if any exceptions to this.
The ‘Saxon Shore’ Reconsidered
Authors: Drinkwater John F.
Published: August 2023

I propose that the usual role of the Notitia Dignitatum's ‘Saxon Shore’ forts was, on both sides of the Channel, to control chronic, ‘everyday’ piracy and to support imperial operations. An exception occurred under Carausius and Allectus when the British forts were augmented to face likely Roman invasion. There was never any integrated cross-Channel system against concerted barbarian seaborne attack, Saxon or otherwise. The ‘Saxon Shore’ was a late fourth-century political expedient, confined to Britain and with minor military significance.
COME, LET US EAT AND DRINK TOGETHER: FEASTING PATTERNS AND THEIR SOCIO-POLITICAL DIMENSIONS IN LATE BRONZE AGE EASTERN CRETE
Authors: Vergaki Anastasia M.A.
Published: August 2023

Feasts in Bronze Age Crete are an important manifestation of material culture. Indications of feasting can be identified in funerary, palatial, and domestic archaeological contexts. As a result of scholarship traditionally focusing on the religious character of funerary practices and palatial feasting, convivial activities within the domestic sphere have been neglected and/or misinterpreted. As a result of this research bias, there is a notable gap in the record of in-depth archaeological analysis of the social, political and ideological reasons of performing a feast in a domestic environment (or within the bounds of a settlement itself). Researchers have found it hard to distinguish between different types of feasts based on the associated cultural material, consequently leading to misinterpretations regarding the differences in feasting symbolism and the contribution of feasting to social organisation. The re-examination of published material from the Neopalatial (c. 1700‒1500/1450 BC or Middle Minoan IIIB‒Late Minoan IB in pottery terms) sites of Pseira, Mochlos and Gournia in eastern Crete reveals that specific patterns of feasts were in fact in existence and socially performed. Furthermore, the data suggest that feasts in settlements functioned as politically motivated rituals which played a leading role in the formation of social organisation through intra-community antagonisms.
Adjustments of factor income tax rates and aggregate (in)stability
Authors: Huang Kevin X. D. , Meng Qinglai , Xue Jianpo
Published: August 2023

A general wisdom, since at least the work of Schmitt-Grohé and Uribe [(1997) Journal of Political Economy 105, 976–1000.], holds that a government that relies on adjusting factor income tax rates to achieve budget objective may induce aggregate instability driven by self-fulfilling expectations. This paper shows that this conventional wisdom may be overturned if the rate of adjustment of the capital income tax rate is bigger than that of the labor income tax rate. How much bigger depends on country specifics and particularly on the levels of the capital and labor income tax rates. Thus, adjustments in capital and labor income tax rates, if properly designed and implemented, can help achieve the budget objective while at the same time preempting extrinsic volatility.
Trustful conversations: a qualitative interview study on older patients’ experiences of the intervention Proactive healthcare in a Swedish primary care setting
Authors: Sax Åsa , Nord Magnus , Cedersund Elisabet , Olaison Anna , Sverker Annette , Kastbom Lisa
Published: August 2023

Aim:

To explore older patients’ experiences of the intervention Proactive healthcare for frail elderly persons.

Background:

Previous research has indicated that continuity and good access to primary care can improve satisfaction in older people seeking care. However, little is known about the older patients’ experiences in taking part of interventions aiming to enhance the care.

Methods:

Individual interviews were conducted with 24 older patients who participated in the intervention Proactive healthcare for frail elderly persons, selected from nine Swedish primary care centres. Interviews were analysed using qualitative content analysis.

Findings:

Older patients’ experiences of the intervention involved five manifest categories: Ways of naming the elder care team, covering the older patients’ lack of understanding regarding their connection to the team, and the need for clarity on this and on how the specialised care provided differed from conventional care; Availability, indicating how older patients associated easy access and a direct telephone number with a team nurse available at certain times with a sense of security; The importance of relations, covering how patients appreciated continuity in their personal and professional conversations with staff; A feeling of safety and trust, stressing the value of older persons attach to being given enough time, to be listened to and being recognised as people; and Finiteness of life, which refers to the difficulty of having end-of-life conversations and the need for experienced staff with personal knowledge of the patients. The latent theme Trustful conversations was created to give a deeper meaning to the content of the categories.

Trustful conversations, created through good personal knowledge of patients and continuity of contact, engender a feeling of safety in older patients. Using elder care teams could result in a better quality of care, with increased satisfaction and feelings of security among patients, and a reduction in healthcare needs.
The Conference on the Future of Europe as a chance for democratic catching up? Towards a citizen-centred perspective on constitutional renewal in the European Union
Authors: Seubert Sandra
Published: August 2023

The Conference on the Future of Europe (CoFoE) was the first initiative to include citizens in deliberations about the future of European democracy since the failed Constitutional Convention of 2002/03. Although embedded within broader trends to involve ordinary citizens in the political process, it is of specific relevance in the European context because it raises expectations of democratic catching up and relates to ongoing discussions and struggles about the constitutional character of the European Union. This article argues for a citizen-centred perspective on constitutional renewal in the European Union that places European citizens as constituent subjects at centre stage. It outlines how making the European Union accessible as a political arena allows citizens to regain control over developments that have evolved behind people’s backs. It concludes that deliberative tools of citizen participation should be used to pave the way for a wider reorganization of public authority and a renewal of the European Union’s constitutional basis.
Mercury Burial in Modern Sedimentary Systems of the East China Marginal Seas: The Role of Coastal Oceans in Global Mercury Cycling
Authors: Sun Xueshi , Hu Limin , Sun Xiang , Fan Dejiang , Liu Ming , Wang Houjie , Yang Zuosheng , Cheng Peng , Liu Xiaohang , Guo Zhigang
Published: August 2023

Coastal oceans, the transition zones between terrestrial and oceanic systems, are susceptible to anthropogenic mercury (Hg) inputs and are regarded as critical dynamic interfaces of the global Hg cycle. However, the extent to which coastal oceans are accountable for sequestering Hg remains largely unknown owing to the lack of data on high‐resolution Hg accumulation in marine sediments. Synthesizing the results of this study (eight cores and 212 surface sediments) and the literature (three cores and 149 surface sediments), we provide a quantitative evaluation of the biogeochemical cycle of sedimentary Hg in the East China Marginal Seas (ECMS), including the response of the coastal marine sediments to anthropogenic disturbance as well as both human‐derived and natural Hg burial fluxes. We find a linear increase in Hg accumulation since the 1950s (2.0 ± 2.5% yr−1) and a decline in Hg accumulation between 2010 and 2016. Modern burial fluxes of total and anthropogenic Hg in the ECMS (covering ∼4.8 × 105 km2 of sea surface) were estimated to be 89.1 ± 48.3 and 35.9 ± 33.1 Mg yr−1, respectively. Using a compilation of 688 surface sediments and 131 sediment cores (819 samples in total) distributed globally in coastal oceans, we estimate that approximately 1,590 (range: 1,190–2,760) Mg yr−1 (Method 1) and 540 (range: 310–960) Mg yr−1 (Method 2) Hg are accumulated in coastal ocean regions. Our findings suggest that coastal oceans are likely the largest global marine sinks for Hg and play a dominant role in regulating the oceanic Hg cycle and budgets.
Revisiting the Potential to Narrow Model Uncertainty in the Projections of Arctic Runoff
Authors: Dutot Emma , Douville Hervé
Published: August 2023

Despite multiple advances in the understanding of the water cycle intensification in a warmer climate, climate models still diverge in their hydrological projections. Here we constrain annual runoff projections over individual and aggregated Arctic river basins. For this purpose, we use two ensembles of global climate models and two statistical methods: a regression scheme assuming similar runoff sensitivities at interannual versus climate change timescales, and a Bayesian method where models are used to derive a posterior runoff response conditioned on historical observations. While both techniques are shown to narrow model uncertainties, more or less substantially depending on rivers, the Bayesian method is less sensitive to the choice of the model ensemble and is more skillful when tested with synthetic observations. It has also been applied over the whole Arctic watershed, showing so far a limited narrowing of the inter‐model spread, but its skill will further improve with increasing climate change.
Amplified Decadal Variability of Extratropical Surface Temperatures by Stratosphere‐Troposphere Coupling
Authors: Butler Amy H. , Karpechko Alexey Yu. , Garfinkel Chaim I.
Published: August 2023

The dominant pattern of Northern Hemisphere extratropical climate variability is the Northern Annular Mode (NAM), which in wintertime represents the coupling of the stratospheric and tropospheric circulations. The internal variability associated with the NAM has been shown to give rise to substantial uncertainty in climate projections of regional surface air temperatures (SATs), but it's unclear how much of this variability arises from stratosphere‐troposphere coupling processes. Here, using three large‐ensemble coupled climate model simulations from 1850 to 2100 with varying fidelity of stratosphere‐troposphere coupling processes, we demonstrate that regional SAT variability across timescales is amplified when the tropospheric NAM is coupled to the stratospheric NAM. Moreover, models that lack adequate simulation of stratosphere‐troposphere coupling processes may not capture the magnitude of uncertainty in near‐term SAT projections associated with this coupling.
A Case Study of the Solar and Lunar Semidiurnal Tide Response to the 2013 Sudden Stratospheric Warming
Authors: van Caspel Willem E. , Espy Patrick , Hibbins Robert , Stober Gunter , Brown Peter , Jacobi Christoph , Kero Johan
Published: August 2023

This study investigates the response of the semidiurnal tide (SDT) to the 2013 major sudden stratospheric warming (SSW) event using meteor radar wind observations and mechanistic tidal model simulations. In the model, the background atmosphere is constrained to meteorological fields from the Navy Global Environmental Model—High Altitude analysis system. The solar (thermal) and lunar (gravitational) SDT components are forced by incorporating hourly temperature tendency fields from the ERA5 forecast model, and by specifying the M2 and N2 lunar gravitational potentials, respectively. The simulated SDT response is compared against meteor wind observations from the CMOR (43.3°N, 80.8°W), Collm (51.3°N, 13.0°E), and Kiruna (67.5°N, 20.1°E) radars, showing close agreement with the observed amplitude and phase variability. Numerical experiments investigate the individual roles of the solar and lunar SDT components in shaping the net SDT response. Further experiments isolate the impact of changing propagation conditions through the zonal mean background atmosphere, non‐linear wave‐wave interactions, and the SSW‐induced stratospheric ozone redistribution. Results indicate that between 80 and 97 km altitude in the northern hemisphere mid‐to‐high latitudes the net SDT response is driven by the solar SDT component, which itself is shaped by changing propagation conditions through the zonal mean background atmosphere and by non‐linear wave‐wave interactions. In addition, it is demonstrated that as a result of the rapidly varying solar SDT during the SSW the contribution of the lunar SDT to the total measured tidal field can be significantly overestimated.
Impacts of SLR Ground Station Geographic Distribution on Time‐Variable Gravity Recovery
Authors: Tucker E. S. , Nerem R. S. , Loomis B. D.
Published: August 2023

Satellite laser ranging (SLR) continues to be an essential technique for estimating Earth's low‐degree gravity field. The Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow‐On (GRACE‐FO) do not accurately recover certain coefficients, which are needed for quantifying large‐scale mass redistribution as part of Earth's time‐variable gravity (TVG) field. In case of an inter‐mission gap, as with GRACE and GRACE‐FO, SLR can continue to provide mass‐change measurements. The current SLR ground network consists of around 40 stations. However, these are not uniformly distributed and the quantity and quality of data varies widely between sites. We anticipate that future stations will improve SLR‐derived gravity estimates and we investigate their potential impact on the solution in this simulation study. A single new station that enhances network geometry, particularly in the Southern hemisphere, increases the sensitivity of the network by up to 12% for certain coefficients. The addition of 5 new future stations improves certain coefficients up to 18%. We find new stations are limited in their ability to decorrelate certain coefficients regardless of their location, but that adding more data and increasing network uniformity still benefits the overall solution.
Diffusion Creep of Sodic Amphibole‐Bearing Blueschist Limited by Microboudinage
Authors: Tokle Leif , Hufford Lonnie J. , Behr Whitney M. , Morales Luiz F. G. , Madonna Claudio
Published: August 2023

To investigate the mechanical and microstructural properties of mafic blueschists, we conducted deformation experiments on powdered natural blueschist aggregates using the general shear geometry in the Griggs apparatus. Experiments were performed at ∼1.0 GPa and temperatures ranging from 650 to 700°C. The blueschist starting material consists primarily of sodic amphibole and epidote, with minor amounts of quartz, titanite, albite, and white mica. Strain rate stepping experiments provided mechanical data with stress exponents ranging from 1.8 to 2.2. Microstructural analysis of the deformed samples show that the blueschist aggregates were deforming by microboudinage of the sodic amphibole, with a chemically new sodic‐calcic amphibole diffused into the boudin neck. Based on these results, we interpret the samples to have deformed by diffusion creep of the sodic‐calcic amphibole, which was rate‐limited by diffusion into the boudin neck. We developed a microboudinage diffusion creep flow law using a least square regression, with parameters of A = 2.43e11 MPa−n μm s−1, n = 2.0 ± 0.3, m = 1.0, and Q = 384 ± 15 kJ/mol. Extrapolation of the flow law to the blueschist stability field suggests viscosities that are higher than metasedimentary rocks (quartz dislocation creep flow law) and lower than eclogitic rocks (omphacite dislocation creep flow law) consistent with field observations. We also show that this type of deformation mechanism matches observations of natural rocks in paleosubduction zone environments, supporting the application of this flow law to estimate amphibole rheology in modern subduction zones.
Trends in Warm Season Mesoscale Convective Systems Over Asia in 2001–2020
Authors: Guo Yuanjing , Fu Qiang , Leung L. Ruby , Na Ying , Lu Riyu
Published: August 2023

Mesoscale convective systems (MCSs) frequently occur over Asia during the warm season, often producing intense precipitation with associated socioeconomic impacts. Here we reveal significant trends in MCS occurrence frequency and related precipitation in Asia during the warm season (March–September) in 2001–2020, using a tracking method that combines cloud and precipitation criteria with high‐resolution satellite data from the Global Precipitation Measurement mission. To examine whether there are differences between MCSs of different scales, both meso‐α scales (MαCSs) and meso‐β scales (MβCSs), with horizontal scales of 200–2,000 km and 20–200 km, are tracked. The distribution pattern of frequency and related precipitation of both MαCSs and MβCSs are quite similar and manifest positive trends over East Asia (EA) and Northeast Asia, and negative trend over Southeast Asia (SEA). The MCS precipitation trend contributes significantly to total precipitation trend, with MαCSs contributing the most. Our analysis indicates the trend in lower‐tropospheric water vapor flux convergence has a similar spatial pattern to the MCS frequency and related precipitation trend. Based on an atmospheric moisture flux decomposition analysis, the water vapor flux convergence trend can largely be explained by the change in horizontal wind convergence, while the specific humidity trend driven largely by temperature change plays a minor role. The trend in wind convergence in EA and SEA is possibly related to the evident trend in the lower‐tropospheric anticyclone over the western North Pacific and SEA, which might be due to the relatively stronger warming in the Indian Ocean during the past two decades.
Targeting LGSN restores sensitivity to chemotherapy in gastric cancer stem cells by triggering pyroptosis
Authors: Li Yu-Ting , Tan Xiang-Yu , Ma Li-Xiang , Li Hua-Hui , Zhang Shu-Hong , Zeng Chui-Mian , Huang Liu-Na , Xiong Ji-Xian , Fu Li
Published: August 2023

Gastric cancer (GC) is notoriously resistant to current therapies due to tumor heterogeneity. Cancer stem cells (CSCs) possess infinite self-renewal potential and contribute to the inherent heterogeneity of GC. Despite its crucial role in chemoresistance, the mechanism of stemness maintenance of gastric cancer stem cells (GCSCs) remains largely unknown. Here, we present evidence that lengsin, lens protein with glutamine synthetase domain (LGSN), a vital cell fate determinant, is overexpressed in GCSCs and is highly correlated with malignant progression and poor survival in GC patients. Ectopic overexpression of LGSN in GCSC-derived differentiated cells facilitated their dedifferentiation and treatment resistance by interacting with vimentin and inducing an epithelial-to-mesenchymal transition. Notably, genetic interference of LGSN effectively suppressed tumor formation by inhibiting GCSC stemness maintenance and provoking gasdermin-D-mediated pyroptosis through vimentin degradation/NLRP3 signaling. Depletion of LGSN combined with the chemo-drugs 5-fluorouracil and oxaliplatin could offer a unique and promising approach to synergistically rendering this deadly cancer eradicable in vivo. Our data place focus on the role of LGSN in GCSC regeneration and emphasize the critical importance of pyroptosis in battling GCSC.
ALKBH5 promotes hypopharyngeal squamous cell carcinoma apoptosis by targeting TLR2 in a YTHDF1/IGF2BP2-mediated manner
Authors: Ye Jing , Wu Yuting , Chen Yao , Ren Yiyue , Jiang Xiaohua , Dong Zhihuai , Zhang Jingna , Jin Mao , Chen Xiaozhen , Wang Zhanggui , Xiao Mang
Published: August 2023

Hypopharyngeal squamous cell carcinoma (HPSCC) is one of the most aggressive cancers and is notorious for its extremely poor prognosis. However, very few molecular biological studies have been performed. As a novel method of epigenetic gene modulation, N6-methyladenosine (m6A) RNA modification occurs in HPSCC. The expression of the m6A demethylase AlkB homolog 5 (ALKBH5) is frequently downregulated in human HPSCC. Furthermore, we found that ALKBH5 impaired cell proliferation by regulating human Toll-like receptor 2 (TLR2) in an m6A-dependent manner in HPSCC cells. ALKBH5 decreased TLR2 m6A modification, which could be recognized by the m6A readers IGF2BP2 and YTHDF1. IGF2BP2 facilitates TLR2 mRNA stability, whereas YTHDF1 promotes TLR2 mRNA translation. The current work uncovered a critical function of ALKBH5 in TLR2 regulation and provides a novel role for m6A demethylation of mRNA in HPSCC. The inhibition of m6A modification of ALKBH5 in HPSCC deserves further clinical investigation.
An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells
Authors: Salerno Fiamma , Howden Andrew J. M. , Matheson Louise S. , Gizlenci Özge , Screen Michael , Lingel Holger , Brunner-Weinzierl Monika C. , Turner Martin
Published: August 2023

During B cell maturation, transitional and mature B cells acquire cell-intrinsic features that determine their ability to exit quiescence and mount effective immune responses. Here we use label-free proteomics to quantify the proteome of B cell subsets from the mouse spleen and map the differential expression of environmental sensing, transcription, and translation initiation factors that define cellular identity and function. Cross-examination of the full-length transcriptome and proteome identifies mRNAs related to B cell activation and antibody secretion that are not accompanied by detection of the encoded proteins. In addition, proteomic data further suggests that the translational repressor PDCD4 restrains B cell responses, in particular those from marginal zone B cells, to a T-cell independent antigen. In summary, our molecular characterization of B cell maturation presents a valuable resource to further explore the mechanisms underpinning the specialized functions of B cell subsets, and suggest the presence of ‘poised’ mRNAs that enable expedited B cell responses.
Atomic-level structure determination of amorphous molecular solids by NMR
Authors: Cordova Manuel , Moutzouri Pinelopi , Nilsson Lill Sten O. , Cousen Alexander , Kearns Martin , Norberg Stefan T. , Svensk Ankarberg Anna , McCabe James , Pinon Arthur C. , Schantz Staffan , Emsley Lyndon
Published: August 2023

Structure determination of amorphous materials remains challenging, owing to the disorder inherent to these materials. Nuclear magnetic resonance (NMR) powder crystallography is a powerful method to determine the structure of molecular solids, but disorder leads to a high degree of overlap between measured signals, and prevents the unambiguous identification of a single modeled periodic structure as representative of the whole material. Here, we determine the atomic-level ensemble structure of the amorphous form of the drug AZD4625 by combining solid-state NMR experiments with molecular dynamics (MD) simulations and machine-learned chemical shifts. By considering the combined shifts of all 1H and 13C atomic sites in the molecule, we determine the structure of the amorphous form by identifying an ensemble of local molecular environments that are in agreement with experiment. We then extract and analyze preferred conformations and intermolecular interactions in the amorphous sample in terms of the stabilization of the amorphous form of the drug.
A glutamatergic DRN–VTA pathway modulates neuropathic pain and comorbid anhedonia-like behavior in mice
Authors: Wang Xin-Yue , Jia Wen-Bin , Xu Xiang , Chen Rui , Wang Liang-Biao , Su Xiao-Jing , Xu Peng-Fei , Liu Xiao-Qing , Wen Jie , Song Xiao-Yuan , Liu Yuan-Yuan , Zhang Zhi , Liu Xin-Feng , Zhang Yan
Published: August 2023

Chronic pain causes both physical suffering and comorbid mental symptoms such as anhedonia. However, the neural circuits and molecular mechanisms underlying these maladaptive behaviors remain elusive. Here using a mouse model, we report a pathway from vesicular glutamate transporter 3 neurons in the dorsal raphe nucleus to dopamine neurons in the ventral tegmental area (VGluT3DRN→DAVTA) wherein population-level activity in response to innocuous mechanical stimuli and sucrose consumption is inhibited by chronic neuropathic pain. Mechanistically, neuropathic pain dampens VGluT3DRN → DAVTA glutamatergic transmission and DAVTA neural excitability. VGluT3DRN → DAVTA activation alleviates neuropathic pain and comorbid anhedonia-like behavior (CAB) by releasing glutamate, which subsequently promotes DA release in the nucleus accumbens medial shell (NAcMed) and produces analgesic and anti-anhedonia effects via D2 and D1 receptors, respectively. In addition, VGluT3DRN → DAVTA inhibition produces pain-like reflexive hypersensitivity and anhedonia-like behavior in intact mice. These findings reveal a crucial role for VGluT3DRN → DAVTA → D2/D1NAcMed pathway in establishing and modulating chronic pain and CAB.
Bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment
Authors: Sulit A. K. , Daigneault M. , Allen-Vercoe E. , Silander O. K. , Hock B. , McKenzie J. , Pearson J. , Frizelle F. A. , Schmeier S. , Purcell R.
Published: August 2023

Immune responses can have opposing effects in colorectal cancer (CRC), the balance of which may determine whether a cancer regresses, progresses, or potentially metastasizes. These effects are evident in CRC consensus molecular subtypes (CMS) where both CMS1 and CMS4 contain immune infiltrates yet have opposing prognoses. The microbiome has previously been associated with CRC and immune response in CRC but has largely been ignored in the CRC subtype discussion. We used CMS subtyping on surgical resections from patients and aimed to determine the contributions of the microbiome to the pleiotropic effects evident in immune-infiltrated subtypes. We integrated host gene-expression and meta-transcriptomic data to determine the link between immune characteristics and microbiome contributions in these subtypes and identified lipopolysaccharide (LPS) binding as a potential functional mechanism. We identified candidate bacteria with LPS properties that could affect immune response, and tested the effects of their LPS on cytokine production of peripheral blood mononuclear cells (PBMCs). We focused on Fusobacterium periodonticum and Bacteroides fragilis in CMS1, and Porphyromonas asaccharolytica in CMS4. Treatment of PBMCs with LPS isolated from these bacteria showed that F. periodonticum stimulates cytokine production in PBMCs while both B. fragilis and P. asaccharolytica had an inhibitory effect. Furthermore, LPS from the latter two species can inhibit the immunogenic properties of F. periodonticum LPS when co-incubated with PBMCs. We propose that different microbes in the CRC tumor microenvironment can alter the local immune activity, with important implications for prognosis and treatment response.
Anharmonic electron-phonon coupling in ultrasoft and locally disordered perovskites
Authors: Zacharias Marios , Volonakis George , Giustino Feliciano , Even Jacky
Published: August 2023

Anharmonicity and local disorder (polymorphism) are ubiquitous in perovskite physics, inducing various phenomena observed in scattering and spectroscopy experiments. Several of these phenomena still lack interpretation from first principles since, hitherto, no approach is available to account for anharmonicity and disorder in electron–phonon couplings. Here, relying on the special displacement method, we develop a unified treatment of both and demonstrate that electron–phonon coupling is strongly influenced when we employ polymorphous perovskite networks. We uncover that polymorphism in halide perovskites leads to vibrational dynamics far from the ideal noninteracting phonon picture and drives the gradual change in their band gap around phase transition temperatures. We also clarify that combined band gap corrections arising from disorder, spin-orbit coupling, exchange–correlation functionals of high accuracy, and electron–phonon coupling are all essential. Our findings agree with experiments, suggesting that polymorphism is the key to address pending questions on perovskites’ technological applications.
Breeding from 1891 to 2010 did not increase the content of amylase/trypsin-inhibitors in wheat (Triticum aestivum)
Authors: Geisslitz Sabrina , Pronin Darina , Neerukonda Manjusha , Curella Valentina , Neufang Sibylle , Koch Sandra , Weichert Heiko , Weber Hans , Börner Andreas , Schuppan Detlef , Scherf Katharina Anne
Published: August 2023

The prevalence of hypersensitivities towards wheat has increased in the last decades. Apart from celiac disease these include allergic and other inflammatory reactions summarized under the term non-celiac wheat sensitivity. One suspected trigger is the family of amylase/trypsin-inhibitors (ATIs), non-gluten proteins that are prominent wheat allergens and that activate the toll-like receptor 4 on intestinal immune cells to promote intestinal and extra-intestinal inflammation. We therefore quantified 13 ATIs in 60 German hexaploid winter wheat cultivars originating from 1891 to 2010 and harvested in three years by targeted liquid chromatography-tandem mass spectrometry combined with stable isotope dilution assay using specific marker peptides as internal standards. The total ATI content and that of the two major ATIs 0.19 and CM3 did not change from old cultivars (first registered from 1891 to 1950) to modern cultivars (1951–2010). There were also no significant changes in ATI distribution.
Recent global climate feedback controlled by Southern Ocean cooling
Authors: Kang Sarah M. , Ceppi Paulo , Yu Yue , Kang In-Sik
Published: August 2023

The magnitude of global warming is controlled by climate feedbacks associated with various aspects of the climate system, such as clouds. The global climate feedback is the net effect of these feedbacks, and its temporal evolution is thought to depend on the tropical Pacific sea surface temperature pattern. However, current coupled climate models fail to simulate the pattern observed in the Pacific between 1979 and 2013 and its associated anomalously negative feedback. Here we demonstrate a mechanism whereby the Southern Ocean controls the global climate feedback. Using climate model experiments in which Southern Ocean sea surface temperatures are restored to observations, we show that accounting for recent Southern Ocean cooling—which is absent in coupled climate models—halves the bias in the global climate feedback by removing the cloud component bias. This global impact is mediated by a teleconnection to the Southeast Pacific, where remote sea surface temperature anomalies cause a strong stratocumulus cloud feedback. We propose that this Southern Ocean-driven pattern effect is underestimated in most climate models, owing to an overly weak stratocumulus cloud feedback. Addressing this bias may shift climate sensitivities to higher values than currently simulated as the Southern Ocean undergoes accelerated warming in future projections.
Multiparameter prediction of myeloid neoplasia risk
Authors: Gu Muxin , Kovilakam Sruthi Cheloor , Dunn William G. , Marando Ludovica , Barcena Clea , Mohorianu Irina , Smith Alexandra , Kar Siddhartha P. , Fabre Margarete A. , Gerstung Moritz , Cargo Catherine A. , Malcovati Luca , Quiros Pedro M. , Vassiliou George S.
Published: August 2023

The myeloid neoplasms encompass acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms. Most cases arise from the shared ancestor of clonal hematopoiesis (CH). Here we analyze data from 454,340 UK Biobank participants, of whom 1,808 developed a myeloid neoplasm 0–15 years after recruitment. We describe the differences in CH mutational landscapes and hematology/biochemistry test parameters among individuals that later develop myeloid neoplasms (pre-MN) versus controls, finding that disease-specific changes are detectable years before diagnosis. By analyzing differences between ‘pre-MN’ and controls, we develop and validate Cox regression models quantifying the risk of progression to each myeloid neoplasm subtype. We construct ‘MN-predict’, a web application that generates time-dependent predictions with the input of basic blood tests and genetic data. Our study demonstrates that many individuals that develop myeloid neoplasms can be identified years in advance and provides a framework for disease-specific prognostication that will be of substantial use to researchers and physicians.
Greenhouse gas emissions from U.S. crude oil pipeline accidents: 1968 to 2020
Authors: Lu Hongfang , Xu Zhao-Dong , Song Kaihui , Frank Cheng Y. , Dong Shaohua , Fang Hongyuan , Peng Haoyan , Fu Yun , Xi Dongmin , Han Zizhe , Jiang Xinmeng , Dong Yao-Rong , Gai Panpan , Shan Zhiwei , Shan Yuli
Published: August 2023

Crude oil pipelines are considered as the lifelines of energy industry. However, accidents of the pipelines can lead to severe public health and environmental concerns, in which greenhouse gas (GHG) emissions, primarily methane, are frequently overlooked. While previous studies examined fugitive emissions in normal operation of crude oil pipelines, emissions resulting from accidents were typically managed separately and were therefore not included in the emission account of oil systems. To bridge this knowledge gap, we employed a bottom-up approach to conducted the first-ever inventory of GHG emissions resulting from crude oil pipeline accidents in the United States at the state level from 1968 to 2020, and leveraged Monte Carlo simulation to estimate the associated uncertainties. Our results reveal that GHG emissions from accidents in gathering pipelines (~720,000 tCO2e) exceed those from transmission pipelines (~290,000 tCO2e), although significantly more accidents have occurred in transmission pipelines (6883 cases) than gathering pipelines (773 cases). Texas accounted for over 40% of total accident-related GHG emissions nationwide. Our study contributes to enhanced accuracy of the GHG account associated with crude oil transport and implementing the data-driven climate mitigation strategies.
Evaluation of paravertebral blocks in improving post-procedural pain and decreasing hospital admission after microwave ablation of liver tumors
Authors: Joseph Nicholos , Sun Virginia H. , Som Avik , Di Capua John , Elsamaloty Lina , Huang Junjian , Vazquez Rafael
Published: August 2023

Although ablations are performed with conscious sedation or general anesthesia, microwave ablations can be painful post procedure. Newer analgesic modalities, including regional blocks, have promoted the proliferation of less invasive anesthesia care for ablative procedures. This study evaluates whether bilateral paravertebral blocks reduce the need for additional analgesics in comparison to unilateral blocks in microwave ablations. In this retrospective study, individuals undergoing microwave ablation who underwent unilateral versus bilateral nerve blocks at a single institution from 2017 to 2019 were compared. Categorical variables were analyzed using Pearson’s chi-squared tests. Comparisons of means were completed using multiple T-tests corrected using the Holm-Sidak method with $$\alpha $$
α
= 0.05. Regression modeling was used to identify factors related to increased MME (milligram morphine equivalent) usage and post-procedure admission rates. A total of 106 patients undergoing 112 liver MWA procedures were included in this analysis, with patients receiving either a bilateral or unilateral block. Pre-procedural characteristics demonstrated no significant differences in age or gender. Bilateral blocks were associated with decreased usage of gabapentin (14% vs. 0%, p = 0.01) and a lower rate of post-procedure admissions (OR 0.23, p = 0.003). Therefore, when using paravertebral blocks, bilateral blocks are superior to unilateral blocks, as demonstrated by decreased rates of hospital admission and reduced use of systemic neuropathic pain medication. Additionally, reducing post-procedural MME may reduce the rate of admission to the hospital.
Broadband radiometric measurements from GPS satellites reveal summertime Arctic Ocean Albedo decreases more rapidly than sea ice recedes
Authors: Dreike Philip L. , Kaczmarowski Amy K. , Garrett Christopher D. , Christiansen Gregory , Roesler Erika L. , Ivey Mark
Published: August 2023

New measurements from the Arctic ± 40 days around the summer solstice show reflected sunlight from north of 80°N decreases 20–35%. Arctic sea ice coverage decreases 7–9% over this same time period (as reported by the NSIDC) implying Arctic sea ice albedo decreases in addition to the sea ice receding. Similar Antarctic measurements provide a baseline to which Arctic measurements are compared. The Antarctic reflected sunlight south of 80°S is up to 30% larger than the Arctic reflectance and is symmetric around the solstice implying constant Antarctic reflectivity. Arctic reflected sunlight 20 days after solstice is > 100W/m2 less than Antarctic reflected sunlight. For perspective, this is enough heat to melt > 1 mm/hour of ice. This finding should be compared with climate models and in reanalysis data sets to further quantify sea ice albedo’s role in Arctic Amplification. The measurements were made with previously unpublished pixelated radiometers on Global Positioning System satellites from 2014 to 2019. The GPS orbits give each radiometer instantaneous and continuous views of 37% of the Earth, two daily full views of the Arctic and Antarctic. Furthermore, the GPS constellation gives full-time full-Earth coverage that may provide data that complements existing limited field of view instruments that provide a less synoptic Earth view.
Neural superstatistics for Bayesian estimation of dynamic cognitive models
Authors: Schumacher Lukas , Bürkner Paul-Christian , Voss Andreas , Köthe Ullrich , Radev Stefan T.
Published: August 2023

Mathematical models of cognition are often memoryless and ignore potential fluctuations of their parameters. However, human cognition is inherently dynamic. Thus, we propose to augment mechanistic cognitive models with a temporal dimension and estimate the resulting dynamics from a superstatistics perspective. Such a model entails a hierarchy between a low-level observation model and a high-level transition model. The observation model describes the local behavior of a system, and the transition model specifies how the parameters of the observation model evolve over time. To overcome the estimation challenges resulting from the complexity of superstatistical models, we develop and validate a simulation-based deep learning method for Bayesian inference, which can recover both time-varying and time-invariant parameters. We first benchmark our method against two existing frameworks capable of estimating time-varying parameters. We then apply our method to fit a dynamic version of the diffusion decision model to long time series of human response times data. Our results show that the deep learning approach is very efficient in capturing the temporal dynamics of the model. Furthermore, we show that the erroneous assumption of static or homogeneous parameters will hide important temporal information.
A new method to compile global multi-hazard event sets
Authors: Claassen Judith N. , Ward Philip J. , Daniell James , Koks Elco E. , Tiggeloven Timothy , de Ruiter Marleen C.
Published: August 2023

This study presents a new method, the MYRIAD-Hazard Event Sets Algorithm (MYRIAD-HESA), that compiles historically-based multi-hazard event sets. MYRIAD-HESA is a fully open-access method that can create multi-hazard event sets from any hazard events that occur on varying time, space, and intensity scales. In the past, multi-hazards have predominately been studied on a local or continental scale, or have been limited to specific hazard combinations, such as the combination between droughts and heatwaves. Therefore, we exemplify our approach by compiling a global multi-hazard event set database, spanning from 2004 to 2017, which includes eleven hazards from varying hazard classes (e.g. meteorological, geophysical, hydrological and climatological). This global database provides new scientific insights on the frequency of different multi-hazard events and their hotspots. Additionally, we explicitly incorporate a temporal dimension in MYRIAD-HESA, the time-lag. The time-lag, or time between the occurrence of hazards, is used to determine potentially impactful events that occurred in close succession. Varying time-lags have been tested in MYRIAD-HESA, and are analysed using North America as a case study. Alongside the MYRIAD-HESA, the multi-hazard event sets, MYRIAD-HES, is openly available to further increase the understanding of multi-hazard events in the disaster risk community. The open-source nature of MYRIAD-HESA provides flexibility to conduct multi-risk assessments by, for example, incorporating higher resolution data for an area of interest.