bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Speciation history of Drosophila pseudoobscura and Close Relatives: Inferences from DNA Sequence Variation at the Period Locus
Authors: Wang Rong-Lin , Hey Jody 
Published: January 2021

Abstract
Thirty-five period locus sequences from Drosophila pseudoobscura and its siblings species, D. p. bogotana, D. persirnilis, and D. miranda, were studied. A large amount of variation was found within D. pseudoobscura and D. persimilis, consistent with histories of large effective population sizes. D. p. bogotana, however, has a severe reduction in diversity. Combined analysis of per with two other loci, in both D. p. bogotana and D. pseudoobscura, strongly suggest this reduction is due to recent directional selection at or near per within D. p. bogotana. Since D. p. bogotana is highly variable and shares variation with D. pseudoobscura at other loci, the low level of variation at per within D. p. bogotana can not be explained by a small effective population size or by speciation via founder event. Both D. pseudoobscura and D. persirnilis have considerable intraspecific gene flow. A large portion of one D. persirnilis sequence appears to have arisen via introgression from D. pseudoobscura. The time of this event appears to be well after the initial separation of these two species. The estimated times since speciation are one mya for D. pseudoobscura and D. persirnilis and 2 mya since the formation of D. miranda.
Discord Between the Phylogenies Inferred From Molecular Versus Functional Data: Uneven Rates of Functional Evolution or Low Levels of Gene Flow?
Authors: Palopoli Michael F , Davis Andrew W , Wu Chung-I 
Published: January 2021

Abstract
According to measures of molecular divergence, the three species of the Drosophila simulans clade are closely related to and essentially equidistant from each other. We introgressed 10% of the D. sechellia X chromosome into a pure D. simulans genetic background and found that males carrying this introgressed region were consistently fertile; in contrast, males carrying the same segment from D. mauritiana are sterile and suffer from incompatibilities at a minimum of four loci. Together with other recent results, these data suggest that D. simulans and D. sechellia are much more closely related to each other than either is to D. mauritiana. How can we reconcile the phylogeny inferred from the density of hybrid sterility genes with that inferred from molecular divergence? If the molecular phylogeny is correct, the discrepancy might be explained by uneven rates of functional evolution, resulting in the uneven accumulation of substitutions with corresponding negative effects in hybrids. If the functional phylogeny is correct, then low levels of gene flow across nascent species boundaries, particularly for loci not tightly linked to a hybrid sterility gene, may have erased the original pattern of lineage splitting. We propose tests that will allow us to discriminate between these hypotheses.
A Dominant Negative Effect of eth-1r, a Mutant Allele of the Neurospora crassa S-Adenosylmethionine Synthetase-Encoding Gene Conferring Resistance to the Methionine Toxic Analogue Ethionine
Authors: Barra José L , Mautino Mario R , Rosa Alberto L 
Published: January 2021

eth-1r a thermosensitive allele of the Neurospora crassa S-adenosylmethionine (AdoMet) synthetase gene that confers ethionine resistance, has been cloned and sequenced. Replacement of an aspartic amino acid residue (D48 → N48), perfectly conserved in prokaryotic, fungal and higher eukaryotic AdoMet synthetases, was found responsible for both thermosensitivity and ethionine resistance conferred by eth-1r. Gene fusion constructs, designed to overexpress eth-1r in vivo, render transformant cells resistant to ethionine. Dominance of ethionine resistance was further demonstrated in eth-1 +/eth-1r partial diploids carrying identical gene doses of both alleles. Heterozygous eth-1 +/eth-1r cells have, at the same time, both the thermotolerance conferred by eth-1 + and the ethionine-resistant phenotype conferred by eth-1r. AdoMet levels and AdoMet synthetase activities were dramatically decreased in heterozygous eth-1 +/eth-1r cells. We propose that this negative effect exerted by eth-1r results from the in vivo formation of heteromeric eth-1 +/eth-1r AdoMet synthetase molecules.
A Functional Analysis of Notch Mutations in Drosophila
Authors: Brennan Keith , Tateson Richard , Lewis Karen , Arias Alfonso Martinez 
Published: January 2021

Abstract
The Notch gene encodes a receptor protein that is involved in many processes during development. Its best understood role is during neurogenesis in a process called “lateral inhibition.” However, it has been proposed that Notch also has a role in defining the proneural clusters in the first place. This raises the possibility that the Notch protein is acting as a multifunctional receptor. To test this hypothesis, we have carried out a genetic analysis of molecularly characterized Notch alleles to identify alleles that affect only one of the two proposed functions. Here we present evidence that Notch alleles can be identified that appear to affect the function of Notch during either lateral inhibition or the definition of proneural clusters. In addition our results indicate that there may be discrete regions of the Notch protein required for each function.
Polymorphism and Divergence at a Drosophila Pseudogene Locus
Authors: Pritchard Jonathan K , Schaeffer Stephen W 
Published: January 2021

Abstract
The larval cuticle protein (Lcp) cluster in Drosophila melanogaster contains four functional genes and a closely related pseudogene. A 630-bp fragment including the larval cuticle pseudogene locus (Lcpψ) was nucleotide sequenced in 10 strains of D. melanogaster and a 458-bp Lcpψ fragment from D. simulans was also sequenced. We used these data to test the hypotheses that the rates of synonymous and nonsynonymous substitution are equal, that the absolute levels of variation are higher than in functional genes, and that intraspecific polymorphism is correlated with interspecific divergence. As predicted, synonymous and nonsynonymous substitution rates were equivalent, and overall nucleotide divergence between D. melanogaster and D. simulans (Jukes-Cantor distance = 0.149 ± 0.150) was extremely high. However, within-species DNA sequence comparisons at Lcpψ revealed lower levels of polymorphism (ϴ^=0.001±0.001) than at many functional loci in D. melanogaster. Using the Hudson, Kreitman, and Aguade (HKA) test, we show that the level of polymorphism in Lcpψ within D. melanogaster is lower than expected given the amount of divergence between D. melanogaster and D. simulans when the pseudogene data are compared to the Adh 5′ flanking region. Because the Lcpψ lies in a region of relatively infrequent recombination, we suggest that the low level of within-species polymorphism is the result of background selection.
Dissection of a Synthesized Quantitative Trait to Characterize Transgene Interactions
Authors: Nap Jan-Peter , Conner Anthony J , Mlynárová Ludmila , Stiekema Willem J , Jansen Ritsert C 
Published: January 2021

Abstract
Six transgenic tobacco lines, each homozygous for the β-glucuronidase (GUS) gene at a different locus, and wild type were selfed and intercrossed to evaluate GUS activity in all possible hemizygous, homozygous and dihybrid combinations of GUS alleles. The transgenic lines are characterized by their GUS activity (two low, three intermediate, one high), T-DNA complexity (four single-copy, two more complex single-locus) and the presence of the chicken lysozyme matrix-associated region (MAR) around the full T-DNA (two lines). Gene action and interaction was analyzed by weighted linear regression with parameters for additivity, dominance and epistasis. The analysis showed that each of the four single-copy lines acted fully additively. In contrast, the two complex single-locus lines showed classical single-locus overdominance and were epistatic dominant over all other GUS alleles. The latter is manifested in severe suppression of GUS activity in dihybrid lines, irrespective of the presence of MAR elements around the GUS gene. Such elements apparently do not protect against epistatic dominance. The quantitative data suggested that the epistatic dominance and overdominance are based on the same molecular mechanism. Our approach of a genetic analysis of quantitative variation in well-characterized transgenic lines provides a powerful tool to gain insight into complex plant traits.
The Evolution of Recombination: Removing the Limits to Natural Selection
Authors: Otto Sarah Perin , Barton Nick H 
Published: January 2021

One of the oldest hypotheses for the advantage of recombination is that recombination allows beneficial mutations that arise in different individuals to be placed together on the same chromosome. Unless recombination occurs, one of the beneficial alleles is doomed to extinction, slowing the rate at which adaptive mutations are incorporated within a population. We model the effects of a modifier of recombination on the fixation probability of beneficial mutations when beneficial alleles are segregating at other loci. We find that modifier alleles that increase recombination do increase the fixation probability of beneficial mutants and subsequently hitchhike along as the mutants rise in frequency. The strength of selection favoring a modifier that increases recombination is proportional to λ2 Sδr/r when linkage is tight and λ2 S 3δr/N when linkage is loose, where λ is the beneficial mutation rate per genome per generation throughout a population of size N, S is the average mutant effect, r is the average recombination rate, and δr is the amount that recombination is modified. We conclude that selection for recombination will be substantial only if there is tight linkage within the genome or if many loci are subject to directional selection as during periods of rapid evolutionary change.
Bottleneck Effect on Evolutionary Rate in the Nearly Neutral Mutation Model
Authors: Araki Hitoshi , Tachida Hidenori 
Published: January 2021

Variances of evolutionary rates among lineages in some proteins are larger than those expected from simple Poisson processes. This phenomenon is called overdispersion of the molecular clock. If population size N is constant, the overdispersion is observed only in a limited range of 2Nσ under the nearly neutral mutation model, where σ represents the standard deviation of selection coefficients of new mutants. In this paper, we investigated effects of changing population size on the evolutionary rate by computer simulations assuming the nearly neutral mutation model. The size was changed cyclically between two numbers, N 1 and N 2 (N 1 &gt; N 2), in the simulations. The overdispersion is observed if 2N 2σ is less than two and the state of reduced size (bottleneck state) continues for more than ∼0.1/u generations, where u is the mutation rate. The overdispersion results mainly because the average fitnesses of only a portion of populations go down when the population size is reduced and only in these populations subsequent advantageous substitutions occur after the population size becomes large. Since the fitness reduction after the bottleneck is stochastic, acceleration of the evolutionary rate does not necessarily occur uniformly among loci. From these results, we argue that the nearly neutral mutation model is a candidate mechanism to explain the overdispersed molecular clock.
Hardy-Weinberg Testing for Continuous Data
Authors: McIntyre Lauren M , Weir B S 
Published: January 2021

Abstract
Estimation of allelic and genotypic distributions for continuous data using kernel density estimation is discussed and illustrated for some variable number of tandem repeat data. These kernel density estimates provide a useful representation of data when only some of the many variants at a locus are present in a sample. Two Hardy-Weinberg test procedures are introduced for continuous data: a continuous chi-square test with test statistic TCCS and a test based on Hellinger's distance with test statistic TCCS. Simulations are used to compare the powers of these tests to each other and to the powers of a test of intraclass correlation TIC, as well as to the power of Fisher's exact test TFET applied to discretized data. Results indicate that the power of TCCS is better than that of THD but neither is as powerful as TFET. The intraclass correlation test does not perform as well as the other tests examined in this article.
Alu Evolution in Human Populations: Using the Coalescent to Estimate Effective Population Size
Authors: Sherry Stephen T , Harpending Henry C , Batzer Mark A , Stoneking Mark 
Published: January 2021

Abstract
There are estimated to be ~1000 members of the Ya5 Alu subfamily of retroposons in humans. This Subfamily has a distribution restricted to humans, with a few copies in gorillas and chimpanzees. Fifty-seven Ya5 elements were previously cloned from a HeLaderived randomly sheared total genomic library, sequenced, and screened for polymorphism in a panel of 120 unrelated humans. Forty-four of the 57 cloned Alu repeats were monomorphic in the sample and 13 Alu repeats were dimorphic for insertion presence/absence. The observed distribution of sample frequencies of the 13 dimorphic elements is consistent with the theoretical expectation for elements ascertained in a single diploid cell line. Coalescence theory is used to compute expected total pedigree branch lengths for monomorphic and dimorphic elements, leading to an estimate of human effective population size of ~18,000 during the last one to two million years.
Architectural Mediator subunits are differentially essential for global transcription in Saccharomyces cerevisiae
Authors: Tourigny Jason P , Schumacher Kenny , Saleh Moustafa M , Devys Didier , Zentner Gabriel E 
Published: January 2021

Abstract
Mediator is a modular coactivator complex involved in the transcription of the majority of RNA polymerase II-regulated genes. However, the degrees to which individual core subunits of Mediator contribute to its activity have been unclear. Here, we investigate the contribution of two essential architectural subunits of Mediator to transcription in Saccharomyces cerevisiae. We show that acute depletion of the main complex scaffold Med14 or the head module nucleator Med17 is lethal and results in global transcriptional downregulation, though Med17 removal has a markedly greater negative effect. Consistent with this, Med17 depletion impairs preinitiation complex (PIC) assembly to a greater extent than Med14 removal. Co-depletion of Med14 and Med17 reduced transcription and TFIIB promoter occupancy similarly to Med17 ablation alone, indicating that the contributions of Med14 and Med17 to Mediator function are not additive. We propose that, while the structural integrity of complete Mediator and the head module are both important for PIC assembly and transcription, the head module plays a greater role in this process and is thus the key functional module of Mediator in this regard.
Induced polarization of volcanic rocks. 4. Large-scale induced polarization imaging
Authors: Gross L , Soueid Ahmed A , Revil A 
Published: January 2021

SUMMARY
Thanks to the emergence of new technologies developed with the goal of performing large-scale galvanometric induced polarization surveys and thanks a better understanding of the underlying physics of induced polarization, this geophysical method can now be applied in the field of volcanology and geothermal resources assessment. A new approach is developed here for directly inverting the primary and secondary electric fields recorded at a set of independent stations when injecting a primary current. The use of independent stations to measure the primary and secondary electrical fields improves the quality of the data by reducing the capacitive coupling effects inherent to systems based on long cables. It avoids issues associated with using the same electrodes for both current injection and voltage measurements and negative apparent resistivity and chargeability values. With such acquisitions, we can perform true 3-D surveys in areas characterized by complex topography such as volcanoes. The numerical scheme we developed returns as output the electrical conductivity and chargeability fields. The implemented methodology presents several advantages. The first is the use of data types at the stations, for example the electric field intensity, that are independent from the local geometrical station parameters such as electrode spacing and dipole orientation. The second advantage lies in the suitability of the proposed approach to perform large-scale applications since we use a matrix-free approach that does not require the assembly of the Jacobian matrices. The third concerns the possibility of performing the inversion on complex geometries through a consistent use of the finite element method on unstructured meshes in combination with algebraic multigrid preconditioning for the regularization and the solution of the forward and adjoint problems. The computation of 3-D sensitivity maps can also be a real asset in survey design. After validating our approach with a benchmark synthetic case study, we test it on a large-scale induced polarization survey that mimic true field conditions on a volcanic environment with rough topography. Our tests demonstrate the high potential of this electric field approach in volcanology especially for deep (3 km) imagining of the internal structure of volcanoes, which in turn could improve our understanding of hydrothermal systems and allow the monitoring of active volcanoes and the potential risk of collapse.
Linking health information seeking to patient-centered communication and healthy lifestyles: an exploratory study in China
Authors: Zhang Lianshan , Jiang Shaohai 
Published: January 2021

Abstract
The existing research routinely measures the influence of health information-seeking behavior (HISB) as a whole, which does not capture the complexity and diversity of media channel usage in HISB. The influence of HISB on patient’s lifestyle behaviors and the mediation process through patient-centered communication (PCC) in medical encounters has been understudied in previous literature. Drawing from Street’s three-stage model, this study conducted a secondary analysis of the Health Information National Trends Survey in China to investigate the influences of HISB across five different media outlets (e.g. information-oriented media, entertainment-oriented media, search engines, social media and mobile health applications) on two types of healthy lifestyles (e.g. physical activity, fruit and vegetable consumption), by the mediation of PCC. PROCESS path-analysis with bootstrapping estimation was used to test the hypothesized relationships. The results revealed that HISB is positively related to PCC, and PCC positively predicts frequent engagement in healthy lifestyles. Moreover, PCC partially mediates the effect of information-oriented media HISB on healthy lifestyles and fully mediates the effect of HISB through the other four media sources. This study highlights the essential stage of PCC transferring HISB to engagement in healthy lifestyles and draws attention to the varying influences of media channels carrying different characteristics.
Exploring the social and emotional representations used by students from the University of the Basque Country to face the first outbreak of COVID-19 pandemic
Authors: Idoiaga Mondragon Nahia , Berasategi Sancho Naiara , Eiguren Munitis Amaia , Dosil Santamaria Maria 
Published: January 2021

Abstract
In 2020, COVID-19, a new emerging infectious disease (EID), was spread throughout the world, including Europe. Spain, in particular, witnessed a significant outbreak of the pandemic. In consequence, all classes were cancelled and the Government declared a state of emergency, ordering the lockdown of the entire population from March to May. The aim of this research is to explore the impact of the COVID-19 outbreak on the representations of young university students from the University of the Basque Country and their emotional response when the crisis started. A free-association exercise was completed by 503 students from the University of the Basque Country (UPV/EHU) (Northern Spain). To analyze the content, the Reinert method was used with the Iramuteq software for lexical analysis. The results showed that students placed COVID-19 at a distance from the self, pointing out issues related to social response and disinformation, while showing concerns for self-related issues that are linked to negative emotions, academic consequences, and potentially close victims. The students’ concerns were categorized at four main levels: the communicative-informative level, health-emotional level, community-social level, and academic level. All of this has created overwhelming feelings of nervousness, along with anger and emotional fatigue. These results indicate the necessity for universities to work from a holistic standpoint, not only in terms of responding to academic needs but also from psychological, communicative, social, health, and well-being perspectives.
Occurrence of Colorectal Cancer and the Influence of Medical Treatment in Patients With Inflammatory Bowel Disease: A Danish Nationwide Cohort Study, 1997 to 2015
Authors: Weimers Petra , Ankersen Dorit Vedel , Løkkegaard Ellen Christine Leth , Burisch Johan , Munkholm Pia 
Published: January 2021

Abstract

Background
The risk of colorectal cancer (CRC) for patients with inflammatory bowel disease (IBD) has previously been investigated with conflicting results. We aimed to investigate the incidence and risk of CRC in IBD, focusing on its modification by treatment.

Methods
All patients with incident IBD (n = 35,908) recorded in the Danish National Patient Register between 1997 and 2015 (ulcerative colitis: n = 24,102; Crohn’s disease: n = 9739; IBD unclassified: n = 2067) were matched to approximately 50 reference individuals (n = 1,688,877). CRC occurring after the index date was captured from the Danish Cancer Registry. Exposure to medical treatment was divided into categories including none, systemic 5-aminosalicylates, immunomodulators, and biologic treatment. The association between IBD and subsequent CRC was investigated by Cox regression and Kaplan-Meier estimates.

Results
Of the IBD patients, 330 were diagnosed with CRC, resulting in a hazard ratio (HR) of 1.15 (95% confidence interval [CI], 1.03-1.28) as compared with the reference individuals. However, when excluding patients diagnosed with CRC within 6 months of their IBD diagnosis, the HR decreased to 0.80 (95% CI, 0.71-0.92). Patients with ulcerative colitis receiving any medical treatment were at significantly higher risk of developing CRC than patients with ulcerative colitis who were not given medical treatment (HR, 1.35; 95% CI, 1.01-1.81), whereas a similar effect of medical treatment was not observed in patients with Crohn’s disease or IBD unclassified.

Conclusions
Medical treatment does not appear to affect the risk of CRC in patients with IBD. The overall risk of developing CRC is significantly increased in patients with IBD as compared with the general population. However, when excluding patients diagnosed with CRC within 6 months of their IBD diagnosis, the elevated risk disappears.