bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting ewe body condition score using adjusted liveweight for conceptus and fleece weight, height at withers, and previous body condition score record
Authors: Semakula Jimmy , Corner-Thomas Rene A , Morris Steve T , Blair Hugh T , Kenyon Paul R 
Published: August 2021

Abstract
The relationship between ewe body condition score (BCS) and liveweight (LW) has been exploited previously to predict the former from LW, LW-change, and previous BCS records. It was hypothesized that if fleece weight and conceptus-free liveweight and LW-change, and in addition, height at withers were used, the accuracy of current approaches to predicting BCS would be enhanced. Ewes born in 2017 (n = 429) were followed from 8 mo to approximately 42 mo of age in New Zealand. Individual ewe data were collected on LW and BCS at different stages of the annual production cycle (i.e., prebreeding, at pregnancy diagnosis, prelambing, and weaning). Additionally, individual lambing dates, ewe fleece weight, and height at withers data were collected. Linear regression models were fitted to predict current BCS at each ewe age and stage of the annual production cycle using two LW-based models, namely, unadjusted for conceptus weight and fleece weight (LW alone1) and adjusted (LW alone2) models. Furthermore, another two models based on a combination of LW, LW-change, previous BCS, and height at withers (combined models), namely, unadjusted (combined1) and adjusted for conceptus and fleece weight (combined2), were fitted. Combined models gave more accurate (with lower root mean square error: RMSE) BCS predictions than models based on LW records alone. However, applying adjusted models did not improve BCS prediction accuracy (or reduce RMSE) or improve model goodness of fit (R2) (P &gt; 0.05). Furthermore, in all models, both LW-alone and combined models, a great proportion of variability in BCS, could not be accounted for (0.25 ≥ R2 ≥ 0.83) and there was substantial prediction error (0.33 BCS ≥ RMSE ≥ 0.49 BCS) across age groups and stages of the annual production cycle and over time (years). Therefore, using additional ewe data which allowed for the correction of LW for fleece and conceptus weight and using height at withers as an additional predictor did not improve model accuracy. In fact, the findings suggest that adjusting LW data for conceptus and fleece weight offer no additional value to the BCS prediction models based on LW. Therefore, additional research to identify alternative methodologies to account for individual animal variability is still needed.
Overexpression of geranyl diphosphate synthase (PmGPPS1) boosts monoterpene and diterpene production involved in the response to pine wood nematode invasion
Authors: Liu Bin , Liu Qinghua , Zhou Zhichun , Yin Hengfu , Xie Yini 
Published: August 2021

Abstract
Outbreaks of pine wood nematode (PWN; Bursaphelenchus xylophilus) represent a severe biotic epidemic for the Pinus massoniana in China. When invaded by the PWN, the resistant P. massoniana might secret abundant oleoresin terpenoid to form certain defensive fronts for survival. However, the regulatory mechanisms of this process remain unclear.
Here, the geranyl diphosphate synthase (PmGPPS1) gene was identified from resistant P. massoniana. Tissue-specific expression patterns of PmGPPS1 at transcript and protein level in resistant P. massoniana were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. Functional characteristics analysis of PmGPPS1 was performed on transgenic Nicotiana benthamiana by overexpression, as genetic transformation of P. massoniana is, so far, not possible.
In summary, we identified and functionally characterized PmGPPS1 from the resistant P. massoniana following PWN inoculation. Tissue-specific expression patterns and localization of PmGPPS1 indicated that it may play a positive role involved in the metabolic and defensive processes of oleoresin terpenes production in response to PWN attack. Furthermore, overexpression of PmGPPS1 may enhance the production of monoterpene, among which limonene reduced the survival of PWN in vitro. In addition, PmGPPS1 upregulated the expression level of key genes involved in mevalonic acid (MVA) pathway, the methylerythritol phosphate (MEP) pathway and gibberellins (GAs) biosynthesis to boost the growth and development of tobacco through a feedback regulation mechanism.
Our results offered new insights into the pivotal role of the PmGPPS1 involved in terpene-based defense mechanisms responding to the PWN invasion in resistant P. massoniana and provided a new metabolic engineering scenario to improve monoterpene production in tobacco.
Agreed payment for non-performance under the Unidroit Principles and Arab region laws
Authors: Dawwas Amin 
Published: August 2021

Abstract
This article deals with parties’ pre-estimation of the amount of compensation for non-performance (liquidated damages, penalty clause). It discusses this agreed payment in terms of definition, validity, invocation, and possibility of adjustment upon the application of either party. The article presents the provisions of this legal institution in the Unidroit Principles, the Egyptian Civil Code, and the Jordanian Civil Code. It, first, draws a comparison between these laws in the Arab region and, second, considers them in relation to the Unidroit Principles to conclude with a solution that best serves the parties’ interests.
Trajectories of Worktime Control From Midlife to Retirement and Working Beyond Retirement Age
Authors: Virtanen Marianna , Myllyntausta Saana , Kauppi Maarit , Kivimäki Mika , Pentti Jaana , Ervasti Jenni , Prakash K C , Vahtera Jussi , Stenholm Sari 
Published: August 2021

Abstract
The extent to which long-term individual-oriented flexibility in working hours is associated with working beyond retirement age is not known. The aims of the present study were to identify trajectories of worktime control (WTC) and to examine whether the membership of WTC trajectories was associated with working beyond individual’s pensionable age. A total of 1,953 older employees participated in the study and had data up to 16 years before pensionable age. Group-based latent trajectory modeling was used to identify WTC trajectories and Cox proportional hazard regression models were used to examine the associations of WTC trajectories with duration of employment. Seven trajectories described WTC: “Stable very low” (7%), “Stable low” (21%), “Declined” (12%), “Stable mid-low” (28%), “Improved” (10%), “Stable high” (16%), and “Stable very high” (5%). When compared with the lowest WTC trajectory groups, trajectories of “Stable high/very high” (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.17–1.54) and “Improved” WTC (HR 1.49, 95% CI 1.25–1.78) were associated with longer duration of employment. Although the memberships of the “Stable high/very high” and “Improved” WTC trajectories correlated with gender, marital status, occupational position, and self-rated health, the association between WTC and duration of employment was not fully confounded or mediated by these factors. These findings support the hypothesis that having improved or constantly high control over working times from midlife to retirement age may prolong working lives at retirement age.
Phylogeny indicates polyphyly in Cnodocentron (Trichoptera: Xiphocentronidae): biogeography and revision of New World species (Caenocentron)
Authors: Vilarino Albane , Dias Everton Santos , Bispo Pitágoras Da Conceição 
Published: August 2021

Abstract
Cnodocentron has a disjunct Laurasian distribution, with species in South-East Asia and the New World. It is divided into two subgenera: Cnodocentron and Caenocentron. Here, we infer the evolutionary history of the genus through phylogenetic and biogeographic data combining COI and 46 morphological characters. Phylogenetic relationships and divergence-time estimation were simultaneously inferred through Bayesian inference. The dating analysis was performed through relaxed morphological and molecular clocks. The historical biogeography was investigated using the dispersal–extinction–cladogenesis model. Our results indicate the polyphyly of the genus Cnodocentron, with each subgenus being more related to other genera than to each other. Therefore, the subgenus Caenocentron is elevated to genus status here. The biogeographical analysis showed that the Oriental Cnodocentron diverged in the Indian subcontinent during the Middle Eocene, while the New World Caenocentron stat. nov. originated in the Chortis Block in the Late Eocene. The dispersal of Caenocentron to South America occurred only after the Late Miocene, around 10 Mya. Additionally, we provide a revision of Caenocentron, with an identification key and description of the male and female of two new species from Costa Rica: Caenocentron carlosdelarosai sp. nov. and Caenocentron rafamoralesi sp. nov..
Cancer-associated fibroblasts exert a pro-angiogenic activity in Merkel cell carcinoma
Authors: Albertini Silvia , Martuscelli Licia , Borgogna Cinzia , Virdi Sanamjeet , Indenbirken Daniela , Cigno Irene Lo , Griffante Gloria , Calati Federica , Boldorini Renzo , Fischer Nicole , Gariglio Marisa 
Published: August 2021

AbstractThe tumor microenvironment (TME) is a complex niche enveloping a tumor formed by extracellular matrix, blood vessels, immune cells, and fibroblasts constantly interacting with cancer cells. Although TME is increasingly recognized as a major player in cancer initiation and progression in many tumor types, its involvement in Merkel cell carcinoma (MCC) pathogenesis is currently unknown. Here, we provide the first molecular and functional characterization of cancer- associated fibroblasts (CAFs), the major TME component, in MCC patient-derived xenografts. We show that subcutaneous co-injection of patient-derived CAFs and human MCC MKL-1 cells into SCID mice significantly promotes tumor growth and metastasis. These fast-growing xenografts are characterized by areas densely populated with human CAFs, mainly localized around blood vessels. We also provide evidence that the growth-promoting activity of MCC-derived CAFs is mediated by the APA/Ang II-III/AT1R axis, with the expression of aminopeptidase A (APA) in CAFs being the upstream triggering event. Altogether, our findings point to APA as a potential marker for MCC prognostic stratification and a novel candidate therapeutic target.
Multi-Task Brain Network Reconfiguration is Inversely Associated with Human Intelligence
Authors: Thiele Jonas A. , Faskowitz Joshua , Sporns Olaf , Hilger Kirsten 
Published: August 2021

AbstractIntelligence describes the general cognitive ability level of a person. It is one of the most fundamental concepts in psychological science and is crucial for effective adaption of behavior to varying environmental demands. Changing external task demands have been shown to induce reconfiguration of functional brain networks. However, whether neural reconfiguration between different tasks is associated with intelligence has not yet been investigated. We used fMRI data from 812 subjects to show that higher scores of general intelligence are related to less brain network reconfiguration between resting state and seven different task states as well as to network reconfiguration between tasks. This association holds for all functional brain networks except the motor system, and replicates in two independent samples (N = 138, N = 184). Our findings suggest that the intrinsic network architecture of individuals with higher intelligence scores is closer to the network architecture as required by various cognitive demands. Multi-task brain network reconfiguration may, therefore, represent a neural reflection of the behavioral positive manifold – the essence of the concept of general intelligence. Finally, our results support neural efficiency theories of cognitive ability and reveal insights into human intelligence as an emergent property from a distributed multi-task brain network.
Membrane channel hypothesis of lysosomal permeabilization by beta-amyloid
Authors: Zaretsky Dmitry V. , Zaretskaia Maria V. , Molkov Yaroslav I. 
Published: August 2021

ABSTRACTAlzheimer’s disease (AD) is the most common cause of dementia affecting millions of people. Neuronal death in AD is initiated by oligomeric amyloid-β (Aβ) peptides. Recently, we proposed the amyloid degradation toxicity hypothesis, which explains multiple major observations associated with AD – such as autophagy failure and a decreased metabolism. According to the hypothesis, the key event in the cellular toxicity of amyloid is the formation of non-selective membrane channels in lysosomal membranes by amyloid fragments that are produced by the digestion of Aβ previously absorbed by endocytosis. Electrophysiological data suggest that amyloid-formed channels have different sizes, which can be explained by the fact that barrel-shaped amyloid aggregates which create channels can consist of different number of monomers.To estimate the ability of channels to leak molecules of various molecular weights, we modeled the channels as saline-filled cylinders in non-conductive membranes that pass spheres with a density of average globular proteins. As a basis, we used the conductance distribution taken from the previously published experimental dataset, in which single channels with a conductance reaching one nanosiemens were registered. Our calculations show that channels with a giant conductance can allow for passing macromolecules such as lysosomal cathepsins implicated in the activation of apoptosis. The formation of giant channels is disproportionally promoted in an acidic environment. Also, amyloid fragments leaking from permeabilized lysosomes can reach the internal leaflet of the plasma membrane and permeabilize it.We conclude that while dissipation of the proton gradient by any – even the smallest amyloid channel – readily explains lysosomal failure, the relatively rare events of lysosomal permeabilization to large macromolecules can be an alternative mechanism of cellular death induced by exposure to Aβ.
Activity Space Maps: a novel human mobility data set for quantifying time spent at risk
Authors: Citron Daniel T. , Iyer Shankar , Reiner Robert C. , Smith David L. 
Published: August 2021

ABSTRACTActivity Space Maps are a novel global-scale movement and mobility data set which describes how people distribute their time through geographic space. The maps are intended for use by researchers for the purposes of epidemiological modeling. Activity Space Maps are designed to complement existing digitally-collected mobility data sets by quantifying the amount of time that people spend in different locations. This information is important for estimating the duration of contact with the environment and the potential risk of exposure to disease. More concretely, the type of information contained in Activity Space Maps will make it easier to model the spatial transmission patterns of vector-borne diseases like malaria and Dengue fever. We will discuss the motivation for designing Activity Space Maps, how the maps are generated from mobile phone user app location history data, and discuss an example use case demonstrating how such data may be used together with spatial epidemiological data to advance our understanding of spatial disease patterns and the relationship between travel behaviors and infection risk.
The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin α5β1 and NF-κB
Authors: Robles Juan Pablo , Zamora Magdalena , de la Escalera Gonzalo Martinez , Clapp Carmen 
Published: August 2021

AbstractVascular endothelial cells (EC) form a critical interface between blood and tissues that maintains whole-body homeostasis. In COVID-19, disruption of the EC barrier results in edema, vascular inflammation, and coagulation, the hallmarks of the severe disease. However, the mechanisms by which EC are dysregulated in COVID-19 are unclear. Here, we show that the spike protein of SARS-CoV-2 alone activates the EC inflammatory phenotype in a manner dependent on integrin α5β1 signaling. Incubation of human umbilical vein EC with whole spike, its receptor-binding domain, or the integrin-binding tripeptide RGD induced the nuclear translocation of NF-κB and enhanced the expression of leukocyte adhesion molecules VCAM1 and ICAM1, the adhesion of peripheral blood leukocytes, and the permeability of the monolayer. Inhibitors of integrin α5β1 activation prevented these effects. We suggest that the spike protein, through its RGD motif in the receptor-binding domain, binds to integrin α5β1 in EC to activate Rho GTPases, eNOS pathways, and the NF-κB gene expression program responsible for vascular leakage and leukocyte infiltration, respectively. These findings uncover a new direct action of SARS-CoV-2 on EC dysfunction and introduce integrin α5β1 as a promising target for treating vascular inflammation in COVID-19.
Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 responses
Authors: Ndeupen Sonia , Bouteau Aurélie , Herbst Christopher , Qin Zhen , Hutchins Zachary , Kurup Drishya , Diba Leila Zabihi , Igyártó Botond Z. 
Published: August 2021

ABSTRACTNucleoside modified mRNA combined with Acuitas Therapeutics’ lipid nanoparticles (LNP) have been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs’ ionizable lipid component. The inflammatory property is key to support the development of potent humoral immune responses. However, the mechanism by which this platform drives T follicular helper cells (Tfh) and humoral immune responses remains unknown. Here we show that lack of Langerhans cells or cDC1s neither significantly affected the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cells and humoral immune responses, nor susceptibility towards the lethal challenge of influenza and SARS-CoV-2. However, the combined deletion of these two DC subsets led to a significant decrease in the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cell and humoral immune responses. Despite these observed defects, the still high antibody titers were sufficient to confer protection towards lethal viral challenges. We further found that IL-6, but not neutrophils, was required to generate Tfh cells and antibody responses.In summary, here we bring evidence that the mRNA-LNP platform can support protective adaptive immune responses in the absence of specific DC subsets through an IL-6 dependent and neutrophil independent mechanism.
A mechanosensing mechanism mediated by IRSp53 controls plasma membrane shape homeostasis at the nanoscale
Authors: Quiroga Xarxa , Walani Nikhil , Chavero Albert , Mittens Alexandra , Disanza Andrea , Tebar Francesc , Trepat Xavier , Parton Robert G. , Scita Giorgio , Geli Maria Isabel , Arroyo Marino , Le Roux Anabel-Lise , Roca-Cusachs Pere 
Published: August 2021

AbstractAs cells migrate and experience forces from their surroundings, they constantly undergo mechanical deformations which reshape their plasma membrane (PM). To maintain homeostasis, cells need to detect and restore such changes, not only in terms of overall PM area and tension as previously described, but also in terms of local, nano-scale topography. Here we describe a novel phenomenon, by which cells sense and restore mechanically induced PM nano-scale deformations. We show that cell stretch and subsequent compression reshape the PM in a way that generates local membrane evaginations in the 100 nm scale. These evaginations are recognized by the I-BAR protein IRSp53, which triggers a burst of actin polymerization mediated by Rac1 and Arp2/3. The actin polymerization burst subsequently re-flattens the evagination, completing the mechanochemical feedback loop. Our results demonstrate a new mechanosensing mechanism for PM shape homeostasis, with potential applicability in different physiological scenarios.TeaserCell stretch cycles generate PM evaginations of ≈100 nm which are sensed by IRSp53, triggering a local event of actin polymerization that flattens and recovers PM shape.
Dynamic inventory of moths of Savitribai Phule Pune University (Pune, India) through crowdsourcing via iNaturalist
Authors: Pujari Bhalchandra 
Published: August 2021

AbstractWe present here the checklist of moths (Lepidoptera: Heterocera) for the campus of Savitribai Phule Pune University, situated in the metropolis of Pune in the state Maharashra in India. We report identification of 189 unique genera along with 154 unique species. Despite the relative small size of the observation area and the location being at the heart of a busy metropolis, the moths were found to be of diverse variety, with 26 different families and 76 tribes.The identifications of the species was crowd-sourced via iNaturalist.org. An automated program was developed to fetch the identification and generate the list. The program is also being made available open source. As a result the checklist remains relevant all the time with newer identification, correcting existing identification (if required) and taxonomic updates of the future.
Allosteric perspective on the mutability and druggability of the SARS-CoV-2 Spike protein
Authors: Tan Zhen Wah , Tee Wei-Ven , Samsudin Firdaus , Guarnera Enrico , Bond Peter J. , Berezovsky Igor N. 
Published: August 2021

SummaryRecent developments in the SARS-CoV-2 pandemic point to its inevitable transformation into an endemic disease, urging both diagnostics of emerging variants of concern (VOCs) and design of the variant-specific drugs in addition to vaccine adjustments. Exploring the structure and dynamics of the SARS-CoV-2 Spike protein, we argue that the high mutability characteristic of RNA viruses coupled with the remarkable flexibility and dynamics of viral proteins result in a substantial involvement of allosteric mechanisms. While allosteric effects of mutations should be considered in predictions and diagnostics of new VOCs, allosteric drugs advantageously avoid escaping mutations via non-competitive inhibition originating from many alternative distal locations. The exhaustive allosteric signalling and probing maps provide a comprehensive picture of allostery in the Spike protein, making it possible to locate sites of potential mutations that could work as new VOCs “drivers”, and to determine binding patches that may be targeted by newly developed allosteric drugs.
Colon epithelial cell-specific Bmal1 deletion impairs bone formation in mice
Authors: Ko Frank C. , Jochum Sarah B. , Wilson Brittany M. , Adra Amal , Patel Nikhil , Wilber Sherry , Shaikh Maliha , Forsyth Christopher , Keshavarzian Ali , Swanson Garth R. , Rick Sumner D. 
Published: August 2021

AbstractThe circadian clock system regulates multiple metabolic processes, including bone metabolism. Previous studies have demonstrated that both central and peripheral circadian signaling regulate skeletal growth and homeostasis. Disruption in central circadian rhythms has been associated with a decline in bone mineral density and the global and osteoblast-specific disruption of clock genes in bone tissue leads to lower bone mass. Gut physiology is highly sensitive to circadian disruption. Since the gut is also known to affect bone remodeling, we sought to test the hypothesis that circadian signaling disruption in colon epithelial cells affects bone. We therefore assessed structural, functional, and cellular properties of bone in 8 week old Ts4-Cre and Ts4-Cre;Bmal1fl/fl (cBmalKO) mice, where the clock gene Bmal1 is deleted in colon epithelial cells. Axial and appendicular trabecular bone volume was significantly lower in cBmalKO compared to Ts4-Cre 8-week old mice in a sex-dependent fashion, with male but not female mice showing the phenotype. Similarly, the whole bone mechanical properties were deteriorated in cBmalKO male mice. The tissue level mechanisms involved suppressed bone formation with normal resorption, as evidenced by serum markers and dynamic histomorphometry. Our studies demonstrate that colon epithelial cell-specific deletion of Bmal1 leads to trabecular and cortical bone loss in male mice.