bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal in vivo platelet labelling in mice reveals age-dependent receptor expression and conservation of specific mRNAs
Authors: Armstrong Paul C , Allan Harriet E , Kirkby Nicholas S , Joshi Abhishek , Gutmann Clemens , Crescente Marilena , Mitchell Jane A , Mayr Manuel , Warner Timothy D
Published: December 2021

The proportion of young platelets, also known as newly formed or reticulated, within the overall platelet population has been clinically correlated with adverse cardiovascular outcomes. Our understanding of this is incomplete, however, because of limitations in the technical approaches available to study platelets of different ages. In this study we have developed and validated an in vivo ‘temporal labelling’ approach using injectable fluorescent anti-platelet antibodies to sub-divide platelets by age and assess differences in functional and molecular characteristics. With this approach we found that young platelets (<24h old) in comparison to older platelets respond to stimuli with greater calcium flux and degranulation, and contribute more to the formation of thrombi in vitro and in vivo. Sequential sampling confirmed this altered functionality to be independent of platelet size with no size differences or changes relative to the global population seen at any age. The age associated decrease in thrombotic function was accompanied by significant decreases in the surface expression of GPVI and CD31 (PECAM-1) and an increase in CD9. Platelet mRNA content also decreased with age but at different rates for individual mRNAs indicating apparent conservation of those encoding granule proteins. Our pulse-chase type approach to define circulating platelet age has allowed timely re-examination of commonly held beliefs regarding size and reactivity of young platelets whilst providing novel insights into the temporal regulation of receptor and protein expression. Overall, future application of this validated tool will inform on age-based platelet heterogeneity in physiology and disease.
An Agent-Based Model of Monocyte Differentiation into Tumour-Associated Macrophages in Chronic Lymphocytic Leukemia
Authors: Verstraete Nina , Marku Malvina , Domagala Marcin , Arduin Hélène , Bordenave Julie , Fournié Jean-Jacques , Ysebaert Loïc , Poupot Mary , Pancaldi Vera
Published: December 2021

Monocyte-derived macrophages help maintain tissue homeostasis and defend the organism against pathogens. In tumors, recent studies have uncovered complex macrophage populations, including tumor-associated macrophages, which support tumorigenesis through cancer hallmarks such as immunosuppression, angiogenesis or matrix remodeling. In the case of chronic lymphocytic leukemia, these macrophages are known as nurse-like cells and they protect leukemic cells from spontaneous apoptosis contributing to their chemoresistance. We propose an agent-based model of monocyte differentiation into nurse-like cells upon contact with leukemic B cellsin vitro. We performed patient-specific model calibrations using cultures of peripheral blood mononuclear cells from patients. Using our model, we were able to reproduce temporal survival dynamics of cancer cells in a patient-specific manner and to identify patient groups related to distinct macrophage phenotypes. Our results show a potentially important role of phagocytosis in the polarization process of nurse-like cells and in promoting cancer cells’ enhanced survival.
“Heat waves” experienced during larval life have species-specific consequences on life-history traits and sexual development in anuran amphibians
Authors: Ujszegi János , Bertalan Réka , Ujhegyi Nikolett , Verebélyi Viktória , Nemesházi Edina , Mikó Zsanett , Kásler Andrea , Herczeg Dávid , Szederkényi Márk , Vili Nóra , Gál Zoltán , Hoffmann Orsolya I. , Bókony Veronika , Hettyey Attila
Published: December 2021

Extreme temperatures during heat waves can induce mass-mortality events, but can also exert sublethal negative effects by compromising life-history traits and derailing sexual development. Ectothermic animals may, however, also benefit from increased temperatures via enhanced physiological performance and the suppression of cold-adapted pathogens. Therefore, it is crucial to address how the intensity and timing of naturally occurring or human-induced heat waves affect life-history traits and sexual development in amphibians, to predict future effects of climate change and to minimise risks arising from the application of elevated temperature in disease mitigation. We raised agile frog (Rana dalmatina) and common toad (Bufo bufo) tadpoles at 19 °C and exposed them to a simulated heat wave of 28 or 30 °C for six days during one of three ontogenetic periods (early, mid or late larval development). In agile frogs, exposure to 30 °C during early larval development increased mortality. Regardless of timing, all heat-treatments delayed metamorphosis, and exposure to 30 °C decreased body mass at metamorphosis. Furthermore, exposure to 30 °C during any period and to 28 °C late in development caused female-to-male sex reversal, skewing sex ratios strongly towards males. In common toads, high temperature only slightly decreased survival and did not influence phenotypic sex ratio, while it reduced metamorph mass and length of larval development. Juvenile body mass measured two months after metamorphosis was not adversely affected by temperature treatments in either species. Our results indicate that heat waves may have devastating effects on amphibian populations, and the severity of these negative consequences, and sensitivity can vary greatly between species and with the timing and intensity of heat. Finally, thermal treatments against cold-adapted pathogens have to be executed with caution, taking into account the thermo-sensitivity of the species and the life stage of animals to be treated.
MicroRNA-like snoRNA-derived RNAs (sdRNAs) promote castration resistant prostate cancer
Authors: Coley Alexander B. , Stahly Ashlyn N. , Kasukurthi Mohan V. , Barchie Addison A. , Hutcheson Sam B. , Houserova Dominika , Huang Yulong , Watters Brianna C. , King Valeria M. , Dean Meghan A. , Roberts Justin T. , DeMeis Jeffrey D. , McInnis Cameron H. , Godang Noel L. , Wright Ryan M. , Haider David F. , Piracha Neha B. , Brown Cana L. , Ijaz Zohaib M. , Li Shengyu , Xi Yaguang , McDonald Oliver G. , Huang Jingshan , Borchert Glen M.
Published: December 2021

We have identified 38 specifically excised, differentially expressed snoRNA fragments (sdRNAs) in TCGA prostate cancer (PCa) patient samples as compared to normal prostate controls. SnoRNA-derived fragments sdRNA-D19b and -A24 emerged among the most differentially expressed and were selected for further experimentation. We found that overexpression of either sdRNA significantly increased PC3 (a well-established model of castration-resistant prostate cancer (CRPC)) cell proliferation, and that sdRNA-D19b overexpression also markedly increased the rate of PC3 cell migration. In addition, both sdRNAs provided drug-specific resistances with sdRNA-D19b levels correlating with paclitaxel resistance and sdRNA-24A conferring dasatinib resistance. In silico and in vitro analyses revealed that two established PCa tumor suppressor genes, CD44 and CDK12, represent targets for sdRNA-D19b and sdRNA-A24 respectively. This outlines a biologically coherent mechanism by which sdRNAs downregulate tumor suppressors in AR-PCa to enhance proliferative and metastatic capabilities and to encourage chemotherapeutic resistance. Aggressive proliferation, rampant metastasis, and recalcitrance to chemotherapy are core characteristics of CRPC that synergize to produce a pathology that ranks 2nd in cancer-related deaths for men. This study defines sdRNA-D19b and -A24 as contributors to AR-PCa potentially providing novel biomarkers and therapeutic targets of use in PCa clinical intervention.
Stimulus-induced changes in 1/f-like background activity in EEG
Authors: Gyurkovics Máté , Clements Grace M. , Low Kathy A. , Fabiani Monica , Gratton Gabriele
Published: December 2021

Research into the nature of 1/f-like, non-oscillatory electrophysiological activity has grown exponentially in recent years in cognitive neuroscience. The shape of this activity has been linked to the balance between excitatory and inhibitory neural circuits, which is thought to be important for information processing. However, to date, it is not known whether the presentation of a stimulus induces changes in the parameters of 1/f activity, which are separable from the emergence of event-related potentials (ERPs). Here, we analyze event-related broadband changes in scalp-recorded EEG both before and after removing ERPs to demonstrate their confounding effect, and to establish whether there are genuine stimulus-induced changes in 1/f. Using data from a passive and an active auditory task (n=23), we found that the shape of the post-event spectra differed significantly from the pre-event spectra even after removing the frequency-content of ERPs. Further, a significant portion of this difference could be accounted for by a rotational shift in 1/f activity, manifesting as an increase in low and a decrease in high frequencies. Importantly, the magnitude of this rotational shift was related to the attentional demands of the task. This change in 1/f is consistent with increased inhibition following the onset of a stimulus, and likely reflects a disruption of ongoing excitatory activity proportional to processing demands. Finally, these findings contradict the central assumption of baseline normalization strategies in time-frequency analyses, namely that background EEG activity is stationary across time. As such, they have far-reaching consequences that cut across several subfields of neuroscience.

Significance statement

Interest in the functional role of the 1/f-like background brain activity has been growing exponentially in neuroscience. Yet, no study to date has demonstrated a clear relationship between information processing and 1/f activity by investigating event-related effects on its parameters. Here, we demonstrate for the first time that stimuli induce rotational changes in 1/f activity, independent from the occurrence of event-related potentials. Not only do these findings suggest that the assumption of stationary background activity in the analysis of neural oscillations is untenable, but they also suggest the presence of large-scale inhibition following stimulus onset, the magnitude of which is dependent on the demands of the task. These findings have far-reaching consequences that cut across several subfields of neuroscience.
Lonafarnib improves cardiovascular function and survival in a mouse model of Hutchinson-Gilford Progeria Syndrome
Authors: Murtada S-I. , Mikush N. , Wang M. , Ren P. , Kawamura Y. , Ramachandra A.B. , Braddock D.T. , Tellides G. , Gordon L.B. , Humphrey J.D.
Published: December 2021

Clinical trials have demonstrated that lonafarnib, a farnesyltransferase inhibitor, extends lifespan in patients afflicted by Hutchinson-Gilford progeria syndrome, a devastating condition that accelerates many characteristics of aging and results in premature death due to cardiovascular sequelae. The US Food and Drug Administration approved Zokinvy™ (lonafarnib) in November 2020 for treating these patients, yet a detailed examination of drug-associated effects on cardiovascular structure, properties, and function has remained wanting. In this paper, we report encouraging outcomes of daily post-weaning treatment with lonafarnib on the composition and biomechanical phenotype of elastic and muscular arteries as well as associated cardiac function in a well-accepted mouse model of progeria that exhibits severe end-stage cardiovascular disease. Lonafarnib resulted in 100% survival of the treated progeria mice to the study end-point (time of 50% survival of untreated mice), with associated improvements in arterial structure and function working together to significantly reduce pulse wave velocity and improve left ventricular diastolic function. By contrast, dual treatment with lonafarnib and rapamycin did not improve outcomes over that achieved with lonafarnib monotherapy.
Efficient Design of Peptide-Binding Polymers Using Active Learning Approaches
Authors: Rakhimbekova A. , Lopukov A. , Klyachko N. , Kabanov A. , Madzhidov T.I. , Tropsha A.
Published: December 2021

Active learning (AL) has become a subject of active recent research both in industry and academia as an efficient approach for rapid design and discovery of novel chemicals, materials, and polymers. The key advantages of this approach relate to its ability to (i) employ relatively small datasets for model development, (ii) iterate between model development and model assessment using small external datasets that can be either generated in focused experimental studies or formed from subsets of the initial training data, and (iii) progressively evolve models toward increasingly more reliable predictions and the identification of novel chemicals with the desired properties. Herein, we first compared various AL protocols for their effectiveness in finding biologically active molecules using synthetic datasets. We have investigated the dependency of AL performance on the size of the initial training set, the relative complexity of the task, and the choice of the initial training dataset. We found that AL techniques as applied to regression modeling offer no benefits over random search, while AL used for classification tasks performs better than models built for randomly selected training sets but still quite far from perfect. Using the best performing AL protocol, we have assessed the applicability of AL for the discovery of polymeric micelle formulations for poorly soluble drugs. Finally, the best performing AL approach was employed to discover and experimentally validate novel binding polymers for a case study of asialoglycoprotein receptor (ASGPR).
Structure of Vibrio phage XM1, a simple contractile DNA injection machine
Authors: Wang Zhiqing , Fokine Andrei , Guo Xinwu , Jiang Wen , Rossmann Michael G. , Kuhn Richard J. , Luo Zhu-Hua , Klose Thomas
Published: December 2021

Antibiotic resistance poses a growing risk to public health requiring new tools to combat pathogenic bacteria. Contractile injection systems, including bacteriophage tails, pyocins, and bacterial type VI secretion systems, can efficiently penetrate cell envelopes and become potential antibacterial agents. Bacteriophage XM1 is a dsDNA virus belonging to the Myoviridae family and infecting Vibrio bacteria. The XM1 virion, made of 18 different proteins, consists of an icosahedral head and a contractile tail, terminated with a baseplate. Here we report cryo-EM reconstructions of all components of the XM1 virion and describe atomic structures of 14 XM1 proteins. The XM1 baseplate is composed of a central hub surrounded by six wedge modules to which twelve spikes are attached. The XM1 tail contains a fewer number of smaller proteins compared with other reported phage baseplates, depicting the minimum requirements for building an effective cell-envelope-penetrating machine. We describe the tail sheath structure in the pre-infection post-infection states and its conformational changes during infection. In addition, we report, for the first time, the in situ structure of the phage neck region to near-atomic resolution. Based on these structures, we propose mechanisms of virus assembly and infection.
Metabolic Processing of Selenium-based Bioisostere of meso-diaminopimelic Acid in Live Bacteria
Authors: Apostolos Alexis J. , Koyasseril-Yehiya Thameez M. , Santamaria Carolina , Silva José Rogério A. , Lameira Jerônimo , Alves M. Cláudio N. , Siegrist M. Sloan , Pires Marcos M.
Published: December 2021

The bacterial cell wall supports cell shape and prevents lysis due to internal turgor pressure. A primary component of all known bacterial cell walls is the peptidoglycan (PG) layer, which is comprised of repeating units of sugars connected to short and unusual peptides. The various steps within PG biosynthesis are often the target of antibiotics as they are essential for cellular growth and survival. Synthetic mimics of PG have proven to be indispensable tools to study bacterial cell growth and remodeling. Yet, a common component of PG, meso-diaminopimelic acid (m-DAP) at the third position of the stem peptide, remains challenging to build synthetically and is not commercially available. Here, we describe the synthesis and metabolic processing of a selenium-based bioisostere of a m-DAP analogue, selenolanthionine. We show that selenolanthionine is installed within the PG of live bacteria by the native cell wall crosslinking machinery in several mycobacteria species. We envision that this probe will supplement the current methods available for investigating PG crosslinking in m-DAP containing organisms.
Global cerebrospinal fluid circulation mapping using gold nanoparticle enhanced X-ray microtomography reveals region-specific brain and spinal cord CSF pathways
Authors: Pan Shelei , DeFreitas Dakota , Ramagiri Sruthi , Bayguinov Peter , Hacker Carl D. , Snyder Abraham Z. , Wilborn Jackson , Huang Hengbo , Yang Peter H. , Raval Dhvanii K. , Svben Sanja , Achilefu Samuel , Tang Rui , Haller Gabriel , Quirk James D. , Fitzpatrick James A. , Esakky Prabagaran , Strahle Jennifer M.
Published: December 2021

Cerebrospinal fluid (CSF) movement within the brain interstitium is essential for the development and functioning of the brain. However, the interstitium has largely been thought of as a single entity through which CSF circulates, and it is not known whether specific cell populations within the CNS preferentially interact with CSF. Here, we developed a novel technique for CSF tracking, gold nanoparticle enhanced X-ray microtomography, to achieve micrometer-scale resolution visualization of CSF pathways during development. Using this method and subsequent histological analysis, we map global CSF pathways and present novel particle size-dependent circulation patterns through the CNS. We identify an intraparenchymal CSF circulation that targets stem cell-rich and cholinergic neuronal populations. CSF solute distribution to these areas is mediated by CSF flow along projections from the basal cisterns which is altered in posthemorrhagic hydrocephalus. Our study uncovers region-specific patterns in a biologically driven CSF circulation that has implications for normal brain development and the pathophysiology of hydrocephalus and neurodegenerative disorders.
The Interferon Resistance of Transmitted HIV-1 is a Consequence of Enhanced Replicative Fitness
Authors: Sugrue Elena , Wickenhagen Arthur , Mollentze Nardus , Aziz Muhamad Afiq , Sreenu Vattipally B , Truxa Sven , Tong Lily , Silva Filipe Ana da , Robertson David L , Hughes Joseph , Rihn Suzannah J , Wilson Sam J
Published: December 2021

HIV-1 transmission via sexual exposure is a relatively inefficient process. When successful transmission does occur, newly infected individuals are colonized by either a single or a very small number of establishing virion(s). These transmitted founder (TF) viruses are more interferon (IFN) resistant than chronic control (CC) viruses present 6 months after transmission. To identify the specific molecular defences that make CC viruses more susceptible to the IFN-induced ‘antiviral state’ than TF viruses, we established a pair of fluorescent GFP-IRES-Nef TF and CC viruses and used arrayed interferon-stimulated gene (ISG) expression screening. The relatively uniform ISG resistance of transmitted HIV-1 directed us to investigate the underlying mechanism. Our subsequent in silico simulations, modelling, and in vitro characterisation of a model TF/CC pair (closely matched in replicative fitness), revealed that small differences in replicative growth rates can explain the broad IFN resistance displayed by transmitted HIV-1. We propose that the apparent IFN resistance of transmitted HIV-1 is a consequence of enhanced replicative fitness, as opposed to specific resistance to individual IFN-induced defences.
Multiparameters dependance of tissue shape maintenance in myoblasts multicellular aggregates: the role of intermediate filaments
Authors: Nagle Irène , Delort Florence , Hénon Sylvie , Wilhelm Claire , Batonnet-Pichon Sabrina , Reffay Myriam
Published: December 2021

Liquid and elastic behavior of tissues drives their morphology and their response to the environment. They appear as the first insight on tissue mechanics. We explore the role of individual cell properties on spheroids of mouse muscle precursor cells by developing a fully automated surface tension and Young’s modulus measurement system. Flattening multicellular aggregates under magnetic constraint, we show that rigidity and surface tension act as highly sensitive macroscopic reporters closely related to microscopic local tension and effective adhesion. Shedding light on the major contributions of acto-myosin contractility, actin organization and intercellular adhesions, we reveal the role of desmin organization on the macroscopic mechanics of this tissue model.
Predicting Nicotine Metabolism Across Ancestries Using Genotypes
Authors: Baurley James W , Bergen Andrew W , Ervin Carolyn M , Park Sung-shim Lani , Murphy Sharon E , McMahan Christopher S
Published: December 2021

Background

There is a need to match characteristics of tobacco users with cessation treatments and risks of tobacco attributable diseases such as lung cancer. The rate in which the body metabolizes nicotine has proven an important predictor of these outcomes. Nicotine metabolism is primarily catalyzed by the enzyme cytochrone P450 (CYP2A6) and CYP2A6 activity can be measured as the ratio of two nicotine metabolites:trans-3’-hydroxycotinine to cotinine (NMR). Measurements of these metabolites are only possible in current tobacco users and vary by biofluid source, timing of collection, and protocols; unfortunately, this has limited their use in clinical practice. The NMR depends highly on genetic variation nearCYP2A6on chromosome 19 as well as ancestry, environmental, and other genetic factors. Thus, we aimed to develop prediction models of nicotine metabolism using easy to obtain genotypes and individual characteristics.

Results

We identified four multiethnic studies with nicotine metabolites and DNA samples. We constructed a 263 marker panel from filtering genome-wide association scans of the NMR in each study. We then applied seven machine learning techniques to train models of nicotine metabolism on the largest and most ancestrally diverse dataset (N=2239). The models were then validated out-of-sample in the other three studies (total N=1415). Using cross-validation, we found the correlations between the observed and predicted NMR ranged from 0.69 to 0.97 depending on the model. When predictions were averaged in an ensemble model, the correlation was 0.81. The ensemble model generalizes well out-of-sample across ancestries, despite differences in the measurements of NMR between studies, with correlations of: 0.52 for African ancestry, 0.61 for Asian ancestry, and 0.46 for European ancestry. The most influential predictors of NMR identified in more than two models were rs56113850, rs11878604, and 21 other genetic variants nearCYP2A6as well as age and ancestry.

Conclusions

We have developed an ensemble of seven models for predicting the NMR across ancestries from genotypes and age, gender and BMI. Predictions from these models validate out-of-sample in three datasets and associate with nicotine dosages. The knowledge of how an individual metabolizes nicotine could be used to help select the optimal path to reducing or quitting tobacco use, as well as, evaluating risks of tobacco use.
Mapping pediatric brain tumors to their origins in the developing cerebellum
Authors: Okonechnikov Konstantin , Joshi Piyush , Sepp Mari , Leiss Kevin , Sarropoulos Ioannis , Murat Florent , Sill Martin , Beck Pengbo , Chan Kenneth Chun-Ho , Korshunov Andrey , Sahm Felix , Deng Maximilian Y. , Sturm Dominik , DeSisto John , Donson Andrew M. , Foreman Nicholas K. , Green Adam L. , Robinson Giles , Orr Brent A. , Gao Qingsong , Darrow Emily , Hadley Jennifer L. , Northcott Paul A. , Gojo Johannes , Ryzhova Marina , Kawauchi Daisuke , Hovestadt Volker , Filbin Mariella G. , Deimling Andreas von , Zuckermann Marc , Pajtler Kristian W. , Kool Marcel , Jones David T.W. , Jäger Natalie , Kutscher Lena M. , Kaessmann Henrik , Pfister Stefan M.
Published: December 2021

Understanding the cellular origins of childhood brain tumors is key for discovering novel tumor-specific therapeutic targets. Previous strategies mapping cellular origins typically involved comparing human tumors to murine embryonal tissues1,2, a potentially imperfect approach due to spatio-temporal gene expression differences between species3. Here we use an unprecedented single-nucleus atlas of the developing human cerebellum (Sepp, Leiss, et al) and extensive bulk and single-cell transcriptome tumor data to map their cellular origins with focus on three most common pediatric brain tumors – pilocytic astrocytoma, ependymoma, and medulloblastoma. Using custom bioinformatics approaches, we postulate the astroglial and glial lineages as the origins for posterior fossa ependymomas and radiation-induced gliomas (secondary tumors after medulloblastoma treatment), respectively. Moreover, we confirm that SHH, Group3 and Group4 medulloblastomas stem from granule cell/unipolar brush cell lineages, whereas we propose pilocytic astrocytoma to originate from the oligodendrocyte lineage. We also identify genes shared between the cerebellar lineage of origin and corresponding tumors, and genes that are tumor specific; both gene sets represent promising therapeutic targets. As a common feature among most cerebellar tumors, we observed compositional heterogeneity in terms of similarity to normal cells, suggesting that tumors arise from or differentiate into multiple points along the cerebellar “lineage of origin”.
Phosphorylation of interfacial phosphosite leads to increased binding of Rap-Raf complex
Authors: Devanand T , Ghosh Susmita , Venkatraman Prasanna , Vemparala Satyavani
Published: December 2021

The effect of phosphorylation of a serine residue in the Rap protein, residing at the complex interface of Rap-Raf complex is studied using atomistic molecular dynamics simulations. As the phosphosite of interest (SER39) is buried at the interface of the Rap-Raf complex, phosphorylation of only Rap protein was simulated and then complexed with the RBD of Raf for further analysis of complex stability. Our simulations reveal that the phosophorylation increases the binding of complex through strong electrostatic interactions and changes the charge distribution of the interface significantly. This is manifested as an increase in stable salt-bridge interactions between the Rap and Raf of the complex. Network analysis clearly shows that the phosphorylation of SER39 reorganizes the community network to include the entire region of Raf chain, including, Raf L4 loop potentially affecting downstream signalling.
Gene expression is a poor predictor of the metabolite abundance in cancer cells
Authors: Li Huaping , Barbour Jayne A. , Zhu Xiaoqiang , Wong Jason W. H.
Published: December 2021

Metabolic reprogramming is a hallmark of cancer characterized by global changes in metabolite levels. However, compared with the study of gene expression, profiling of metabolites in cancer samples remains relatively understudied. We obtained metabolomic profiling and gene expression data from 454 human solid cancer cell lines across 24 cancer types from the Cancer Cell Line Encyclopedia (CCLE) database, to evaluate the feasibility of inferring metabolite levels from gene expression data. For each metabolite, we trained multivariable LASSO regression models to identify gene sets that are most predictive of the level of each metabolite profiled. Even when accounting for cell culture conditions or cell lineage in the model, few metabolites could be accurately predicted. In some cases, the inclusion of the upstream and downstream metabolites improved prediction accuracy, suggesting that gene expression is a poor predictor of steady-state metabolite levels. Our analysis uncovered a single robust relationship between the expression of nicotinamide N-methyltransferase (NNMT) and 1-methylnicotinamide (MNA), however, this relationship could only be validated in cancer samples with high purity, as NNMT is not expressed in immune cells. Together, our findings reveal the challenge of inferring metabolite levels from metabolic enzyme levels and suggest that direct metabolomic profiling is necessary to study metabolism in cancer.
Molecular identification of bats from Wavulgalge cave, Wellawaya, Sri Lanka
Authors: Perera Thejanee , Schwarz Franziska , Muzeniek Therese , Siriwardana Sahan , Becker-Ziaja Beate , Perera Inoka C. , Handunnetti Shiroma , Weerasena Jagathpriya , Premawansa Gayani , Premawansa Sunil , Nitsche Andreas , Yapa Wipula , Kohl Claudia
Published: December 2021

This is the first report on the molecular identification and phylogeny of Rousettus leschenaultii, Rhinolophus rouxii, Hipposideros speoris, Hipposideros lankadiva, Miniopterus fuliginosus bat species in Sri Lanka, inferred from mitochondrially encoded cytochrome b gene sequences. Wellawaya Wavulgalge cave in Sri Lanka is one of the largest sympatric colonies found on the island, occupied by five species of bats. Recent research has indicated that bats show enormous cryptic genetic diversity. Moreover, even in the same species, acoustic properties of echolocation calls and morphological features such as fur colour could vary in different populations. Therefore, we have used molecular techniques for the accurate identification of five bat species recorded in one of the largest cave populations in Sri Lanka. Bats were caught using a hand net and saliva samples were collected non-invasively from each bat using a sterile oral swab. Nucleic acids were extracted from oral swab samples and mitochondrial DNA was amplified using primers targeting the mitochondrially encoded cytochrome b gene. This study identified the bat species recorded in the Wellawaya cave as Rousettus leschenaultii, Rhinolophus rouxii, Hipposideros speoris, Hipposideros lankadiva and Miniopterus fuliginosus. Our findings will contribute to future conservation and systematic studies of bats in Sri Lanka. This study will also provide the basis for a genetic database of Sri Lankan bats.
The transcriptional hallmarks of intra-tumor heterogeneity across a thousand tumors
Authors: Gavish Avishai , Tyler Michael , Simkin Dor , Kovarsky Daniel , Gonzalez Castro L. Nicolas , Halder Debdatta , Chanoch-Myers Rony , Laffy Julie , Mints Michael , Greenwald Alissa R. , Wider Adi , Tal Rotem , Spitzer Avishay , Hara Toshiro , Tirosh Amit , Puram Sidharth V. , Suva Mario L. , Tirosh Itay
Published: December 2021

Each tumor contains malignant cells that differ in genotype, phenotype, and in their interactions with the tumor micro-environment (TME). This results in distinct integrated cellular states that govern intra-tumor heterogeneity (ITH), a central challenge of cancer therapeutics. Dozens of recent studies have begun to describe ITH by single cell RNA-seq, but each study typically profiledonly a small number of tumors and provided a narrow view of transcriptional ITH. Here, we curate, annotate and integrate the data from 77 different studies to reveal the patterns of ITH across 1,163 tumor samples covering 24 tumor types. Focusing on the malignant cells, we find thousands of transcriptional ITH programs that can be described by 41 consensus meta-programs (MPs), each consisting of dozens of genes that are coordinately upregulated in subpopulations of cells within many different tumors. The MPs cover diverse cellular processes and differ in their cancer-type distribution. General MPs associated with processes such as cell cycle and stress vary within most tumors, while context-specific MPs reflect the unique biology of particular cancer types, often resembling developmental cell types and suggesting the co-existence of variable differentiation states within tumors. Some of the MPs are further associated with overall tumor proliferation or immune state, highlighting their potential clinical significance. Based on functional similarities among MPs, we propose a set of 11 hallmarks that together account for the majority of observed ITH programs. Given the breadth and scope of the investigated cohort, the MPs and hallmarks described here reflect the first comprehensive pan-cancer description of transcriptional ITH.
Haplotype-resolved inversion landscape reveals hotspots of mutational recurrence associated with genomic disorders
Authors: Porubsky David , Höps Wolfram , Ashraf Hufsah , Hsieh PingHsun , Rodriguez-Martin Bernardo , Yilmaz Feyza , Ebler Jana , Hallast Pille , Maria Maggiolini Flavia Angela , Harvey William T. , Henning Barbara , Audano Peter A. , Gordon David S. , Ebert Peter , Hasenfeld Patrick , Benito Eva , Zhu Qihui ,   Human Genome Structural Variation Consortium (HGSVC), Lee Charles , Antonacci Francesca , Steinrücken Matthias , Beck Christine R. , Sanders Ashley D. , Marschall Tobias , Eichler Evan E. , Korbel Jan O.
Published: December 2021

Unlike copy number variants (CNVs), inversions remain an underexplored genetic variation class. By integrating multiple genomic technologies, we discover 729 inversions in 41 human genomes. Approximately 85% of inversions <2 kbp form by twin-priming during L1-retrotransposition; 80% of the larger inversions are balanced and affect twice as many base pairs as CNVs. Balanced inversions show an excess of common variants, and 72% are flanked by segmental duplications (SDs) or mobile elements. Since this suggests recurrence due to non-allelic homologous recombination, we developed complementary approaches to identify recurrent inversion formation. We describe 40 recurrent inversions encompassing 0.6% of the genome, showing inversion rates up to 2.7×10-4per locus and generation. Recurrent inversions exhibit a sex- chromosomal bias, and significantly co-localize to the critical regions of genomic disorders. We propose that inversion recurrence results in an elevated number of heterozygous carriers and structural SD diversity, which increases mutability in the population and predisposes to disease- causing CNVs.
The intrinsic group–subgroup structures of the Diamond and Gyroid minimal surfaces in their conventional unit cells
Authors: Pedersen Martin Cramer , Robins Vanessa , Hyde Stephen T.
Published: December 2021

The intrinsic, hyperbolic crystallography of the Diamond and Gyroid minimal surfaces in their conventional unit cells is introduced and analysed. Tables are constructed of symmetry subgroups commensurate with the translational symmetries of the surfaces as well as group–subgroup lattice graphs.
A peg-in-hole controller for cable-driven serial robots with compliant wrist based on cable tensions and joint positions
Authors: Lou Ya'nan , Quan Pengkun , Lin Haoyu , Liang Zhuo , Wei Dongbo , Di Shichun
Published: December 2021

Purpose

This purpose of this paper is to design a peg-in-hole controller for a cable-driven serial robot with compliant wrist (CDSR-CW) using cable tensions and joint positions. The peg is connected to the robot link through a CW. It is required that the controller does not rely on any external sensors such as 6-axis wrist force/torque (F/T) sensor, and only the compliance matrix’s estimated value of the CW is known.

Design/methodology/approach

First, the peg-in-hole assembly system based on a CDSR-CW is analyzed. Second, a characterization algorithm using micro cable tensions and joint positions to express the elastic F/T at the CW is established. Next, under the premise of only knowing the compliance matrix’s estimate, a peg-in-hole controller based on force/position hybrid control is proposed.

Findings

The experiment results show that the plug contact F/T can be tracked well. This verifies the validity and correctness of the characterization algorithm and peg-in-hole controller for CDSR-CWs in this paper.

Originality/value

First, to the authors’ knowledge, there is no relevant work about the peg-in-hole assembly task using a CDSR-CW. Besides, the proposed characterization algorithm for the elastic F/T makes the peg-in-hole controller get rid of the dependence on the F/T sensor, which expands the application scenarios of the peg-in-hole controller. Finally, the controller does not require an accurate compliance matrix, which also increases its applicability.
Inspiring workplace happiness: religiosity and organizational trust in the academic context
Authors: Mousa Mohamed , Chaouali Walid
Published: December 2021

Purpose

This paper focuses on academics in public universities in Egypt. It explores the effect of perceptions of the rector's religiosity and trust on workplace happiness among academics.

Design/methodology/approach

A total of 600 academics are contacted. After two follow-ups, a total of 540 responses are collected, of which 525 are valid. This study uses SmartPLS 3 to test the hypotheses.

Findings

This paper finds that academics' perceptions of their rector's religiosity have a positive effect on engagement, job satisfaction and affective organizational commitment. Moreover, academics' perceptions of their rector's religiosity positively affect their perceptions of their rector's ability, benevolence and honesty. Furthermore, academics' trust in their rector has a positive effect on their engagement, job satisfaction and affective organizational commitment.

Originality/value

This paper contributes by filling a gap in management and organization literature, in which empirical studies of the relationship between religiosity, organizational trust and workplace happiness are limited or scarce.
Environmental regulation and location dynamics of the livestock industry: evidence from 279 Chinese prefecture-level cities
Authors: Pan Dan , Zhou Yingheng , Zhang Liguo
Published: December 2021

Purpose

This paper examines the impact of livestock environment regulations (LERs) on the location dynamics of the livestock farming industry. Specifically, it tests whether a “pollution haven effect” (PHE) exists in the Chinese livestock industry.

Design/methodology/approach

The authors manually collected LERs data based on the frequency of livestock-related vocabulary in government work reports from 279 prefecture-level cities from 2010 to 2017. Using China's implementation of LERs since 2014 as a natural experiment, the authors employed difference-in-difference (DID) to avoid the endogeneity problem.

Findings

LERs have led to a decline in livestock production in regulated areas. Moreover, compared with areas with more stringent LERs – southern China and developed areas, areas where LERs are less stringent – northern China and undeveloped areas, attract more livestock industry. As a result, people in northern China and undeveloped areas are exposed to higher livestock pollution.

Originality/value

First, most empirical studies on PHE focus on industrial firms. PHE in the livestock industry has received limited attention. This paper aims to fill this gap. Second, this paper regards LERs as an endogenous process and uses the DID method to generate unbiased results. Third, this paper introduces a novel measurement of LERs based on the frequency of livestock-related vocabulary in government work reports from each prefecture city. Fourth, this paper uses prefecture-level data to analyze the PHE of LERs, and thus obtains more reliable results.
Households' intentions under financial vulnerability conditions: is it likely for the COVID-19 pandemic to leave a permanent scar?
Authors: Alhenawi Yasser , Yazdanparast Atefeh
Published: December 2021

Purpose

The authors draw on psychological reactance theory, collective mental programming, psychological profiles and financial vulnerability experiences to assess the possibility that the pandemic may induce transformative changes in households' behavioral intentions related to financial decisions after the pandemic is over.

Design/methodology/approach

Using a unique survey data drawn from four different countries located in North America, Europe, Africa and Latin America, the authors show that the stressful conditions that accompanied the pandemic have instigated a state of financial vulnerability and stimulated instinctual defensive mechanisms among consumers.

Findings

The study results indicate that households have intentions to make defensive decisions in spending, consumption, planning and investment. Furthermore, the authors report evidence that personal psychological heterogeneity (as an individual factor) and collective mental programming (as a cultural factor) play a significant role in shaping households' postpandemic financial intentions.

Research limitations/implications

The study findings carry important practical implications. For financial institutions, marketers and financial advisors, the authors’ work implies that individual and collective factors affect people's perception and behavioral intentions in response to financial adversities. For social planners and legislators, the authors’ work shows that they should expect not only short-term but also long-term reactions to the COVID-19 pandemic.

Originality/value

Most research on the impact of COVID-19 pandemic on households' financial behavior focuses on transitional adjustments made during the pandemic, and little emphasis has been placed on potential postpandemic adjustments. The authors contend that it would be a mistake to analyze the pandemic-induced crisis as a temporary financial hardship.
The multilabel fault diagnosis model of bearing based on integrated convolutional neural network and gated recurrent unit
Authors: Han Shanling , Zhang Shoudong , Li Yong , Chen Long
Published: December 2021

Purpose

Intelligent diagnosis of equipment faults can effectively avoid the shutdown caused by equipment faults and improve the safety of the equipment. At present, the diagnosis of various kinds of bearing fault information, such as the occurrence, location and degree of fault, can be carried out by machine learning and deep learning and realized through the multiclassification method. However, the multiclassification method is not perfect in distinguishing similar fault categories and visual representation of fault information. To improve the above shortcomings, an end-to-end fault multilabel classification model is proposed for bearing fault diagnosis.

Design/methodology/approach

In this model, the labels of each bearing are binarized by using the binary relevance method. Then, the integrated convolutional neural network and gated recurrent unit (CNN-GRU) is employed to classify faults. Different from the general CNN networks, the CNN-GRU network adds multiple GRU layers after the convolutional layers and the pool layers.

Findings

The Paderborn University bearing dataset is utilized to demonstrate the practicability of the model. The experimental results show that the average accuracy in test set is 99.7%, and the proposed network is better than multilayer perceptron and CNN in fault diagnosis of bearing, and the multilabel classification method is superior to the multiclassification method. Consequently, the model can intuitively classify faults with higher accuracy.

Originality/value

The fault labels of each bearing are labeled according to the failure or not, the fault location, the damage mode and the damage degree, and then the binary value is obtained. The multilabel problem is transformed into a binary classification problem of each fault label by the binary relevance method, and the predicted probability value of each fault label is directly output in the output layer, which visually distinguishes different fault conditions.
An optimized complex motion prediction approach based on a video synopsis
Authors: Thirumalaiah G. , Immanuel Alex Pandian S.
Published: December 2021

Purpose

The space-time variants algorithm will not give good results in practical scenarios; when no tubes increase, these techniques will not give the results. It is challenging to reduce the energy of the output synopsis videos. In this paper, a new optimized technique has been implemented that models and covers every frame in the output video.

Design/methodology/approach

In the video synopsis, condensing a video to produce a low frame rate (FR) video using their spatial and temporal coefficients is vital in complex environments. Maintaining a database is also feasible and consumes space. In recent years, many algorithms were proposed.

Findings

The main advantage of this proposed technique is that the output frames are selected by the user definitions and stored in low-intensity communication systems and also it gives tremendous support to the user to select desired tubes and thereby stops the criterion in the output video, which can be further suitable for the user's knowledge and creates nonoverlapping tube-oriented synopsis that can provide excellent visual experience.

Research limitations/implications

In this research paper, four test videos are utilized with complex environments (high-density objects) and show that the proposed technique gives better results when compared to other existing techniques.

Originality/value

The proposed method provides a unique technique in video synopsis for compressing the data without loss.
A syndemic examination of injecting drug use, incarceration and multiple drug-related harms in French opioid users
Authors: Mezaache Salim , Briand-Madrid Laélia , Laporte Virginie , Rojas Castro Daniela , Carrieri Patrizia , Roux Perrine
Published: December 2021

Purpose

People who inject drugs (PWID) face multiple health problems, including infectious diseases and drug overdoses. Applying syndemic and risk environment frameworks, this paper aims to examine the co-occurrence and clustering of drug-related harms and their association with incarceration experience with or without in-prison drug injection.

Design/methodology/approach

The authors used data from a cross-sectional survey conducted in 2015 among 557 active opioid injectors. Self-reported data were collected through face-to-face or online questionnaires. They distinguished three harm categories, namely, viral infections, bacterial infections and overdoses, and built an index variable by summing the number of harm categories experienced, yielding a score from 0 to 3. Association between incarceration experience and co-occurrence of harms was modelled using a multinomial logistic regression.

Findings

Of the 557 participants, 30% reported lifetime experience of drug-related viral infection, 46% bacterial infection and 22% drug overdose. Multinomial logistic models showed that those who injected drugs during incarceration were more likely to report two (aOR = 2.35, 95% CI: 1.03–5.36) and three (aOR = 9.72, 95% CI: 3.23–29.22) harm categories than those who had never been incarcerated. They were also more likely to report three harm categories than formerly incarcerated respondents who did not inject drugs in prison (aOR = 5.14, 95% CI: 1.71–15.48).

Originality/value

This study provides insights of the syndemic nature of drug-related harms and highlights that drug injection during incarceration is associated with co-occurring harms. Public health interventions and policy changes are needed to limit the deleterious impact of prison on PWID.