bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulating General Mutation Rates: Examination of the Hypermutable State Model for Cairnsian Adaptive Mutation
Authors: Roth John R , Kofoid Eric , Roth Frederick P , Berg Otto G , Seger Jon , Andersson Dan I 
Published: April 2021

Abstract
In the lac adaptive mutation system of Cairns, selected mutant colonies but not unselected mutant types appear to arise from a nongrowing population of Escherichia coli. The general mutagenesis suffered by the selected mutants has been interpreted as support for the idea that E. coli possesses an evolved (and therefore beneficial) mechanism that increases the mutation rate in response to stress (the hypermutable state model, HSM). This mechanism is proposed to allow faster genetic adaptation to stressful conditions and to explain why mutations appear directed to useful sites. Analysis of the HSM reveals that it requires implausibly intense mutagenesis (105 times the unselected rate) and even then cannot account for the behavior of the Cairns system. The assumptions of the HSM predict that selected revertants will carry an average of eight deleterious null mutations and thus seem unlikely to be successful in long-term evolution. The experimentally observed 35-fold increase in the level of general mutagenesis cannot account for even one Lac+ revertant from a mutagenized subpopulation of 105 cells (the number proposed to enter the hypermutable state). We conclude that temporary general mutagenesis during stress is unlikely to provide a long-term selective advantage in this or any similar genetic system.
Evolutionary, Structural and Biochemical Evidence for a New Interaction Site of the Leptin Obesity Protein
Authors: Gaucher Eric A , Miyamoto Michael M , Benner Steven A 
Published: April 2021

AbstractThe Leptin protein is central to the regulation of energy metabolism in mammals. By integrating evolutionary, structural, and biochemical information, a surface segment, outside of its known receptor contacts, is predicted as a second interaction site that may help to further define its roles in energy balance and its functional differences between humans and other mammals.
Prodigal Children: Why Older Mothers Favor Their Once-Deviant Adult Children
Authors: Kincaid Reilly , Rurka Marissa , Suitor J Jill , Gilligan Megan , Pillemer Karl , Mohebbi Liam , Mundell Nicholas 
Published: April 2021

Abstract

Objectives
Past research suggests that adult children who reform their deviant behaviors (i.e., problems with drugs/alcohol or the law) are more likely to become favored by their mothers, yet the reasons underlying this phenomenon are unclear. This study employs a longitudinal, qualitative approach to explore why adult children’s behavioral reforms shape changes in maternal favoritism.

Method
Analyses are based on qualitative interview data collected at 2 points 7 years apart from older mothers regarding their adult children in 20 families. Each of these families had a “prodigal child”—a child for whom desistance from deviant behaviors between the 2 waves was accompanied by newfound maternal favoritism.

Results
Findings revealed 2 conditions under which mothers came to favor reformed deviants over their siblings. First, this occurred when adult children’s behavioral reformations were accompanied by mothers’ perceptions of these children as having grown more family-oriented. Second, this occurred when mothers came to see reformed deviants as exhibiting a stronger need and appreciation for maternal support, relative to their siblings.

Discussion
Mothers’ perceptions of children’s behavioral reformations as being accompanied by greater dedication to family or reflecting a need for their mothers’ support offer 2 explanations for why previously deviant adult children may become mothers’ favored offspring. These findings contribute to a growing body of scholarship on the complexity of intergenerational relations by shedding new light on changing patterns of favoritism in families with a history of parental disappointment, conflict, and strain.
Noncovalent microarrays from synthetic amino-terminating glycans: Implications in expanding glycan microarray diversity and platform comparison
Authors: Li Chunxia , Palma Angelina S , Zhang Pengtao , Zhang Yibing , Gao Chao , Silva Lisete M , Li Zhen , Trovão Filipa , Weishaupt Markus , Seeberger Peter H , Likhosherstov Leonid M , Piskarev Vladimir , Yu Jin , Westerlind Ulrika , Chai Wengang 
Published: April 2021

AbstractGlycan microarrays have played important roles in detection and specificity assignment of glycan recognition by proteins. However, the size and diversity of glycan libraries in current microarray systems are small compared to estimated glycomes, and these may lead to missed detection or incomplete assignment. For microarray construction, covalent and noncovalent immobilization are the two types of methods used, but a direct comparison of results from the two platforms is required. Here we develop a chemical strategy to prepare lipid-linked probes from both naturally derived aldehyde-terminating and synthetic amino-terminating glycans that addresses the two aspects: expansion of sequence-defined glycan libraries and comparison of the two platforms. We demonstrate the specific recognition by plant and mammalian lectins, carbohydrate-binding modules and antibodies and the overall similarities from the two platforms. Our results provide new knowledge on unique glycan-binding specificities for the immune receptor Dectin-1 toward β-glucans and the interaction of rotavirus P[19] adhesive protein with mucin O-glycan cores.
Cis-acting modifiers in the ABCA4 locus contribute to the penetrance of the major disease-causing variant in Stargardt disease
Authors: Lee Winston , Zernant Jana , Nagasaki Takayuki , Molday Laurie L , Su Pei-Yin , Fishman Gerald A , Tsang Stephen H , Molday Robert S , Allikmets Rando 
Published: April 2021

Abstract
Over 1200 variants in the ABCA4 gene cause a wide variety of retinal disease phenotypes, the best known of which is autosomal recessive Stargardt disease (STGD1). Disease-causing variation encompasses all mutation categories, from large copy number variants to very mild, hypomorphic missense variants. The most prevalent disease-causing ABCA4 variant, present in ~ 20% of cases of European descent, c.5882G &gt; A p.(Gly1961Glu), has been a subject of controversy since its minor allele frequency (MAF) is as high as ~ 0.1 in certain populations, questioning its pathogenicity, especially in homozygous individuals. We sequenced the entire ~140Kb ABCA4 genomic locus in an extensive cohort of 644 bi-allelic, i.e. genetically confirmed, patients with ABCA4 disease and analyzed all variants in 140 compound heterozygous and 10 homozygous cases for the p.(Gly1961Glu) variant. A total of 23 patients in this cohort additionally harbored the deep intronic c.769-784C &gt; T variant on the p.(Gly1961Glu) allele, which appears on a specific haplotype in ~ 15% of p.(Gly1961Glu) alleles. This haplotype was present in 5/7 of homozygous cases, where the p.(Gly1961Glu) was the only known pathogenic variant. Three cases had an exonic variant on the same allele with the p.(Gly1961Glu). Patients with the c.[769-784C &gt; T;5882G &gt; A] complex allele exhibit a more severe clinical phenotype, as seen in compound heterozygotes with some more frequent ABCA4 mutations, e.g. p.(Pro1380Leu). Our findings indicate that the c.769-784C &gt; T variant is major cis-acting modifier of the p.(Gly1961Glu) allele. The absence of such additional allelic variation on most p.(Gly1961Glu) alleles largely explains the observed paucity of affected homozygotes in the population.
Protein instability associated with AARS1 and MARS1 mutations causes trichothiodystrophy
Authors: Botta Elena , Theil Arjan F , Raams Anja , Caligiuri Giuseppina , Giachetti Sarah , Bione Silvia , Accadia Maria , Lombardi Anita , Smith Desiree E C , Mendes Marisa I , Swagemakers Sigrid M A , van der Spek Peter J , Salomons Gajja S , Hoeijmakers Jan H J , Yesodharan Dhanya , Nampoothiri Sheela , Ogi Tomoo , Lehmann Alan R , Orioli Donata , Vermeulen Wim 
Published: April 2021

Abstract
Trichothiodystrophy (TTD) is a rare hereditary neurodevelopmental disorder defined by sulfur-deficient brittle hair and nails and scaly skin, but with otherwise remarkably variable clinical features. The photosensitive TTD (PS-TTD) forms exhibits in addition to progressive neuropathy and other features of segmental accelerated aging and is associated with impaired genome maintenance and transcription. New factors involved in various steps of gene expression have been identified for the different non-photosensitive forms of TTD (NPS-TTD), which do not appear to show features of premature aging. Here, we identify alanyl-tRNA synthetase 1 and methionyl-tRNA synthetase 1 variants as new gene defects that cause NPS-TTD. These variants result in the instability of the respective gene products alanyl- and methionyl-tRNA synthetase. These findings extend our previous observations that TTD mutations affect the stability of the corresponding proteins and emphasize this phenomenon as a common feature of TTD. Functional studies in skin fibroblasts from affected individuals demonstrate that these new variants also impact on the rate of tRNA charging, which is the first step in protein translation. The extension of reduced abundance of TTD factors to translation as well as transcription redefines TTD as a syndrome in which proteins involved in gene expression are unstable.
Pseudogenized Amelogenin Reveals Early Tooth Loss in True Toads (Anura: Bufonidae)
Authors: Shaheen John , Mudd Austin B , Diekwisch Thomas G H , Abramyan John 
Published: April 2021

SynopsisExtant anurans (frogs and toads) exhibit reduced dentition, ranging from a lack of mandibular teeth to complete edentulation, as observed in the true toads of the family Bufonidae. The evolutionary time line of these reductions remains vague due to a poor fossil record. Previous studies have demonstrated an association between the lack of teeth in edentulous vertebrates and the pseudogenization of the major tooth enamel gene amelogenin (AMEL) through accumulation of deleterious mutations and the disruption of its coding sequence. In this study, we have harnessed the pseudogenization of AMEL as a molecular dating tool to correlate loss of dentition with genomic mutation patterns during the rise of the family Bufonidae. Specifically, we have utilized AMEL pseudogenes in three members of the family as a tool to estimate the putative date of edentulation in true toads. Comparison of AMEL sequences from Rhinella marina, Bufo gargarizans and Bufo bufo, with nine extant, dentulous frogs, revealed mutations confirming AMEL inactivation in Bufonidae. AMEL pseudogenes in modern bufonids also exhibited remarkably high 86–93% sequence identity among each other, with only a slight increase in substitution rate and relaxation of selective pressure, in comparison with functional copies in other anurans. Moreover, using selection intensity estimates and synonymous substitution rates, analysis of functional and pseudogenized AMEL resulted in an estimated inactivation window of 46–60 million years ago in the lineage leading to modern true toads, a time line that coincides with the rise of the family Bufonidae.
Biometric encryption of smartphones: a charted ship in the ocean of adversarial system?
Authors: Bhalotia Kartikey Sanjeev , Pareek Divyansh 
Published: April 2021

Abstract
India has recently been flooded with smartphones having features of biometric encryption that allows users to encrypt the data on their devices using their biometric features, such as finger impressions or iris patterns. This technology assures users of precluding impermissible intrusions into their private data. However, this idea behind biometric encryption has witnessed critical considerations in the recent past, when Courts of various jurisdictions in the USA were faced with the issue of whether an investigating agency has the power to unlock such smartphones by compelling an accused to depress his fingerprints on the touch ID of the same. The courts have tried to strike a balance between the competing interests of the State and of the accused. While on the one side is the consideration that such power to the investigating agencies are essential for combating crime, on the other, there are the individualistic fundamental rights of the accused. The courts have weighed the prospective impact of giving the investigating agency the said power against an accused’s fundamental rights against self-incrimination, and privacy. This article, after analysing these judgments, endeavours to provide answers to the questions that Indian Courts might face in future concerning search and seizure of smartphones and its implications on the fundamental rights of an accused. This discussion becomes important especially due to the absence of any judicial pronouncements on the issue in India and more so, because even existing pronouncements by the courts in the USA have been quite contradictory.
A discrete dynamics approach to interbank financial contagion
Authors: Leventides John , Poulios Costas , Camouzis Elias 
Published: April 2021

Abstract
The purpose of this paper is to describe in terms of mathematical models and systems theory the dynamics of interbank financial contagion. Such a description gives rise to a model that can be studied with mathematical tools and will provide a new framework for the study of contagion dynamics complementary to research by simulation studied so far. It provides a better understanding of such financial networks and a unifying network for the research of financial contagion. The mathematical description we present is in terms of Boolean dynamical systems and a linear operator. We relate the properties of the dynamical systems to the properties of the operator.
Decline in Vaccine-Type Streptococcus pneumoniae Serotypes Following Pneumococcal Conjugate Vaccine Introduction in Madagascar
Authors: Raboba Julia L , Rahajamanana Vonintsoa L , Andriatahirintsoa Emilson P R , Razafindrakoto Ainamalala C , Andrianarivelo Andry M , Nimpa Mengouo Marcellin , Vuo Masembe Yolande , Weldegebriel Goitom G , de Gouveia Linda , Mwenda Jason M , Robinson Annick L 
Published: April 2021

Abstract

Background
The 10-valent conjugate vaccine (PCV10) was introduced into the Extended Program on Immunization in Madagascar. We assessed the impact of PCV10 on the targeted pneumococcal serotypes among children &lt; 5 years of age at Centre Hospitalier Universitaire Mère Enfant Tsaralalàna.

Method
Between 2012 and December 2018, cerebrospinal fluid (CSF) samples were collected and tested for S. pneumoniae by culture, and antigen tests. The Sentinel Site Laboratory (SSL) referred available CSF samples to the Regional Reference Laboratory (RRL) for real-time polymerase chain reaction confirmatory testing and serotyping.

Results
In total, 3616 CSF specimens were collected. The SSL referred 2716 to the RRL; 125 were positive for S. pneumoniae. At the RRL, 115 samples that tested positive for S. pneumoniae were serotyped; PCV10 serotypes accounted for 20%. Compared to the pre-PCV period, the proportion of S. pneumoniae detected declined from 22% to 6.6%, (P &lt; .05), the proportion of PCV10 serotypes as the cause of pneumococcal meningitis cases declined by 26% following vaccine introduction.

Conclusions
In our findings, PCV10 introduction resulted in a decline of meningitis caused by S. pneumoniae and PCV10 vaccine serotypes.
In vitroactivity of imipenem/relebactam, meropenem/vaborbactam, ceftazidime/avibactam, cefepime/zidebactam and other novel antibiotics against imipenem-non-susceptible Gram-negative bacilli from Taiwan
Authors: Kuo Shu-Chen , Wang Yung-Chih , Tan Mei-Chen , Huang Wei-Cheng , Shiau Yih-Ru , Wang Hui-Ying , Lai Jui-Fen , Huang I-Wen , Lauderdale Tsai-Ling 
Published: April 2021

AbstractObjectivesTo investigate the susceptibility of imipenem-non-susceptible Escherichia coli (INS-EC), Klebsiella pneumoniae (INS-KP), Acinetobacter baumannii (INS-AB) and Pseudomonas aeruginosa (INS-PA) to novel antibiotics.MethodsMICs were determined using the broth microdilution method. Carbapenemase and ESBL phenotypic testing and PCR for genes encoding ESBLs, AmpCs and carbapenemases were performed.ResultsZidebactam, avibactam and relebactam increased the respective susceptibility rates to cefepime, ceftazidime and imipenem of 17 INS-EC by 58.8%, 58.8% and 70.6%, of 163 INS-KP by 77.9%, 88.3% and 76.1% and of 81 INS-PA by 45.7%, 38.3% and 85.2%, respectively. Vaborbactam increased the meropenem susceptibility of INS-EC by 41.2% and of INS-KP by 54%. Combinations of β-lactams and novel β-lactamase inhibitors or β-lactam enhancers (BLI-BLE) were inactive against 136 INS-AB. In 58 INS-EC and INS-KP with exclusively blaKPC-like genes, zidebactam, avibactam, relebactam and vaborbactam increased the susceptibility of the partner β-lactams by 100%, 96.6%, 84.5% and 75.9%, respectively. In the presence of avibactam, ceftazidime was active in an additional 85% of 20 INS-EC and INS-KP with exclusively blaOXA-48-like genes while with zidebactam, cefepime was active in an additional 75%. INS-EC and INS-KP with MBL genes were susceptible only to cefepime/zidebactam. The β-lactam/BLI-BLE combinations were active against INS-EC and INS-KP without detectable carbapenemases. For INS-EC, INS-KP and INS-AB, tigecycline was more active than omadacycline and eravacycline but eravacycline had a lower MIC distribution. Lascufloxacin and delafloxacin were active in &lt;35% of these INS isolates.Conclusionsβ-Lactam/BLI-BLE combinations were active in a higher proportion of INS-EC, INS-KP and INS-PA. The susceptibility of novel fluoroquinolones and tetracyclines was not superior to that of old ones.
Low Bottleneck Detection in Long-Lived Species Despite Lost Genetic Diversity: A Case Study of Tuatara and Eastern Massasauga Rattlesnakes
Authors: Bradke Danielle R , Altobelli Joseph T , Russell Amy L , Jaeger Collin P , Moore Jennifer A 
Published: April 2021

AbstractPopulation bottlenecks can reduce genetic diversity and may lead to inbreeding depression. However, some studies have provided evidence that long lifespans buffer negative genetic effects of bottlenecks. Others have cautioned that longevity might merely mask the effects of genetic drift, which will still affect long-term population viability. We used microsatellite data from actual populations of tuatara (Sphenodon punctatus) and eastern massasaugas (Sistrurus catenatus) as a starting point for simulated population declines to evaluate the performance of bottleneck tests under a range of scenarios. We quantified losses in genetic diversity for each scenario and assessed the power of commonly used tests (i.e., M-ratio, heterozygosity excess, and mode-shift) to detect known bottlenecks in these moderate- to long-lived species. Declines in genetic diversity were greater in bottlenecks simulated for eastern massasaugas, the shorter-lived species, and mode-shift and heterozygosity excess tests were more sensitive to population declines in this species. Conversely, M-ratio tests were more sensitive to bottlenecks simulated in tuatara. Despite dramatic simulated population declines, heterozygosity excess and mode-shift tests often failed to detect bottlenecks in both species, even when large losses in genetic diversity had occurred (both allelic diversity and heterozygosity). While not eliminating type II error, M-ratio tests generally performed best and were most reliable when a critical value (Mc) of 0.68 was used. However, in tuatara simulations, M-ratio tests had high rates of type I error when Mc was calculated assuming θ = 10. Our results suggest that reliance on these tests could lead to misguided species management decisions.
Keeping institutional logics in arm’s length: emerging of rogue practices in a gray zone of everyday work life in healthcare
Authors: Gürses Serdal , Danışman Ali 
Published: April 2021

AbstractWe set out to explore the practice-level cognitive structures and associated practices characterizing the daily routine work of physicians by conducting a qualitative study in the Turkish healthcare field, in which a recent government-led healthcare reform was implemented causing logic multiplicity. Contrary to the accumulated knowledge in institutional logics literature, a bulk of which suggests that actors craft and enact various practices in managing plural and at times conflicting institutional templates strictly within the confines of higher order societal logics, this study shows that while ground level actors may not exercise complete freedom and maneuverability in relation to pre-established social structures, they do incorporate unconventional schemas of action; namely rogue practices, into their embodied practical activity, which over time become routinized in their day-to-day work lives. Unraveling the dynamics of micro-level practices of highly professionalized ground level actors as they pertain to atypical logical orientations substantially advances our understanding of the unknown or unseen side of how and under which conditions certain or various combinations of institutional logics are employed during day-to-day activities.
A Model-Assisted Approach for Finding Coding Errors in Manual Coding of Open-Ended Questions
Authors: He Zhoushanyue , Schonlau Matthias 
Published: April 2021

Abstract
Text answers to open-ended questions are typically manually coded into one of several codes. Usually, a random subset of text answers is double-coded to assess intercoder reliability, but most of the data remain single-coded. Any disagreement between the two coders points to an error by one of the coders. When the budget allows double coding additional text answers, we propose employing statistical learning models to predict which single-coded answers have a high risk of a coding error. Specifically, we train a model on the double-coded random subset and predict the probability that the single-coded codes are correct. Then, text answers with the highest risk are double-coded to verify. In experiments with three data sets, we found that this method identifies two to three times as many coding errors in the additional text answers as compared to random guessing, on average. We conclude that this method is preferred if the budget permits additional double-coding. When there are a lot of intercoder disagreements, the benefit can be substantial.
Mild radial variations of the stellar IMF in the bulge of M31
Authors: La Barbera F , Vazdekis A , Ferreras I , Pasquali A 
Published: April 2021

ABSTRACT
Using new, homogeneous, long-slit spectroscopy in the wavelength range from ∼0.35 to $\sim 1 \, \mu$m, we study radial gradients of optical and near-infrared (NIR) initial mass function (IMF)-sensitive features along the major axis of the bulge of M31, out to a galactocentric distance of ∼200 arcsec (∼800 pc). Based on state-of-the-art stellar population synthesis models with varying Na abundance ratio, we fit a number of spectral indices, from different chemical species (including TiO’s, Ca, and Na indices), to constrain the low-mass (≲0.5 M⊙) end slope (i.e. the fraction of low-mass stars) of the stellar IMF, as a function of galactocentric distance. Outside a radial distance of ∼10 arcsec, we infer an IMF similar to a Milky Way-like distribution, while at small galactocentric distances, an IMF radial gradient is detected, with a mildly bottom-heavy IMF in the few inner arcsec. We are able to fit Na features (both NaD and $\rm Na\,{\small I}8190$), without requiring extremely high Na abundance ratios. $\rm [Na/Fe]$ is ∼0.4 dex for most of the bulge, rising up to ∼0.6 dex in the innermost radial bins. Our results imply an overall, luminosity-weighted, IMF and mass-to-light ratio for the M31 bulge, consistent with those for a Milky Way-like distribution, in contrast to results obtained, in general, for most massive early-type galaxies.