bluuebunny/crossref_metadata_2025 huggingface dataset:
The Making of Bad Gentry: The Abolition of Keju, Local Governance, and Anti-Elite Protests, 1902–1911
Authors: Hao Yu , Liu Zhengcheng , Weng Xi , Zhou Li-an
Published: June 2022

This paper investigates the impact of the abolition of the civil service exam on local governance in early twentieth-century China. Before the abolition, local elites collected surtaxes that financed local public goods, but they were supervised by the state and could lose candidacy for higher status if they engaged in corrupt behavior. This prospect of upward mobility (POUM) gave them incentives to behave well, which the abolition of the exam removed. Using anti-elite protests as a proxy for the deterioration of local governance, we find that prefectures with a higher POUM experienced more incidents of anti-elite protests after the abolition.
Institute for Atmospheric and Earth System Research (INAR): Showcases for making science diplomacy
Authors: Lappalainen Hanna K. , Petäjä T. , Lintunen A. , Kulmala Markku
Published: June 2022

Science diplomacy can be defined as “the use of scientific collaborations between countries to address joint problems and to build constructive international partnerships for delivering effective scientific advice for policy making”. During the last 10 years, the Institute for Atmospheric and Earth System Research (INAR) has been active in finding ways to solve global Grand Challenges, particularly climate change and poor air quality in polluted megacities, and at the same time, better bridge research to international climate policy and science diplomacy processes. INAR has introduced Pan-Eurasian Experiment programme running since the year 2012 (www.atm.helsinki.fi/peex) to better address the scientific challenge to understand Atmosphere – Earth Surface – Biosphere interactions and feedbacks in the Northern Eurasian context. INAR has also launched a measurement concept called the Global Network of Stations Measuring Earth Surface and Atmosphere Interactions (GlobalSMEAR) and has hosted the European Centre of the International Eurasian Academy of Sciences since 2015. Most recently, INAR has coordinated the Arena for the gap analysis of the existing Arctic Science Co-Operations (AASCO), 2020–2021, to promote research with a holistic and integrated approach in understanding feedbacks and interactions globally and locally at the Arctic and outside the Arctic environments.
Sandwiching biregular random graphs
Authors: Klimošová Tereza , Reiher Christian , Ruciński Andrzej , Šileikis Matas
Published: June 2022

Let
${\mathbb{G}(n_1,n_2,m)}$
be a uniformly random m-edge subgraph of the complete bipartite graph
${K_{n_1,n_2}}$
with bipartition
$(V_1, V_2)$
, where
$n_i = |V_i|$
,
$i=1,2$
. Given a real number
$p \in [0,1]$
such that
$d_1 \,{:\!=}\, pn_2$
and
$d_2 \,{:\!=}\, pn_1$
are integers, let
$\mathbb{R}(n_1,n_2,p)$
be a random subgraph of
${K_{n_1,n_2}}$
with every vertex
$v \in V_i$
of degree
$d_i$
,
$i = 1, 2$
. In this paper we determine sufficient conditions on
$n_1,n_2,p$
and m under which one can embed
${\mathbb{G}(n_1,n_2,m)}$
into
$\mathbb{R}(n_1,n_2,p)$
and vice versa with probability tending to 1. In particular, in the balanced case
$n_1=n_2$
, we show that if
$p\gg\log n/n$
and
$1 - p \gg \left(\log n/n \right)^{1/4}$
, then for some
$m\sim pn^2$
, asymptotically almost surely one can embed
${\mathbb{G}(n_1,n_2,m)}$
into
$\mathbb{R}(n_1,n_2,p)$
, while for
$p\gg\left(\log^{3} n/n\right)^{1/4}$
and
$1-p\gg\log n/n$
the opposite embedding holds. As an extension, we confirm the Kim–Vu Sandwich Conjecture for degrees growing faster than
$(n \log n)^{3/4}$
.
“Je suis … Charlie, Samuel, Muhammed”: Practicing Muhammed Cartoons in Far Right and Islamist Politics
Authors: de Groot Heupner Susan
Published: June 2022

Since the 2005 Jyllands-Posten controversy, both far right and Islamist actors have employed Muhammed cartoons to construct a radical frontier between Muslims and non-Muslims. This article aims to provide a better understanding of the linkages between two opposing forms of popular identification by looking at the utilization of the Muhammed cartoons to crystallize a multitude of (conflicting) subjects, affects, and demands. Following a vantage point of mutual relations, the article investigates the discursive performances of the Dutch branch of the transnational Islamist party Hizb ut-Tahrir and the far right Party for Freedom with respect to the Jyllands-Posten affair, the 2015 Charlie Hebdo attacks, and the 2020 killing of a French schoolteacher. Considering its cultural and political foundations of mutual respect and tolerance, the Dutch case is pertinent for examining the tension between the right to free speech and support for extremist and popular forms of (far right and Islamist) identification.
A Reference Section Through Fast‐Spread Lower Oceanic Crust, Wadi Gideah, Samail Ophiolite (Sultanate of Oman): Whole Rock Geochemistry
Authors: Garbe‐Schönberg Dieter , Koepke Jürgen , Müller Samuel , Mock Dominik , Müller Tim
Published: June 2022

Due to its inaccessibility, no complete and coherent data set exists for the composition of modern fast‐spreading oceanic crust. We sampled outcrops through 6,500 m of fossil oceanic crust in the Oman Ophiolite (Wadi Gideah Transect) that is regarded as best analogue of fast‐spreading crust on land. Here we report a complete set of whole‐rock major and trace element data displaying systematic and contrasting compositional trends in lower and upper gabbros being correlated with stratigraphic depth. A significant discontinuity in crystallization regime is observed at ∼3,525 m above the mantle‐crust boundary: gabbros below ∼3,525 m have in general very low incompatible element mass fractions which develop upwards in a barely noticeable way to more differentiated compositions while Mg# decreases. More pronounced trends indicating progressive fractionation of ascending melts can be observed for incompatible elements and their element ratios as a consequence of in situ crystallization. Locally, more variable compositions within narrow depth intervals testify for advanced differentiation in situ within individual sills. Gabbros above ∼3,525 m become significantly more evolved and show considerable variations in composition. Fractional crystallization and mixing processes in a transient axial melt lens control the composition of isotropic “varitextured” gabbros and sheeted dike basalts where fractionation of high field strength elemental ratios is minor. New average compositions of fast‐spread (paleo) oceanic crust are reported for major and 38 trace elements. Comparison with new data from Wadi Khafifah close to Wadi Gideah suggests robustness of crustal accretion processes in both space and time.
Toward Efficient Calibration of Higher‐Resolution Earth System Models
Authors: Fletcher Christopher G. , McNally William , Virgin John G. , King Fraser
Published: June 2022

Projections of future climate change to support decision‐making require Earth system models (ESMs) running at high spatial resolution, but at present this is computationally prohibitive. A major challenge is the calibration (parameter tuning) during the development of ESMs, which requires running large numbers of simulations to identify optimal values for parameters that are poorly constrained by observations. Here, we train a convolutional neural network (CNN) to emulate perturbed parameter ensembles from two lower‐resolution (and thus much less expensive) versions of the same ESM, and a smaller number of higher‐resolution simulations. Cross‐validated results show that the CNN's skill exceeds that of a climatological baseline for most variables with as few as 5–10 examples of the higher‐resolution ESM, and for all variables (including precipitation) with at least 20 examples. This proof‐of‐concept study demonstrates a machine learning based approach that makes the process of constructing a higher‐resolution emulator 20%–40% more computationally efficient, and thus offers the prospect of significantly more efficient calibration of ESMs.
A Novel Machine Learning Method for Accelerated Modeling of the Downwelling Irradiance Field in the Upper Ocean
Authors: Hao Xuanting , Shen Lian
Published: June 2022

The downwelling irradiance is a crucial part of the air‐sea heat flux and a major energy source for the photosynthesis processes in the upper ocean. The modeling of the irradiance field is often time‐consuming in conventional Monte Carlo (MC) simulations. We propose an accelerated model based on machine learning to significantly reduce the computational cost. By introducing a generalized beam spreading function, we transform the raw data generated with the MC simulation into training data of reduced dimensions, which is then used to develop an artificial neural network. To validate the machine learning model, we use the MC model to simulate the irradiance field under a broadband wave field. For both clear and turbid seawater, the irradiance field predicted by the machine learning model agrees well with the MC simulation result. Compared with the MC simulation that is computationally expensive, our machine learning model is O(1,000) times faster.
From Microorganisms to Biosignatures: Subcritical Water Extraction as a Sample Preparation Technique for Future Life Detection Missions
Authors: Cieslarova Zuzana , Noell Aaron C. , Willis Peter A. , Mora Maria F.
Published: June 2022

Amino acids are important targets in the search for life beyond Earth. The types of amino acids, their relative abundances, and enantiomeric excess all serve as biosignatures. To detect such biosignatures, identification and quantification of individual amino acids are required. Regardless of the analytical workflow used, it is critical to release amino acids from the sample without altering their molecular distributions. Subcritical water extraction (SCWE) is a promising technique for the release of organics from a variety of samples that has been under development for flight implementation for over 20 years. However, there is a risk of racemization and/or degradation of amino acids during extraction that could alter their distributions. This work demonstrates for the first time that SCWE (200°C for 30 min) can release amino acids from bacterial cells and spores, while maintaining their native distributions and enantiomeric excess.
Improved Field‐Aligned Current and Radial Current Estimates at Low and Middle Latitudes Deduced by the Swarm Dual‐Spacecraft
Authors: Wang Fengjue , Lühr Hermann , Xiong Chao , Zhou Yunliang
Published: June 2022

Ionospheric currents have widely been investigated by using magnetic measurements from low‐Earth orbiting satellites. However, the assumptions of deriving currents from the magnetic measurements have not always been well considered. In this study we performed a detailed analysis of the ionospheric radial current (IRC) and inter‐hemispheric field‐aligned current (IHFAC) estimates at equatorial and low latitudes derived from the single‐satellite and dual‐spacecraft (dual‐SC) approaches of European Space Agency (ESA's) Swarm constellation. Data considered cover a 5‐year period, from 17 April 2014 to 16 April 2019. We found for most of the cases, the IRCs and IHFACs derived from both approaches show consistent latitudinal profiles. However, there are several cases with discrepancy exceeding 5 nA/m2 between two approaches. On average, the diurnal variations of IHFACs from both approaches agree well with each other for all seasons. But the amplitudes of single‐satellite results reach only about 70% of those from the dual‐SC. This difference is attributed to the fact that only the magnetic field By component is utilized in the single‐satellite approach, while both Bx and By components are considered in the dual‐SC approach. Above the magnetic equator, the IRCs derived from single‐satellite approach show clear tidal signatures, while such signature cannot be found in the IRCs from dual‐SC approach. We interpret these tidal‐signature of IRCs as spurious results, caused by equatorial electrojet contributions to the ∆By component. The dual‐SC derived IRCs show notable differences between ascending and descending orbits. Such differences might be due to a violation of the assumed perfect calibration of Swarm A and C. We suggest a systematic spacecraft‐fixed bias in the along‐track magnetic field component (Bx) between Swarm A and C. By interpreting the IRC differences, we obtain bias values of ∆Bx reaching 1 nT. Our results reveal that ionospheric currents are better characterized by the dual‐SC approach. But comparison with single‐satellite current estimates can help to identify weakness.
Circulation Patterns and Associated Rainfall Over South Tropical South America: GCMs Evaluation During the Dry‐To‐Wet Transition Season
Authors: Olmo M. E. , Espinoza J.‐C. , Bettolli M. L. , Sierra J. P. , Junquas C. , Arias P. A. , Moron V. , Balmaceda‐Huarte R.
Published: June 2022

The representation of the South American Monsoon System (SAMS) by general circulation models (GCMs) is of key relevance for a better understanding of the physical rationale behind the recent climate changes over South Tropical South America (STSA) and their expected changes in a global warming scenario. During the last four decades, STSA experienced a lengthening of the dry season associated with diverse forcings. In this work, a set of 16 GCMs historical Coupled Model Intercomparison Project Phase 6 coupled simulations were evaluated during 1979–2014 in terms of how well they reproduced the atmospheric circulation over STSA through a circulation‐patterns (CPs) approach. Nine CPs were first identified based on low‐level winds from the ERA5 reanalysis. Focus was put on the representation of CPs during the dry‐to‐wet transition season (July‐October). Model performance depended on the seasonal cycle and spatial structure of the CPs. GCMs adequately reproduced the different CPs, with lower skills in the transition seasons. GCMs tended to go from dry to wet conditions too quickly, evidencing deficiencies in the representation of the SAMS onset, related to a poor representation of the southerly wind intrusions to STSA and the variability of the South American low‐level jet. Some GCMs were able to associate the occurrence of anomalous dry and wet years with specific CPs, suggesting well‐represented physical mechanisms controlling precipitation variability. This study could identify a few GCMs that adequately simulated the CPs in STSA (among them, CESM2, CMCC‐CM2‐HR4 and MPI‐ESM1‐2‐HR), which is relevant for driving high‐resolution models and the analysis of future projections.
Past to Present: An Update to the Aims and Scope of JGR: Biogeosciences
Authors: Xenopoulos Marguerite A. , Desai Ankur R. , Huntzinger Deborah
Published: June 2022

Plain Language Summary

The Journal of Geophysical Research‐Biogeosciences focuses on the interactions between biology, hydrology, geology, chemistry, and physics within the Earth system. Here, we are presenting a brief early history of the journal and evolution of the topics and papers published over the past 20 years. We present an updated aims and scope which now explicitly considers method and data articles.
Eocene to Quaternary Deformation of the Southern Puna Plateau: Thermochronology, Geochronology, and Structural Geology of an Andean Hinterland Basin (NW Argentina)
Authors: McMillan Mitchell , Schoenbohm Lindsay M. , Tye Alexander , McMillan Malcolm F. , Zhou Renjie
Published: June 2022

Cordilleran orogens are complex tectonic systems, strongly influenced by lithospheric deformation and exhumation. However, in the type region of the Central Andes, the timing and mechanisms of deformation and mountain building remain poorly constrained, especially for the high‐elevation Puna Plateau of NW Argentina. We use geologic mapping, structural cross‐sections, low‐temperature thermochronology, and U‐Pb dating of ash and detrital zircons to elucidate the history and style of orogenic deformation in the Antofalla region of the Puna Plateau. Cooling ages of major reverse fault hanging walls and dated growth strata indicate that crustal shortening activated major reverse faults during the Eocene and continued out‐of‐sequence through the Early Miocene. This protracted period of shortening, which resulted in the filling of the Antofalla Basin, was followed by a transient episode of upper‐crustal E‐W extension on a major normal fault system during the Late Miocene. Pliocene to Quaternary time saw E‐W shortening return to the region. Our structural cross‐section permits only a low magnitude of shortening (∼15–25%), which stands in contrast to the 60‐km thick crust. Triassic to Cretaceous cooling ages from footwall rocks and minor structures indicate that the entire region experienced little exhumation or sedimentation during the Mesozoic, perhaps retaining a crust thickened during multiple episodes of Paleozoic orogenesis. The crust may also reflect lower‐crustal thickening due to the growth of a lithospheric drip during the Late Miocene.
Integrated hybrid sensing and microenergy for compact active microsystems
Authors: Deng Hai-Tao , Wang Zhi-Yong , Wang Yi-Lin , Wen Dan-Liang , Zhang Xiao-Sheng
Published: June 2022

Wearable electronics, as essential components of the Internet of Things (IoT), have attracted widespread attention, and the trend is to configure attractive wearable smart microsystems by integrating sensing, powering, and other functions. Herein, we developed an elastic hybrid triboelectric–electromagnetic microenergy harvester (named EHTE) to realize hybrid sensing and microenergy simultaneously. This EHTE is a highly integrated triboelectric nanogenerator (TENG) and electromagnetic nanogenerator (EMG). Based on the triboelectric–electromagnetic hybrid mechanism, an enhanced electrical output of the EHTE was achieved successfully, which demonstrates the feasibility of the EHTE for microelectronics powering. Moreover, with the merits of the EMG, the developed hybrid microenergy harvester integrated both active frequency sensing and passive inductive sensing capabilities. Specifically, the almost linear correlation of the electromagnetic outputs to the frequencies of the external stimulus endowed the proposed EHTE with an outstanding active frequency sensing ability. In addition, due to the unique structural configuration of the EMG (i.e., a conductive permanent magnet (PM), hybrid deformation layer, and flexible printed circuit board (FPCB) coil), an opportunity was provided for the developed EHTE to serve as a passive inductive sensor based on the eddy current effect (i.e., a form of electromagnetic induction). Therefore, the developed EHTE successfully achieved the integration of hybrid sensing (i.e., active frequency sensing and passive inductive sensing) and microenergy (i.e., the combination of electromagnetic effect and triboelectric effect) within a single device, which demonstrates the potential of this newly developed EHTE for wearable electronic applications, especially in applications of compact active microsystems.
Deleterious effects of nervous system in the offspring following maternal SARS-CoV-2 infection during the COVID-19 pandemic
Authors: Wang Ruting , Wu Zifeng , Huang Chaoli , Hashimoto Kenji , Yang Ling , Yang Chun
Published: June 2022

During the Coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is universally susceptible to all types of populations. In addition to the elderly and children becoming the groups of great concern, pregnant women carrying new lives need to be even more alert to SARS-CoV-2 infection. Studies have shown that pregnant women infected with SARS-CoV-2 can lead to brain damage and post-birth psychiatric disorders in offspring. It has been widely recognized that SARS-CoV-2 can affect the development of the fetal nervous system directly or indirectly. Pregnant women are recommended to mitigate the effects of COVID-19 on the fetus through vaccination, nutritional supplements, and psychological support. This review summarizes the possible mechanisms of the nervous system effects of SARS-CoV-2 infection on their offspring during the pregnancy and analyzes the available prophylactic and treatment strategies to improve the prognosis of fetal-related neuropsychiatric diseases after birth.
Reduced nucleus accumbens functional connectivity in reward network and default mode network in patients with recurrent major depressive disorder
Authors: Ding Yu-Dan , Chen Xiao , Chen Zuo-Bing , Li Le , Li Xue-Ying , Castellanos Francisco Xavier , Bai Tong-Jian , Bo Qi-Jing , Cao Jun , Chang Zhi-Kai , Chen Guan-Mao , Chen Ning-Xuan , Chen Wei , Cheng Chang , Cheng Yu-Qi , Cui Xi-Long , Duan Jia , Fang Yi-Ru , Gong Qi-Yong , Hou Zheng-Hua , Hu Lan , Kuang Li , Li Feng , Li Hui-Xian , Li Kai-Ming , Li Tao , Liu Yan-Song , Liu Zhe-Ning , Long Yi-Cheng , Lu Bin , Luo Qing-Hua , Meng Hua-Qing , Peng Dai-Hui , Qiu Hai-Tang , Qiu Jiang , Shen Yue-Di , Shi Yu-Shu , Si Tian-Mei , Tang Yan-Qing , Wang Chuan-Yue , Wang Fei , Wang Kai , Wang Li , Wang Xiang , Wang Ying , Wang Yu-Wei , Wu Xiao-Ping , Wu Xin-Ran , Xie Chun-Ming , Xie Guang-Rong , Xie Hai-Yan , Xie Peng , Xu Xiu-Feng , Yang Hong , Yang Jian , Yao Jia-Shu , Yao Shu-Qiao , Yin Ying-Ying , Yuan Yong-Gui , Zang Yu-Feng , Zhang Ai-Xia , Zhang Hong , Zhang Ke-Rang , Zhang Lei , Zhang Zhi-Jun , Zhao Jing-Ping , Zhou Ru-Bai , Zhou Yi-Ting , Zhu Jun-Juan , Zhu Zhi-Chen , Zou Chao-Jie , Zuo Xi-Nian , Yan Chao-Gan , Guo Wen-Bin
Published: June 2022

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.
Rare CACNA1H and RELN variants interact through mTORC1 pathway in oligogenic autism spectrum disorder
Authors: Teles e Silva André Luíz , Glaser Talita , Griesi-Oliveira Karina , Corrêa-Velloso Juliana , Wang Jaqueline Yu Ting , da Silva Campos Gabriele , Ulrich Henning , Balan Andrea , Zarrei Mehdi , Higginbotham Edward J. , Scherer Stephen W. , Passos-Bueno Maria Rita , Sertié Andrea Laurato
Published: June 2022

Oligogenic inheritance of autism spectrum disorder (ASD) has been supported by several studies. However, little is known about how the risk variants interact and converge on causative neurobiological pathways. We identified in an ASD proband deleterious compound heterozygous missense variants in the Reelin (RELN) gene, and ade novosplicing variant in the Cav3.2 calcium channel (CACNA1H) gene. Here, by using iPSC-derived neural progenitor cells (NPCs) and a heterologous expression system, we show that the variant in Cav3.2 leads to increased calcium influx into cells, which overactivates mTORC1 pathway and, consequently, further exacerbates the impairment of Reelin signaling. Also, we show that Cav3.2/mTORC1 overactivation induces proliferation of NPCs and that both mutant Cav3.2 and Reelin cause abnormal migration of these cells. Finally, analysis of the sequencing data from two ASD cohorts—a Brazilian cohort of 861 samples, 291 with ASD; the MSSNG cohort of 11,181 samples, 5,102 with ASD—revealed that the co-occurrence of risk variants in both alleles of Reelin pathway genes and in one allele of calcium channel genes confer significant liability for ASD. Our results support the notion that genes with co-occurring deleterious variants tend to have interconnected pathways underlying oligogenic forms of ASD.
Metabolic disturbances, hemoglobin A1c, and social cognition impairment in Schizophrenia spectrum disorders
Authors: Tang Sunny X. , Oliver Lindsay D. , Hänsel Katrin , DeRosse Pamela , John Majnu , Khairullah Ammar , Gold James M. , Buchanan Robert W. , Voineskos Aristotle , Malhotra Anil K.
Published: June 2022

Social cognitive impairments are core features of schizophrenia spectrum disorders (SSD) and are associated with greater functional impairment and decreased quality of life. Metabolic disturbances have been related to greater impairment in general neurocognition, but their relationship to social cognition has not been previously reported. In this study, metabolic measures and social cognition were assessed in 245 participants with SSD and 165 healthy comparison subjects (HC), excluding those with hemoglobin A1c (HbA1c) > 6.5%. Tasks assessed emotion processing, theory of mind, and social perception. Functional connectivity within and between social cognitive networks was measured during a naturalistic social task. Among SSD, a significant inverse relationship was found between social cognition and cumulative metabolic burden (β = −0.38,p < 0.001) and HbA1c (β = −0.37,p < 0.001). The relationship between social cognition and HbA1c was robust across domains and measures of social cognition and after accounting for age, sex, race, non-social neurocognition, hospitalization, and treatment with different antipsychotic medications. Negative connectivity between affect sharing and motor resonance networks was a partial mediator of this relationship across SSD and HC groups (β = −0.05,p = 0.008). There was a group x HbA1c effect indicating that SSD participants were more adversely affected by increasing HbA1c. Thus, we provide the first report of a robust relationship in SSD between social cognition and abnormal glucose metabolism. If replicated and found to be causal, insulin sensitivity and blood glucose may present as promising targets for improving social cognition, functional outcomes, and quality of life in SSD.
The LCK-14-3-3ζ-TRPM8 axis regulates TRPM8 function/assembly and promotes pancreatic cancer malignancy
Authors: Huang Yuan , Li Shi , Liu Qinfeng , Wang Zhijie , Li Shunyao , Liu Lei , Zhao Weiwei , Wang Kai , Zhang Rui , Wang Longfei , Wang Ming , William Ali Declan , Michalak Marek , Chen Xing-Zhen , Zhou Cefan , Tang Jingfeng
Published: June 2022

Transient receptor potential melastatin 8 (TRPM8) functions as a Ca2+-permeable channel in the plasma membrane (PM). Dysfunction of TRPM8 is associated with human pancreatic cancer and several other diseases in clinical patients, but the underlying mechanisms are unclear. Here, we found that lymphocyte-specific protein tyrosine kinase (LCK) directly interacts with TRPM8 and potentiates TRPM8 phosphorylation at Y1022. LCK positively regulated channel function characterized by increased TRPM8 current densities by enhancing TRPM8 multimerization. Furthermore, 14-3-3ζ interacted with TRPM8 and positively modulated channel multimerization. LCK significantly enhanced the binding of 14-3-3ζ and TRPM8, whereas mutant TRPM8-Y1022F impaired TRPM8 multimerization and the binding of TRPM8 and 14-3-3ζ. Knockdown of 14-3-3ζ impaired the regulation of TRPM8 multimerization by LCK. In addition, TRPM8 phosphotyrosine at Y1022 feedback regulated LCK activity by inhibiting Tyr505 phosphorylation and modulating LCK ubiquitination. Finally, we revealed the importance of TRPM8 phosphorylation at Y1022 in the proliferation, migration, and tumorigenesis of pancreatic cancer cells. Our findings demonstrate that the LCK-14-3-3ζ-TRPM8 axis for regulates TRPM8 assembly, channel function, and LCK activity and maybe provide potential therapeutic targets for pancreatic cancer.
Interactions between EGFR and EphA2 promote tumorigenesis through the action of Ephexin1
Authors: Kim Jeeho , Chang In-Youb , You Ho Jin
Published: June 2022

The cell signaling factors EGFR, EphA2, and Ephexin1 are associated with lung and colorectal cancer and play an important role in tumorigenesis. Although the respective functional roles of EGFR and EphA2 are well known, interactions between these proteins and a functional role for the complex is not understood. Here, we showed that Ephexin1, EphA2, and EGFR are each expressed at higher levels in lung and colorectal cancer patient tissues, and binding of EGFR to EphA2 was associated with both increased tumor grade and metastatic cases in both cancer types. Treatment with Epidermal Growth Factor (EGF) induced binding of the RR domain of EGFR to the kinase domain of EphA2, and this binding was promoted by Ephexin1. Additionally, the AKT-mediated phosphorylation of EphA2 (at Ser897) promoted interactions with EGFR, pointing to the importance of this pathway. Two mutations in EGFR, L858R and T790M, that are frequently observed in lung cancer patients, promoted binding to EphA2, and this binding was dependent on Ephexin1. Our results indicate that the formation of a complex between EGFR, EphA2, and Ephexin1 plays an important role in lung and colorectal cancers, and that inhibition of this complex may be an effective target for cancer therapy.
Coupling of growth rate and developmental tempo reduces body size heterogeneity in C. elegans
Authors: Stojanovski Klement , Großhans Helge , Towbin Benjamin D.
Published: June 2022

Animals increase by orders of magnitude in volume during development. Therefore, small variations in growth rates among individuals could amplify to a large heterogeneity in size. By live imaging of C. elegans, we show that amplification of size heterogeneity is prevented by an inverse coupling of the volume growth rate to the duration of larval stages and does not involve strict size thresholds for larval moulting. We perturb this coupling by changing the developmental tempo through manipulation of a transcriptional oscillator that controls the duration of larval development. As predicted by a mathematical model, this perturbation alters the body volume. Model analysis shows that an inverse relation between the period length and the growth rate is an intrinsic property of genetic oscillators and can occur independently of additional complex regulation. This property of genetic oscillators suggests a parsimonious mechanism that counteracts the amplification of size differences among individuals during development.
Inhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis
Authors: Damsky William , Wang Alice , Kim Daniel J. , Young Bryan D. , Singh Katelyn , Murphy Michael J. , Daccache Joseph , Clark Abigale , Ayasun Ruveyda , Ryu Changwan , McGeary Meaghan K. , Odell Ian D. , Fazzone-Chettiar Ramesh , Pucar Darko , Homer Robert , Gulati Mridu , Miller Edward J. , Bosenberg Marcus , Flavell Richard A. , King Brett
Published: June 2022

Sarcoidosis is an idiopathic inflammatory disorder that is commonly treated with glucocorticoids. An imprecise understanding of the immunologic changes underlying sarcoidosis has limited therapeutic progress. Here in this open-label trial (NCT03910543), 10 patients with cutaneous sarcoidosis are treated with tofacitinib, a Janus kinase inhibitor. The primary outcome is the change in the cutaneous sarcoidosis activity and morphology instrument (CSAMI) activity score after 6 months of treatment. Secondary outcomes included change in internal organ involvement, molecular parameters, and safety. All patients experience improvement in their skin with 6 patients showing a complete response. Improvement in internal organ involvement is also observed. CD4+ T cell-derived IFN-γ is identified as a central cytokine mediator of macrophage activation in sarcoidosis. Additional type 1 cytokines produced by distinct cell types, including IL-6, IL-12, IL-15 and GM-CSF, also associate with pathogenesis. Suppression of the activity of these cytokines, especially IFN-γ, correlates with clinical improvement. Our results thus show that tofacitinib treatment is associated with improved sarcoidosis symptoms, and predominantly acts by inhibiting type 1 immunity.
The piston Riemann problem in a photon superfluid
Authors: Bendahmane Abdelkrim , Xu Gang , Conforti Matteo , Kudlinski Alexandre , Mussot Arnaud , Trillo Stefano
Published: June 2022

Light flow in nonlinear media can exhibit quantum hydrodynamical features which are profoundly different from those of classical fluids. Here, we show that a rather extreme regime of quantum hydrodynamics can be accessed by exploring the piston problem (a paradigm in gas dynamics) for light, and its generalization, named after the celebrated mathematician Riemann, where the piston acts on a concomitant abrupt change of photon density. Our experiment reveals regimes featuring optical rarefaction (retracting piston) or shock (pushing piston) wave pairs, and most importantly the transition to a peculiar type of flow, occurring above a precise critical piston velocity, where the light shocks are smoothly interconnected by a large contrast, periodic, fully nonlinear wave. The transition to such extreme hydrodynamic state is generic for superfluids, but to date remained elusive to any other quantum fluid system. Our full-fiber setup used to observe this phenomenon in temporal domain proves to be a versatile alternative to other platforms currently employed to investigate the hydrodynamical properties of quantum fluids of light.
Implementation of a MS/MS database for isoquinoline alkaloids and other annonaceous metabolites
Authors: Agnès Salemon Akpa , Okpekon Timothée , Kouadio Yvette Affoué , Jagora Adrien , Bréard Dimitri , Costa Emmanoel V. , da Silva Felipe M. A. , Koolen Hector H. F. , Le Ray-Richomme Anne-Marie , Richomme Pascal , Champy Pierre , Beniddir Mehdi A. , Le Pogam Pierre
Published: June 2022

This data descriptor reports on the upload to a public repository (GNPS) of the IQAMDB, IsoQuinoline and Annonaceous Metabolites Data Base, comprising 320 tandem mass spectra. This project originated from our in-house collection of isoquinolines. The diversity of compounds included in this database was further extended through the contribution of two additional laboratories involved in isoquinoline alkaloids research: University of Angers and University of Manaus. The generated MS/MS data were processed and annotated on an individual basis to promote their straightforward reuse by natural product chemists interested in either the description of new isoquinoline alkaloids or the dereplication of isoquinoline-containing samples. The interest of the current repertoire for dereplication purposes has been validated based on the molecular networking of the well-investigated plant modelAnnona montanaagainst the IQAMDB‐implemented GNPS.
On-chip complex refractive index detection at multiple wavelengths for selective sensing
Authors: El Shamy Raghi S. , Swillam Mohamed A. , Li Xun
Published: June 2022

In this work we propose a method for on-chip detection of the complex refractive index of the sensing medium at multiple wavelengths for selective sensing. For the optical sensor to be selective, i.e. able to determine the substance present in the medium, either surface functionalization or absorption spectroscopy is often used. Surface functionalization is a complex process and is mainly limited to biological media. On the other hand, absorption spectroscopy is not suitable for on-chip sensing with micrometer dimensions as this will result in poor sensitivity, especially when working far from the substance absorption peaks. Here, we detect the dispersion of both the real n and imaginary k parts of the refractive index which are unique for each substance. This is done using a single micro-ring resonator (MRR) that exhibits multiple resonances over the operating wavelength range. The real and imaginary parts of the medium refractive index are determined at each resonance using the resonance wavelength and the absorption coefficient, respectively. In addition, using this technique the concentration composition of a multi-element medium can be determined by solving a system of linear equations that corresponds to the different wavelengths (resonances). We designed a silicon-on-insulator (SOI) ring-resonator operating in the near-infrared region from λ = 1.46 µm to λ = 1.6 µm. The ring exhibits 11 resonances over the 140 nm operating wavelength range where the corresponding medium refractive index is obtained. This design can detect four different substances namely, methanol, ethanol, propanol, and water. An average error of less than 0.0047% and 1.65% in the detection of the real and imaginary parts, respectively were obtained. Finally, the concentration composition of different multi-element media were successfully determined using the least square method with 97.4% detection accuracy.
Usefulness of low tidal volume ventilation strategy for patients with acute respiratory distress syndrome: a systematic review and meta-analysis
Authors: Yamamoto Ryohei , Okazaki Satoru Robert , Fujita Yoshihito , Seki Nozomu , Kokei Yoshufumi , Sekine Shusuke , Wada Soichiro , Norisue Yasuhiro , Narita Chihiro
Published: June 2022

The effects of lower tidal volume ventilation (LTV) were controversial for patients with acute respiratory distress syndrome (ARDS). This systematic review and meta-analysis aimed to evaluate the use of LTV strategy in patients with ARDS. We performed a literature search on MEDLINE, CENTRAL, EMBASE, CINAHL, “Igaku-Chuo-Zasshi”, clinical trial registration sites, and the reference of recent guidelines. We included randomized controlled trials (RCTs) to compare the LTV strategy with the higher tidal volume ventilation (HTV) strategy in patients with ARDS. Two authors independently evaluated the eligibility of studies and extracted the data. The primary outcomes were 28-day mortality. We used the GRADE methodology to assess the certainty of evidence. Among the 19,864 records screened, 13 RCTs that recruited 1874 patients were included in our meta-analysis. When comparing LTV (4–8 ml/kg) versus HTV (> 8 ml/kg), the pooled risk ratio for 28-day mortality was 0.79 (11 studies, 95% confidence interval [CI] 0.66–0.94, I2 = 43%, n = 1795, moderate certainty of evidence). Subgroup-analysis by combined high positive end-expiratory pressure with LTV showed interaction (P = 0.01). Our study indicated that ventilation with LTV was associated with reduced risk of mortality in patients with ARDS when compared with HTV.

Trial registration: UMIN-CTR (UMIN000041071).
Label-free multiplex electrochemical immunosensor for early diagnosis of lysosomal storage disorders
Authors: Abdulkarim Haya , Siaj Mohamed
Published: June 2022

Pompe, Gaucher and Krabbe disease are lysosomal storage disorders (LSDs) which are a group of genetic diseases that causes the accumulation of lipids in tissues and cells. Pompe, Gaucher and Krabbe are characterized by the deficiency of acid α-glucosidase (GAA), β-Glucocerebrosidase (GBA) and galactocerebrosidase (GALC), and treatable if detected in their early stages. Here, we present the fabrication of an electrochemical immunosensor for the multiplexed quantification and simultaneous detection of GAA, GBA and GALC. The sensor was developed by electrodepositing gold nanoparticles (AuNPs) on an array of carbon electrodes, followed by the immobilization of GAA, GBA and GALC specific antibodies via functionalization with cysteamine and glutaraldehyde. The multiplexed immunosensor was able to successfully detect GAA, GBA and GALC at the femtomolar level with respective low detection limits of 0.12 pg/ml, 0.31 pg/ml and 0.18 pg/ml. The immunosensor showed good selectivity, sensitivity and good recovery when spiked in human serum, which confirms its possible applicability in point-of-care testing for the early diagnosis of LSDs.
Forecasting induced seismicity in Oklahoma using machine learning methods
Authors: Qin Yan , Chen Ting , Ma Xiaofei , Chen Xiaowei
Published: June 2022

Oklahoma earthquakes in the past decade have been mostly associated with wastewater injection. Here we use a machine learning technique—the Random Forest to forecast induced seismicity rate in Oklahoma based on injection-related parameters. We split the data into training (2011.01–2015.05) and test (2015.06–2020.12) periods. The model forecasts seismicity rate during the test period based on input features, including operational parameters (injection rate and pressure), geological information (depth to basement), and modeled pore pressure and poroelastic stress. The results show overall good match with observed seismicity rate (adjusted$$R^2$$R2of 0.75). The model shows that pore pressure rate and poroelastic stressing rates are the two most important features in forecasting. The absolute values of pore pressure and poroelastic stress, and the injection rate itself, are less important than the stressing rates. These findings further emphasize that temporal changes of stressing rates would lead to significant changes in seismicity rates.
High-throughput metabolomics reveals dysregulation of hydrophobic metabolomes in cancer cell lines by Eleusine indica
Authors: Puah Perng Yang , Lee Dexter Jiunn Herng , Puah Soo Huan , Lah Nik Amin Sahid Nik , Ling Yee Soon , Fong Siat Yee
Published: June 2022

Eleusine indica, which is used in traditional medicine, exhibits antiproliferative activity against several cancer cell lines. However, metabolomic studies to evaluate the metabolite changes induced by E. indica in cancer cells are still lacking. The present study investigated the anticancer effects of a root fraction of E. indica (R-S5-C1-H1) on H1299, MCF-7, and SK-HEP-1 cell lines and analyzed metabolic changes in the treated cancer cells using ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS). Cell metabolic activity assays demonstrated that the cell viability of the three cancer cell lines was significantly reduced following treatment with R-S5-C1-H1, with half-maximal inhibitory concentrations values of 12.95 µg/mL, 15.99 µg/mL, and 13.69 µg/mL at 72 h, respectively. Microscopy analysis using Hoechst 33342 and Annexin V fluorescent dyes revealed that cells treated with R-S5-C1-H1 underwent apoptotic cell death, while chemometric analysis suggested that apoptosis was triggered 48 h after treatment with R-S5-C1-H1. Deconvoluted cellular metabolomics revealed that hydrophobic metabolites were significantly altered, including triacylglycerols, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and ceramide, suggesting that apoptosis induction by R-S5-C1-H1 potentially occurred through modulation of phospholipid synthesis and sphingolipid metabolism. These metabolomic profiling results provide new insights into the anticancer mechanisms of E. indica and facilitate the overall understanding of molecular events following therapeutic interventions.
Accuracy of real-time PCR and digital PCR for the monitoring of total HIV DNA under prolonged antiretroviral therapy
Authors: Renault Constance , Bolloré Karine , Pisoni Amandine , Motto-Ros Camille , Van de Perre Philippe , Reynes Jacques , Tuaillon Edouard
Published: June 2022

Total HIV DNA is a standard marker to monitor the HIV reservoir in people living with HIV. We investigated HIV DNA quantification accuracy by a real-time PCR kit (qPCR) and digital PCR (dPCR) method within the same set of primers and probes. Among 48 aviremic patients followed for up to 7 years with qPCR, the mean coefficient of variation of total HIV DNA between two successive measurements was 77% (± 0.42log10 HIVDNA copies/106 PBMC). The total HIV DNA quantified by the two PCR methods has a high correlation (0.99 and 0.83, for 8E5 and PLHIV samples, respectively), but we observed better repeatability and reproducibility of the dPCR compared to the qPCR (CV of 11.9% vs. 24.7% for qPCR, p-value = 0.024). Furthermore, we highlighted a decay of the number of HIV copies in the 8E5 cell line qPCR standard over time (from 0.73 to 0.43 copies per cell), contributing to variations of HIV DNA results in patients whose HIV reservoir should be theoretically stabilized. Our study highlighted that absolute quantification of total HIV DNA by dPCR allows more accurate monitoring of the HIV reservoir than qPCR in patients under prolonged antiretroviral therapy.
Autologous matrix-induced chondrogenesis is effective for focal chondral defects of the knee
Authors: Migliorini Filippo , Maffulli Nicola , Baroncini Alice , Bell Andreas , Hildebrand Frank , Schenker Hanno
Published: June 2022

Focal chondral defects of the knee are common and their management is challenging. This study investigated the efficacy and safety of Autologous Matrix-Induced Chondrogenesis (AMIC) for focal chondral defects of the knee. A systematic review and meta-analysis was conducted (according to the 2020 PRISMA statement) to investigate the efficacy of AMIC in improving symptoms and to compare AMIC versus microfracture (MFx). In January 2022, the following databases were accessed: Pubmed, Web of Science, Google Scholar, Embase. No time constrain was used for the search. All the clinical trials investigating AMIC and/or those comparing AMIC versus MFx for focal chondral defects of the knee were accessed. Only studies published in peer reviewed journals were considered. Studies which investigated other locations of the defects rather than knee were not eligible, nor those reporting data form mixed locations. Studies which reported data on revision settings, as well as those investigating efficacy on kissing lesions or multiple locations, were not suitable. The mean difference (MD) and odd ratio (OR) effect measure were used for continuous and binary data, respectively. Data from 18 studies (548 patients) were retrieved with a mean follow-up of 39.9 ± 26.5 months. The mean defect size was 3.2 ± 1.0 cm2. The visual analogue scale (VAS) decreased of − 3.9/10 (95% confidence interval (CI) − 4.0874 to -3.7126), the Tegner Activity Scale increased of + 0.8/10 (95% CI 0.6595 to 0.9405). The Lysholm Knee Scoring System increased of + 28.9/100 (95% CI 26.8716 to 29.1284), as did the International Knee Documentation Committee (IKDC) + 33.6/100 (95% CI 32.5800 to 34.6200). At last follow-up no patient showed signs of hypertrophy. 4.3% (9 of 210) of patients underwent revision procedures. The rate of failure was 3.8% (9 of 236). Compared to MFx, AMIC demonstrated lower VAS score (MD: − 1.01; 95% CI − 1.97 to 0.05), greater IKDC (MD: 11.80; 95% CI 6.65 to 16.94), and lower rate of revision (OR: 0.16; 95% CI 0.06 to 0.44). AMIC is effective for focal chondral defects of the knee. Furthermore, AMIC evidenced greater IKDC, along with a lower value of VAS and rate of revision compared to MFx.
Confined-based catalyst investigation through the comparative functionalization and defunctionalization of Zr-MOF
Authors: Karimi Meghdad , Sadeghi Samira , Mohebali Haleh , Bakhti Hamzeh , Mahjoub Alireza , Heydari Akbar
Published: June 2022

In metal–organic frameworks, confined space as a chemical nanoreactor is as important as organocatalysis or coordinatively unsaturated metal site catalysis.
Polycrystalline SnSx nanofilm enables CO2 electroreduction to formate with high current density
Authors: Wang Xinzhong , Liu Shuai , Zhang Hao , Zhang Shusheng , Meng Ge , Liu Qian , Sun Zhiyong , Luo Jun , Liu Xijun
Published: June 2022

We report a polycrystalline SnSx nanofilm deposited on carbon paper via simple vacuum evaporation for CO2-to-formate conversion. When paired with an IrO2 anode in a MEA electrolyzer, it demonstrates a high faradaic efficiency (>75%).