bluuebunny/crossref_metadata_2025 huggingface dataset:
Small molecule splicing modifiers with systemic HTT-lowering activity
Authors: Bhattacharyya Anuradha , Trotta Christopher R. , Narasimhan Jana , Wiedinger Kari J. , Li Wencheng , Effenberger Kerstin A. , Woll Matthew G. , Jani Minakshi B. , Risher Nicole , Yeh Shirley , Cheng Yaofeng , Sydorenko Nadiya , Moon Young-Choon , Karp Gary M. , Weetall Marla , Dakka Amal , Gabbeta Vijayalakshmi , Naryshkin Nikolai A. , Graci Jason D. , Tripodi Thomas , Southwell Amber , Hayden Michael , Colacino Joseph M. , Peltz Stuart W.
Published: December 2021

Huntington’s disease (HD) is a hereditary neurodegenerative disorder caused by expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin (HTT) gene. Consequently, the mutant protein is ubiquitously expressed and drives pathogenesis of HD through a toxic gain-of-function mechanism. Animal models of HD have demonstrated that reducing huntingtin (HTT) protein levels alleviates motor and neuropathological abnormalities. Investigational drugs aim to reduce HTT levels by repressingHTTtranscription, stability or translation. These drugs require invasive procedures to reach the central nervous system (CNS) and do not achieve broad CNS distribution. Here, we describe the identification of orally bioavailable small molecules with broad distribution throughout the CNS, which lowerHTTexpression consistently throughout the CNS and periphery through selective modulation of pre-messenger RNA splicing. These compounds act by promoting the inclusion of a pseudoexon containing a premature termination codon (stop-codon psiExon), leading toHTTmRNA degradation and reduction of HTT levels.
Single-cell transcriptomics captures features of human midbrain development and dopamine neuron diversity in brain organoids
Authors: Fiorenzano Alessandro , Sozzi Edoardo , Birtele Marcella , Kajtez Janko , Giacomoni Jessica , Nilsson Fredrik , Bruzelius Andreas , Sharma Yogita , Zhang Yu , Mattsson Bengt , Emnéus Jenny , Ottosson Daniella Rylander , Storm Petter , Parmar Malin
Published: December 2021

Three-dimensional brain organoids have emerged as a valuable model system for studies of human brain development and pathology. Here we establish a midbrain organoid culture system to study the developmental trajectory from pluripotent stem cells to mature dopamine neurons. Using single cell RNA sequencing, we identify the presence of three molecularly distinct subtypes of human dopamine neurons with high similarity to those in developing and adult human midbrain. However, despite significant advancements in the field, the use of brain organoids can be limited by issues of reproducibility and incomplete maturation which was also observed in this study. We therefore designed bioengineered ventral midbrain organoids supported by recombinant spider-silk microfibers functionalized with full-length human laminin. We show that silk organoids reproduce key molecular aspects of dopamine neurogenesis and reduce inter-organoid variability in terms of cell type composition and dopamine neuron formation.
Epithelial phenotype restoring drugs suppress macular degeneration phenotypes in an iPSC model
Authors: Sharma Ruchi , George Aman , Nimmagadda Malika , Ortolan Davide , Karla Barbosa-Sabanero , Qureshy Zoya , Bose Devika , Dejene Roba , Liang Genqing , Wan Qin , Chang Justin , Jha Balendu Shekhar , Memon Omar , Miyagishima Kiyoharu Joshua , Rising Aaron , Lal Madhu , Hanson Eric , King Rebecca , Campos Mercedes Maria , Ferrer Marc , Amaral Juan , McGaughey David , Bharti Kapil
Published: December 2021

Age-related Macular Degeneration (AMD), a blinding eye disease, is characterized by pathological protein- and lipid-rich drusen deposits underneath the retinal pigment epithelium (RPE) and atrophy of the RPE monolayer in advanced disease stages - leading to photoreceptor cell death and vision loss. Currently, there are no drugs that stop drusen formation or RPE atrophy in AMD. Here we provide an iPSC-RPE AMD model that recapitulates drusen and RPE atrophy. Drusen deposition is dependent on AMD-risk-allele CFH(H/H) and anaphylatoxin triggered alternate complement signaling via the activation of NF-κB and downregulation of autophagy pathways. Through high-throughput screening we identify two drugs, L-745,870, a dopamine receptor antagonist, and aminocaproic acid, a protease inhibitor that reduce drusen deposits and restore RPE epithelial phenotype in anaphylatoxin challenged iPSC-RPE with or without the CFH(H/H) genotype. This comprehensive iPSC-RPE model replicates key AMD phenotypes, provides molecular insight into the role of CFH(H/H) risk-allele in AMD, and discovers two candidate drugs to treat AMD.
Oxicam-type non-steroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway
Authors: Ishihama Nobuaki , Choi Seung-won , Noutoshi Yoshiteru , Saska Ivana , Asai Shuta , Takizawa Kaori , He Sheng Yang , Osada Hiroyuki , Shirasu Ken
Published: December 2021

Nonsteroidal anti-inflammatory drugs (NSAIDs), including salicylic acid (SA), target mammalian cyclooxygenases. In plants, SA is a defense hormone that regulates NON-EXPRESSOR OF PATHOGENESIS RELATED GENES 1 (NPR1), the master transcriptional regulator of immunity-related genes. We identify that the oxicam-type NSAIDs tenoxicam (TNX), meloxicam, and piroxicam, but not other types of NSAIDs, exhibit an inhibitory effect on immunity to bacteria and SA-dependent plant immune response. TNX treatment decreases NPR1 levels, independently from the proposed SA receptors NPR3 and NPR4. Instead, TNX induces oxidation of cytosolic redox status, which is also affected by SA and regulates NPR1 homeostasis. A cysteine labeling assay reveals that cysteine residues in NPR1 can be oxidized in vitro, leading to disulfide-bridged oligomerization of NPR1, but not in vivo regardless of SA or TNX treatment. Therefore, this study indicates that oxicam inhibits NPR1-mediated SA signaling without affecting the redox status of NPR1.
Network-driven anomalous transport is a fundamental component of brain microvascular dysfunction
Authors: Goirand Florian , Le Borgne Tanguy , Lorthois Sylvie
Published: December 2021

Blood microcirculation supplies neurons with oxygen and nutrients, and contributes to clearing their neurotoxic waste, through a dense capillary network connected to larger tree-like vessels. This complex microvascular architecture results in highly heterogeneous blood flow and travel time distributions, whose origin and consequences on brain pathophysiology are poorly understood. Here, we analyze highly-resolved intracortical blood flow and transport simulations to establish the physical laws governing the macroscopic transport properties in the brain micro-circulation. We show that network-driven anomalous transport leads to the emergence of critical regions, whether hypoxic or with high concentrations of amyloid-β, a waste product centrally involved in Alzheimer’s Disease. We develop a Continuous-Time Random Walk theory capturing these dynamics and predicting that such critical regions appear much earlier than anticipated by current empirical models under mild hypoperfusion. These findings provide a framework for understanding and modelling the impact of microvascular dysfunction in brain diseases, including Alzheimer’s Disease.
Decoding non-canonical mRNA decay by the endoplasmic-reticulum stress sensor IRE1α
Authors: Le Thomas Adrien , Ferri Elena , Marsters Scot , Harnoss Jonathan M. , Lawrence David A. , Zuazo-Gaztelu Iratxe , Modrusan Zora , Chan Sara , Solon Margaret , Chalouni Cécile , Li Weihan , Koeppen Hartmut , Rudolph Joachim , Wang Weiru , Wu Thomas D. , Walter Peter , Ashkenazi Avi
Published: December 2021

Inositol requiring enzyme 1 (IRE1) mitigates endoplasmic-reticulum (ER) stress by orchestrating the unfolded-protein response (UPR). IRE1 spans the ER membrane, and signals through a cytosolic kinase-endoribonuclease module. The endoribonuclease generates the transcription factor XBP1s by intron excision between similar RNA stem-loop endomotifs, and depletes select cellular mRNAs through regulated IRE1-dependent decay (RIDD). Paradoxically, in mammals RIDD seems to target only mRNAs with XBP1-like endomotifs, while in flies RIDD exhibits little sequence restriction. By comparing nascent and total IRE1α-controlled mRNAs in human cells, we identify not only canonical endomotif-containing RIDD substrates, but also targets without such motifs—degraded by a process we coin RIDDLE, for RIDD lacking endomotif. IRE1α displays two basic endoribonuclease modalities: highly specific, endomotif-directed cleavage, minimally requiring dimers; and more promiscuous, endomotif-independent processing, requiring phospho-oligomers. An oligomer-deficient IRE1α mutant fails to support RIDDLE in vitro and in cells. Our results advance current mechanistic understanding of the UPR.
The global loss of floristic uniqueness
Authors: Yang Qiang , Weigelt Patrick , Fristoe Trevor S. , Zhang Zhijie , Kreft Holger , Stein Anke , Seebens Hanno , Dawson Wayne , Essl Franz , König Christian , Lenzner Bernd , Pergl Jan , Pouteau Robin , Pyšek Petr , Winter Marten , Ebel Aleksandr L. , Fuentes Nicol , Giehl Eduardo L. H. , Kartesz John , Krestov Pavel , Kukk Toomas , Nishino Misako , Kupriyanov Andrey , Villaseñor Jose Luis , Wieringa Jan J. , Zeddam Abida , Zykova Elena , van Kleunen Mark
Published: December 2021

Regional species assemblages have been shaped by colonization, speciation and extinction over millions of years. Humans have altered biogeography by introducing species to new ranges. However, an analysis of how strongly naturalized plant species (i.e. alien plants that have established self-sustaining populations) affect the taxonomic and phylogenetic uniqueness of regional floras globally is still missing. Here, we present such an analysis with data from native and naturalized alien floras in 658 regions around the world. We find strong taxonomic and phylogenetic floristic homogenization overall, and that the natural decline in floristic similarity with increasing geographic distance is weakened by naturalized species. Floristic homogenization increases with climatic similarity, which emphasizes the importance of climate matching in plant naturalization. Moreover, floristic homogenization is greater between regions with current or past administrative relationships, indicating that being part of the same country as well as historical colonial ties facilitate floristic exchange, most likely due to more intensive trade and transport between such regions. Our findings show that naturalization of alien plants threatens taxonomic and phylogenetic uniqueness of regional floras globally. Unless more effective biosecurity measures are implemented, it is likely that with ongoing globalization, even the most distant regions will lose their floristic uniqueness.
CD137 (4-1BB) costimulation of CD8+ T cells is more potent when provided in cis than in trans with respect to CD3-TCR stimulation
Authors: Otano Itziar , Azpilikueta Arantza , Glez-Vaz Javier , Alvarez Maite , Medina-Echeverz José , Cortés-Domínguez Ivan , Ortiz-de-Solorzano Carlos , Ellmark Peter , Fritzell Sara , Hernandez-Hoyos Gabriela , Nelson Michelle Hase , Ochoa María Carmen , Bolaños Elixabet , Cuculescu Doina , Jaúregui Patricia , Sanchez-Gregorio Sandra , Etxeberria Iñaki , Rodriguez-Ruiz María E. , Sanmamed Miguel F. , Teijeira Álvaro , Berraondo Pedro , Melero Ignacio
Published: December 2021

CD137 (4-1BB; TNFSR9) is an activation-induced surface receptor that through costimulation effects provide antigen-primed T cells with augmented survival, proliferation and effector functions as well as metabolic advantages. These immunobiological mechanisms are being utilised for cancer immunotherapy with agonist CD137-binding and crosslinking-inducing agents that elicit CD137 intracellular signaling. In this study, side-by-side comparisons show that provision of CD137 costimulation in-cis with regard to the TCR-CD3-ligating cell is superior to that provided in-trans in terms of T cell activation, proliferation, survival, cytokine secretion and mitochondrial fitness in mouse and human. Cis ligation of CD137 relative to the TCR-CD3 complex results in more intense canonical and non-canonical NF-κB signaling and provides a more robust induction of cell cycle and DNA damage repair gene expression programs. Here we report that the superiority of cis versus trans CD137-costimulation is readily observed in vivo and is relevant for understanding the immunotherapeutic effects of CAR T cells and CD137 agonistic therapies currently undergoing clinical trials, which may provide costimulation either in cis or in trans.
Epigenetic loss of heterogeneity from low to high grade localized prostate tumours
Authors: Eksi Sebnem Ece , Chitsazan Alex , Sayar Zeynep , Thomas George V. , Fields Andrew J. , Kopp Ryan P. , Spellman Paul T. , Adey Andrew C.
Published: December 2021

Identifying precise molecular subtypes attributable to specific stages of localized prostate cancer has proven difficult due to high levels of heterogeneity. Bulk assays represent a population-average, which mask the heterogeneity that exists at the single-cell level. In this work, we sequence the accessible chromatin regions of 14,424 single-cells from 18 flash-frozen prostate tumours. We observe shared chromatin features among low-grade prostate cancer cells are lost in high-grade tumours. Despite this loss, high-grade tumours exhibit an enrichment for FOXA1, HOXB13 and CDX2 transcription factor binding sites, indicating a shared trans-regulatory programme. We identify two unique genes encoding neuronal adhesion molecules that are highly accessible in high-grade prostate tumours. We show NRXN1 and NLGN1 expression in epithelial, endothelial, immune and neuronal cells in prostate cancer using cyclic immunofluorescence. Our results provide a deeper understanding of the active gene regulatory networks in primary prostate tumours, critical for molecular stratification of the disease.
Genomic signatures of pre-resistance in Mycobacterium tuberculosis
Authors: Torres Ortiz Arturo , Coronel Jorge , Vidal Julia Rios , Bonilla Cesar , Moore David A. J. , Gilman Robert H. , Balloux Francois , Kon Onn Min , Didelot Xavier , Grandjean Louis
Published: December 2021

Recent advances in bacterial whole-genome sequencing have resulted in a comprehensive catalog of antibiotic resistance genomic signatures in Mycobacterium tuberculosis. With a view to pre-empt the emergence of resistance, we hypothesized that pre-existing polymorphisms in susceptible genotypes (pre-resistance mutations) could increase the risk of becoming resistant in the future. We sequenced whole genomes from 3135 isolates sampled over a 17-year period. After reconstructing ancestral genomes on time-calibrated phylogenetic trees, we developed and applied a genome-wide survival analysis to determine the hazard of resistance acquisition. We demonstrate that M. tuberculosis lineage 2 has a higher risk of acquiring resistance than lineage 4, and estimate a higher hazard of rifampicin resistance evolution following isoniazid mono-resistance. Furthermore, we describe loci and genomic polymorphisms associated with a higher risk of resistance acquisition. Identifying markers of future antibiotic resistance could enable targeted therapy to prevent resistance emergence in M. tuberculosis and other pathogens.
Unraveling the origin of ferroelectric resistance switching through the interfacial engineering of layered ferroelectric-metal junctions
Authors: Xue Fei , He Xin , Ma Yinchang , Zheng Dongxing , Zhang Chenhui , Li Lain-Jong , He Jr-Hau , Yu Bin , Zhang Xixiang
Published: December 2021

Ferroelectric memristors have found extensive applications as a type of nonvolatile resistance switching memories in information storage, neuromorphic computing, and image recognition. Their resistance switching mechanisms are phenomenally postulated as the modulation of carrier transport by polarization control over Schottky barriers. However, for over a decade, obtaining direct, comprehensive experimental evidence has remained scarce. Here, we report an approach to experimentally demonstrate the origin of ferroelectric resistance switching using planar van der Waals ferroelectric α-In2Se3 memristors. Through rational interfacial engineering, their initial Schottky barrier heights and polarization screening charges at both terminals can be delicately manipulated. This enables us to find that ferroelectric resistance switching is determined by three independent variables: ferroelectric polarization, Schottky barrier variation, and initial barrier height, as opposed to the generally reported explanation. Inspired by these findings, we demonstrate volatile and nonvolatile ferroelectric memristors with large on/off ratios above 104. Our work can be extended to other planar long-channel and vertical ultrashort-channel ferroelectric memristors to reveal their ferroelectric resistance switching regimes and improve their performances.
Protein phosphatase 2A inactivation induces microsatellite instability, neoantigen production and immune response
Authors: Yen Yu-Ting , Chien May , Wu Pei-Yi , Ho Chi-Chang , Ho Chun-Te , Huang Kevin Chih-Yang , Chiang Shu-Fen , Chao K. S. Clifford , Chen William Tzu-Liang , Hung Shih-Chieh
Published: December 2021

Microsatellite-instable (MSI), a predictive biomarker for immune checkpoint blockade (ICB) response, is caused by mismatch repair deficiency (MMRd) that occurs through genetic or epigenetic silencing of MMR genes. Here, we report a mechanism of MMRd and demonstrate that protein phosphatase 2A (PP2A) deletion or inactivation converts cold microsatellite-stable (MSS) into MSI tumours through two orthogonal pathways: (i) by increasing retinoblastoma protein phosphorylation that leads to E2F and DNMT3A/3B expression with subsequent DNA methylation, and (ii) by increasing histone deacetylase (HDAC)2 phosphorylation that subsequently decreases H3K9ac levels and histone acetylation, which induces epigenetic silencing of MLH1. In mouse models of MSS and MSI colorectal cancers, triple-negative breast cancer and pancreatic cancer, PP2A inhibition triggers neoantigen production, cytotoxic T cell infiltration and ICB sensitization. Human cancer cell lines and tissue array effectively confirm these signaling pathways. These data indicate the dual involvement of PP2A inactivation in silencing MLH1 and inducing MSI.
ER proteins decipher the tubulin code to regulate organelle distribution
Authors: Zheng Pengli , Obara Christopher J. , Szczesna Ewa , Nixon-Abell Jonathon , Mahalingan Kishore K. , Roll-Mecak Antonina , Lippincott-Schwartz Jennifer , Blackstone Craig
Published: December 2021

Organelles move along differentially modified microtubules to establish and maintain their proper distributions and functions1,2. However, how cells interpret these post-translational microtubule modification codes to selectively regulate organelle positioning remains largely unknown. The endoplasmic reticulum (ER) is an interconnected network of diverse morphologies that extends promiscuously throughout the cytoplasm3, forming abundant contacts with other organelles4. Dysregulation of endoplasmic reticulum morphology is tightly linked to neurologic disorders and cancer5,6. Here we demonstrate that three membrane-bound endoplasmic reticulum proteins preferentially interact with different microtubule populations, with CLIMP63 binding centrosome microtubules, kinectin (KTN1) binding perinuclear polyglutamylated microtubules, and p180 binding glutamylated microtubules. Knockout of these proteins or manipulation of microtubule populations and glutamylation status results in marked changes in endoplasmic reticulum positioning, leading to similar redistributions of other organelles. During nutrient starvation, cells modulate CLIMP63 protein levels and p180–microtubule binding to bidirectionally move endoplasmic reticulum and lysosomes for proper autophagic responses.
Safety and tolerability of asunercept plus standard radiotherapy/temozolomide in Asian patients with newly-diagnosed glioblastoma: a phase I study
Authors: Wei Kuo-Chen , Hsu Peng-Wei , Tsai Hong-Chieh , Lin Ya-Jui , Chen Ko-Ting , Toh Cheng-Hong , Huang Hui-Lin , Jung Shih-Ming , Tseng Chen-Kan , Ke Yu-Xiong
Published: December 2021

Asunercept (company code APG101 [Apogenix AG]; company code CAN008 [CANbridge Pharmaceuticals]) is a novel glycosylated fusion protein that has shown promising effectiveness in glioblastoma. This Phase I study was initiated to evaluate the tolerability and safety of asunercept in combination with standard radiotherapy and temozolomide (RT/TMZ) in Asian patients with newly diagnosed glioblastoma. This was the Phase I portion of a Phase I/II open label, multicenter trial of asunercept plus standard RT/TMZ. Adults with newly-diagnosed glioblastoma received surgical resection followed by standard RT/TMZ plus asunercept 200 mg/week (Cohort 1) or 400 mg/week (Cohort 2) by 30-min IV infusion. The primary endpoint was the safety and tolerability of asunercept during concurrent asunercept and RT/TMZ; dose-limiting toxicities were observed for each dose. Secondary endpoints included pharmacokinetics (PK) and 6-month progression-free survival (PFS6). All patients (Cohort 1, n = 3; Cohort 2, n = 7) completed ≥ 7 weeks of asunercept treatment. No DLTs were experienced. Only one possibly treatment-related treatment emergent adverse event (TEAE), Grade 1 gingival swelling, was observed. No Grade > 3 TEAEs were reported and no TEAE led to treatment discontinuation. Systemic asunercept exposure increased proportionally with dose and showed low inter-patient variability. The PFS6 rate was 33.3% and 57.1% for patients in Cohort 1 and 2, respectively. Patients in Cohort 2 maintained a PFS rate of 57.1% at Month 12. Adding asunercept to standard RT/TMZ was safe and well tolerated in patients with newly-diagnosed glioblastoma and 400 mg/week resulted in encouraging efficacy.

Trial registration NCT02853565, August 3, 2016.
Circulating PIK3CA mutation detection at diagnosis in non-metastatic inflammatory breast cancer patients
Authors: Allouchery Violette , Perdrix Anne , Calbrix Céline , Berghian Anca , Lequesne Justine , Fontanilles Maxime , Leheurteur Marianne , Etancelin Pascaline , Sarafan-Vasseur Nasrin , Di Fiore Frédéric , Clatot Florian
Published: December 2021

Inflammatory breast cancer (IBC) is an aggressive BC subtype with poor outcomes. A targetable somatic PIK3CA mutation is reported in 30% of IBC, allowing for treatment by PI3Kα-specific inhibitors, such as alpelisib. The aim of this study was to evaluate the detection rate of circulating PIK3CA mutation in locally-advanced IBC (LAIBC) patients harbouring a PIK3CA mutation on initial biopsy. This monocentric retrospective study was based on available stored plasma samples and tumour biopsies at diagnosis from all LAIBC patients treated with neo-adjuvant chemotherapy (NCT) between 2008 and 2018 at the Centre Henri Becquerel. PIK3CA mutations (E542K, E545K, H1047R/L) were assessed by droplet digital PCR (ddPCR) in plasma samples and tumoral tissue at diagnosis. A total of 55 patients were included. Overall, 14/55 patients (25%) had a PIK3CA mutation identified on baseline biopsy (H1047R = 8; H1047L = 3; E545K = 2; E542K = 1). Among them, 11 (79%) patients had enough DNA for circulating DNA analyses, and corresponding circulating PIK3CA mutations were found in 6/11 (55%). Among the 41 patients without PIK3CA mutations on biopsy, 32 (78%) had enough DNA for circulating DNA analysis, and no circulating PIK3CA mutation was identified. Our results revealed no prognostic or predictive value of PIK3CA mutations at the diagnosis of non-metastatic IBC but highlighted the prognostic value of the cfDNA rate at diagnosis. Our study showed that a corresponding circulating PIK3CA mutation was identified in 55% of LAIBC patients with PIK3CA-mutated tumours, while no circulating mutation was found among patients with PI3KCA wild-type tumours.
MRFGRO: a hybrid meta-heuristic feature selection method for screening COVID-19 using deep features
Authors: Dey Arijit , Chattopadhyay Soham , Singh Pawan Kumar , Ahmadian Ali , Ferrara Massimiliano , Senu Norazak , Sarkar Ram
Published: December 2021

COVID-19 is a respiratory disease that causes infection in both lungs and the upper respiratory tract. The World Health Organization (WHO) has declared it a global pandemic because of its rapid spread across the globe. The most common way for COVID-19 diagnosis is real-time reverse transcription-polymerase chain reaction (RT-PCR) which takes a significant amount of time to get the result. Computer based medical image analysis is more beneficial for the diagnosis of such disease as it can give better results in less time. Computed Tomography (CT) scans are used to monitor lung diseases including COVID-19. In this work, a hybrid model for COVID-19 detection has developed which has two key stages. In the first stage, we have fine-tuned the parameters of the pre-trained convolutional neural networks (CNNs) to extract some features from the COVID-19 affected lungs. As pre-trained CNNs, we have used two standard CNNs namely, GoogleNet and ResNet18. Then, we have proposed a hybrid meta-heuristic feature selection (FS) algorithm, named as Manta Ray Foraging based Golden Ratio Optimizer (MRFGRO) to select the most significant feature subset. The proposed model is implemented over three publicly available datasets, namely, COVID-CT dataset, SARS-COV-2 dataset, and MOSMED dataset, and attains state-of-the-art classification accuracies of 99.15%, 99.42% and 95.57% respectively. Obtained results confirm that the proposed approach is quite efficient when compared to the local texture descriptors used for COVID-19 detection from chest CT-scan images.
Ectoparasitic fungi of Myrmica ants alter the success of parasitic butterflies
Authors: Tartally András , Szabó Norbert , Somogyi Anna Ágnes , Báthori Ferenc , Haelewaters Danny , Mucsi András , Fürjes-Mikó Ágnes , Nash David R.
Published: December 2021

Exploitation of organisms by multiple parasite species is common in nature, but interactions among parasites have rarely been studied.Myrmicaants are rich in parasites. Among others, the ectoparasiticRickia wasmanniifungus and the parasitic caterpillars of myrmecophilousPhengarisbutterflies often infect the sameMyrmicacolonies. In this study, we examined the effects ofR. wasmanniion the adoption, long-term development, and survival ofP. alcon. In laboratory conditions, caterpillars introduced into nests ofMyrmica scabrinodisuninfected withR. wasmanniisurvived significantly longer compared to caterpillars introduced into infected nests. In the field, joint infection was less common than expected if both parasites exploitedM. scabrinodiscolonies independently. Pre-pupal caterpillars ofP. alconwere somewhat larger in nests infected withR. wasmanniithan those found in uninfected nests. Based on these results it seems thatR. wasmanniiinfection ofM. scabrinodisaffects the survival and development ofP. alconcaterpillars, suggesting competition between these two ant parasites.
i-RheoFT: Fourier transforming sampled functions without artefacts
Authors: Smith Matthew G. , Gibson Graham M. , Tassieri Manlio
Published: December 2021

In this article we present a new open-access code named “i-RheoFT” that implements the analytical method first introduced in [PRE, 80, 012501 (2009)] and then enhanced in [New J Phys 14, 115032 (2012)], which allows to evaluate the Fourier transform of any generic time-dependent function that vanishes for negative times, sampled at a finite set of data points that extend over a finite range, andneed notbe equally spaced. I-RheoFT has been employed here to investigate three important experimental factors: (i) the ‘density of initial experimental points’ describing the sampled function, (ii) the interpolation function used to perform the “virtual oversampling” procedure introduced in [New J Phys 14, 115032 (2012)], and (iii) the detrimental effect of noises on the expected outcomes. We demonstrate that, at relatively high signal-to-noise ratios and density of initial experimental points, all three built-in MATLAB interpolation functions employed in this work (i.e., Spline, Makima and PCHIP) perform well in recovering the information embedded within the original sampled function; with the Spline function performing best. Whereas, by reducingeitherthe number of initial data pointsorthe signal-to-noise ratio, there exists a threshold below which all three functions perform poorly; with the worst performance given by the Spline function in both the cases and the least worst by the PCHIP function at low density of initial data points and by the Makima function at relatively low signal-to-noise ratios. We envisage that i-RheoFT will be of particular interest and use to all those studies where sampled or time-averaged functions, often defined by a discrete set of data points within a finite time-window, are exploited to gain new insights on the systems’ dynamics.
COVID-19 vaccination strategies depend on the underlying network of social interactions
Authors: Saunders Helena A. , Schwartz Jean-Marc
Published: December 2021

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, different mitigation and management strategies limiting economic and social activities have been implemented across many countries. Despite these strategies, the virus continues to spread and mutate. As a result, vaccinations are now administered to suppress the pandemic. Current COVID-19 epidemic models need to be expanded to account for the change in behaviour of new strains, such as an increased virulence and higher transmission rate. Furthermore, models need to account for an increasingly vaccinated population. We present a network model of COVID-19 transmission accounting for different immunity and vaccination scenarios. We conduct a parameter sensitivity analysis and find the average immunity length after an infection to be one of the most critical parameters that define the spread of the disease. Furthermore, we simulate different vaccination strategies and show that vaccinating highly connected individuals first is the quickest strategy for controlling the disease.
Acoustic monitoring of laser-induced phase transitions in minerals: implication for Mars exploration with SuperCam
Authors: Chide Baptiste , Beyssac Olivier , Gauthier Michel , Benzerara Karim , Estève Imène , Boulliard Jean-Claude , Maurice Sylvestre , Wiens Roger C.
Published: December 2021

The SuperCam instrument suite onboard the Mars 2020 Perseverance rover uses the laser-induced breakdown spectroscopy (LIBS) technique to determine the elemental composition of rocks and soils of the Mars surface. It is associated with a microphone to retrieve the physical properties of the ablated targets when listening to the laser-induced acoustic signal. In this study, we report the monitoring of laser-induced mineral phase transitions in acoustic data. Sound data recorded during the laser ablation of hematite, goethite and diamond showed a sharp increase of the acoustic signal amplitude over the first laser shots. Analyses of the laser-induced craters with Raman spectroscopy and scanning electron microscopy indicate that both hematite and goethite have been transformed into magnetite and that diamond has been transformed into amorphous-like carbon over the first laser shots. It is shown that these transitions are the root cause of the increase in acoustic signal, likely due to a change in target’s physical properties as the material is transformed. These results give insights into the influence of the target’s optical and thermal properties over the acoustic signal. But most importantly, in the context of the Mars surface exploration with SuperCam, as this behavior occurs only for specific phases, it demonstrates that the microphone data may help discriminating mineral phases whereas LIBS data only have limited capabilities.
Association of metformin use with Alzheimer’s disease in patients with newly diagnosed type 2 diabetes: a population-based nested case–control study
Authors: Ha Junghee , Choi Dong-Woo , Kim Kwang Joon , Cho So Yeon , Kim Hyunjeong , Kim Keun You , Koh Youngseung , Nam Chung Mo , Kim Eosu
Published: December 2021

Metformin reduces insulin resistance, which constitutes a pathophysiological connection of diabetes with Alzheimer’s disease (AD), but the evidence of metformin on AD development was still insufficient and conflicting. We investigated AD risk in patients with newly diagnosed type 2 DM treated with metformin. This retrospective, observational, nested case–control study included patients with newly diagnosed type 2 DM obtained from the Korean National Health Insurance Service DM cohort (2002–2017). Among 70,499 dementia-free DM patients, 1675 AD cases were matched to 8375 controls for age, sex, and DM onset and duration. The association between AD and metformin was analyzed by multivariable regression analyses, adjusted for comorbidities and cardiometabolic risk profile. Metformin use was associated with an increased odds of AD (adjusted odds ratio [AOR] 1.50; 95% CI 1.23–1.83). The risk of AD was higher in patients with a longer DM duration. Furthermore, AD risk was significantly high in DM patients with depression (AOR 2.05; 95% CI 1.02–4.12). Given the large number of patients with DM who are taking metformin worldwide, a double-blinded, prospective study is required to determine the long-term cognitive safety of metformin.
Inversion in the permeability evolution of deforming Westerly granite near the brittle–ductile transition
Authors: Petrini Claudio , Madonna Claudio , Gerya Taras
Published: December 2021

Fluid flow through crustal rocks is controlled by permeability. Underground fluid flow is crucial in many geotechnical endeavors, such as CO2 sequestration, geothermal energy, and oil and gas recovery. Pervasive fluid flow and pore fluid pressure control the strength of a rock and affect seismicity in tectonic and geotechnical settings. Despite its relevance, the evolution of permeability with changing temperature and during deformation remains elusive. In this study, the permeability of Westerly granite at an effective pressure of 100 MPa was measured under conditions near its brittle–ductile transition, between 650 °C and 850 °C, with a strain rate on the order of 2·10–6 s−1. To capture the evolution of permeability with increasing axial strain, the samples were continuously deformed in a Paterson gas-medium triaxial apparatus. The microstructures of the rock were studied after testing. The experiments reveal an inversion in the permeability evolution: an initial decrease in permeability due to compaction and then an increase in permeability shortly before and immediately after failure. The increase in permeability after failure, also present at high temperatures, is attributed to the creation of interconnected fluid pathways along the induced fractures. This systematic increase demonstrates the subordinate role that temperature dilatancy plays in permeability control compared to stress and its related deformation. These new experimental results thus demonstrate that permeability enhancement under brittle–ductile conditions unveils the potential for EGS exploitation in high-temperature rocks.
Use of a disposable vascular pressure device to guide balloon inflation of resuscitative endovascular balloon occlusion of the aorta: a bench study
Authors: Levis Anja , Egli Nives , Jenni Hansjoerg , Hautz Wolf E. , Daley James I. , Haenggi Matthias
Published: December 2021

Resuscitative endovascular balloon occlusion of the aorta (REBOA) for rapid hemorrhage control is increasingly being used in trauma management. Its beneficial hemodynamic effects on unstable patients beyond temporal hemostasis has led to growing interest in its use in other patient populations, such as during cardiac arrest from nontraumatic causes. The ability to insert the catheters without fluoroscopic guidance makes the technique available in the prehospital setting. However, in addition to correct positioning, challenges include reliably achieving aortic occlusion while minimizing the risk of balloon rupture. Without fluoroscopic control, inflation of the balloon relies on estimated aortic diameters and on the disappearing pulse in the contralateral femoral artery. In the case of cardiac arrest or absent palpable pulses, balloon inflation is associated with excess risk of overinflation and adverse events (vessel damage, balloon rupture). In this bench study, we examined how the pressure in the balloon is related to the surrounding blood pressure and the balloon's contact with the vessel wall in two sets of experiments, including a pulsatile circulation model. With this data, we developed a rule of thumb to guide balloon inflation of the ER-REBOA catheter with a simple disposable pressure-reading device (COMPASS). We recommend slowly filling the balloon with saline until the measured balloon pressure is 160 mmHg, or 16 mL of saline have been used. If after 16 mL the balloon pressure is still below 160 mmHg, saline should be added in 1-mL increments, which increases the pressure target about 10 mmHg at each step, until the maximum balloon pressure is reached at 240 mmHg (= 24 mL inflation volume). A balloon pressure greater than 250 mmHg indicates overinflation. With this rule and a disposable pressure-reading device (COMPASS), ER-REBOA balloons can be safely filled in austere environments where fluoroscopy is unavailable. Pressure monitoring of the balloon allows for recognition of unintended deflation or rupture of the balloon.
SWI/SNF chromatin remodeling complex is required for initiation of sex-dependent differentiation in mouse germline
Authors: Ito Toshiaki , Osada Atsuki , Ohta Masami , Yokota Kana , Nishiyama Akira , Niikura Yuichi , Tamura Tomohiko , Sekita Yoichi , Kimura Tohru
Published: December 2021

Sexual reproduction involves the creation of sex-dependent gametes, oocytes and sperm. In mammals, sexually dimorphic differentiation commences in the primordial germ cells (PGCs) in embryonic gonads; PGCs in ovaries and testes differentiate into meiotic primary oocytes and mitotically quiescent prospermatogonia, respectively. Here, we show that the transition from PGCs to sex-specific germ cells was abrogated in conditional knockout mice carrying a null mutation of Smarcb1 (also known as Snf5) gene, which encodes a core subunit of the SWI/SNF chromatin remodeling complex. In female mutant mice, failure to upregulate meiosis-related genes resulted in impaired meiotic entry and progression, including defects in synapsis formation and DNA double strand break repair. Mutant male mice exhibited delayed mitotic arrest and DNA hypomethylation in retrotransposons and imprinted genes, resulting from aberrant expression of genes related to growth and de novo DNA methylation. Collectively, our results demonstrate that the SWI/SNF complex is required for transcriptional reprogramming in the initiation of sex-dependent differentiation of germ cells.
Thermal hazard evaluation on spontaneous combustion characteristics of nitrocellulose solution under different atmospheric conditions
Authors: Li Zhi-Ping , Jiang Jun-Cheng , Huang An-Chi , Tang Yan , Miao Chun-Feng , Zhai Juan , Huang Chung-Fu , Xing Zhi-Xiang , Shu Chi-Min
Published: December 2021

Nitrocellulose (NC) is widely used in both military and civilian fields. Because of its high chemical sensitivity and low decomposition temperature, NC is prone to spontaneous combustion. Due to the dangerous properties of NC, it is often dissolved in other organic solvents, then stored and transported in the form of a solution. Therefore, this paper took NC solutions (NC-S) with different concentrations as research objects. Under different atmospheric conditions, a series of thermal analysis experiments and different reaction kinetic methods investigated the influence of solution concentration and oxygen concentration on NC-S’s thermal stability. The variation rules of NC-S’s thermodynamic parameters with solution and oxygen concentrations were explored. On this basis, the spontaneous combustion characteristics of NC-S under actual industrial conditions were summarized to put forward the theoretical guidance for the spontaneous combustion treatment together with the safety in production, transportation, and storage.
Ultrasensitive electrochemical sensor for mercury ion detection based on molybdenum selenide and Au nanoparticles via thymine–Hg2+–thymine coordination
Authors: Zhou Ting , Li Meijuan , Li Na , Dong Yulin , Liu Dan , Hu Xiaosong , Xie Zhizhong , Qu Deyu , Li Xi , Zhang Chaocan
Published: December 2021

An ultrasensitive and specific-selection electrochemical sensor was constructed for Hg2+ detection based on Au nanoparticles and molybdenum selenide (Au NPs@MoSe2) as well as the thymine–Hg2+–thymine (T–Hg2+–T) coordination.
Colorimetric detection of acidic pesticides in water
Authors: Smith Kyle T. , Ramsperger Chloe A. , Hunter Kye E. , Zuehlsdorff Tim J. , Stylianou Kyriakos C.
Published: December 2021

A water stable, porphyrin-based metal–organic framework as a colorimetric sensor for the detection of acidic pesticides.
Photocaged dicarbonyl probe provides spatiotemporal control over protein glycation
Authors: Hurben Alexander K. , Ge Peng , Bouchard Jacob L. , Doran Todd M. , Tretyakova Natalia Y.
Published: December 2021

On demand dicarbonyl-protein adduct formation in live cells is achieved with subcellular specificity by a targetable, light triggered probe.
Concentration-dependent ion correlations impact the electrochemical behavior of calcium battery electrolytes
Authors: Hahn Nathan T. , Self Julian , Driscoll Darren M. , Dandu Naveen , Han Kee Sung , Murugesan Vijayakumar , Mueller Karl T. , Curtiss Larry A. , Balasubramanian Mahalingam , Persson Kristin A. , Zavadil Kevin R.
Published: December 2021

Emergent calcium battery electrolytes in ethereal solvents exhibit concentration-dependent ion correlations involving significant second-shell interactions. These interactions have a strong influence on both conductivity and metal cycling efficiency.
Quantum vibration perturbation approach with polyatomic probe in simulating infrared spectra
Authors: Cong Yang , Zhai Yu , Yang Jitai , Grofe Adam , Gao Jiali , Li Hui
Published: December 2021

The Quantum Vibration Perturbation (QVP) approach embeds quantum vibration in Newtonian molecule dynamics.
The effect of separation of blocks on the crystallization kinetics and phase composition of poly(butylene adipate) in multi-block thermoplastic polyurethanes
Authors: Gorbunova Marina A. , Komov Evgenii V. , Grunin Leonid Yu. , Ivanova Mariya S. , Abukaev Ainur F. , Imamutdinova Arina M. , Ivanov Dimitri A. , Anokhin Denis V.
Published: December 2021

Control of the phase separation process of soft and hard segments by selecting diisocyanates and by varying the thermal program allows defining the final degree of crystallinity and phase composition of TPUs.
A simple and highly efficient composite based on g-C3N4for super rapid removal of multiple organic dyes from water under sunlight
Authors: Yang Siwei , Sun Qiang , Han Weihang , Shen Yuanfang , Ni Zhigang , Zhang Shijie , Chen Liangchen , Zhang Luping , Cao Jun , Zheng Hui
Published: December 2021

A simple and highly efficient porous compositeviaa solvent evaporation method using g-C3N4and NiSO4was developed.
2-(4-Hydroxyphenyl)benzothiazole dicarboxylate ester TACN chelators for64Cu PET imaging in Alzheimer's disease
Authors: Wang Yujue , Huynh Truc T. , Bandara Nilantha , Cho Hong-Jun , Rogers Buck E. , Mirica Liviu M.
Published: December 2021

A series of bifunctional chelators (BFCs) with high affinity for amyloid β aggregates, a strong Cu(ii) chelating ability, and favorable lipophilicity for potential blood–brain barrier penetration are reported.
Grafting redox-active molecules on graphene oxide through a diamine linker: length optimization for electron transfer
Authors: Khan Rizwan , Nishina Yuta
Published: December 2021

A redox-active molecule is grafted on graphene oxide through a diamine linker. Ethylenediamine is the best linker when applied to the electrodes of supercapacitors.
Electronically modulated nickel boron by CeOx doping as a highly efficient electrocatalyst towards overall water splitting
Authors: Wang Huimin , Liu Huixiang , Feng Tao , Wang Lincai , Yuan Wenyi , Huang Qing , Guo Yanhui
Published: December 2021

A novel CeOx-NiB@NF catalyst with high activity and good stability towards both the HER and OER has been fabricated.
Hybrid organic–inorganic triguanidine arsenate dihydrate for ultraviolet nonlinear optical application
Authors: Wang Dongmei , Wei Zhuangzhuang , Bai Zhiyong , Liu Lehui , Lin Zhoubin , Zhang Lizhen
Published: December 2021

Introduction of the planar organic cation [C(NH2)3]+ into tetrahedronal inorganic arsenate generates a new ultraviolet nonlinear optical crystal.
Reduction of tert-butylphosphaalkyne and trimethylsilylnitrile with magnesium(i) dimers
Authors: Wilson Daniel W. N. , Jones Dafydd D. L. , Smith Cory D. , Mehta Meera , Jones Cameron , Goicoechea Jose M.
Published: December 2021

We describe the reactivity of magnesium(i) dimers, [(nacnac)Mg]2 towards phosphaalkynes and Me3SiCN in an effort to understand how steric bulk influences the outcome of these reduction processes.
Investigation of perfluoroalkyl substances in proglacial rivers and permafrost seep in a high Arctic watershed
Authors: MacInnis John , De Silva Amila O. , Lehnherr Igor , Muir Derek C. G. , St. Pierre Kyra A. , St. Louis Vincent L. , Spencer Christine
Published: December 2021

We measured perfluoroalkyl substances (PFAS) in proglacial rivers and along a non-glacial freshwater continuum to investigate the role of snow and ice melting in their transport and fate within the Lake Hazen watershed (82° N).
Comment on “The association between carotenoids and subjects with overweight or obesity: a systematic review and meta-analysis” by N. Yao, S. Yan, Y. Guo, H. Wang, X. Li, L. Wang, W. Hu, B. Li and W. Cui, Food Funct., 2021, 12, 4768.
Authors: Shokri-mashhadi Nafiseh , Saadat Saeed
Published: December 2021

The association between carotenoids and subjects with overweight or obesity: reanalysis is needed.
A nascent protein labeling strategy disclosed mitochondrial proteomic responses in punicalagin intervened insulin resistance of HepG2 cells
Authors: Zhang Zhengyi , Zeng Mengqi , Han Xiao , Hou Zhanwu , Wang Zhen , Su Tian , Zhao Wei , Liu Jiankang , Liu Huadong
Published: December 2021

Insulin Resistance (IR), as a common pathophysiological basis, is closely related to a variety of metabolic diseases, such as obesity and diabetes.
Supplementation of amino acids and organic acids prevents the increase in blood pressure induced by high salt in Dahl salt-sensitive rats
Authors: Yang Pengfei , Zhou Luxin , Chen Meng , Zeng Li , Ouyang Yanan , Zheng Xuewei , Chen Xiangbo , Yang Zhe , Tian Zhongmin
Published: December 2021

A high-salt (HS) diet leads to metabolic disorders in Dahl salt-sensitive (SS) rats, and promotes the development of hypertension.
Dibenzo[d,d′]benzo[2,1-b:3,4-b′]difurans with extended π-conjugated chains: synthetic approaches and properties
Authors: Hirano Masafumi , Okada Harumi , Hayasaka Chikara , Komine Nobuyuki , Kiyota Sayori , Nakano Koji
Published: December 2021

Ru-Catalysed reaction of 3,8-di(hexyn-1-yl)dibenzo[d,d']benzo[2,1-b,3,4-b′]difuran [3,8-di(hexyn-1-yl)-DBBDF] with 2 equivalents of methyl (E)-penta-2,4-dienoate produces 3,8-bis[(1E,3E,5E)-2-butyl-6-methoxycarbonylhexa-1,3,5-trien-1-yl]-DBBDF (9a).
Neutral Mo6Q8-clusters with terminal phosphane ligands – a route to water-soluble molecular units of Chevrel phases
Authors: Novikova Evgeniya D. , Gassan Alena D. , Ivanov Anton A. , Vorotnikov Yuri A. , Shestopalov Michael A.
Published: December 2021

Neutral clusters [{Mo6Q8}(Ph2PC2H4COOH)6] (Q = S or Se) readily dissolve in slightly alkaline water forming a highly stable solution. Compounds are redox-active and demonstrate absorbance in all major regions of the spectra – UV, visible and NIR.