bluuebunny/crossref_metadata_2025 huggingface dataset:
Massive Volcanism May Have Foreshortened the Marinoan Snowball Earth
Authors: Lan Zhongwu , Huyskens Magdalena H. , Le Hir Guillaume , Mitchell Ross N. , Yin Qing‐Zhu , Zhang Gangyang , Li Xian‐Hua
Published: March 2022

The Cryogenian Period (717–635 Ma) experienced two low‐latitude “snowball Earth” glaciations, the Sturtian and the Marinoan of contrasting 57 and <16 Myr durations, respectively. A lack of reliable age controls on extensional tectonics and associated magmatic rocks during the Marinoan has hampered an understanding of the deglaciation. Furthermore, although deglaciation is generally assumed to have occurred once ongoing magmatism accumulated enough atmospheric CO2, as suggested by cap carbonates, specific geologic evidence linking volcanic events with deglaciation are lacking. Here, we present high‐precision zircon geochronology with chemical abrasion‐isotope‐dilution isotope ratio mass spectrometry that indicates an extensive and thick sequence of rift‐related magmatic rocks in South Qinling, Central China, erupted 2–6 Myr before the termination of the Marinoan. Climate modeling proposes a scenario explaining why the Marinoan was the shorter snowball and how volcanism may have driven the deglaciation.
Impact of Tropical Cyclones on Pelagic Sargassum
Authors: Sosa‐Gutierrez Rosmery , Jouanno Julien , Berline Leo , Descloitres Jacques , Chevalier Cristèle
Published: March 2022

The strong proliferation of holopelagic Sargassum in the Tropical Atlantic from 2011, raises many questions on the environmental factors controlling their growth and decay at interannual, seasonal, and intraseasonal scales. In this work, we specifically investigate the response of the Sargassum aggregations to high wind events such as those found in Tropical Cyclones (TCs). The evolution of Sargassum coverage obtained from MODIS observations in the north tropical Atlantic Ocean (from 0 to 30°N and from 0 to 100°W) was analyzed under 86 historical paths of TCs and tropical storms from 2011 to 2020 that crossed Sargassum aggregations. Our results show on average a 40% drop in Sargassum coverage under TC trajectories, which can exceed 60% for the most intense TCs. We associate this drop with a sinking of Sargassum toward the deep ocean. Our estimates suggest that TCs contribute to the seasonal decay of Sargassum biomass from August to November.
Shear Wave Splitting Across Antarctica: Implications for Upper Mantle Seismic Anisotropy
Authors: Lucas Erica M. , Nyblade Andrew A. , Accardo Natalie J. , Lloyd Andrew J. , Wiens Douglas A. , Aster Richard C. , Wilson Terry J. , Dalziel Ian W. , Stuart Graham W. , O’Donnell John Paul , Winberry J. Paul , Huerta Audrey D.
Published: March 2022

We examine upper mantle anisotropy across the Antarctic continent using 102 new shear wave splitting measurements obtained from teleseismic SKS, SKKS, and PKS phases combined with 107 previously published results. For the new measurements, an eigenvalue technique is used to estimate the fast polarization direction and delay time for each phase arrival, and high‐quality measurements are stacked to determine the best‐fit splitting parameters at each seismic station. The ensemble of splitting measurements shows largely NE‐SW‐oriented fast polarization directions across Antarctica, with a broadly clockwise rotation in polarization directions evident moving from west to east across the continent. Although the first‐order pattern of NE‐SW‐oriented polarization directions is suggestive of a single plate‐wide source of anisotropy, we argue the observed pattern of anisotropy more likely arises from regionally variable contributions of both lithospheric and sub‐lithospheric mantle sources. Anisotropy observed in the interior of East Antarctica, a region underlain by thick lithosphere, can be attributed to relict fabrics associated with Precambrian tectonism. In contrast, anisotropy observed in coastal East Antarctica, the Transantarctic Mountains (TAM), and across much of West Antarctica likely reflects both lithospheric and sub‐lithospheric mantle fabrics. While sub‐lithospheric mantle fabrics are best associated with either plate motion‐induced asthenospheric flow or small‐scale convection, lithospheric mantle fabrics in coastal East Antarctica, the TAM, and West Antarctica generally reflect Jurassic—Cenozoic tectonic activity.
Dynamics and Near‐Field Surface Motions of Transitioned Supershear Laboratory Earthquakes in Thrust Faults
Authors: Tal Yuval , Rubino Vito , Rosakis Ares J. , Lapusta Nadia
Published: March 2022

We study how the asymmetric geometry of thrust faults affects the dynamics of supershear ruptures and their associated trailing Rayleigh ruptures as they interact with the free surface, and investigate the resulting near‐field ground motions. Earthquakes are mimicked by propagating laboratory ruptures along a frictional interface with a 61° dip angle. Using an experimental technique that combines ultrahigh‐speed photography with digital image correlation, we produce sequences of full‐field evolving measurements of particle displacements and velocities. Our full‐field measurement capability allows us to confirm and quantify the asymmetry between the experimental motions of the hanging and footwalls, with larger velocity magnitudes occurring at the hanging wall. Interestingly, because the motion of the hanging wall is generally near‐vertical, while that of the footwall is at dip direction shallower than the dip angle of the fault, the horizontal surface velocity components are found to be larger at the footwall than at the hanging wall. The attenuation in surface velocity with distance from the fault trace is generally larger at the hanging wall than at the footwall and it is more pronounced in the vertical component than in the horizontal one. Measurements of the rotations in surface motions confirm experimentally that the interaction of the rupture with the free surface can be interpreted through a torqueing mechanism that leads to reduction in normal stress near the free surface for thrust earthquakes. Nondimensional analysis shows that the experimental measurements are consistent with larger‐scale numerical simulations as well as field observations from thrust earthquakes.
Spatial collagen stiffening promotes collective breast cancer cell invasion by reinforcing extracellular matrix alignment
Authors: Koorman Thijs , Jansen Karin A. , Khalil Antoine , Haughton Peter D. , Visser Daan , Rätze Max A. K. , Haakma Wisse E. , Sakalauskaitè Gabrielè , van Diest Paul J. , de Rooij Johan , Derksen Patrick W. B.
Published: March 2022

The tumor micro-environment often contains stiff and irregular-bundled collagen fibers that are used by tumor cells to disseminate. It is still unclear how and to what extent, extracellular matrix (ECM) stiffness versus ECM bundle size and alignment dictate cancer cell invasion. Here, we have uncoupled Collagen-I bundling from stiffness by introducing inter-collagen crosslinks, combined with temperature induced aggregation of collagen bundling. Using organotypic models from mouse invasive ductal and invasive lobular breast cancers, we show that increased collagen bundling in 3D induces a generic increase in breast cancer invasion that is independent of migration mode. However, systemic collagen stiffening using advanced glycation end product (AGE) crosslinking prevents collective invasion, while leaving single cell invasion unaffected. Collective invasion into collagen matrices by ductal breast cancer cells depends on Lysyl oxidase-like 3 (Loxl3), a factor produced by tumor cells that reinforces local collagen stiffness. Finally, we present clinical evidence that collectively invading cancer cells at the invasive front of ductal breast carcinoma upregulate LOXL3. By uncoupling the mechanical, chemical, and structural cues that control invasion of breast cancer in three dimensions, our data reveal that spatial control over stiffness and bundling underlie collective dissemination of ductal-type breast cancers.
Targeted Tshz3 deletion in corticostriatal circuit components segregates core autistic behaviors
Authors: Caubit Xavier , Gubellini Paolo , Roubertoux Pierre L. , Carlier Michèle , Molitor Jordan , Chabbert Dorian , Metwaly Mehdi , Salin Pascal , Fatmi Ahmed , Belaidouni Yasmine , Brosse Lucie , Kerkerian-Le Goff Lydia , Fasano Laurent
Published: March 2022

We previously linkedTSHZ3haploinsufficiency to autism spectrum disorder (ASD) and showed that embryonic or postnatalTshz3deletion in mice results in behavioral traits relevant to the two core domains of ASD, namely social interaction deficits and repetitive behaviors. Here, we provide evidence that cortical projection neurons (CPNs) and striatal cholinergic interneurons (SCINs) are two main and complementary players in the TSHZ3-linked ASD syndrome. In the cerebral cortex, TSHZ3 is expressed in CPNs and in a proportion of GABAergic interneurons, but not in cholinergic interneurons or glial cells. In the striatum, TSHZ3 is expressed in all SCINs, while its expression is absent or partial in the other main brain cholinergic systems. We then characterized two new conditional knockout (cKO) models generated by crossingTshz3flox/floxwithEmx1-Cre(Emx1-cKO) orChat-Cre(Chat-cKO) mice to decipher the respective role of CPNs and SCINs.Emx1-cKOmice show altered excitatory synaptic transmission onto CPNs and impaired plasticity at corticostriatal synapses, with neither cortical neuron loss nor abnormal layer distribution. These animals present social interaction deficits but no repetitive patterns of behavior.Chat-cKOmice exhibit no loss of SCINs but changes in the electrophysiological properties of these interneurons, associated with repetitive patterns of behavior without social interaction deficits. Therefore, dysfunction in either CPNs or SCINs segregates with a distinct ASD behavioral trait. These findings provide novel insights onto the implication of the corticostriatal circuitry in ASD by revealing an unexpected neuronal dichotomy in the biological background of the two core behavioral domains of this disorder.
ARL6IP5 reduces cisplatin-resistance by suppressing DNA repair and promoting apoptosis pathways in ovarian carcinoma
Authors: Kim Ji-Ye , Bahar Entaz , Lee Jung-Yun , Chang Sunhee , Kim Se Hoon , Park Eun Young , Do Sung-Im , Yoon Hyonok , Kim Hyun-Soo
Published: March 2022

Ovarian carcinoma (OC) is the most lethal gynecological malignancy due to frequent recurrence resulting from cisplatin-resistance. ARL6IP5 is a novel gene implicated to suppress cisplatin-resistance by activating apoptosis and inhibiting DNA repair through XRCC1 and PARP1. We investigated the clinicopathological and prognostic significance of the immunohistochemical ARL6IP5 expression on 79 post-chemotherapy OC patient tissue samples; in vitro, the effect of ARL6IP5 overexpression (OE) and knockdown (KD) on cancer hallmark functions and the effect of ARL6IP5 on the expression of DNA repair and apoptosis-related proteins were observed in OC cells and their cisplatin-resistant (CisR) counterparts. ARL6IP5 expression was significantly associated with chemotherapeutic response and was an independent prognosticator of progression-free and overall survival of high-grade serous OC patients. ARL6IP5-OE decreased cellular proliferation, invasion, migration, adhesion, and increased apoptosis (p < 0.05); the opposite was observed for ARL6IP5-KD. Notably, ARL6IP5-OE reduced cisplatin-resistance of both OC and CisR OC cells, while ARL6IP5-KD increased cisplatin-resistance (p < 0.05). ARL6IP5-OE suppressed the expressions of DNA repair proteins and increased those of pro-apoptotic proteins; the opposite was observed for ARL6IP5-KD. The recombinant ARL6IP5 protein (rARL6IP5) had the greatest apoptotic effect among cisplatin and olaparib, in both OC and CisR OC cells; moreover, rARL6IP5 was the only single agent in CisR OC cells to retain higher apoptotic efficacy compared with control (p < 0.05), indicating that the apoptotic pathway influenced by rARL6IP5 remained effective in CisR OC cells compared to cisplatin and olaparib. In conclusion, we demonstrated that ARL6IP5 is an independent prognosticator of OC patients with cellular functions of a tumor-suppressor, possibly influencing the development of cisplatin-resistance and progression of OC cells through regulation of DNA repair and apoptosis. rARL6IP5 had significantly greater apoptotic efficacy compared to conventional chemotherapeutic agents in both OC and CisR OC cells, suggesting that ARL6IP5 may be a valuable novel chemotherapeutic against CisR OC.
MYC inhibition reprograms tumor immune microenvironment by recruiting T lymphocytes and activating the CD40/CD40L system in osteosarcoma
Authors: Jiang Kuo , Zhang Qianfeng , Fan Yong , Li Jia , Zhang Jitao , Wang Wentao , Fan Jinzhu , Guo Yunshan , Liu Shichang , Hao Dingjun , Wang Yongxiang , Wang Lei , Shan Lequn
Published: March 2022

The efficacy of immune checkpoint blockade (ICB) therapy depends on sufficient infiltration and activation of primed tumor-specific cytotoxic T lymphocytes (CTLs) in the tumor microenvironment. However, many tumor types, including osteosarcoma, mainly display immune-desert or immune-excluded phenotypes, which are characterized by a lack of tumor-infiltrating lymphocytes and a poor response to ICB monotherapy. Thus, novel therapeutic strategies are urgently needed to surmount these obstacles. In this study, we found that the expression of the c-Myc oncogene is negatively correlated with the T cell infiltration rate in osteosarcoma. Pharmacological inhibition of c-Myc with JQ-1 significantly reduced tumor burden and improved overall survival in an immunocompetent syngeneic murine model of osteosarcoma (K7M2). A mechanistic study revealed that JQ-1 administration dramatically reprogrammed the tumor immune microenvironment (TIME) within K7M2 tumors. On the one hand, JQ-1 can promote T cell trafficking into tumors by increasing the expression and secretion of T cell-recruiting chemokines. On the other hand, JQ-1 is capable of facilitating crosstalk between antigen-presenting dendritic cells and T cells through the CD40/CD40L costimulatory pathway, leading to activation of tumor-specific CTLs. Combined treatment with anti-PD-1 antibody and JQ-1 resulted in more pronounced tumor regression than either monotherapy, showing an obvious synergistic effect. These findings uncover for the first time that c-Myc inhibition can promote T cell infiltration and activation in osteosarcoma in multiple ways, delivering a one-two punch for modulating TIME. The present work also provides the basis for establishing c-Myc inhibitor and ICB coadministration as a novel therapeutic regimen for patients with osteosarcoma.
CRISPR signal conductor 2.0 for redirecting cellular information flow
Authors: Zhan Yonghao , Li Aolin , Cao Congcong , Liu Yuchen
Published: March 2022

A key challenge in designing intelligent artificial gene circuits is generating flexible connections between arbitrary components and directly coupling them with endogenous signaling pathways. The CRISPR signal conductor based on conditionally inducible artificial transcriptional regulators can link classic cellular protein signals with targeted gene expression, but there are still problems with multiple signal processing and gene delivery. With the discovery and characterization of new Cas systems and long noncoding RNA (lncRNA) functional motifs, and because of the compatibility of guide RNA with noncoding RNA elements at multiple sites, it is increasingly possible to solve these problems. In this study, we developed CRISPR signal conductor version 2.0 by integrating various lncRNA functional motifs into different parts of the crRNA in the CRISPR-dCasΦ system. This system can directly regulate the expression of target genes by recruiting cellular endogenous transcription factors and efficiently sense a variety of protein signals that are not detected by a classical synthetic system. The new system solved the problems of background leakage and insensitive signaling responses and enabled the construction of logic gates with as many as six input signals, which can be used to specifically target cancer cells. By rewiring endogenous signaling networks, we further demonstrated the effectiveness and biosafety of this system for in vivo cancer gene therapy.
Comprehensive evaluation of deconvolution methods for human brain gene expression
Authors: Sutton Gavin J. , Poppe Daniel , Simmons Rebecca K. , Walsh Kieran , Nawaz Urwah , Lister Ryan , Gagnon-Bartsch Johann A. , Voineagu Irina
Published: March 2022

Transcriptome deconvolution aims to estimate the cellular composition of an RNA sample from its gene expression data, which in turn can be used to correct for composition differences across samples. The human brain is unique in its transcriptomic diversity, and comprises a complex mixture of cell-types, including transcriptionally similar subtypes of neurons. Here, we carry out a comprehensive evaluation of deconvolution methods for human brain transcriptome data, and assess the tissue-specificity of our key observations by comparison with human pancreas and heart. We evaluate eight transcriptome deconvolution approaches and nine cell-type signatures, testing the accuracy of deconvolution using in silico mixtures of single-cell RNA-seq data, RNA mixtures, as well as nearly 2000 human brain samples. Our results identify the main factors that drive deconvolution accuracy for brain data, and highlight the importance of biological factors influencing cell-type signatures, such as brain region and in vitro cell culturing.
A high-performance capillary-fed electrolysis cell promises more cost-competitive renewable hydrogen
Authors: Hodges Aaron , Hoang Anh Linh , Tsekouras George , Wagner Klaudia , Lee Chong-Yong , Swiegers Gerhard F. , Wallace Gordon G.
Published: March 2022

Renewable, or green, hydrogen will play a critical role in the decarbonisation of hard-to-abate sectors and will therefore be important in limiting global warming. However, renewable hydrogen is not cost-competitive with fossil fuels, due to the moderate energy efficiency and high capital costs of traditional water electrolysers. Here a unique concept of water electrolysis is introduced, wherein water is supplied to hydrogen- and oxygen-evolving electrodes via capillary-induced transport along a porous inter-electrode separator, leading to inherently bubble-free operation at the electrodes. An alkaline capillary-fed electrolysis cell of this type demonstrates water electrolysis performance exceeding commercial electrolysis cells, with a cell voltage at 0.5 A cm−2 and 85 °C of only 1.51 V, equating to 98% energy efficiency, with an energy consumption of 40.4 kWh/kg hydrogen (vs. ~47.5 kWh/kg in commercial electrolysis cells). High energy efficiency, combined with the promise of a simplified balance-of-plant, brings cost-competitive renewable hydrogen closer to reality.
Stereodivergent propargylic alkylation of enals via cooperative NHC and copper catalysis
Authors: Wen Yu-Hua , Zhang Zi-Jing , Li Shuai , Song Jin , Gong Liu-Zhu
Published: March 2022

Despite that asymmetric stereodivergent synthesis has experienced great success to provide unusual processes for the creation of chirality complexity, concepts appliable to asymmetric stereodivergent catalysis are still limited. The dependence on the unusual capacity of each catalyst to precisely control the reactive site planar in the region poses unparalleled constraints on this field. Here, we first demonstrate that the chiral Cu-allenylidene species can participate in the stereodivergent propargylic alkylation of enals, in concert with chiral N-heterocyclic carbenes (NHCs). Thus, all four stereoisomers were obtained with excellent enantioselectivity and diastereoselectivity (up to >99% e.e. and >95:5 d.r.) from the same starting materials by simply altering chiral Cu-Pybox complex and NHC combinations. The rich chemistry workable in the products enables the structurally diverse synthesis of chiral functional molecules and holds great potential in alkaloid synthesis, as showcased by the preparation of the key building block to access (-)-perophoramidine.
In situ photodeposition of platinum clusters on a covalent organic framework for photocatalytic hydrogen production
Authors: Li Yimeng , Yang Li , He Huijie , Sun Lei , Wang Honglei , Fang Xu , Zhao Yanliang , Zheng Daoyuan , Qi Yu , Li Zhen , Deng Weiqiao
Published: March 2022

Photocatalytic hydrogen production has been considered a promising approach to obtain green hydrogen energy. Crystalline porous materials have arisen as key photocatalysts for efficient hydrogen production. Here, we report a strategy to in situ photodeposit platinum clusters as cocatalyst on a covalent organic framework, which makes it an efficient photocatalyst for light-driven hydrogen evolution. Periodically dispersed adsorption sites of platinum species are constructed by introducing adjacent hydroxyl group and imine-N in the region of the covalent organic framework structural unit where photogenerated electrons converge, leading to the in situ reduction of the adsorbed platinum species into metal clusters by photogenerated electrons. The widespread platinum clusters on the covalent organic framework expose large active surface and greatly facilitate the electron transfer, finally contributing to a high photocatalytic hydrogen evolution rate of 42432 μmol g−1 h−1 at 1 wt% platinum loading. This work provides a direction for structural design on covalent organic frameworks to precisely manipulate cocatalyst morphologies and positions at the atomic level for developing efficient photocatalysts.
Corrosion and metal release characterization of stainless steel 316L weld zones in whey protein solution
Authors: Varmaziar Sadegh , Atapour Masoud , Hedberg Yolanda S.
Published: March 2022

Stainless steel ASTM 316 L is often used in the food industry as contact material with protein-rich dairy products. It has to be welded at some locations for many of these contact materials. This study aimed at i) determining any combined effects of the presence of whey protein (WP) and welding-induced weaknesses on corrosion and metal release, and ii) determining the appropriate welding procedure and filler metal (316 L, 309 L, 312). All weld metals (WMs) showed a higher pitting corrosion susceptibility as compared to the base metal (BM). Under induced friction (stirring), WP significantly enhanced the metal release from all materials, which was accelerated between 1 and 3 days of exposure. Post-imaging indicated pits. 312-WM released significantly higher amounts of metals as compared to the BM and the other WMs. This study indicated that the presence of WP, friction, and weldment-induced corrosion susceptibilities could synergistically cause metal release and corrosion of food contact materials.
Change in the incidence of Parkinson’s disease in a large UK primary care database
Authors: Okunoye Olaitan , Marston Louise , Walters Kate , Schrag Anette
Published: March 2022

Parkinson’s disease (PD) has the fastest rising prevalence of all neurodegenerative diseases worldwide. However, it is unclear whether its incidence has increased after accounting for age and changes in diagnostic patterns in the same population. We conducted a cohort study in individuals aged ≥50 years within a large UK primary care database between January 2006 and December 2016. To account for possible changes in diagnostic patterns, we calculated the incidence of PD using four case definitions with different stringency derived from the combination of PD diagnosis, symptoms, and treatment. Using the broadest case definition, the incidence rate (IR) per 100,000 person years at risk (PYAR) was 149 (95% CI 143.3–155.4) in 2006 and 144 (95% CI 136.9–150.7) in 2016. In conclusion, the incidence of PD in the UK remained stable between 2006 and 2016, when accounting for age and diagnostic patterns, suggesting no major change in underlying risk factors for PD during this time period in the UK.
Mutant LRRK2 in lymphocytes regulates neurodegeneration via IL-6 in an inflammatory model of Parkinson’s disease
Authors: Kozina Elena , Byrne Matthew , Smeyne Richard Jay
Published: March 2022

Mutations in a number of genes contribute to development of Parkinson’s disease (PD), including several within the LRRK2 gene. However, little is known about the signals that underlie LRRK2-mediated neuronal loss. One clue resides in the finding that the neurodegenerative cascades emanate from signals arising from the peripheral immune system. Here, using two chimeric mouse models, we demonstrate that: 1) the replacement of mutant LRRK2 with wt form of the protein in T- and B-lymphocytes diminishes LPS-mediated inflammation and rescues the SNpc DA neuron loss in the mutant LRRK2 brain; 2) the presence of G2019S or R1441G LRRK2 mutation in lymphocytes alone is sufficient for LPS-induced DA neuron loss in the genotypically wt brain; and 3) neutralization of peripheral IL-6 overproduction prevents the SNpc DA neuron loss in LPS-treated mutant LRRK2 mice. These results represent a major paradigm shift in our understanding of PD pathogenesis and suggest that immune dysfunction in some forms of familial PD may have primacy over the CNS as the initiating site of the disorder.
Restricted truncal sagittal movements of rapid eye movement behaviour disorder
Authors: Wasserman Danielle , Gullone Silvia , Duncan Iain , Veronese Mattia , Gnoni Valentina , Higgins Sean , Birdseye Adam , Gelegen Emine Cigdem , Goadsby Peter J. , Ashkan Keyoumars , Ray Chaudhuri K. , Tononi Giulio , Drakatos Panagis , Rosenzweig Ivana
Published: March 2022

Unlike sleep-walkers, patients with rapid-eye-movement-behaviour disorder (RBD) rarely leave the bed during the re-enactment of their dreams. RBD movements may be independent of spatial co-ordinates of the ‘outside-world’, and instead rely on (allocentric) brain-generated virtual space-maps, as evident by patients’ limited truncal/axial movements. To confirm this, a semiology analysis of video-polysomnography records of 38 RBD patients was undertaken and paradoxically restricted truncal/thoraco-lumbar movements during complex dream re-enactments demonstrated.
Gasdermin E mediates resistance of pancreatic adenocarcinoma to enzymatic digestion through a YBX1–mucin pathway
Authors: Lv Jiadi , Liu Yuying , Mo Siqi , Zhou Yabo , Chen Fengye , Cheng Feiran , Li Cong , Saimi Dilizhatai , Liu Mengyu , Zhang Huafeng , Tang Ke , Ma Jingwei , Wang Zhenfeng , Zhu Qiangqiang , Tong Wei-Min , Huang Bo
Published: March 2022

Pancreatic ductal adenocarcinoma (PDAC) originates from normal pancreatic ducts where digestive juice is regularly produced. It remains unclear how PDAC can escape autodigestion by digestive enzymes. Here we show that human PDAC tumour cells use gasdermin E (GSDME), a pore-forming protein, to mediate digestive resistance. GSDME facilitates the tumour cells to express mucin 1 and mucin 13, which form a barrier to prevent chymotrypsin-mediated destruction. Inoculation of GSDME−/− PDAC cells results in subcutaneous but not orthotopic tumour formation in mice. Inhibition or knockout of mucin 1 or mucin 13 abrogates orthotopic PDAC growth in NOD-SCID mice. Mechanistically, GSDME interacts with and transports YBX1 into the nucleus where YBX1 directly promotes mucin expression. This GSDME–YBX1–mucin axis is also confirmed in patients with PDAC. These findings uncover a unique survival mechanism of PDAC cells in pancreatic microenvironments.
Larvicidal and adulticidal effects of some Egyptian oils against Culex pipiens
Authors: Baz Mohamed M. , Selim Abdelfattah , Radwan Ibrahim Taha , Alkhaibari Abeer Mousa , Khater Hanem F.
Published: March 2022

Mosquitoes and mosquito-borne diseases represent an increasing global challenge. Plant extract and/or oils could serve as alternatives to synthetic insecticides. The larvicidal effects of 32 oils (1000 ppm) were screened against the early 4th larvae of Culex pipiens and the best oils were evaluated against adults and analyzed by gas chromatography-mass spectrometry (GC mass) and HPLC. All oils had larvicidal activity (60.0–100%, 48 h Post-treatment, and their Lethal time 50 (LT50) values ranged from 9.67 (Thymus vulgaris) to 37.64 h (Sesamum indicum). Oils were classified as a highly effective group (95–100% mortalities), including Allium sativum, Anethum graveolens, Camellia sinensis, Foeniculum vulgare, Nigella sativa, Salvia officinalis, T. vulgaris, and Viola odorata. The moderately effective group (81–92% mortalities) included Boswellia serrata, Cuminum cyminum, Curcuma aromatic, Allium sativum, Melaleuca alternifolia, Piper nigrum, and Simmondsia chinensis. The least effective ones were C. sativus and S. indicum. Viola odorata, Anethum graveolens, T. vulgaris, and N. sativa provide 100% adult mortalities PT with 10, 25, 20, and 25%. The mortality percentages of the adults subjected to 10% of oils (H group) were 48.89%, 88.39%, 63.94%, 51.54%, 92.96%, 44.44%, 72.22%, and 100% for A. sativum, An. graveolens, C. sinensis, F. vulgare, N. sativa, S. officinalis, T. vulgaris, and V. odorata, respectively. Camellia sinensis and F. vulgare were the most potent larvicides whereas V. odorata, T. vulgaris, An. graveolens and N. sativa were the best adulticides and they could be used for integrated mosquito control.
Shared antibiotic resistance and virulence genes in Staphylococcus aureus from diverse animal hosts
Authors: Bruce Spencer A. , Smith Joshua T. , Mydosh Jennifer L. , Ball John , Needle David B. , Gibson Robert , Andam Cheryl P.
Published: March 2022

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) poses an important threat in human and animal health. In this study, we ask whether resistance and virulence genes in S. aureus are homogeneously distributed or constrained by different animal hosts. We carried out whole genome sequencing of 114 S. aureus isolates from ten species of animals sampled from four New England states (USA) in 2017–2019. The majority of the isolates came from cats, cows and dogs. The maximum likelihood phylogenetic tree based on the alignment of 89,143 single nucleotide polymorphisms of 1173 core genes reveal 31 sequence types (STs). The most common STs were ST5, ST8, ST30, ST133 and ST2187. Every genome carried at least eight acquired resistance genes. Genes related to resistance found in all genomes included norA (fluoroquinolone), arlRS (fluoroquinolone), lmrS (multidrug), tet(38) (tetracycline) and mepAR (multidrug and tigecycline resistance). The most common superantigen genes were tsst-1, sea and sec. Acquired antibiotic resistance (n = 10) and superantigen (n = 9) genes of S. aureus were widely shared between S. aureus lineages and between strains from different animal hosts. These analyses provide insights for considering bacterial gene sharing when developing strategies to combat the emergence of high-risk clones in animals.
Genetic diversity and population structure of an African yam bean (Sphenostylis stenocarpa) collection from IITA GenBank
Authors: Shitta Ndenum Suzzy , Unachukwu Nnanna , Edemodu Alex Chukwudi , Abebe Abush Tesfaye , Oselebe Happiness O. , Abtew Wosene Gebreselassie
Published: March 2022

African yam bean, AYB (Sphenostylisstenocarpa), is an underutilized legume of tropical Africa. AYB can boost food and nutritional security in sub-Saharan Africa through its nutrient-rich seeds and tubers. However, inadequate information on germplasm with desirable agro-morphological traits, including insufficient data at the genomic level, has prevented the full exploitation of its food and breeding potentials. Notably, assessing the genetic diversity and population structure in a species is a prerequisite for improvement and eventual successful exploitation. The present study evaluated the population structure and genetic diversity of 169 accessions from the International Institute of Tropical Agriculture (IITA) collection using 26 phenotypic characters and 1789 single nucleotide polymorphism (SNP) markers. The phenotypic traits and SNP markers revealed their usefulness in uniquely distinguishing each AYB accession. The hierarchical cluster of phenotypes grouped accessions into three sub-populations; SNPs analysis also clustered the accessions into three sub-populations. The genetic differentiation (FST) among the three sub-populations was sufficiently high (0.14–0.39) and significant at P = 0.001. The combined analysis revealed three sub-populations; accessions in sub-population 1 were high yielding, members in sub-population 2 showed high polymorphic loci and heterozygosity. This study provides essential information for the breeding and genetic improvement of AYB.
Forage grass growth under future climate change scenarios affects fermentation and ruminant efficiency
Authors: Hart Elizabeth H. , Christofides Sarah R. , Davies Teri E. , Rees Stevens Pauline , Creevey Christopher J. , Müller Carsten T. , Rogers Hilary J. , Kingston-Smith Alison H.
Published: March 2022

With an increasing human population access to ruminant products is an important factor in global food supply. While ruminants contribute to climate change, climate change could also affect ruminant production. Here we investigated how the plant response to climate change affects forage quality and subsequent rumen fermentation. Models of near future climate change (2050) predict increases in temperature, CO2, precipitation and altered weather systems which will produce stress responses in field crops. We hypothesised that pre-exposure to altered climate conditions causes compositional changes and also primes plant cells such that their post-ingestion metabolic response to the rumen is altered. This “stress memory” effect was investigated by screening ten forage grass varieties in five differing climate scenarios, including current climate (2020), future climate (2050), or future climate plus flooding, drought or heat shock. While varietal differences in fermentation were detected in terms of gas production, there was little effect of elevated temperature or CO2compared with controls (2020). All varieties consistently showed decreased digestibility linked to decreased methane production as a result of drought or an acute flood treatment. These results indicate that efforts to breed future forage varieties should target tolerance of acute stress rather than long term climate.
A study on diameter-dependent support selection of the tendrils of Cayratia japonica
Authors: Saito Kazuya
Published: March 2022

Organisms make decisions when they perceive cues of varying intensities. In case of climbing plants, the diameter of supports in contact (tree or stem) is an important cue for their growth as plants that coil around a support with large diameter are unable to maintain tensional forces required for continued attachment to the support. The negative association between the diameter and the climbing success has been reported since Darwin published his study on climbing plants. However, it is not known if a climbing plant makes a decision to avoid a support with larger diameter. Here, we tested this possibility by observing the coiling response of tendrils of Cayratia japonica to supports with different diameters. The coiling success of the tendrils was affected by the diameter of the support and the tendril lengths. We propose a decision tree to describe the different phases of the coiling response and demonstrated that the tendrils change their coiling shape depending on the support diameter and the tendril length. To understand the behavioural rules regulating the phase pattern, we constructed a simple model with two assumptions on the tendril movement, (1) when the tendrils receive a contact stimulus, they begin to coil from around the contact point and (2) there is a minimum coiling angle at which the tendrils coil up, once the tendril starts coiling. Image analysis and 3D motion tracking technique revealed that the movement of the tendrils were consistent with the two assumptions of the model. The results suggested that the tendrils flexibly changed the coiling shapes depending on the support diameter and simple behavioural rules could regulate this diameter-dependent response.
Short- and long-term recurrence of early-stage invasive ductal carcinoma in middle-aged and old women with different treatments
Authors: Kao Yuan , Wu Ying-Jhen , Hsu Chien-Chin , Lin Hung-Jung , Wang Jhi-Joung , Tian Yu-Feng , Weng Shih-Feng , Huang Chien-Cheng
Published: March 2022

Most new cases and the highest mortality rates of breast cancer occur among middle-aged and old women. The recurrence rate of early-stage invasive ductal carcinoma (IDC) among women aged ≥ 50 years and receiving different treatments remains unclear. Therefore, this study was conducted to determine these rates. We used Surveillance, Epidemiology, and End Results (SEER) data for this nationwide population-based cohort study. All women aged ≥ 50 years and diagnosed with early-stage IDC between 2000 and 2015 were identified and divided into three treatment groups, namely, breast conservation therapy (BCT), mastectomy alone (MAS), and mastectomy with radiation therapy (MAS + RT). The recurrence rates of IDC among these groups were then compared. The BCT group had a lower short-term recurrence risk than the MAS and MAS + RT groups (hazard ratio [HR]: 1.00 vs. 2.90 [95% CI 1.36–2.66] vs. 2.07 [95% CI 0.97–4.44]); however, the BCT group also had a higher long-term recurrence risk than MAS and MAS + RT groups (HR 1.00 vs. 0.30 [95% CI 0.26–0.35] vs. 0.43 [95% CI 0.30–0.63]). The high long-term recurrence rate of the BCT group was especially prominent at the 10- and 15-year follow-ups. The results provide valuable evidence of the most reliable treatment strategy for this population. Further studies including more variables and validation in other countries are warranted to confirm our findings.
Predictors of Covid-19 level of concern among older adults from the health and retirement study
Authors: Beydoun Hind A. , Beydoun May A. , Weiss Jordan , Gautam Rana S. , Hossain Sharmin , Alemu Brook T. , Zonderman Alan B.
Published: March 2022

The purpose of this longitudinal study is to construct a prediction model for Covid-19 level of concern using established Covid-19 socio-demographic, lifestyle and health risk characteristics and to examine specific contributions of obesity-related cardiometabolic health characteristics as predictors of Covid-19 level of concern among a representative sample of U.S. older adults. We performed secondary analyses of existing data on 2872 2006–2020 Health and Retirement Study participants and examined 19 characteristics in relation to the outcome of interest using logistic regression and machine learning algorithms. In mixed-effects ordinal logistic regression models, a history of diabetes, stroke as well as 1–2 cardiometabolic risk factors and/or chronic conditions were associated with greater Covid-19 level of concern, after controlling for confounders. Female sex, birth cohort, minority race, Hispanic ethnicity and total wealth as well as depressive symptoms were associated with higher level of Covid-19 concern, and education was associated with lower level of Covid-19 concern in fully adjusted mixed-effects ordinal logistic regression models. The selected socio-demographic, lifestyle and health characteristics accounted for < 70% of the variability in Covid-19 level of concern based on machine learning algorithms. Independent risk factors for Covid-19 level of concern among U.S. older adults include socio-demographic characteristics and depressive symptoms. Advanced research is needed to identify relevant predictors and elucidate underlying mechanisms of observed relationships.
Simultaneous assessment of spontaneous cage activity and voluntary wheel running in group-housed mice
Authors: Reuser Annika , Wenzel Kristin , Felix Stephan B. , Dörr Marcus , Bahls Martin , Könemann Stephanie
Published: March 2022

Small animal models are frequently used to improve our understanding of the molecular and biological signaling pathways underlying the beneficial effects of physical activity and exercise. Unfortunately, when running wheels are employed, mice and rats are often kept single-housed to determine the individual running distance of each animal. However, social isolation can be stressful for rodents, and may alter an individual’s propensity for or response to exercise. For example, increased stress from single housing may significantly affect the results when investigating systemic metabolic responses to exercise. We have combined two already available and well-established systems, a radiotelemetry system and a running wheel, to determine spontaneous cage activity (SCA) as well as voluntary exercise (VE) levels of the individual animal in group-housed rodents. Further, we developed a simple software tool which allows monitoring and analyzing the data. Specifically, the radiotelemetry-system utilizes radio-frequency identification via a small, implanted chip to determine the location of each animal. Since, in addition to the animals’ position, also the location of the running wheel in the cage is known, the conclusion of which animal is exercising can be drawn. The developed software enables a fast and reliable assignment of the VE data to the individual animal and a simple analysis of the data collected. Hence, our combined method may be used to investigate the beneficial effects of physical activity, as well as the impact of therapeutic interventions on animal behavior in group-housed rodents.
Blood–brain barrier and gut barrier dysfunction in chronic kidney disease with a focus on circulating biomarkers and tight junction proteins
Authors: Hernandez Leah , Ward Liam J. , Arefin Samsul , Ebert Thomas , Laucyte-Cibulskiene Agne ,   GOING-FWD Collaborators, Pilote Louise , Norris Colleen M. , Raparelli Valeria , Kautzky-Willer Alexandra , Herrero Maria Trinidad , Kublickiene Karolina , Heimbürger Olof , Barany Peter , Wennberg Lars , Stenvinkel Peter , Kublickiene Karolina
Published: March 2022

Kidney failure and associated uraemia have implications for the cardiovascular system, brain, and blood–brain barrier (BBB). We aim to examine BBB disruption, by assessing brain-derived neurotropic factor (BDNF), neuron-specific enolase (NSE) levels, and gut-blood barrier (GBB) disruption by trimethylamine N-oxide (TMAO), in chronic kidney disease (CKD) patients. Additionally, endothelial tight-junction protein expressions and modulation via TMAO were assessed. Serum from chronic kidney disease (CKD) female and male haemodialysis (HD) patients, and controls, were used to measure BDNF and NSE by enzyme-linked immunosorbent assays, and TMAO by mass spectrometry. Immunofluorescent staining of subcutaneous fat biopsies from kidney transplant recipients, and controls, were used to measure microvascular expression of tight-junction proteins (claudin-5, occludin, JAM-1), and control microvasculature for TMAO effects. HD patients versus controls, had significantly lower and higher serum levels of BDNF and NSE, respectively. In CKD biopsies versus controls, reduced expression of claudin-5, occludin, and JAM-1 were observed. Incubation with TMAO significantly decreased expression of all tight-junction proteins in the microvasculature. Uraemia affects BBB and GBB resulting in altered levels of circulating NSE, BDNF and TMAO, respectively, and it also reduces expression of tight-junction proteins that confer BBB maintenance. TMAO serves as a potential candidate to alter BBB integrity in CKD.
Deep cascaded multitask framework for detection of temporal orientation, sentiment and emotion from suicide notes
Authors: Ghosh Soumitra , Ekbal Asif , Bhattacharyya Pushpak
Published: March 2022

With the upsurge in suicide rates worldwide, timely identification of the at-risk individuals using computational methods has been a severe challenge. Anyone presenting with suicidal thoughts, mainly recurring and containing a deep desire to die, requires urgent and ongoing psychiatric treatment. This work focuses on investigating the role of temporal orientation and sentiment classification (auxiliary tasks) in jointly analyzing the victims’ emotional state (primary task). Our model leverages the effectiveness of multitask learning by sharing features among the tasks through a novel multi-layer cascaded shared-private attentive network. We conducted our experiments on a diversified version of the prevailing standard emotion annotated corpus of suicide notes in English, CEASE-v2.0. Experiments show that our proposed multitask framework outperforms the existing state-of-the-art system by 3.78% in the Emotion task, with a cross-validation Mean Recall (MR) of 60.90%. From our empirical and qualitative analysis of results, we observe that learning the tasks of temporality and sentiment together has a clear correlation with emotion recognition.
Disease correlates of rim lesions on quantitative susceptibility mapping in multiple sclerosis
Authors: Marcille Melanie , Hurtado Rúa Sandra , Tyshkov Charles , Jaywant Abhishek , Comunale Joseph , Kaunzner Ulrike W. , Nealon Nancy , Perumal Jai S. , Zexter Lily , Zinger Nicole , Bruvik Olivia , Wang Yi , Sweeney Elizabeth , Kuceyeski Amy , Nguyen Thanh D. , Gauthier Susan A.
Published: March 2022

Quantitative susceptibility mapping (QSM), an imaging technique sensitive to brain iron, has been used to detect paramagnetic rims of iron-laden active microglia and macrophages in a subset of multiple sclerosis (MS) lesions, known as rim+ lesions, that are consistent with chronic active lesions. Because of the potential impact of rim+ lesions on disease progression and tissue damage, investigating their influence on disability and neurodegeneration is critical to establish the impact of these lesions on the disease course. This study aimed to explore the relationship between chronic active rim+ lesions, identified as having a hyperintense rim on QSM, and both clinical disability and imaging measures of neurodegeneration in patients with MS. The patient cohort was composed of 159 relapsing–remitting multiple sclerosis patients. The Expanded Disability Status Scale (EDSS) and Brief International Cognitive Assessment for Multiple Sclerosis, which includes both the Symbol Digit Modalities Test and California Verbal Learning Test-II, were used to assess clinical disability. Cortical thickness and thalamic volume were evaluated as imaging measures of neurodegeneration. A total of 4469 MS lesions were identified, of which 171 QSM rim+ (3.8%) lesions were identified among 57 patients (35.8%). In a multivariate regression model, as the overall total lesion burden increased, patients with at least one rim+ lesion on QSM performed worse on both physical disability and cognitive assessments, specifically the Symbol Digit Modalities Test (p = 0.010), California Verbal Learning Test-II (p = 0.030), and EDSS (p = 0.001). In a separate univariate regression model, controlling for age (p < 0.001) and having at least one rim+ lesion was related to more cortical thinning (p = 0.03) in younger patients (< 45 years). Lower thalamic volume was associated with older patients (p = 0.038) and larger total lesion burden (p < 0.001); however, the association did not remain significant with rim+ lesions (p = 0.10). Our findings demonstrate a novel observation that chronic active lesions, as identified on QSM, modify the impact of lesion burden on clinical disability in MS patients. These results support further exploration of rim+ lesions for therapeutic targeting in MS to reduce disability and subsequent neurodegeneration.