bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healing Liberal Democracies: The Role of Restorative Constitutionalism
Authors: Dixon Rosalind , Landau David 
Published: December 2022

AbstractThis brief essay contrasts two modes of constitutional change: abusive constitutional projects that seek to erode democracy and restorative constitutional projects that aim to repair eroded democratic constitutional orders. Constitutional democracies are eroded and restored via the same mechanisms: formal processes of constitutional amendment and replacement, legislative amendment, changes to executive policies and practices (or respect for conventions), and processes of judicial decision-making. Under the right conditions, abusive uses of these mechanisms for antidemocratic ends can be reversed by prodemocratic or restorative uses. The more difficult question is what kinds of political discourses are most likely to sustain successful processes of democratic rebuilding. In recent work, we have pointed to the role sometimes played by liberal democratic discourses as purported justifications for processes of abusive constitutional change: we label this the rise of “abusive constitutional borrowing.” Less well understood are the kind of discourses likely to sustain successful democratic healing or rebuilding. Often, the most popular discourse is a restorative one, which focuses on repairing damage caused by authoritarians and returning to a constitutional status quo ante. In this essay, we discuss the advantages and disadvantages of restorative constitutionalism as a response to prior episodes of democratic erosion.
Conflict over Congressional Reapportionment: The Deadlock of the 1920s
Authors: NAPOLIO NICHOLAS G. , JENKINS JEFFERY A. 
Published: December 2022

AbstractIn 1929, Congress passed a law capping the US House of Representatives at 435 seats, delegating the power to reapportion to the Executive Branch, and empowering state legislatures to redistrict with few federal limitations. The 1929 law was a compromise after nearly ten years of squabbling over how to apportion pursuant to the 1920 Census. In this article, we consider the apportionment debates of the 1920s both to better understand the politics of the era and to draw lessons that might apply to a potential reapportionment debate today. Throughout the decade, partisanship and political self-interest structured members’ votes on reapportionment. The legislation that eventually passed resulted from a compromise that greatly empowered state legislatures to redistrict freely by removing federal requirements that had been in effect since the 1870s, effectively shifting the battle over congressional representation from one over reapportionment in Congress to one over redistricting in the states.
Electron Accepting Capacities of a Wide Variety of Peat Materials From Around the Globe Similarly Explain CO2 and CH4 Formation
Authors: Guth Patrick , Gao Chuanyu , Knorr Klaus‐Holger 
Published: December 2022

AbstractIn organic soils, the availability of terminal electron acceptors (TEAs) determines the ratio of CO2 to CH4 formation under anoxic conditions. While the importance of electron accepting capacities (EACs) of organic matter is increasingly acknowledged, redox properties of organic matter have only been investigated in a limited set of peat and reference materials. Therefore, we incubated 60 peat samples from 15 sites covering a variety of both bog and poor to intermediate fen samples and characterized their capacities to serve as TEA for anaerobic CO2 formation. We quantified CO2 and CH4 formation and changes in available EAC in anoxic incubations of 56 days. In our experiment, on average 36.5% of CO2 could be attributed to CH4 formation, assuming an CO2:CH4 ratio for methanogenesis of 1:1. Regarding the remaining CO2 formed, for which a corresponding TEA would be needed, we could on average explain 70.8% by corresponding consumption of EAC from both organic and inorganic TEAs, the latter contributing less than 0.1%. When the initial EAC was high, CO2 formation from the apparent consumption of EAC was high and outweighed CO2 formation from methanogenesis. Rapid depletion of available EAC, especially in reactive peat, resulted in a higher share of CO2 from CH4 formation. Our study demonstrates that EAC provides the most important redox buffer for competitive suppression of methanogenesis in peat soils, particularly under fluctuating water table levels, when EAC is repeatedly regenerated. Moreover, electron budgets including EAC of organic matter could largely explain anaerobic CO2 production.
On the Deep Western Boundary Current Separation and Anticyclone Genesis off Northeast Brazil
Authors: Vilela‐Silva Felipe , Silveira Ilson C. A. , Napolitano Dante C. , Souza‐Neto Pedro W. M. , Biló Tiago C. , Gangopadhyay Avijit 
Published: December 2022

AbstractThe Deep Western Boundary Current (DWBC) is the main component of the deep limb of the Atlantic Meridional Overturning Circulation (AMOC). Off northeast Brazil, the DWBC breaks up into southwestward‐propagating anticyclones. In this study, we investigate the breakup mechanism with hydrographic observations, eddy‐resolving numerical model outputs, and theory. Here, we present a quasi‐synoptic map of geostrophic velocities and stream function at the DWBC core level between 2.5°S and 11°S. We observe, in horizontal distributions of velocities, that the DWBC breakup site is linked to a topographic feature of the Brazilian continental margin centered at 8°S: the Pernambuco Plateau (PP). Moreover, both observations and model outputs hint at a possible DWBC separation near the PP preceding anticyclone genesis. We test, with three different theories from the literature, whether or not the DWBC separates at 8°S. The results of the tests converge to indicate that the DWBC undergoes a local and intermittent inertial separation while contouring the PP. Downstream of its separation at the plateau, the DWBC sheds eddies similarly to previously reported laboratory experiments. In addition, a regional analysis of energy transfer shows that barotropic instability significantly contributes to the anticyclones growth between 8°S and 13°S. Analysis of the energy budget and separation of waters related to the AMOC pathways into the basin interior provide a better understanding for later studies about heat fluxes and ventilation in the deep tropical South Atlantic.
Intensification of Global Hydrological Droughts Under Anthropogenic Climate Warming
Authors: Gu Lei , Yin Jiabo , Slater Louise J. , Chen Jie , Do Hong Xuan , Wang Hui‐Min , Chen Lu , Jiang Zhiqiang , Zhao Tongtiegang 
Published: December 2022

AbstractAnthropogenic climate warming is expected to accelerate the hydrological cycle with significant consequences for hydrological droughts. However, a systematic understanding of climate warming impacts on the global hydrological droughts and their driving mechanisms is still lacking. Here, we integrate bias‐corrected climate experiments, multiple hydrological models (HYs), and a multivariate analysis of variance (ANOVA) with a machine learning modeling framework, to examine the evolving frequency and multivariate characteristics of hydrological droughts and their mechanisms under climate warming for 6,688 catchments in the five principal Köppen‐Geiger climate zones. Results show that the total frequency of hydrological droughts is likely to stay unchanged while extreme hydrological droughts (e.g., events with a 30 yr joint return period, JRP) are projected to occur more frequently across the 21st century. The historical 30 yr JRP events assessed during the historical baseline period of 1985–2014 could become twice as frequent over ∼60% of global catchments by 2071–2100 under the middle and high emission scenarios (ESs). Climate uncertainty (i.e., from global climate models and ESs) is the major source of uncertainty over temperate and tropical catchments, versus HY uncertainty in arid catchments with locally complex runoff regimes. Our machine learning framework indicates that precipitation stress controls the development of historical droughts over ∼87% of global catchments. However, with climate warming, air temperature variations are expected to become the new primary driver of droughts in high‐latitude cold catchments. This study highlights an increasing risk of global extreme hydrological droughts with warming and suggests that rising temperatures in high latitudes may lead to more extreme hydrological droughts.
Six Decades of Hindsight Into Yesa Reservoir (Central Spanish Pyrenees): River Flow Dwindles as Vegetation Cover Increases and Mediterranean Atmospheric Dynamics Take Control
Authors: Juez C. , Garijo N. , Vicente‐Serrano S. M. , Beguería S. 
Published: December 2022

AbstractRiver discharge has experienced diverse changes in the last decades due to modification of hydrological patterns, anthropogenic intervention, re‐vegetation or annual and interannual climatic and atmospheric fluctuations. Assessing the recent changes in river discharge and understanding the main drivers of these changes is thus extremely important from theoretical and applied points of view. More specifically, here we want to draw attention toward the impacts of streamflow changes on reservoir storage and operation. We describe the hydrological dynamics of the Yesa reservoir draining catchment, located in the central Spanish Pyrenees, and characterize the reservoir operation modes over the last 60 years (1956–2020). We analyze concurrent climatic (precipitation, air temperature, drought index), atmospheric mechanisms, land cover (Normalized Different Vegetation Index) and discharge (inlet and outlet of Yesa reservoir) time‐series. By using the wavelet transform methodology, we detect historical breakpoints in the hydrological dynamics at different time‐scales. Distinctive periods are thus identified. More regular seasonal flows characterized the catchment's dynamics during the first decades of the study period, while the last decades were characterized by a high inter‐annual variability. These changes are primarily attributed to the natural re‐vegetation process that the catchment experienced. Furthermore, we related changes in atmospheric circulation with a decline of the long‐term discharge temporal features. This research contributes to the understanding of long‐term river discharge changes and helps to improve the reservoir management practices.
BAP1 loss induces mitotic defects in mesothelioma cells through BRCA1-dependent and independent mechanisms
Authors: Singh Anita , Busacca Sara , Gaba Aarti , Sheaff Michael , Poile Charlotte , Nakas Apostolos , Dzialo Joanna , Bzura Aleksandra , Dawson Alan G. , Fennell Dean A. , Fry Andrew M. 
Published: December 2022

AbstractThe tumour suppressor BRCA1-associated protein 1 (BAP1) is the most frequently mutated cancer gene in mesothelioma. Here we report novel functions for BAP1 in mitotic progression highlighting the relationship between BAP1 and control of genome stability in mesothelioma cells with therapeutic implications. Depletion of BAP1 protein induced proteasome-mediated degradation of BRCA1 in mesothelioma cells while loss of BAP1 correlated with BRCA1 loss in mesothelioma patient tumour samples. BAP1 loss also led to mitotic defects that phenocopied the loss of BRCA1 including spindle assembly checkpoint failure, centrosome amplification and chromosome segregation errors. However, loss of BAP1 also led to additional mitotic changes that were not observed upon BRCA1 loss, including an increase in spindle length and enhanced growth of astral microtubules. Intriguingly, these consequences could be explained by loss of expression of the KIF18A and KIF18B kinesin motors that occurred upon depletion of BAP1 but not BRCA1, as spindle and astral microtubule defects were rescued by re-expression of KIF18A and KIF18B, respectively. We therefore propose that BAP1 inactivation causes mitotic defects through BRCA1-dependent and independent mechanisms revealing novel routes by which mesothelioma cells lacking BAP1 may acquire genome instability and exhibit altered responses to microtubule-targeted agents.
The Neuropilin-1/PKC axis promotes neuroendocrine differentiation and drug resistance of prostate cancer
Authors: Blanc Charly , Moktefi Anissa , Jolly Ariane , de la Grange Pierre , Gay Denise , Nicolaiew Nathalie , Semprez Fannie , Maillé Pascale , Soyeux Pascale , Firlej Virginie , Vacherot Francis , Destouches Damien , Amiche Mohamed , Terry Stéphane , de la Taille Alexandre , Londoño-Vallejo Arturo , Allory Yves , Delbé Jean , Hamma-Kourbali Yamina 
Published: December 2022

AbstractBackgroundNeuroendocrine prostate cancer (NEPC) is a multi-resistant variant of prostate cancer (PCa) that has become a major challenge in clinics. Understanding the neuroendocrine differentiation (NED) process at the molecular level is therefore critical to define therapeutic strategies that can prevent multi-drug resistance.MethodsUsing RNA expression profiling and immunohistochemistry, we have identified and characterised a gene expression signature associated with the emergence of NED in a large PCa cohort, including 169 hormone-naïve PCa (HNPC) and 48 castration-resistance PCa (CRPC) patients. In vitro and preclinical in vivo NED models were used to explore the cellular mechanism and to characterise the effects of castration on PCa progression.ResultsWe show for the first time that Neuropilin-1 (NRP1) is a key component of NED in PCa cells. NRP1 is upregulated in response to androgen deprivation therapies (ADT) and elicits cell survival through induction of the PKC pathway. Downmodulation of either NRP1 protein expression or PKC activation suppresses NED, prevents tumour evolution toward castration resistance and increases the efficacy of docetaxel-based chemotherapy in preclinical models in vivo.ConclusionsThis study reveals the NRP1/PKC axis as a promising therapeutic target for the prevention of neuroendocrine castration-resistant variants of PCa and indicates NRP1 as an early transitional biomarker.
Structural insights into the covalent regulation of PAPP-A activity by proMBP and STC2
Authors: Zhong Qihang , Chu Honglei , Wang Guopeng , Zhang Cheng , Li Rong , Guo Fusheng , Meng Xinlu , Lei Xiaoguang , Zhou Youli , Ren Ruobing , Tao Lin , Li Ningning , Gao Ning , Wei Yuan , Qiao Jie , Hang Jing 
Published: December 2022

AbstractOriginally discovered in the circulation of pregnant women as a protein secreted by placental trophoblasts, the metalloprotease pregnancy-associated plasma protein A (PAPP-A) is also widely expressed by many other tissues. It cleaves insulin-like growth factor-binding proteins (IGFBPs) to increase the bioavailability of IGFs and plays essential roles in multiple growth-promoting processes. While the vast majority of the circulatory PAPP-A in pregnancy is proteolytically inactive due to covalent inhibition by proform of eosinophil major basic protein (proMBP), the activity of PAPP-A can also be covalently inhibited by another less characterized modulator, stanniocalcin-2 (STC2). However, the structural basis of PAPP-A proteolysis and the mechanistic differences between these two modulators are poorly understood. Here we present two cryo-EM structures of endogenous purified PAPP-A in complex with either proMBP or STC2. Both modulators form 2:2 heterotetramer with PAPP-A and establish extensive interactions with multiple domains of PAPP-A that are distal to the catalytic cleft. This exosite-binding property results in a steric hindrance to prevent the binding and cleavage of IGFBPs, while the IGFBP linker region-derived peptides harboring the cleavage sites are no longer sensitive to the modulator treatment. Functional investigation into proMBP-mediated PAPP-A regulation in selective intrauterine growth restriction (sIUGR) pregnancy elucidates that PAPP-A and proMBP collaboratively regulate extravillous trophoblast invasion and the consequent fetal growth. Collectively, our work reveals a novel covalent exosite-competitive inhibition mechanism of PAPP-A and its regulatory effect on placental function.
Rare diseases and space health: optimizing synergies from scientific questions to care
Authors: Puscas Maria , Martineau Gabrielle , Bhella Gurjot , Bonnen Penelope E. , Carr Phil , Lim Robyn , Mitchell John , Osmond Matthew , Urquieta Emmanuel , Flamenbaum Jaime , Iaria Giuseppe , Joly Yann , Richer Étienne , Saary Joan , Saint-Jacques David , Buckley Nicole , Low-Decarie Etienne 
Published: December 2022

AbstractKnowledge transfer among research disciplines can lead to substantial research progress. At first glance, astronaut health and rare diseases may be seen as having little common ground for such an exchange. However, deleterious health conditions linked to human space exploration may well be considered as a narrow sub-category of rare diseases. Here, we compare and contrast research and healthcare in the contexts of rare diseases and space health and identify common barriers and avenues of improvement. The prevalent genetic basis of most rare disorders contrasts sharply with the occupational considerations required to sustain human health in space. Nevertheless small sample sizes and large knowledge gaps in natural history are examples of the parallel challenges for research and clinical care in the context of both rare diseases and space health. The two areas also face the simultaneous challenges of evidence scarcity and the pressure to deliver therapeutic solutions, mandating expeditious translation of research knowledge into clinical care. Sharing best practices between these fields, including increasing participant involvement in all stages of research and ethical sharing of standardized data, has the potential to contribute to humankind’s efforts to explore ever further into space while caring for people on Earth in a more inclusive fashion.
A novel intradermal tattoo-based injection device enhances the immunogenicity of plasmid DNA vaccines
Authors: Gomez Alejandro M. , Babuadze George , Plourde-Campagna Marc-André , Azizi Hiva , Berger Alice , Kozak Robert , de La Vega Marc-Antoine , XIII Ara , Naghibosadat Maedeh , Nepveu-Traversy Marie-Edith , Ruel Jean , Kobinger Gary P. 
Published: December 2022

AbstractIn recent years, tattooing technology has shown promising results toward evaluating vaccines in both animal models and humans. However, this technology has some limitations due to variability of experimental evaluations or operator procedures. The current study evaluated a device (intradermal oscillating needle array injection device: IONAID) capable of microinjecting a controlled dose of any aqueous vaccine into the intradermal space. IONAID-mediated administration of a DNA-based vaccine encoding the glycoprotein (GP) from the Ebola virus resulted in superior T- and B-cell responses with IONAID when compared to single intramuscular (IM) or intradermal (ID) injection in mice. Moreover, humoral immune responses, induced after IONAID vaccination, were significantly higher to those obtained with traditional passive DNA tattooing in guinea pigs and rabbits. This device was well tolerated and safe during HIV vaccine delivery in non-human primates (NHPs), while inducing robust immune responses. In summary, this study shows that the IONAID device improves vaccine performance, which could be beneficial to the animal and human health, and importantly, provide a dose-sparing approach (e.g., monkeypox vaccine).
Treatment of peanut allergy and colitis in mice via the intestinal release of butyrate from polymeric micelles
Authors: Wang Ruyi , Cao Shijie , Bashir Mohamed Elfatih H. , Hesser Lauren A. , Su Yanlin , Hong Sung Min Choi , Thompson Andrew , Culleen Elliot , Sabados Matthew , Dylla Nicholas P. , Campbell Evelyn , Bao Riyue , Nonnecke Eric B. , Bevins Charles L. , Wilson D. Scott , Hubbell Jeffrey A. , Nagler Cathryn R. 
Published: December 2022

AbstractThe microbiome modulates host immunity and aids the maintenance of tolerance in the gut, where microbial and food-derived antigens are abundant. Yet modern dietary factors and the excessive use of antibiotics have contributed to the rising incidence of food allergies, inflammatory bowel disease and other non-communicable chronic diseases associated with the depletion of beneficial taxa, including butyrate-producing Clostridia. Here we show that intragastrically delivered neutral and negatively charged polymeric micelles releasing butyrate in different regions of the intestinal tract restore barrier-protective responses in mouse models of colitis and of peanut allergy. Treatment with the butyrate-releasing micelles increased the abundance of butyrate-producing taxa in Clostridium cluster XIVa, protected mice from an anaphylactic reaction to a peanut challenge and reduced disease severity in a T-cell-transfer model of colitis. By restoring microbial and mucosal homoeostasis, butyrate-releasing micelles may function as an antigen-agnostic approach for the treatment of allergic and inflammatory diseases.
Arithmetic value representation for hierarchical behavior composition
Authors: Makino Hiroshi 
Published: December 2022

AbstractThe ability to compose new skills from a preacquired behavior repertoire is a hallmark of biological intelligence. Although artificial agents extract reusable skills from past experience and recombine them in a hierarchical manner, whether the brain similarly composes a novel behavior is largely unknown. In the present study, I show that deep reinforcement learning agents learn to solve a novel composite task by additively combining representations of prelearned action values of constituent subtasks. Learning efficacy in the composite task was further augmented by the introduction of stochasticity in behavior during pretraining. These theoretical predictions were empirically tested in mice, where subtask pretraining enhanced learning of the composite task. Cortex-wide, two-photon calcium imaging revealed analogous neural representations of combined action values, with improved learning when the behavior variability was amplified. Together, these results suggest that the brain composes a novel behavior with a simple arithmetic operation of preacquired action-value representations with stochastic policies.
Region-selective control of the thalamic reticular nucleus via cortical layer 5 pyramidal cells
Authors: Hádinger Nóra , Bősz Emília , Tóth Boglárka , Vantomme Gil , Lüthi Anita , Acsády László 
Published: December 2022

AbstractCorticothalamic pathways, responsible for the top-down control of the thalamus, have a canonical organization such that every cortical region sends output from both layer 6 (L6) and layer 5 (L5) to the thalamus. Here we demonstrate a qualitative, region-specific difference in the organization of mouse corticothalamic pathways. Specifically, L5 pyramidal cells of the frontal cortex, but not other cortical regions, establish monosynaptic connections with the inhibitory thalamic reticular nucleus (TRN). The frontal L5–TRN pathway parallels the L6–TRN projection but has distinct morphological and physiological features. The exact spike output of the L5-contacted TRN cells correlated with the level of cortical synchrony. Optogenetic perturbation of the L5–TRN connection disrupted the tight link between cortical and TRN activity. L5-driven TRN cells innervated thalamic nuclei involved in the control of frontal cortex activity. Our data show that frontal cortex functions require a highly specialized cortical control over intrathalamic inhibitory processes.