bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mitochondrial blood-based patient stratification candidate biomarker for Parkinson’s disease
Authors: Qi Rui , Sammler Esther , Gonzalez-Hunt Claudia P. , Pena Nicholas , Rouanet Jeremy P. , Goodson Steven , Fuzatti Marie , Blandini Fabio , Erickson Kirk I. , Weinstein Andrea M. , Padmanabhan Shalini ,   Fox BioNet (FBN) investigators, Tonelli Francesca , Alessi Dario R. , Shiva Sruti , Sanders Laurie H. 
Published: February 2022

AbstractParkinson’s disease (PD) is the most common neurodegenerative movement disorder and neuroprotective interventions remain elusive. High throughput biomarkers aimed to stratify patients based on shared etiology is one critical path to the success of disease-modifying therapies in clinical trials. Mitochondrial dysfunction plays a prominent role in the pathogenesis of PD. Previously, we found brain region-specific mitochondrial DNA (mtDNA) damage accumulation in neuronal and in vivo PD models, as well as human PD postmortem brain tissue. In this study, to investigate mtDNA damage as a potential blood biomarker for PD, we describe a novel Mito DNADX assay that allows for the accurate real-time quantification of mtDNA damage in a 96-well platform, compatible with assessing large cohorts of patient samples. We found that levels of mtDNA damage were increased in blood derived from early-stage idiopathic PD patients or those harboring the pathogenic LRRK2 G2019S mutation compared to age-matched healthy controls. Given that increased mtDNA damage was also found in non-manifesting LRRK2 mutation carriers, mtDNA damage may begin to accumulate prior to a clinical PD diagnosis. LRRK2 kinase inhibition mitigated mtDNA damage in idiopathic PD models and patient-derived cells. The latter observations further substantiate a mechanistic role for wild-type LRRK2 kinase activity in idiopathic PD and support mtDNA damage reversal as a suitable approach to slow PD-related pathology. In light of recent advances in the field of precision medicine, the analysis of mtDNA damage as a blood-based patient stratification biomarker should be included in future clinical trials.One Sentence SummaryBlood test identifies Parkinson’s patients most likely to respond to mitochondria-targeted therapeutics facilitating a precision medicine approach.
The Brazilian population of Fusarium oxysporum f. sp. cubense is not structured by VCG or by geographic origin
Authors: Batista Izabel C.A. , Heck Daniel W. , Santos Alessandro , Alves Gabriel , Ferro Camila G. , Dita Miguel , Haddad Fernando , Michereff Sami J. , Correia Kamilla C. , da Silva Christiana F. B. , Mizubuti Eduardo S. G. 
Published: February 2022

AbstractFusarium wilt, caused by the soil-borne fungus Fusarium oxysporum f. sp. cubense (Foc), is considered one of the most destructive diseases of bananas. Paradoxically, knowledge of the genetics of the pathogen population in the Americas is very limited. In this study, a collection of 178 monosporic isolates from several banana producing regions, located in different climatic zones along a South to North transect in Brazil, was formed to assess the genetic structure of the population of Foc. The isolates underwent pathogenicity tests, PCR diagnosis for the detection of Tropical race 4 and screening to SIX homologs. The VCG of 119 isolates was determined by pairing against 17 testers. A group of 158 isolates was selected for microsatellite genotyping. There was moderate diversity of Foc in Brazil. Eight VCGs were identified: 0120, 0122, 0124, 0125, 0128, 01215, 01220, and 01222, of which 78% of isolates belong to a single VCG, while 22% of isolates belong to complexes of VCGs. The distribution of VCGs is uneven and independent of the banana genotype. VCGs were correlated with homologs of the SIX genes and varied according to geographic regions. Four SSR loci were polymorphic and on average 7.5 alleles were detected per locus. Thirty-five multilocus genotypes (MLGs) were identified. There was no association between VCG and MLGs and no genetic structure of the population of Foc in Brazil was detected.
Plasticity in structure and assembly of SARS-CoV-2 nucleocapsid protein
Authors: Zhao Huaying , Nguyen Ai , Wu Di , Li Yan , Hassan Sergio A. , Chen Jiji , Shroff Hari , Piszczek Grzegorz , Schuck Peter 
Published: February 2022

AbstractWorldwide SARS-CoV-2 sequencing efforts track emerging mutations in its spike protein, as well as characteristic mutations in other viral proteins. Besides their epidemiological importance, the observed SARS-CoV-2 sequences present an ensemble of viable protein variants, and thereby a source of information on viral protein structure and function. Charting the mutational landscape of the nucleocapsid (N) protein that facilitates viral assembly, we observe variability exceeding that of the spike protein, with more than 86% of residues that can be substituted, on average by 3-4 different amino acids. However, mutations exhibit an uneven distribution that tracks known structural features but also reveals highly protected stretches of unknown function. One of these conserved regions is in the central disordered linker proximal to the N-G215C mutation that has become dominant in the Delta variant, outcompeting G215 variants without further spike or N-protein substitutions. Structural models suggest that the G215C mutation stabilizes conserved transient helices in the disordered linker serving as protein-protein interaction interfaces. Comparing Delta variant N-protein to its ancestral version in biophysical experiments, we find a significantly more compact and less disordered structure. N-G215C exhibits substantially stronger self-association, shifting the unliganded protein from a dimeric to a tetrameric oligomeric state, which leads to enhanced co-assembly with nucleic acids. This suggests that the sequence variability of N-protein is mirrored by high plasticity of N-protein biophysical properties, which we hypothesize can be exploited by SARS-CoV-2 to achieve greater efficiency of viral assembly, and thereby enhanced infectivity.
Dynamic reorganization and selective segregation of mitochondria under DarT-mediated mtDNA damage
Authors: Dua Nitish , Seshadri Akshaya , Badrinarayanan Anjana 
Published: February 2022

AbstractMitochondria are dynamic organelles that play essential roles in cell growth and survival. Processes of fission and fusion are critical for distribution, segregation and maintenance of mitochondria and their genomes (mtDNA). While recent work has revealed the significance of mitochondrial organization for mtDNA maintenance, impact of mtDNA perturbations on mitochondrial dynamics remains less understood. Here we develop a tool to induce mitochondria-specific DNA damage, using a mitochondrial-targeted base modifying bacterial toxin, DarT. Following damage, we observe dynamic reorganization of mitochondrial networks, likely driven by mitochondrial dysfunction. Changes in organization are associated with loss of mtDNA, independent of mitophagy. Unexpectedly, perturbation to exonuclease function of mtDNA replicative polymerase, Mip1, results in rapid loss of mtDNA. Our data suggest that, under damage, partitioning of defective mtDNA and organelle are de-coupled, with emphasis on mitochondrial segregation independent of its DNA. Together, our works underscores the importance of genome maintenance on mitochondrial function, that can act as a modulator of organelle organization and segregation.
Finding mutations in all the wrong places: Prevalence of knock-down resistance F1534S mutations among Aedes albopictus (family: Culicidae, order: Diptera) in North Carolina
Authors: Abernathy Haley A. , Hollingsworth Brandon D. , Giandomenico Dana A. , Moser Kara A. , Juliano Jonathan J. , Bowman Natalie M. , George Phillip J. , Reiskind Michael H. , Boyce Ross M. 
Published: February 2022

ABSTRACTBackgroundKnock-down resistance (kdr) mutations in the voltage gated sodium channel gene of Aedes species mosquitoes are biomarkers for resistance to pyrethroid insecticides. In the United States, few studies have reported kdr mutations among Aedes albopictus(family: Culicidae, order: Diptera, Skuse, 1895) populations. In this study we sought to explore the potential for permethrin-impregnated uniforms worn by military servicemembers to drive kdr emergence.Methods and ResultsWe collected 538 Aedes albopictus mosquitoes, including 156 from 4 sites at Fort Bragg (exposed), North Carolina and 382 from 15 sites in Wake County (control), North Carolina to compare the prevalence of kdr mutations. Of those successfully sequenced, we identified 12 (3.0%) mosquitoes with kdr mutations, all of which were attributed to variants at position 1534 within domain 3. All mutations were found in mosquitoes collected at Wake County sites; no mutations were identified at Fort Bragg. There was a focus of mutations observed at the Wake County sites with approximately 92% (11 of 12) of the mosquitoes with the mutation coming from one site, where kdr mutations represented 24.4% (11 of 45) of all mosquitoes collected.ConclusionsOur study did not show any evidence that universal implementation of permethrin-impregnated uniforms drives the development of resistance. In contrast, we observed highly focal resistance in a suburban area of Raleigh, which may be attributable to peri-domestic mosquito control activities that involve area dispersal of pyrethroid insecticides. More robust surveillance is needed to monitor the emergence and spread of resistance.AUTHOR SUMMARYResistance to commonly employed insecticides among Aedes albopictus(family: Culicidae, order: Diptera, Skuse, 1895) mosquitoes poses as a substantial public health threat. In this study we sought to explore the potential for permethrin-impregnated uniforms worn by military servicemembers to drive emergence of resistance to pyrethroid insecticides by collecting and testing mosquitoes from both military and civilian sites. Overall, we did not identify mosquitoes harboring resistance at Ft. Bragg, but did find a focus of resistance in sub-urban Raleigh, which may be driven by commercial, peri-domestic mosquito control activities. These results suggest that resistance to pyrethroid insecticides may be more prevalent in the United States than previously known, but highly heterogenous. More robust surveillance is needed to monitor the emergence and spread of resistance.
Influenza A virus reassortment in mammals gives rise to genetically distinct within-host sub-populations
Authors: Ganti Ketaki , Bagga Anish , Carnaccini Silvia , Ferreri Lucas M. , Geiger Ginger , Caceres C. Joaquin , Seibert Brittany , Li Yonghai , Wang Liping , Kwon Taeyong , Li Yuhao , Morozov Igor , Ma Wenjun , Richt Juergen A. , Perez Daniel R. , Koelle Katia , Lowen Anice C. 
Published: February 2022

AbstractInfluenza A virus (IAV) genetic exchange through reassortment has the potential to accelerate viral evolution and has played a critical role in the generation of multiple pandemic strains. For reassortment to occur, distinct viruses must co-infect the same cell. The spatio-temporal dynamics of viral dissemination within an infected host therefore define opportunity for reassortment. Here, we used wild type and synonymously barcoded variant viruses of a pandemic H1N1 strain to examine the within-host viral dynamics that govern reassortment in guinea pigs, ferrets and swine. The first two species are well-established models of human influenza, while swine are a natural host and a frequent conduit for cross-species transmission and reassortment. Our results show reassortment to be pervasive in all three hosts but less frequent in swine than in ferrets and guinea pigs. In ferrets, tissue-specific differences in the opportunity for reassortment are also evident, with more reassortants detected in the nasal tract than the lower respiratory tract. While temporal trends in viral diversity are limited, spatial patterns are clear, with heterogeneity in the viral genotypes detected at distinct anatomical sites revealing extensive compartmentalization of reassortment and replication. Our data indicate that the dynamics of viral replication in mammals allow diversification through reassortment but that the spatial compartmentalization of variants likely shapes their evolution and onward transmission.
Partitioning variance in reproductive success, within years and across lifetimes
Authors: Waples Robin S. 
Published: February 2022

AbstractVariance in reproductive success (, withk=number of offspring) plays a large role in determining the rate of genetic drift and the scope within which selection acts. Various frameworks have been proposed to parse factors that contribute to, but none has focused on age-specific values of, which indicate the degree to which reproductive skew is overdispersed (compared to the random Poisson expectation) among individuals of the same age and sex. Here, an ANOVA sums-of-squares framework is used to partition variance in annual and lifetime reproductive success into between-group and within-group components. For annual reproduction, the between-age effect depends on age-specific fecundity (bx), but relatively few empirical data are available on the within-age effect, which depends onϕx. By defining groups by age-at-death rather than age, the same ANOVA framework can be used to partition variance in lifetime reproductive success into between-group, within-group, and longevity components. Analyses of simulated data and worked examples for black bears and great tits illustrate the methods and show that the largely-neglected within-age effect a) typically represents a substantial component of the overall variance (even under a null model of random reproductive success), and b) can dominate the overall variance whenϕx>1.
The oral drug nitazoxanide restricts SARS-CoV-2 infection and attenuates disease pathogenesis in Syrian hamsters
Authors: Miorin Lisa , Mire Chad E. , Ranjbar Shahin , Hume Adam J. , Huang Jessie , Crossland Nicholas A. , White Kris M , Laporte Manon , Kehrer Thomas , Haridas Viraga , Moreno Elena , Nambu Aya , Jangra Sonia , Cupic Anastasija , Dejosez Marion , Abo Kristine A. , Tseng Anna E. , Werder Rhiannon B. , Rathnasinghe Raveen , Mutetwa Tinaye , Ramos Irene , de Aja Julio Sainz , de Alba Rivas Carolina Garcia , Schotsaert Michael , Corley Ronald B. , Falvo James V. , Fernandez-Sesma Ana , Kim Carla , Rossignol Jean-François , Wilson Andrew A. , Zwaka Thomas , Kotton Darrell N. , Mühlberger Elke , García-Sastre Adolfo , Goldfeld Anne E. 
Published: February 2022

AbstractA well-tolerated and cost-effective oral drug that blocks SARS-CoV-2 growth and dissemination would be a major advance in the global effort to reduce COVID-19 morbidity and mortality. Here, we show that the oral FDA-approved drug nitazoxanide (NTZ) significantly inhibits SARS-CoV-2 viral replication and infection in different primate and human cell models including stem cell-derived human alveolar epithelial type 2 cells. Furthermore, NTZ synergizes with remdesivir, and it broadly inhibits growth of SARS-CoV-2 variants B.1.351 (beta), P.1 (gamma), and B.1617.2 (delta) and viral syncytia formation driven by their spike proteins. Strikingly, oral NTZ treatment of Syrian hamsters significantly inhibits SARS-CoV-2-driven weight loss, inflammation, and viral dissemination and syncytia formation in the lungs. These studies show that NTZ is a novel host-directed therapeutic that broadly inhibits SARS-CoV-2 dissemination and pathogenesis in human and hamster physiological models, which supports further testing and optimization of NTZ-based therapy for SARS-CoV-2 infection alone and in combination with antiviral drugs.
Very small spontaneous structural mutation rate in green algae
Authors: Léger-Pigout Matéo , Krasovec Marc 
Published: February 2022

ABSTRACTStructural mutations led to major innovations, but our knowledge of the spontaneous structural mutation rate is very limited. We cannot have a complete view of the adaptive potential of species and new variants in a population without addressing this question. Here, we used Illumina genomic data from mutation accumulation experiments of five green algae species and measured very low structural mutation rate, between 5×10-12 to 2×10-11 mutations per site, at least ten times lower than the nucleotide mutation rate in these species. Such low rates of structural mutations may be a consequence of selection. Assuming that structural mutations have higher fitness effect than point mutations because they impact a larger portion of the genome, selection toward a small structural mutation rate may be stronger than for point mutations. A second explanation could be the rate of true positive detection of de novo structural mutations, that is globally poor and variable between methods. This highlights the necessity of long read sequencing in future mutation accumulation studies.SIGNIFICANCE STATEMENTMutations are the first source of all biodiversity. Biologists tried since a century to measure the spontaneous mutation rate, but our knowledge on the structural spontaneous mutation rate, μst, is still poor. Here we measured μst in five species of phytoplankton, and found a very small rate compared to nucleotide and short insertion-deletion mutations.
BlotIt - Optimal alignment of western blot and qPCR experiments
Authors: Kemmer Svenja , Bang Severin , Rosenblatt Marcus , Timmer Jens , Kaschek Daniel 
Published: February 2022

AbstractBiological systems are frequently analyzed by means of mechanistic mathematical models. In order to infer model parameters and provide a useful model that can be employed for systems understanding and hypothesis testing, the model is often calibrated on quantitative, time-resolved data. To do so, it is typically important to compare experimental measurements over broad time ranges and various experimental conditions, e.g. perturbations of the biological system. However, most of the established experimental techniques such as Western blot, or quantitative real-time polymerase chain reaction only provide measurements on a relative scale, since different sample volumes, experimental adjustments or varying development times of a gel lead to systematic shifts in the data. In turn, the number of measurements corresponding to the same scale enabling comparability is limited. Here, we present a new flexible method to align measurement data that obeys different scaling factors. We propose an alignment model to estimate these scaling factors and provide the possibility to adapt this model depending on the measurement technique of interest. In addition, an error model can be specified to adequately weight the different data points and obtain scaling-model based confidence intervals of the finally scaled data points. Our approach is applicable to all sorts of relative measurements and does not need a particular experimental condition that has been measured over all available scales. An implementation of the method is provided with the R package blotIt including refined ways of visualization.
Emerging from the shadow of the Soviet Union: the case of the accountancy field in Latvia
Authors: Praulins Arturs , Spence Crawford William , Voulgaris Georgios 
Published: February 2022

PurposeThis paper aims to explore the structure of the accounting field in a post-Soviet context – Latvia. This study also aims to generate insights into the extent to which professionalization processes are shaped by national particularities and to demonstrate how self-styled professional fields change over time.Design/methodology/approachDrawing from the relational sociology of Pierre Bourdieu and drawing on 83 interviews, the paper highlights the forms of capital (cultural and social primarily) that help define what constitutes appropriate conduct for successful career progression in the accounting field.FindingsThe values ascribed to forms of capital that structure the Latvian accounting field fluctuate across time and space. This suggests that the structure of professional fields – as understood by the structuring properties of different forms of capital – is variable and fluid. Additionally, fields themselves can become more or less desirable over time to those who possess certain forms of capital.Research limitations/implicationsAlthough the results may be specific to one national accounting field, the idiosyncrasies constitute the contribution of the paper, showing that the form and structure of accounting fields vary in accordance with national particularities. Overall, the paper highlights the importance of fit between habitus and field and of adjustment to the surrounding rules of the game in professional contexts.Originality/valueThe findings are important for understanding the form that an accounting field can take in an emerging economy that has fully embraced neoliberalism while maintaining strong residues of the Soviet system. The findings are also relevant for understanding the dynamics of change more broadly in self-styled professional fields.
The determinants of risk reporting during the period of adoption of Basel II Accord: evidence from the Portuguese commercial banks
Authors: Azevedo Graça , Oliveira Jonas , Sousa Luiza , Borges Maria Fátima Ribeiro 
Published: February 2022

PurposeThe purpose of this paper to analyze the risk reporting practices and its determinants of commercial banks during the period of the adoption of the Basel II Accord in Portugal.Design/methodology/approachThe paper conducts a content analysis of the risk and risk management sections included in the management reports and the notes of the annual reports of Portuguese commercial banks, for the years 2007, 2010 and 2013.FindingsFindings show that theoretical frameworks underpinned in agency and legitimacy theories continue to provide valid explanations for risk reporting by Portuguese banks. More specifically, findings indicate that agency costs, public visibility and reputation are crucial drivers of risk reporting. Findings also indicate that younger banks with lower risk management skills use risk reporting either as an informational process or as a channel to manage organizational legitimacy.Research limitations/implicationsThe content analysis does not allow readily for in-depth qualitative inquiry. The coding instrument is subject to coder bias. Information about risk can be provided in sources other than annual reports. Additionally, not all banks disclose information on corporate governance-related variables that could also influence risk reporting.Originality/valueThe current research setting has never been studied hitherto. In this sense, this study seems to be of great relevance given the scarcity of literature on the subject in Portugal.