bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular adhesion protein-1 (VAP-1) in vascular inflammatory	diseases
Authors: Danielli Marianna , Thomas Roisin Clare , Quinn Lauren Marie , Tan Bee Kang
Published: October 2022

Summary: Vascular adhesion protein-1 (VAP-1) also known as amino oxidase copper containing 3 (AOC3) is a pro-inflammatory and versatile molecule with adhesive and enzymatic properties. VAP-1 is a primary amine oxidase belonging to the semicarbazide-sensitive amine oxidase (SSAO) family, which catalyzes the oxidation of primary amines leading to the production of ammonium, formaldehyde, methylglyoxal, and hydrogen peroxide. VAP-1 is mainly expressed by endothelial cells, smooth muscle cells, adipocytes and pericytes. It is involved in a repertoire of biological functions, e.g., immune cell extravasation, angiogenesis, and vascularization. Research into VAP-1 has intensified within the last decade on its role as a novel clinical biomarker and as a potential therapeutic target of vascular inflammatory disorders such as atherosclerosis, stroke, diabetes, neurovascular disorders (e.g., Alzheimer’s Disease), hepatic disease (e.g., non-alcoholic steatohepatitis), and skin conditions (e.g., psoriasis). This is the most up-to-date and comprehensive review on VAP-1 focusing on the translational aspects of VAP-1. Compared to recent reviews, our review provides novel insights on VAP-1 and heart failure, stroke and frailty, diabetes, endometriosis, osteoarthritis, COVID-19, conjunctivitis associated systemic lupus erythematosus, hematopoietic stem cells, gliomas, treatment of colorectal cancer with a novel VAP-1 inhibitor (U-V269), promoting recovery of motor functions and habit learning with a novel VAP-1 inhibitor (PXS-4681A), and 68Ga-DOTA-Siglec-9, a labelled peptide of Siglec-9 (a VAP-1 ligand), which appears to be a safe PET tracer for inflammation in rheumatoid arthritis. Finally, we present the emerging role of VAP-1 in pregnancy as a gatekeeper of immune cells, which are critical for spiral arterial remodeling, the deficiency of which could lead to vascular disorders of pregnancy such as preeclampsia. Future research should prioritize clinical trials on VAP-1 small-molecule inhibitors and monoclonal antibodies, thus, maximizing the potential of VAP-1 targeted therapy as well as research into sVAP-1 as a clinical biomarker of diseases and its prognosis.
An Improved IASI Temperature and Humidity Retrieval Method Based on Double Channel Differences
Authors: Cui Xindong , Zhao Zengliang , Yao Zhigang , Wang Yang , Su Xingtao , Chen Jian , Zhang Yisheng , Tang Pengyu
Published: October 2022

Due to surface emissivity, the retrieval accuracy of hyperspectral infrared temperature and humidity profiles is typically poor in the lower atmosphere. To solve this problem, we use the double channel differences method (DCDM) to retrieve the temperature and humidity profiles of the Infrared Atmospheric Sounding Interferometer (IASI) with different surfaces, zenith angles, and data sources. Results show that DCDM can effectively improve IASI retrieval performance. The root mean square error (RMSE) reductions are large and exhibit no marked change with the zenithal angle. Compared with prior profiles, prior near‐surface temperatures can markedly improve the retrieval performance of temperature profiles. Humidity profile retrieval using both humidity and temperature channels can reduce the RMSE and the dependence on the precision of the prior inputs. The DCDM can markedly reduce errors in temperature and relative humidity retrievals, and the retrievals agree with ERA‐Interim better than IASI L2. With the DCDM, the lower temperature and relative humidity RMSE can be ∼3.5 K/14% (land), ∼3 K/13% (coast), ∼1.4 K/7% (sea). Compared with radiosonde observations and ERA‐Interim, the DCDM can reduce errors in temperature and humidity retrievals, and the improvement in performance is equivalent.
Food Deficits in Africa Will Grow in a Warmer World
Authors: Sidder Aaron
Published: October 2022

Under the combined stress of growing populations and current warming trends, many African nations will face increasing shortfalls in food production in the coming decades.
Inter‐Model Spread of the Simulated East Asian Summer Monsoon Rainfall and the Associated Atmospheric Circulations From the CMIP6 Models
Authors: Huang Danqing , Liu Anqi , Zheng Yanxin , Zhu Jian
Published: October 2022

The model uncertainty, one of the major sources of projection uncertainty, is still a challenge in the climate change projection. In this study, the model uncertainty in simulating the East Asian summer monsoon rainfall and its physical link to the upper‐level jet streams and the western North Pacific subtropical high (WNPSH) are investigated from the Coupled Model Inter‐comparison Project Phase 6 (CMIP6) models. The results show that extracted by the inter‐model Empirical Orthogonal Function method, the leading inter‐model mode of the rainfall is characterized as a meridional pattern. The positive mode (a continent‐wet‐ocean‐dry pattern) is closely associated with a northward shift of the oceanic branch of the East Asian subtropical jet and a northward movement of the WNPSH, while the negative mode (a continent‐dry‐ocean‐wet pattern) is highly correlated with an enhanced East Asian polar‐front jet combined with a weakened land branch of the East Asian subtropical jet as well as a weakened and eastward recess of the WNPSH. This systematic link among the atmospheric circulations and the leading inter‐model mode is maintained by the negative phase of the Victoria Mode in the North Pacific and warming over the Atlantic Ocean in the positive mode, and the cooling over the Indian Ocean, Atlantic Ocean and the warming over the central Pacific in the negative mode. Our findings suggest that the physical linkage between the atmospheric circulations and monsoon rainfall is useful to understand the model uncertainty, which would be helpful in providing potential indicators of the East Asia summer monsoon change.
Effects of Sea‐Level Rise on Dredging and Dredged Estuary Morphology
Authors: Cox J. R. , Lingbeek J. , Weisscher S. A. H. , Kleinhans M. G.
Published: October 2022

Estuaries and deltas worldwide are facing land loss and drowning due to sea‐level rise (SLR). Commonly home to ports, their channels are dredged and deepened for navigation. However, little is known about how such sediment management will interact with changing sediment transport patterns due to SLR. Using scale experiments, empirical relations and real world examples from global estuaries and deltas, we identify that dredging and SLR combined enhance bend migration whereas SLR alone leads to decentralizing of channels and drowning of intertidal area. In estuaries where channels are fixed, excess energy due to increasing tidal prism will manifest as bed and bank erosion, placing flood safety measures like dikes at risk. SLR increases dredging volumes in upstream reaches due to the rapid collapse of shoals and river banks along the whole estuary. Channel deepenings are ineffective under SLR conditions due to sediment import induced by increasingly flood‐dominant tides. Non‐dredged systems which have more regular and level elevations will lose intertidal area more quickly than dredged systems that have disconnected higher intertidal flats and a single deep channel. Mid‐size dredged European systems are more likely to drown due to dredging in the present century than from SLR. Effects can be avoided by pursuing sediment management strategies that help restore the morphology disrupted by dredging.
AZIN1 RNA editing alters protein interactions, leading to nuclear translocation and worse outcomes in prostate cancer
Authors: Ghalali Aram , Wang Liangzhe , Stopsack Konrad H. , Rice James M. , Wu Shulin , Wu Chin-Lee , Zetter Bruce R. , Rogers Michael S.
Published: October 2022

The transcript encoding Antizyme Inhibitor 1 (AZIN1) is frequently edited in various cancers, and this editing is associated with enhanced tumor aggressiveness. After comparison of wild-type AZIN1 (wtAZIN1) and edited AZIN1 (edAZIN1, which contains a Ser367Gly substitution), we report differential binding of edAZIN1 to a small set of proteins; specifically, edAZIN1 binds to alpha-smooth muscle actin (ACTA2), gamma actin 1 (ACTG1), and myosin9, whereas wtAZIN1 does not. This binding enables nuclear translocation of edAZIN1. In contrast to overexpression of edAZIN1 and, to a lesser extent, (editable) wtAZIN1, overexpression of an uneditable AZIN1 allele does not promote a cellular phenotype associated with increased tumorigenicity. In patients, both editing and nuclear localization of AZIN1 are common and are associated with tumor aggressiveness, i.e., a higher Gleason score, higher genomic instability, and a shorter progression-free survival time. In conclusion, the data indicate that binding of edAZIN1 to the actin/myosin9 complex supports its nuclear translocation, leading to enhanced cellular aggressiveness, and is associated with worse prostate cancer outcomes.
Targeting epiregulin in the treatment-damaged tumor microenvironment restrains therapeutic resistance
Authors: Wang Changxu , Long Qilai , Fu Qiang , Xu Qixia , Fu Da , Li Yan , Gao Libin , Guo Jianming , Zhang Xiaoling , Lam Eric W.-F. , Campisi Judith , Sun Yu
Published: October 2022

The tumor microenvironment (TME) represents a milieu enabling cancer cells to develop malignant properties, while concerted interactions between cancer and stromal cells frequently shape an “activated/reprogramed” niche to accelerate pathological progression. Here we report that a soluble factor epiregulin (EREG) is produced by senescent stromal cells, which non-cell-autonomously develop the senescence-associated secretory phenotype (SASP) upon DNA damage. Genotoxicity triggers EREG expression by engaging NF-κB and C/EBP, a process supported by elevated chromatin accessibility and increased histone acetylation. Stromal EREG reprograms the expression profile of recipient neoplastic cells in a paracrine manner, causing upregulation of MARCHF4, a membrane-bound E3 ubiquitin ligase involved in malignant progression, specifically drug resistance. A combinational strategy that empowers EREG-specific targeting in treatment-damaged TME significantly promotes cancer therapeutic efficacy in preclinical trials, achieving response indices superior to those of solely targeting cancer cells. In clinical oncology, EREG is expressed in tumor stroma and handily measurable in circulating blood of cancer patients post-chemotherapy. This study establishes EREG as both a targetable SASP factor and a new noninvasive biomarker of treatment-damaged TME, thus disclosing its substantial value in translational medicine.
TrkC-mediated inhibition of DJ-1 degradation is essential for direct regulation of pathogenesis of hepatocellular carcinoma
Authors: Kim Min Soo , Lee Won Sung , Park Yeonmi , Jin Wook
Published: October 2022

None of the previous studies has systematically explored how upregulation of TrkC plays a central role in the pathogenesis of hepatocellular carcinoma (HCC) by regulating the underlying mechanisms that promote invasion and metastasis. In this report, we demonstrated the possible association between upregulation of TrkC and acquisition of cancer stem cells traits or chemoresistance in HCC. We show that upregulation of TrkC is closely associated with the survival and progression of HCC in vivo and in vitro. Most strikingly, activation of STAT3 by TrkC-mediated inhibition of DJ-1 degradation significantly enhances the efficacy of invasion and metastasis during the progression of HCC cells. Acquiring the traits of cancer stem cells (CSCs) by TrkC/DJ-1/STAT3 signaling pathway leads to the induction of chemoresistance via upregulation of ABC transporters and anti-apoptotic genes. Also, activating the epithelial-mesenchymal transition (EMT) program by inducing EMT-transcription factor (TF)s by TrkC/DJ-1/STAT3 signaling pathway is the direct cause of multiple tumor malignancies of HCC. Thus, understanding the mechanisms by which acquisition of anticancer drug resistance by TrkC-mediated inhibition of DJ-1 degradation can help enhance the efficacy of anticancer therapies.
Consequences of telomere dysfunction in fibroblasts, club and basal cells for lung fibrosis development
Authors: Piñeiro-Hermida Sergio , Martínez Paula , Bosso Giuseppe , Flores Juana María , Saraswati Sarita , Connor Jane , Lemaire Raphael , Blasco Maria A.
Published: October 2022

TRF1 is an essential component of the telomeric protective complex or shelterin. We previously showed that dysfunctional telomeres in alveolar type II (ATII) cells lead to interstitial lung fibrosis. Here, we study the lung pathologies upon telomere dysfunction in fibroblasts, club and basal cells. TRF1 deficiency in lung fibroblasts, club and basal cells induced telomeric damage, proliferative defects, cell cycle arrest and apoptosis. While Trf1 deletion in fibroblasts does not spontaneously lead to lung pathologies, upon bleomycin challenge exacerbates lung fibrosis. Unlike in females, Trf1 deletion in club and basal cells from male mice resulted in lung inflammation and airway remodeling. Here, we show that depletion of TRF1 in fibroblasts, Club and basal cells does not lead to interstitial lung fibrosis, underscoring ATII cells as the relevant cell type for the origin of interstitial fibrosis. Our findings contribute to a better understanding of proper telomere protection in lung tissue homeostasis.
Solar reduction of carbon dioxide on copper-tin electrocatalysts with energy conversion efficiency near 20%
Authors: Gao Jing , Li Jun , Liu Yuhang , Xia Meng , Finfrock Y. Zou , Zakeeruddin Shaik Mohammed , Ren Dan , Grätzel Michael
Published: October 2022

Copper catalysts modified with tin have been demonstrated to be selective for the electroreduction of carbon dioxide to carbon monoxide. However, such catalysts require the precise control of tin loading amount. Here, we develop a copper/tin-oxide catalyst with dominant tin oxide surface being formed via a spontaneous exchange reaction between sputtered tin and copper oxide. Even though the surface of this catalyst is tin-rich, it achieves an excellent performance towards carbon monoxide production in a flow cell. This contrasts with copper/tin-oxide prepared via atomic layer deposition since it yields selectivity towards carbon monoxide only on a copper-rich surface. Mechanism studies reveal that the tin sites on the tin-rich copper/tin-oxide surface achieve a suitable binding with adsorbed carbon monoxide under the presence of copper. Powered by a triple-junction solar cell, the copper/tin-oxide based electrolyzer sets a new benchmark solar-to-chemical energy conversion efficiency of 19.9 percent with a Faradaic efficiency of 98.9 percent towards carbon monoxide under simulated standard air mass 1.5 global illumination.
Effectiveness of an inactivated Covid-19 vaccine with homologous and heterologous boosters against Omicron in Brazil
Authors: Ranzani Otavio T. , Hitchings Matt D. T. , de Melo Rosana Leite , de França Giovanny V. A. , Fernandes Cássia de Fátima R. , Lind Margaret L. , Torres Mario Sergio Scaramuzzini , Tsuha Daniel Henrique , David Leticia C. S. , Said Rodrigo F. C. , Almiron Maria , de Oliveira Roberto D. , Cummings Derek A. T. , Dean Natalie E. , Andrews Jason R. , Ko Albert I. , Croda Julio
Published: October 2022

The effectiveness of inactivated vaccines (VE) against symptomatic and severe COVID-19 caused by omicron is unknown. We conducted a nationwide, test-negative, case-control study to estimate VE for homologous and heterologous (BNT162b2) booster doses in adults who received two doses of CoronaVac in Brazil in the Omicron context. Analyzing 1,386,544 matched-pairs, VE against symptomatic disease was 8.6% (95% CI, 5.6–11.5) and 56.8% (95% CI, 56.3–57.3) in the period 8–59 days after receiving a homologous and heterologous booster, respectively. During the same interval, VE against severe Covid-19 was 73.6% (95% CI, 63.9–80.7) and 86.0% (95% CI, 84.5–87.4) after receiving a homologous and heterologous booster, respectively. Waning against severe Covid-19 after 120 days was only observed after a homologous booster. Heterologous booster might be preferable to individuals with completed primary series inactivated vaccine.
Early stages of sympatric homoploid hybrid speciation in crater lake cichlid fishes
Authors: Olave Melisa , Nater Alexander , Kautt Andreas F. , Meyer Axel
Published: October 2022

Homoploid hybrid speciation (i.e., hybrid speciation without a change in ploidy) has traditionally been considered to be rare in animals. Only few accepted empirical examples of homoploid hybrid speciation in nature exist, and in only one previous case (insects) was it convincingly shown that this process occurred in complete sympatry. Here, we report an instance of sympatric homoploid hybrid speciation in Midas cichlid fishes in Crater Lake Xiloá, Nicaragua. The hybrid lineage, albeit at an early stage of speciation, has genomically and phenotypically diverged from both of its two parental species. Together with a distinct stable isotope signature this suggests that this hybrid lineages occupies a different trophic niche compared to the other sympatric Midas cichlid species in Crater Lake Xiloá.
Endothelial cell cycle state determines propensity for arterial-venous fate
Authors: Chavkin Nicholas W. , Genet Gael , Poulet Mathilde , Jeffery Erin D. , Marziano Corina , Genet Nafiisha , Vasavada Hema , Nelson Elizabeth A. , Acharya Bipul R. , Kour Anupreet , Aragon Jordon , McDonnell Stephanie P. , Huba Mahalia , Sheynkman Gloria M. , Walsh Kenneth , Hirschi Karen K.
Published: October 2022

During blood vessel development, endothelial cells become specified toward arterial or venous fates to generate a circulatory network that provides nutrients and oxygen to, and removes metabolic waste from, all tissues. Arterial-venous specification occurs in conjunction with suppression of endothelial cell cycle progression; however, the mechanistic role of cell cycle state is unknown. Herein, using Cdh5-CreERT2;R26FUCCI2aR reporter mice, we find that venous endothelial cells are enriched for the FUCCI-Negative state (early G1) and BMP signaling, while arterial endothelial cells are enriched for the FUCCI-Red state (late G1) and TGF-β signaling. Furthermore, early G1 state is essential for BMP4-induced venous gene expression, whereas late G1 state is essential for TGF-β1-induced arterial gene expression. Pharmacologically induced cell cycle arrest prevents arterial-venous specification defects in mice with endothelial hyperproliferation. Collectively, our results show that distinct endothelial cell cycle states provide distinct windows of opportunity for the molecular induction of arterial vs. venous fate.
Neutralizing and interfering human antibodies define the structural and mechanistic basis for antigenic diversion
Authors: Patel Palak N. , Dickey Thayne H. , Hopp Christine S. , Diouf Ababacar , Tang Wai Kwan , Long Carole A. , Miura Kazutoyo , Crompton Peter D. , Tolia Niraj H.
Published: October 2022

Defining mechanisms of pathogen immune evasion and neutralization are critical to develop potent vaccines and therapies. Merozoite Surface Protein 1 (MSP-1) is a malaria vaccine antigen and antibodies to MSP-1 are associated with protection from disease. However, MSP-1-based vaccines performed poorly in clinical trials in part due to a limited understanding of the protective antibody response to MSP-1 and of immune evasion by antigenic diversion. Antigenic diversion was identified as a mechanism wherein parasite neutralization by a MSP-1-specific rodent antibody was disrupted by MSP-1-specific non-inhibitory blocking/interfering antibodies. Here, we investigated a panel of MSP-1-specific naturally acquired human monoclonal antibodies (hmAbs). Structures of multiple hmAbs with diverse neutralizing potential in complex with MSP-1 revealed the epitope of a potent strain-transcending hmAb. This neutralizing epitope overlaps with the epitopes of high-affinity non-neutralizing hmAbs. Strikingly, the non-neutralizing hmAbs outcompete the neutralizing hmAb enabling parasite survival. These findings demonstrate the structural and mechanistic basis for a generalizable pathogen immune evasion mechanism through neutralizing and interfering human antibodies elicited by antigenic diversion, and provides insights required to develop potent and durable malaria interventions.
Sub-optical-cycle light-matter energy transfer in molecular vibrational spectroscopy
Authors: Peschel Martin T. , Högner Maximilian , Buberl Theresa , Keefer Daniel , de Vivie-Riedle Regina , Pupeza Ioachim
Published: October 2022

The evolution of ultrafast-laser technology has steadily advanced the level of detail in studies of light-matter interactions. Here, we employ electric-field-resolved spectroscopy and quantum-chemical modelling to precisely measure and describe the complete coherent energy transfer between octave-spanning mid-infrared waveforms and vibrating molecules in aqueous solution. The sub-optical-cycle temporal resolution of our technique reveals alternating absorption and (stimulated) emission on a few-femtosecond time scale. This behaviour can only be captured when effects beyond the rotating wave approximation are considered. At a femtosecond-to-picosecond timescale, optical-phase-dependent coherent transients and the dephasing of the vibrations of resonantly excited methylsulfonylmethane (DMSO2) are observed. Ab initio modelling using density functional theory traces these dynamics back to molecular-scale sample properties, in particular vibrational frequencies and transition dipoles, as well as their fluctuation due to the motion of DMSO2 through varying solvent environments. Future extension of our study to nonlinear interrogation of higher-order susceptibilities is fathomable with state-of-the-art lasers.
Using domain knowledge for robust and generalizable deep learning-based CT-free PET attenuation and scatter correction
Authors: Guo Rui , Xue Song , Hu Jiaxi , Sari Hasan , Mingels Clemens , Zeimpekis Konstantinos , Prenosil George , Wang Yue , Zhang Yu , Viscione Marco , Sznitman Raphael , Rominger Axel , Li Biao , Shi Kuangyu
Published: October 2022

Despite the potential of deep learning (DL)-based methods in substituting CT-based PET attenuation and scatter correction for CT-free PET imaging, a critical bottleneck is their limited capability in handling large heterogeneity of tracers and scanners of PET imaging. This study employs a simple way to integrate domain knowledge in DL for CT-free PET imaging. In contrast to conventional direct DL methods, we simplify the complex problem by a domain decomposition so that the learning of anatomy-dependent attenuation correction can be achieved robustly in a low-frequency domain while the original anatomy-independent high-frequency texture can be preserved during the processing. Even with the training from one tracer on one scanner, the effectiveness and robustness of our proposed approach are confirmed in tests of various external imaging tracers on different scanners. The robust, generalizable, and transparent DL development may enhance the potential of clinical translation.
A pathway for chitin oxidation in marine bacteria
Authors: Jiang Wen-Xin , Li Ping-Yi , Chen Xiu-Lan , Zhang Yi-Shuo , Wang Jing-Ping , Wang Yan-Jun , Sheng Qi , Sun Zhong-Zhi , Qin Qi-Long , Ren Xue-Bing , Wang Peng , Song Xiao-Yan , Chen Yin , Zhang Yu-Zhong
Published: October 2022

Oxidative degradation of chitin, initiated by lytic polysaccharide monooxygenases (LPMOs), contributes to microbial bioconversion of crystalline chitin, the second most abundant biopolymer in nature. However, our knowledge of oxidative chitin utilization pathways, beyond LPMOs, is very limited. Here, we describe a complete pathway for oxidative chitin degradation and its regulation in a marine bacterium, Pseudoalteromonas prydzensis. The pathway starts with LPMO-mediated extracellular breakdown of chitin into C1-oxidized chitooligosaccharides, which carry a terminal 2-(acetylamino)−2-deoxy-D-gluconic acid (GlcNAc1A). Transmembrane transport of oxidized chitooligosaccharides is followed by their hydrolysis in the periplasm, releasing GlcNAc1A, which is catabolized in the cytoplasm. This pathway differs from the known hydrolytic chitin utilization pathway in enzymes, transporters and regulators. In particular, GlcNAc1A is converted to 2-keto-3-deoxygluconate 6-phosphate, acetate and NH3 via a series of reactions resembling the degradation of D-amino acids rather than other monosaccharides. Furthermore, genomic and metagenomic analyses suggest that the chitin oxidative utilization pathway may be prevalent in marine Gammaproteobacteria.
RNA export through the nuclear pore complex is directional
Authors: Ashkenazy-Titelman Asaf , Atrash Mohammad Khaled , Boocholez Alon , Kinor Noa , Shav-Tal Yaron
Published: October 2022

The changes occurring in mRNA organization during nucleo-cytoplasmic transport and export, are not well understood. Moreover, directionality of mRNA passage through the nuclear pore complex (NPC) has not been examined within individual NPCs. Here we find that an mRNP is compact during nucleoplasmic travels compared to a more open structure after transcription and at the nuclear periphery. Compaction levels of nuclear transcripts can be modulated by varying levels of SR proteins and by changing genome organization. Nuclear mRNPs are mostly rod-shaped with distant 5'/3'-ends, although for some, the ends are in proximity. The latter is more abundant in the cytoplasm and can be modified by translation inhibition. mRNAs and lncRNAs exiting the NPC exhibit predominant 5’-first export. In some cases, several adjacent NPCs are engaged in export of the same mRNA suggesting 'gene gating'. Altogether, we show that the mRNP is a flexible structure during travels, with 5'-directionality during export.
Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection thymocytes
Authors: Ratiu Jeremy J. , Barclay William E. , Lin Elliot , Wang Qun , Wellford Sebastian , Mehta Naren , Harnois Melissa J. , DiPalma Devon , Roy Sumedha , Contreras Alejandra V. , Shinohara Mari L. , Wiest David , Zhuang Yuan
Published: October 2022

Production of a functional peripheral T cell compartment typically involves massive expansion of the bone marrow progenitors that seed the thymus. There are two main phases of expansion during T cell development, following T lineage commitment of double-negative (DN) 2 cells and after successful rearrangement and selection for functional TCRβ chains in DN3 thymocytes, which promotes the transition of DN4 cells to the DP stage. The signals driving the expansion of DN2 thymocytes are well studied. However, factors regulating the proliferation and survival of DN4 cells remain poorly understood. Here, we uncover an unexpected link between the transcription factor Zfp335 and control of cGAS/STING-dependent cell death in post-β-selection DN4 thymocytes. Zfp335 controls survival by sustaining expression of Ankle2, which suppresses cGAS/STING-dependent cell death. Together, this study identifies Zfp335 as a key transcription factor regulating the survival of proliferating post-β-selection thymocytes and demonstrates a key role for the cGAS/STING pathway in driving apoptosis of developing T cells.
Prion-like low complexity regions enable avid virus-host interactions during HIV-1 infection
Authors: Wei Guochao , Iqbal Naseer , Courouble Valentine V. , Francis Ashwanth C. , Singh Parmit K. , Hudait Arpa , Annamalai Arun S. , Bester Stephanie , Huang Szu-Wei , Shkriabai Nikoloz , Briganti Lorenzo , Haney Reed , KewalRamani Vineet N. , Voth Gregory A. , Engelman Alan N. , Melikyan Gregory B. , Griffin Patrick R. , Asturias Francisco , Kvaratskhelia Mamuka
Published: October 2022

Cellular proteins CPSF6, NUP153 and SEC24C play crucial roles in HIV-1 infection. While weak interactions of short phenylalanine-glycine (FG) containing peptides with isolated capsid hexamers have been characterized, how these cellular factors functionally engage with biologically relevant mature HIV-1 capsid lattices is unknown. Here we show that prion-like low complexity regions (LCRs) enable avid CPSF6, NUP153 and SEC24C binding to capsid lattices. Structural studies revealed that multivalent CPSF6 assembly is mediated by LCR-LCR interactions, which are templated by binding of CPSF6 FG peptides to a subset of hydrophobic capsid pockets positioned along adjoining hexamers. In infected cells, avid CPSF6 LCR-mediated binding to HIV-1 cores is essential for functional virus-host interactions. The investigational drug lenacapavir accesses unoccupied hydrophobic pockets in the complex to potently impair HIV-1 inside the nucleus without displacing the tightly bound cellular cofactor from virus cores. These results establish previously undescribed mechanisms of virus-host interactions and antiviral action.
Investigating the effects of absolute humidity and movement on COVID-19 seasonality in the United States
Authors: Lin Gary , Hamilton Alisa , Gatalo Oliver , Haghpanah Fardad , Igusa Takeru , Klein Eili
Published: October 2022

Mounting evidence suggests the primary mode of SARS-CoV-2 transmission is aerosolized transmission from close contact with infected individuals. While transmission is a direct result of human encounters, falling humidity may enhance aerosolized transmission risks similar to other respiratory viruses (e.g., influenza). Using Google COVID-19 Community Mobility Reports, we assessed the relative effects of absolute humidity and changes in individual movement patterns on daily cases while accounting for regional differences in climatological regimes. Our results indicate that increasing humidity was associated with declining cases in the spring and summer of 2020, while decreasing humidity and increase in residential mobility during winter months likely caused increases in COVID-19 cases. The effects of humidity were generally greater in regions with lower humidity levels. Given the possibility that COVID-19 will be endemic, understanding the behavioral and environmental drivers of COVID-19 seasonality in the United States will be paramount as policymakers, healthcare systems, and researchers forecast and plan accordingly.
A study by the lattice discrete element method for exploring the fractal nature of scale effects
Authors: Kosteski Luis Eduardo , Iturrioz Ignacio , Friedrich Leandro Ferreira , Lacidogna Giuseppe
Published: October 2022

Nowadays, there are many applications in the field of Engineering related to quasi-brittle materials such as ceramics, natural stones, and concrete, among others. When damage is produced, two phenomena can take place: the damage produced governs the collapse process when working with this type of material, and its random nature rules the nonlinear behavior up to the collapse. The interaction among clouds of micro-cracks generates the localization process that implies transforming a continuum domain into a discontinue one. This process also governs the size effect, that is, the changes of the global parameters as the strength and characteristic strain and energies when the size of the structure changes. Some aspects of the scaling law based on the fractal concepts proposed by Prof Carpinteri are analyzed in this work. On the other hand, the Discrete Method is an interesting option to be used in the simulation collapse process of quasi-brittle materials. This method can allow failures with relative ease. Moreover, it can also help to relax the continuum hypothesis. In the present work, a version of the Discrete Element Method is used to simulate the mechanical behavior of different size specimens until collapse by analyzing the size effect represented by this method. This work presents two sets of examples. Its results allow the researchers to see the connection between the numerical results regarding the size effect and the theoretical law based on the fractal dimension of the parameter studied. Two main aspects appear as a result of the analysis presented here. Understand better some aspects of the size effect using the numerical tool and show that the Lattice Discrete Element Method has enough robustness to be applied in the nonlinear analysis of structures built by quasi-brittle materials.
Detecting and mitigating simultaneous waves of COVID-19 infections
Authors: Souyris Sebastian , Hao Shuai , Bose Subhonmesh , England Albert Charles III , Ivanov Anton , Mukherjee Ujjal Kumar , Seshadri Sridhar
Published: October 2022

The sudden spread of COVID-19 infections in a region can catch its healthcare system by surprise. Can one anticipate such a spread and allow healthcare administrators to prepare for a surge a priori? We posit that the answer lies in distinguishing between two types of waves in epidemic dynamics. The first kind resembles a spatio-temporal diffusion pattern. Its gradual spread allows administrators to marshal resources to combat the epidemic. The second kind is caused by super-spreader events, which provide shocks to the disease propagation dynamics. Such shocks simultaneously affect a large geographical region and leave little time for the healthcare system to respond. We use time-series analysis and epidemiological model estimation to detect and react to such simultaneous waves using COVID-19 data from the time when the B.1.617.2 (Delta) variant of the SARS-CoV-2 virus dominated the spread. We first analyze India’s second wave from April to May 2021 that overwhelmed the Indian healthcare system. Then, we analyze data of COVID-19 infections in the United States (US) and countries with a high and low Indian diaspora. We identify the Kumbh Mela festival as the likely super-spreader event, the exogenous shock, behind India’s second wave. We show that a multi-area compartmental epidemiological model does not fit such shock-induced disease dynamics well, in contrast to its performance with diffusion-type spread. The insufficient fit to infection data can be detected in the early stages of a shock-wave propagation and can be used as an early warning sign, providing valuable time for a planned healthcare response. Our analysis of COVID-19 infections in the US reveals that simultaneous waves due to super-spreader events in one country (India) can lead to simultaneous waves in other places. The US wave in the summer of 2021 does not fit a diffusion pattern either. We postulate that international travels from India may have caused this wave. To support that hypothesis, we demonstrate that countries with a high Indian diaspora exhibit infection growth soon after India’s second wave, compared to countries with a low Indian diaspora. Based on our data analysis, we provide concrete policy recommendations at various stages of a simultaneous wave, including how to avoid it, how to detect it quickly after a potential super-spreader event occurs, and how to proactively contain its spread.
Test–retest reliability of upper limb robotic exoskeleton assessments in children and youths with brain lesions
Authors: Graser Judith V. , Prospero Laura , Liesch Monica , Keller Urs , van Hedel Hubertus J. A.
Published: October 2022

In children with congenital or acquired brain lesions, impaired upper limb function can affect independence. Assessing upper limb function is important for planning and evaluating neurorehabilitative interventions. Robotic devices increase measurement-objectivity and enable measuring parameters reflecting more complex motor functions. We investigated the relative and absolute test–retest reliability of assessments to measure upper limb functions in children and adolescents with brain lesions with the exoskeleton ChARMin. Thirty children (9 females, mean age ± SD = 12.5 ± 3.3 years) with congenital brain injuries (n = 15), acquired (n = 14), both (n = 1) and impaired upper limb function participated. They performed the following ChARMin assessments and repeated them within three to seven days: active and passive Range of Motion (ROM), Strength, Resistance to Passive Movement, Quality of Movement, Circle, and Workspace. We calculated the systematic difference, Intraclass Correlation Coefficient (ICC) and Smallest Real Difference (SRD) for each parameter. Six parameters of three assessments showed systematic errors. ICCs ranged from little to very high and SRD values varied considerably. Test–retest reliability and measurement errors ranged widely between the assessments. Systematic differences indicated that random day-to-day variability in performance would be responsible for reduced reliability of those parameters. While it remains debatable whether robot-derived outcomes should replace certain routine assessments (e.g., ROM, strength), we recommend applying certain technology-based assessments also in clinical practice.

Trial registration: This study was registered prospectively at ClinicalTrials.gov (identifier: NCT02443857) on May 14, 2015.
Cholecystectomy reduces the risk of myocardial and cerebral infarction in patients with gallstone-related infection
Authors: Park Seon Mee , Kim Hyun Jung , Kang Tae Uk , Swan Heather , Ahn Hyeong Sik
Published: October 2022

We compared the risk of myocardial infarction (MI) or cerebral infarction (CI) in patients with or without-gallstone-related infection (GSI) and change in the risk following cholecystectomy. GSI (n = 84,467) and non-GSI (n = 406,800) patients with age- and sex-matched controls (n = 4,912,670) were identified from Korean population based data. The adjusted hazard ratios (aHRs) of MI or CI were analyzed in both groups treated with or without cholecystectomy. Subgroup analysis was performed for both sexes and different ages. The risk of MI or CI was higher in the GSI group than in the non-GSI group (aHR for MI; 1.32 vs. 1.07, aHR for CI; 1.24 vs. 1.06, respectively). The risk reduction rate of MI following cholecystectomy was 11.4% in the GSI group, whereas it was 0% in the non-GSI group. The risk of CI after cholecystectomy was more reduced in the GSI group than in the non-GSI group (16.1% and 4.7%, respectively). The original risk of MI or CI in patients with gallstones and risk reduction rates following cholecystectomy were higher in females and younger patients than in males and older patients. Increased risk of MI or CI and greater risk reduction following cholecystectomy were seen in patients with GSI.
Production of biodiesel from non-edible feedstocks using environment friendly nano-magnetic Fe/SnO catalyst
Authors: Hanif Maryam , Bhatti Ijaz Ahmad , Zahid Muhammad , Shahid Muhammad
Published: October 2022

Environmental problems associated with chemical catalysts to fulfil an ever-increasing energy demand have led to the search for an alternative environment friendly heterogeneous catalyst. If a catalyst being used in the biodiesel production is not environment friendly, then the environment is being contaminated in another way while trying to avoid pollution caused by burning of fossil fuels. The present study reports the use of nano-magnetic catalyst Fe/SnO supported on feldspar for the transesterification of various non-edible feedstocks oil, including Pongamiapinnata (karanja), Carthamusoxyacantha (wild safflower), Citrulluscolocynthis (bitter apple), Sinapisarvensis (wildmustard) and Ricinuscommunis (castor). The optimized transesterification parameter was oil to methanol ratio (1:5, 1:10, 1:15, 1:20 and 1:25), catalyst amount (0.5, 1, 1.5, 2, 2.5%), temperature (40, 50, 60, 70 and 80 °C), and reaction times (30, 60, 90, 120 and 150 min). The biodiesel yield was found to be more than 97% for all the tested feedstocks with a maximum biodiesel yield of 98.1 ± 0.6% obtained for bitter apple seed oil under optimum conditions (oil to methanol ratio of 1:10, catalyst amount of 1% at 50 °C for 120 min). The catalysts used for transesterification were magnetically extracted after completion of the reaction. Different physico-chemical parameters like pour point, density, cloud point, iodine value, acid value, saponification and cetane number were determined and the quality of all the biodiesel samples were found to be in the standard range (ASTM D6751 and EN 1404). Different techniques like XRD, FTIR, SEM and EDX were used to characterize the prepared nano-magnetic (Fe/SnO/Feldspar) catalyst.
Global human-edible nutrient supplies, their sources, and correlations with agricultural environmental impact
Authors: White R. R. , Gleason C. B.
Published: October 2022

Food production, sustainable development, population growth, and agricultural environmental impacts are linked global problems that require complex solutions. Many efforts evaluating these challenges primarily evaluate dietary strategies designed for health and environmental objectives without considering the subsequent adaptations required by the global food supply. Here we use a complementary approach to summarize trends and variability in the current agricultural system in the context of the growing population and impending environmental challenges. Globally, agricultural systems produce sufficient nutrients to feed 10 billion people with the exception of Ca, DHA + EPA, vitamins B4, D, and E. In a network analysis, greenhouse gas emissions were conditionally dependent on ruminant meat and milk, while water use was conditionally dependent on vegetable and fruit production; however, supplies of most nutrients were also dependent on these same production categories, suggesting trade-offs between nutritional and environmental objectives. Future work should evaluate strategies to address these compromises (i.e., improving water use efficiency and reducing greenhouse gas emissions), to explore to what extent such compromises are biophysically essential or merely a product of the current agricultural system structures. Given the time-sensitive nature of population growth and environmental concerns, strategies to make more effective use of currently produced agricultural products will also be critical complementary strategies to sustainably feed the growing population which can work in concert with other agricultural-, diet- and policy-focused efforts.
Guiding principle of reservoir computing based on “small-world” network
Authors: Kitayama Ken-ichi
Published: October 2022

Reservoir computing is a computational framework of recurrent neural networks and is gaining attentions because of its drastically simplified training process. For a given task to solve, however, the methodology has not yet been established how to construct an optimal reservoir. While, “small-world” network has been known to represent networks in real-world such as biological systems and social community. This network is categorized amongst those that are completely regular and totally disordered, and it is characterized by highly-clustered nodes with a short path length. This study aims at providing a guiding principle of systematic synthesis of desired reservoirs by taking advantage of controllable parameters of the small-world network. We will validate the methodology using two different types of benchmark tests—classification task and prediction task.
A novel glucagon analog with an extended half-life, HM15136, normalizes glucose levels in rodent models of congenital hyperinsulinism
Authors: Heo Yong Ho , Kim Jung Kuk , Lee Jong Suk , Lee Sang-Hyun , Shin Seung-Hyun , Choi In Young , Kim Ha Hyung
Published: October 2022

Congenital hyperinsulinism (CHI) is a rare genetic condition characterized by uncontrolled insulin secretion, resulting in hypoglycemia. Although glucagon has lately been regarded as a therapeutic option for CHI, its use is severely hampered by its poor solubility and stability at physiological pH, as well as its short duration of action. To address these constraints, we developed HM15136, a novel long-acting glucagon analog composed of a glucagon analog conjugated to the Fc fragment of human immunoglobulin G4 via a polyethylene glycol linker. In this study, we established that HM15136 was more soluble than natural glucagon (≥ 150 mg/mL vs 0.03 mg/mL). Next, we confirmed that HM15136 activated glucagon receptor in vitro and induced glycogenolysis and gluconeogenesis in rat primary hepatocytes. Pharmacokinetics (PK)/Pharmacodynamics (PD) analysis of HM15136 shows that HM15136 has a markedly longer half-life (36 h vs. < 5 min) and increased bioavailability (90%) compared to native glucagon in mice. Further, HM15136 could effectively reverse acute hypoglycemia induced by insulin challenge, and multiple doses of HM15136 could sustain increased blood glucose levels in CHI rats. In conclusion, our findings indicate that HM15136 promotes sustained elevation of blood glucose, demonstrating the potential for development as a once-weekly therapy for CHI.
CAMSAP2 promotes colorectal cancer cell migration and invasion through activation of JNK/c-Jun/MMP-1 signaling pathway
Authors: Wang Xiaojuan , Liu Yumin , Ding Yawen , Feng Gang
Published: October 2022

CAMSAP2 has been reported to act as an oncogene in hepatocellular carcinoma. However, the expression CAMSAP2 and its potential roles in colorectal cancer remain unclear. In this study, qRT-PCR and immunoblotting analysis were used to detect the mRNA and protein levels of CAMSAP2 in colorectal cancer tissues and cell lines. Wound-healing, transwell migration and invasion assay were performed to determine whether CAMSAP2 promotes the capabilities of migration and invasion of colorectal cancer cells. The results showed that CAMSAP2 was highly elevated in colorectal cancer tissues and cell lines. Moreover, the high CAMSAP2 expression was positively correlated with tumor invasion depth, lymph node metastasis, distant metastasis, and the poor prognosis of colorectal cancer. Additionally, ectopic expression of CAMSAP2 in colorectal cancer cells promoted the migration and invasion in vitro and enhanced the lung metastasis in nude mice. Conversely, silencing CAMSAP2 resulted in an opposite phenomenon. By gain- and loss-of function experiments, we demonstrated that MMP-1 was a substantial downstream target of CAMSAP2, and it played a crucial role in regulating the migration and invasion induced by CAMSAP2 in colorectal cancer cells. Mechanistically, CAMSAP2 promoted the activation of JNK/c-Jun signaling pathway and subsequently upregulated the transcription activity of MMP-1. Taken together, our findings demonstrated that CAMSAP2 promoted colorectal cancer cell migration, invasion and metastasis through activation of JNK/c-Jun/MMP-1 signaling pathway, indicating CAMSAP2 is a promising therapeutic target for the treatment of metastatic colorectal cancer patients.
Exploration of defined 2-dimensional working electrode shapes through additive manufacturing
Authors: Garcia-Miranda Ferrari Alejandro , Hurst Nicholas J. , Bernalte Elena , Crapnell Robert D. , Whittingham Matthew J. , Brownson Dale A. C. , Banks Craig E.
Published: October 2022

In this work, the electrochemical response of different morphologies (shapes) and dimensions of additively manufactured (3D-printing) carbon black(CB)/poly-lactic acid (PLA) electrodes are reported.
Correction: Bioconjugation of 2-arachidonoyl glycerol (2-AG) biotinylated antibody with gold nano-flowers toward immunosensing of 2-AG in human plasma samples: a novel immuno-platform for the screening of immunomodulation and neuroprotection using biosensing
Authors: Mobed Ahmad , Kohansal Fereshteh , Ahmadalipour Ali. , Hasanzadeh Mohammad , Zargari Flor
Published: October 2022

Correction for ‘Bioconjugation of 2-arachidonoyl glycerol (2-AG) biotinylated antibody with gold nano-flowers toward immunosensing of 2-AG in human plasma samples: a novel immuno-platform for the screening of immunomodulation and neuroprotection using biosensing’ by Ahmad Mobed et al., Anal. Methods, 2021, 13, 311–321, https://doi.org/10.1039/D0AY02135K.
Oxime ester-enabled anti-Markovnikov hydrosilylation of alkenes
Authors: Shen Guo , Fu Shaomin , Liu Bo
Published: October 2022

An oxime ester-enabled anti-Markovnikov hydrosilylation of alkenes is developed.
An electrochemiluminescence dual “turn-on” strategy for alkaline phosphatase detection using a dual quenching Ru(bpy)32+ encapsulated zeolite imidazole metal organic framework
Authors: Du Chengpei , Wang Yi , Pei Kanglin , Wu Di , Qi Wenjing
Published: October 2022

An electrochemiluminescence (ECL) dual “turn-on” strategy is first designed to detect alkaline phosphatase (ALP) using a dual quenching Ru(bpy)32+ encapsulated zeolite imidazole metal organic framework (Ru(bpy)32+@ZIF-90).