bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue-specific modifier alleles determineMertkloss-of-function traits
Authors: Akalu Yemsratch T. , Mercau Maria E. , Ansems Marleen , Wagage Sagie , Hughes Lindsey D. , Nevin James , Alberto Emily , Liu Xinran , He Li-Zhen , Alvarado Diego , Keler Tibor , Kong Yong , Philbrick William M. , Finnemann Silvia C. , Iavarone Antonio , Lasorella Anna , Rothlin Carla V. , Ghosh Sourav 
Published: May 2022

ABSTRACTKnockout (KO) mouse models play critical roles in elucidating biological processes behind disease-associated or disease-resistant traits. As a consequence of gene KO, mice display certain phenotypes. Based on insight into the molecular role of said gene in a biological process, it is inferred that the particular biological process causally underlies the trait. This approach has been crucial towards understanding the basis of pathological and/or advantageous traits associated withMertkKO. MERTK is a receptor tyrosine kinase with a critical role in phagocytosis of apoptotic cells or cellular debris. Therefore, early-onset, severe retinal degeneration was described to be a direct consequence of failed phagocytosis of photoreceptor outer segments by retinal pigment epithelia. Similarly, enhanced anti-tumor immunity was inferred to result from the failure of macrophages to dispose cancer cell corpses, resulting in a pro-inflammatory tumor microenvironment. Here we report that the loss ofMertkalone is not sufficient for retinal degeneration. This trait only manifests when the function of the paralogTyro3is concomitantly lost. Additionally, the dramatic resistance against two syngeneic mouse tumor models observed inMertkKO cannot, at least entirely, be ascribed to the loss ofMertk. The widely usedMertkKO carries multiple coincidental changes in its genome that affect the expression of a number of genes, includingTyro3. Nonetheless, neitherTyro3, nor macrophage phagocytosis by alternate genetic redundancy, accounts for the absence of anti-tumor immunity in two independentMertkKOs. Collectively, our results indicate that context-dependent epistasis of independent modifier alleles determineMertkKO traits.
Thirty years of deforestation within the entire ranges of nine endangered lemur species (3 CR, 4 EN, 2 VU) in northwestern Madagascar
Authors: Schüßler Dominik , Andriamalala Yves Rostant , van der Bach Robin , Katzur Cheyenne , Kolbe Christoph , Rabe Maheritafika Mamy Hasina , Rasolozaka Misa , Razafitsalama Mamy , Renz Marten , Steffens Travis S. , Radespiel Ute , Brenner Jana 
Published: May 2022

AbstractForest cover change is of particular concern in tropical regions. In this study, we investigate the degree of deforestation in the entire ranges of nine highly threatened lemur species in northwestern Madagascar. Landsat satellite images were acquired from four different time stages (1990, 2000, 2011, 2020), classified into forest/non-forest, and changes quantified. Forest cover declined from 17.5% to 9.3% within the last 30 years. This decline varied across four protected areas (PAs) investigated: the forest cover of Ankarafantsika National Park (ANP) declined only moderately over time (from 76.3% to 67.4%), while it declined drastically in other PAs (e.g., from 54.9% to 18.9%, Bongolava Forest Corridor). Two lemur taxa are most affected (Lepilemur otto, Microcebus bongolavensis) by having only very few isolated forest patches left within their ranges (approximately 542.7 km²). For two other species (L. ahmansoni, L. aeeclis), most of the remaining forest is concentrated in two coastal PAs (in total 627.2 and 477.9 km², respectively), while those species occurring inside ANP (5 taxa) experienced rather stable forest coverage until 2020. A reversal of these deforestation trends and active reforestation measures are desperately needed to reduce habitat loss for these nine lemur species. A practical experience-based guideline is therefore provided.
Derivation of the immortalized cell line-UM51-PrePodo-hTERT and its responsiveness to Angiotensin II and activation of RAAS
Authors: Erichsen Lars , Friedel Kloss Lea Doris , Thimm Chantelle , Bohndorf Martina , Schichel Kira , Wruck Wasco , Adjaye James 
Published: May 2022

AbstractRecent demographic studies predict there will be a considerable increase of elderly people within the next decades. Aging has been recognized as one of the main risk factors of the world’s most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease, and metabolic disease. During the process of aging a gradual loss of tissue volume and organ function is observed, which is partially caused by replicative senescence. The capacity of cellular proliferation and replicative senescence is tightly regulated by their telomere length. When the telomere length with progressive cell division is critically shortened, the cell becomes proliferative arrested and DNA damage response and cellular senescence are triggered. At this time point the so called “Hayflick limit” is attained.Podocytes are a cell type that is found in the kidney glomerulus where they have major implications in blood filtration. Mature podocytes are terminal differentiated cells that are unable to undergo cell division in vivo. For this reason, the establishment of podocyte cell cultures has been very challenging. In our present study, we present the successful immortalization of a human podocyte progenitor cell line, of which the primary cell cells were isolated directly from the urine of a 51-year-old male. The immortalized cell line has been cultured over the course of one year (∼100 passages) with high proliferation capacity, while still endowed with contact inhibition and P53 expression and activation. Furthermore, by immunofluorescent-based expression and quantitative Real-Time PCR for the podocyte markers NPHS1, SYNPO and WT1 we confirmed the differentiation capacity of the immortalized cells. Finally, we evaluated and confirmed the responsiveness of the immortalized cells on the main mediator Angiotensin II (ANGII) of the renin-angiotensin-system (RAS). Elevated levels of ANGII have been identified as a main risk factor for the initiation and progression of chronic kidney disease (CKD). CKD is characterized by an impairment of podocyte function and subsequently podocyte apoptosis. As a major risk factor for patients to develop CKD, diabetes, hypertension, heart disease and stroke have been recognized - all of which show increased incidence in elderly people. In conclusion, we have shown that it is possible to by-pass cellular replicative senescence (Hayflicks limit) by TERT-driven immortalization of human urine-derived pre-podocyte cells from a 51-year-old African male.
Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course
Authors: Muri Jonathan , Cecchinato Valentina , Cavalli Andrea , Shanbhag Akanksha A. , Matkovic Milos , Biggiogero Maira , Maida Pier Andrea , Moritz Jacques , Toscano Chiara , Ghovehoud Elaheh , Furlan Raffaello , Barbic Franca , Voza Antonio , Nadai Guendalina De , Cervia Carlo , Zurbuchen Yves , Taeschler Patrick , Murray Lilly A. , Danelon-Sargenti Gabriela , Moro Simone , Gong Tao , Piffaretti Pietro , Bianchini Filippo , Crivelli Virginia , Podešvová Lucie , Pedotti Mattia , Jarrossay David , Sgrignani Jacopo , Thelen Sylvia , Uhr Mario , Bernasconi Enos , Rauch Andri , Manzo Antonio , Ciurea Adrian , Rocchi Marco B.L. , Varani Luca , Moser Bernhard , Bottazzi Barbara , Thelen Marcus , Fallon Brian A. , Boyman Onur , Mantovani Alberto , Garzoni Christian , Franzetti-Pellanda Alessandra , Uguccioni Mariagrazia , Robbiani Davide F. 
Published: May 2022

AbstractInfection by SARS-CoV-2 leads to diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse COVID-19 outcomes. Instead, we discovered that antibodies against specific chemokines are omnipresent after COVID-19, associated with favorable disease, and predictive of lack of long COVID symptoms at one year post infection. Anti-chemokine antibodies are present also in HIV-1 infection and autoimmune disorders, but they target different chemokines than those in COVID-19. Monoclonal antibodies derived from COVID- 19 convalescents that bind to the chemokine N-loop impair cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising anti-chemokine antibodies associated with favorable COVID-19 may be beneficial by modulating the inflammatory response and thus bear therapeutic potential.One-Sentence Summary:Naturally arising anti-chemokine antibodies associate with favorable COVID-19 and predict lack of long COVID.
Secreted filarial nematode galectins modulate host immune cells
Authors: Loghry Hannah J. , Sondjaja Noelle A , Minkler Sarah J , Kimber Michael J 
Published: May 2022

AbstractLymphatic filariasis (LF) is a mosquito-borne disease caused by filarial nematodes includingBrugia malayi. Over 860 million people worldwide are infected or at risk of infection in 72 endemic countries. The absence of a protective vaccine means that current control strategies rely on mass drug administration programs that utilize inadequate drugs that cannot effectively kill adult parasites, thus established infections are incurable. Progress to address deficiencies in the approach to LF control is hindered by a poor mechanistic understanding of host-parasite interactions, including mechanisms of host immunomodulation by the parasite, a critical adaptation for establishing and maintaining infections. The canonical type 2 host response to helminth infection characterized by anti-inflammatory and regulatory immune phenotypes is modified by filarial nematodes during chronic LF. Current efforts at identifying parasite-derived factors driving this modification focus on parasite excretory-secretory products (ESP), including extracellular vesicles (EVs). We have previously profiled the cargo ofB. malayiEVs and identifiedB. malayigalectin-1 and galectin-2 as among the most abundant EV proteins. In this study we further investigated the function of these proteins. Sequence analysis of the parasite galectins revealed highest homology to mammalian galectin-9 and functional characterization identified similar substrate affinities consistent with this designation. Immunological assays showed that Bma-LEC-2 is a bioactive protein that can polarize macrophages to an alternatively activated phenotype and selectively induce apoptosis in Th1 cells. Our data shows that an abundantly secreted parasite galectin is immunomodulatory and induces phenotypes consistent with the modified type 2 response characteristic of chronic LF infection.
Selection on the joint actions of pairs leads to divergent adaptation and coadaptation of care-giving parents during pre-hatching care
Authors: Jarrett Benjamin J. M. , Mashoodh Rahia , Issar Swastika , Pascoal Sonia , Rebar Darren , Sun Syuan-Jyun , Schrader Matthew , Kilner Rebecca M. 
Published: May 2022

AbstractThe joint actions of animals in partnerships or social groups evolve under both natural selection, from the wider environment, and social selection, imposed by other members of the pair or group. We used experimental evolution to investigate how jointly expressed actions evolve upon exposure to a new environmental challenge. Our work focused on the evolution of carrion nest preparation by pairs of burying beetlesNicrophorus vespilloides, a joint activity undertaken by the pair but typically led by the male. In previous work, we found that carrion nest preparation evolved to be faster in experimental populations without post-hatching care (No Care lines) than with post-hatching care (Full Care lines). Here we investigate how this joint activity evolved. After 15 generations of experimental evolution, we created heterotypic pairs (No Care females with Full Care males, and No Care males with Full Care females) and compared their carrion nest making with homotypic No Care and Full Care pairs. We found that pairs with No Care males prepared the nest more rapidly than pairs with Full Care males, regardless of the female’s line of origin. This suggests that males led the way by adapting their nest preparation behaviour to the No Care environment first, with females secondarily co-adapting their behaviour to the male’s behaviour by reducing their nest preparation behaviour. We discuss how social coadaptations within pairs or groups could act as a post-mating barrier to gene flow.
Intrinsically disordered interaction network in an RNA chaperone revealed by native mass spectrometry
Authors: Sarni Samantha H. , Roca Jorjethe , Du Chen , Jia Mengxuan , Li Hantian , Damjanovic Ana , Małecka Ewelina M. , Wysocki Vicki H. , Woodson Sarah A. 
Published: May 2022

AbstractRNA-binding proteins contain intrinsically disordered regions whose functions in RNA recognition are poorly understood. The RNA chaperone Hfq is a homohexamer that contains six flexible C-terminal domains (CTDs). The effect of the CTDs on Hfq’s integrity and RNA binding has been challenging to study because of their sequence identity and inherent disorder. We used native mass spectrometry (nMS) coupled with surface-induced dissociation (SID) and molecular dynamics (MD) simulations to disentangle the arrangement of the CTDs and their impact on the stability ofE. coliHfq with and without RNA. The results show that the CTDs stabilize the Hfq hexamer through multiple interactions with the core and between CTDs. RNA binding perturbs this network of CTD interactions, destabilizing the Hfq ring. This destabilization is partially compensated by binding of RNAs that contact multiple surfaces of Hfq. By contrast, binding of short RNAs that only contact one or two subunits results in net destabilization of the complex. Together, the results show that a network of intrinsically disordered interactions integrate RNA contacts with the six subunits of Hfq. We propose that this CTD network raises the selectivity of RNA binding.Significance StatementHfq is a protein hexamer necessary for gene regulation by non-coding RNA in bacteria, during infection or under stress. In the cell, Hfq must distinguish its RNA partners from many similar nucleic acids. Mass spectrometry dissociation patterns, together with molecular dynamics simulations, showed that flexible extensions of each Hfq subunit form a dense network that interconnects the entire hexamer. This network is disrupted by RNA binding, but the lost interactions are compensated by RNAs that contact multiple Hfq subunits. By measuring interactions that are too irregular to be counted by other methods, mass spectrometry shows how flexible protein extensions help chaperones like Hfq recognize their RNA partners in the messy interior of the cell.
Temperature-dependent small RNA expression depends on wild genetic backgrounds of Caenorhabditis briggsae
Authors: Fusca Daniel D. , Sharma Eesha , Weiss Jörg G. , Claycomb Julie M. , Cutter Asher D. 
Published: May 2022

AbstractGeographically distinct populations can adapt to the temperature conditions of their local environment, leading to temperature-dependent fitness differences between populations. Consistent with local adaptation, phylogeographically distinct Caenorhabditis briggsae nematodes show distinct fitness responses to temperature. The genetic mechanisms underlying local adaptation, however, remain unresolved. To investigate the potential role of small noncoding RNAs in genotype-specific responses to temperature, we quantified small RNA expression using high-throughput sequencing of C. briggsae nematodes from tropical and temperate strain genotypes reared under three temperature conditions (14°C, 20°C, 30°C). Strains representing both tropical and temperate regions showed significantly lower expression of PIWI-interacting RNAs (piRNAs) at high temperatures, primarily mapping to a large ∼7 Mb long piRNA cluster on chromosome IV. We also documented decreased expression of 22G-RNAs antisense to protein-coding genes and other genomic features at high rearing temperatures for the thermally-intolerant temperate strain genotype, but not for the tropical strain genotype. Reduced 22G-RNA expression was widespread along chromosomes and among feature types, indicative of a genome-wide response. Targets of the EGO-1/CSR-1 22G-RNA pathway were most strongly impacted compared to other 22G-RNA pathways, implicating the CSR-1 Argonaute and its RNA-dependent RNA polymerase EGO-1 in the genotype-dependent modulation of C. briggsae 22G-RNAs under chronic thermal stress. Our work suggests that gene regulation via small RNAs may be an important contributor to the evolution of local adaptations.
Toward a goal-based paradigm of contagion
Authors: Kim TaeWoo , Duhachek Adam , Herd Kelly , Kim SunAh 
Published: May 2022

PurposeThis study aims to extend the previous research on contagion and proposes an integrative paradigm in which consumer goals and contagion recipient factors are identified as the key variables leading to the emergence of the contagion phenomenon. When a consumer has an active goal, a product touched by goal-congruent sources leads to positive product evaluation and enhances consumer performance when the product is used.Design/methodology/approachThis research conducted five experimental studies in online and offline retail settings to examine the effect of contagion on evaluations of contagion objects and performance in goal-related tasks.FindingsAcross five studies, the authors demonstrated that the activation of a goal leads to contagion-based product evaluation and performance enhancement effects. The authors theorized and showed that the contagion-based process triggered during goal pursuit led to a more favorable evaluation of contagion products (Studies 1, 2 and 3). The authors also showed that enhanced consumers’ commitment toward a goal, which in turn led to enhanced performance in a real task that contributed to achieving one’s goal (Study 4). These effects emerged only when the object was physically touched by a goal-congruent contagion source and were more pronounced for the consumers who experience a high (vs low) degree of goal discrepancy (Study 5).Research limitations/implicationsThe current research examined the contagion phenomenon in a few predetermined goal domains (e.g. health improvement goals, career success goals, marriage success goals). Although the authors found consistent effects across different types of goals, future research can examine a more comprehensive set of consumer goals and improve the limitation of the current research to generalize the goal-based contagion phenomenon to various consumer goals.Practical implicationsThis study suggests that it is important for retailers, in particular sellers and buyers in the secondhand markets, to understand consumer goals and prepare an appropriate contagion environment for favorable evaluation of their offerings. One possible implication is that sellers may be best served as priming certain goals. The findings also indicate that secondhand sellers may be well served to emphasize seller characteristics in certain instances and de-emphasize them in others to maximize sales.Originality/valueThis research proposes a new variable, namely, goal activation, and presents an integrative contagion paradigm that not only helps explain previous research findings but also offers a new perspective on the contagion phenomenon.
Online food delivery research: a systematic literature review
Authors: Shroff Arvind , Shah Bhavin J. , Gajjar Hasmukh 
Published: May 2022

Purpose
Online food delivery (OFD) has witnessed momentous consumer adoption in the past few years, and COVID-19, if anything, is only accelerating its growth. This paper captures numerous intricate issues arising from the complex relationship among the stakeholders because of the enhanced scale of the OFD business. The purpose of this paper is to highlight publication trends in OFD and identify potential future research themes.

Design/methodology/approach
The authors conducted a tri-method study – systematic literature review, bibliometric and thematic content analysis – of 43 articles on OFD published in 24 journals from 2015 to 2021 (March). The authors used VOSviewer to perform citation analysis.

Findings
Systematic literature review of the existing OFD research resulted in six potential research themes. Further, thematic content analysis synthesized and categorized the literature into four knowledge clusters, namely, (i) digital mediation in OFD, (ii) dynamic OFD operations, (iii) OFD adoption by consumers and (iv) risk and trust issues in OFD. The authors also present the emerging trends in terms of the most influential articles, authors and journals.

Practical implications
This paper captures the different facets of interactions among various OFD stakeholders and highlights the intricate issues and challenges that require immediate attention from researchers and practitioners.

Originality/value
This is one of the few studies to synthesize OFD literature that sheds light on unexplored aspects of complex relationships among OFD stakeholders through four clusters and six research themes through a conceptual framework.
Evaluating sustainability of mobile learning framework for higher education: a machine learning approach
Authors: Dolawattha Dhammika Manjula , Premadasa H.K. Salinda , Jayaweera Prasad M. 
Published: May 2022

PurposeThe purpose of this study is to evaluate the sustainability of the proposed mobile learning framework for higher education. Most sustainability evaluation studies use quantitative and qualitative methods with statistical approaches. Sometimes, in previous studies, machine learning models were utilized conventionally.Design/methodology/approachIn the proposed method, the authors use a novel machine learning-based ensemble approach with severity indexes to evaluate the sustainability of the proposed mobile learning system. In this severity indexes, consider the cause-and-effect relationship to identify the hidden correlation among sustainability factors. Also, the proposed novel sustainability evaluation algorithm helps to evaluate and improve sustainability iteratively to have an optimal sustainable mobile learning system. In total, 150 learners and 150 teachers in the university community engaged in the study by taking the sustainability questionnaire. The questionnaire consists of 20 questions that represent 20 sustainable factors in five sustainability dimensions, i.e. economic, social, political, technological and pedagogical.FindingsThe results reveal that the proposed system has achieved its economic and pedagogical sustainability. However, the results further reveal that the proposed system needs to be improved on technological, social and political sustainability.Originality/valueThe study focused novel machine learning approach and technique for evaluating sustainability of the proposed mobile learning framework.