bluuebunny/crossref_metadata_2025 huggingface dataset:
Social and spatial conflict drive resident aggression toward outsiders in a group-living fish
Authors: Gübel Jakob , Bose Aneesh P H , Jordan Alex
Published: April 2021

Group-living animals often experience within-group competition for resources like shelter and space, as well as for social status. Because of this conflict, residents may aggressively resist joining attempts by new members. Here, we asked whether different forms of competition mediate this response, specifically competition over 1) shelter, 2) spatial position within groups, and 3) social or sexual roles. We performed experiments on wild groups of Neolamprologus multifasciatus cichlids in Lake Tanganyika, either increasing or decreasing the number of shelters (empty snail shells) within their territories. We predicted that increases in resource abundance would reduce conflict and lower the aggression of residents toward presented conspecifics, while decreases in resources would increase aggression. We explored the effects of social conflict and spatial arrangement by introducing same or opposite sex conspecifics, at greater or lesser distances from resident subterritories. We found that changing the abundance of shells had no detectable effect on the responses of residents to presented conspecifics. Rather, aggression was strongly sex-dependent, with male residents almost exclusively aggressing presented males, and female residents almost exclusively aggressing presented females. For females, this aggression was influenced by the spatial distances between the presented conspecific and the resident female subterritory, with aggression scaling with proximity. In contrast, presentation distance did not influence resident males, which were aggressive to all presented males regardless of location. Overall, our results show that group residents respond to presented conspecifics differently depending on the type of competitive threat these potential joiners pose.
ARAMIS: From systematic errors of NGS long reads to accurate assemblies
Authors: Sacristán-Horcajada E , González-de la Fuente S , Peiró-Pastor R , Carrasco-Ramiro F , Amils R , Requena J M , Berenguer J , Aguado B
Published: April 2021

NGS long-reads sequencing technologies (or third generation) such as Pacific BioSciences (PacBio) have revolutionized the sequencing field over the last decade improving multiple genomic applications like de novo genome assemblies. However, their error rate, mostly involving insertions and deletions (indels), is currently an important concern that requires special attention to be solved. Multiple algorithms are available to fix these sequencing errors using short reads (such as Illumina), although they require long processing times and some errors may persist.

Here, we present Accurate long-Reads Assembly correction Method for Indel errorS (ARAMIS), the first NGS long-reads indels correction pipeline that combines several correction software in just one step using accurate short reads. As a proof OF concept, six organisms were selected based on their different GC content, size and genome complexity, and their PacBio-assembled genomes were corrected thoroughly by this pipeline. We found that the presence of systematic sequencing errors in long-reads PacBio sequences affecting homopolymeric regions, and that the type of indel error introduced during PacBio sequencing are related to the GC content of the organism. The lack of knowledge of this fact leads to the existence of numerous published studies where such errors have been found and should be resolved since they may contain incorrect biological information.

ARAMIS yields better results with less computational resources needed than other correction tools and gives the possibility of detecting the nature of the found indel errors found and its distribution along the genome. The source code of ARAMIS is available at https://github.com/genomics-ngsCBMSO/ARAMIS.git
A machine learning framework to predict antibiotic resistance traits and yet unknown genes underlying resistance to specific antibiotics in bacterial strains
Authors: Sunuwar Janak , Azad Rajeev K
Published: April 2021

Recently, the frequency of observing bacterial strains without known genetic components underlying phenotypic resistance to antibiotics has increased. There are several strains of bacteria lacking known resistance genes; however, they demonstrate resistance phenotype to drugs of that family. Although such strains are fewer compared to the overall population, they pose grave emerging threats to an already heavily challenged area of antimicrobial resistance (AMR), where death tolls have reached ~700 000 per year and a grim projection of ~10 million deaths per year by 2050 looms. Considering the fact that development of novel antibiotics is not keeping pace with the emergence and dissemination of resistance, there is a pressing need to decipher yet unknown genetic mechanisms of resistance, which will enable developing strategies for the best use of available interventions and show the way for the development of new drugs. In this study, we present a machine learning framework to predict novel AMR factors that are potentially responsible for resistance to specific antimicrobial drugs. The machine learning framework utilizes whole-genome sequencing AMR genetic data and antimicrobial susceptibility testing phenotypic data to predict resistance phenotypes and rank AMR genes by their importance in discriminating the resistance from the susceptible phenotypes. In summary, we present here a bioinformatics framework for training machine learning models, evaluating their performances, selecting the best performing model(s) and finally predicting the most important AMR loci for the resistance involved.
Chrom-Lasso: a lasso regression-based model to detect functional interactions using Hi-C data
Authors: Lu Jingzhe , Wang Xu , Sun Keyong , Lan Xun
Published: April 2021

Hi-C is a genome-wide assay based on Chromosome Conformation Capture and high-throughput sequencing to decipher 3D chromatin organization in the nucleus. However, computational methods to detect functional interactions utilizing Hi-C data face challenges including the correction for various sources of biases and the identification of functional interactions with low counts of interacting fragments. We present Chrom-Lasso, a lasso linear regression model that removes complex biases assumption-free and identifies functional interacting loci with increased power by combining information of local reads distribution surrounding the area of interest. We showed that interacting regions identified by Chrom-Lasso are more enriched for 5C validated interactions and functional GWAS hits than that of GOTHiC and Fit-Hi-C. To further demonstrate the ability of Chrom-Lasso to detect interactions of functional importance, we performed time-series Hi-C and RNA-seq during T cell activation and exhaustion. We showed that the dynamic changes in gene expression and chromatin interactions identified by Chrom-Lasso were largely concordant with each other. Finally, we experimentally confirmed Chrom-Lasso’s finding that Erbb3 was co-regulated with distinct neighboring genes at different states during T cell activation. Our results highlight Chrom-Lasso’s utility in detecting weak functional interaction between cis-regulatory elements, such as promoters and enhancers.
Assessing the performance of computational predictors for estimating protein stability changes upon missense mutations
Authors: Iqbal Shahid , Li Fuyi , Akutsu Tatsuya , Ascher David B , Webb Geoffrey I , Song Jiangning
Published: April 2021

Understanding how a mutation might affect protein stability is of significant importance to protein engineering and for understanding protein evolution genetic diseases. While a number of computational tools have been developed to predict the effect of missense mutations on protein stability protein stability upon mutations, they are known to exhibit large biases imparted in part by the data used to train and evaluate them. Here, we provide a comprehensive overview of predictive tools, which has provided an evolving insight into the importance and relevance of features that can discern the effects of mutations on protein stability. A diverse selection of these freely available tools was benchmarked using a large mutation-level blind dataset of 1342 experimentally characterised mutations across 130 proteins from ThermoMutDB, a second test dataset encompassing 630 experimentally characterised mutations across 39 proteins from iStable2.0 and a third blind test dataset consisting of 268 mutations in 27 proteins from the newly published ProThermDB. The performance of the methods was further evaluated with respect to the site of mutation, type of mutant residue and by ranging the pH and temperature. Additionally, the classification performance was also evaluated by classifying the mutations as stabilizing (∆∆G ≥ 0) or destabilizing (∆∆G < 0). The results reveal that the performance of the predictors is affected by the site of mutation and the type of mutant residue. Further, the results show very low performance for pH values 6–8 and temperature higher than 65 for all predictors except iStable2.0 on the S630 dataset. To illustrate how stability and structure change upon single point mutation, we considered four stabilizing, two destabilizing and two stabilizing mutations from two proteins, namely the toxin protein and bovine liver cytochrome. Overall, the results on S268, S630 and S1342 datasets show that the performance of the integrated predictors is better than the mechanistic or individual machine learning predictors. We expect that this paper will provide useful guidance for the design and development of next-generation bioinformatic tools for predicting protein stability changes upon mutations.
Circles of Peace. A Video Analysis of Situational Group Formation and Collective Third-Party Intervention in Violent Incidents
Authors: Weenink Don , Dhattiwala Raheel , van der Duin David
Published: April 2021

We seek to understand collective third-party intervention in violent incidents. Based on analyses of 131 video clips captured on mobile phones, we argue that bodily alignment between bystanders creates situational groups that encourage collective de-escalatory action. Qualitative analysis reveals that third parties generate situational groups when they create circular formations, providing greater opportunities to notice each other’s monitoring of the situation while separating those focused on the incident from others just passing by. Statistical analysis shows that the formation of situational groups facilitates the collectivization of de-escalatory action. In contrast to popular but outdated ideas about the dangerous influence of assemblies on individual behaviour (allegedly leading to disorder or apathy), our findings emphasize the self-regulatory, defusing capacity of gatherings.
An in vivo Caenorhabditis elegans model for therapeutic research in human prion diseases
Authors: Bizat Nicolas , Parrales Valeria , Laoues Sofian , Normant Sébastien , Levavasseur Etienne , Roussel Julian , Privat Nicolas , Gougerot Alexianne , Ravassard Philippe , Beaudry Patrice , Brandel Jean-Philippe , Laplanche Jean-Louis , Haïk Stéphane
Published: April 2021

Human prion diseases are fatal neurodegenerative disorders that include sporadic, infectious and genetic forms. Inherited Creutzfeldt-Jakob disease due to the E200K mutation of the prion protein-coding gene is the most common form of genetic prion disease. The phenotype resembles that of sporadic Creutzfeldt-Jakob disease at both the clinical and pathological levels, with a median disease duration of 4 months. To date, there is no available treatment for delaying the occurrence or slowing the progression of human prion diseases. Existing in vivo models do not allow high-throughput approaches that may facilitate the discovery of compounds targeting pathological assemblies of human prion protein or their effects on neuronal survival.

Here, we generated a genetic model in the nematode Caenorhabditis elegans, which is devoid of any homologue of the prion protein, by expressing human prion protein with the E200K mutation in the mechanosensitive neuronal system.

Expression of E200K prion protein induced a specific behavioural pattern and neurodegeneration of green fluorescent protein-expressing mechanosensitive neurons, in addition to the formation of intraneuronal inclusions associated with the accumulation of a protease-resistant form of the prion protein. We demonstrated that this experimental system is a powerful tool for investigating the efficacy of anti-prion compounds on both prion-induced neurodegeneration and prion protein misfolding, as well as in the context of human prion protein. Within a library of 320 compounds that have been approved for human use and cross the blood–brain barrier, we identified five molecules that were active against the aggregation of the E200K prion protein and the neurodegeneration it induced in transgenic animals.

This model breaks a technological limitation in prion therapeutic research and provides a key tool to study the deleterious effects of misfolded prion protein in a well-described neuronal system.
Plasma amyloid-β ratios in autosomal dominant Alzheimer’s disease: the influence of genotype
Authors: O'Connor Antoinette , Pannee Josef , Poole Teresa , Arber Charles , Portelius Erik , Swift Imogen J , Heslegrave Amanda J , Abel Emily , Willumsen Nanet , Rice Helen , Weston Philip S J , Ryan Natalie S , Polke James M , Nicholas Jennifer M , Mead Simon , Wray Selina , Chávez-Gutiérrez Lucía , Frost Chris , Blennow Kaj , Zetterberg Henrik , Fox Nick C
Published: April 2021

In vitro studies of autosomal dominant Alzheimer’s disease implicate longer amyloid-β peptides in disease pathogenesis; however, less is known about the behaviour of these mutations in vivo. In this cross-sectional cohort study, we used liquid chromatography-tandem mass spectrometry to analyse 66 plasma samples from individuals who were at risk of inheriting a mutation or were symptomatic. We tested for differences in amyloid-β (Aβ)42:38, Aβ42:40 and Aβ38:40 ratios between presenilin 1 (PSEN1) and amyloid precursor protein (APP) carriers. We examined the relationship between plasma and in vitro models of amyloid-β processing and tested for associations with parental age at onset. Thirty-nine participants were mutation carriers (28 PSEN1 and 11 APP). Age- and sex-adjusted models showed marked differences in plasma amyloid-β between genotypes: higher Aβ42:38 in PSEN1 versus APP (P < 0.001) and non-carriers (P < 0.001); higher Aβ38:40 in APP versus PSEN1 (P < 0.001) and non-carriers (P < 0.001); while Aβ42:40 was higher in both mutation groups compared to non-carriers (both P < 0.001). Amyloid-β profiles were reasonably consistent in plasma and cell lines. Within the PSEN1 group, models demonstrated associations between Aβ42:38, Aβ42:40 and Aβ38:40 ratios and parental age at onset. In vivo differences in amyloid-β processing between PSEN1 and APP carriers provide insights into disease pathophysiology, which can inform therapy development.
Impaired sensory evidence accumulation and network function in Lewy body dementia
Authors: O’Callaghan Claire , Firbank Michael , Tomassini Alessandro , Schumacher Julia , O’Brien John T , Taylor John-Paul
Published: April 2021

Deficits in attention underpin many of the cognitive and neuropsychiatric features of Lewy body dementia. These attention-related symptoms remain difficult to treat and there are many gaps in our understanding of their neurobiology. An improved understanding of attention-related impairments can be achieved via mathematical modelling approaches, which identify cognitive parameters to provide an intermediate level between observed behavioural data and its underlying neural correlate. Here, we apply this approach to identify the role of impaired sensory evidence accumulation in the attention deficits that characterize Lewy body dementia. In 31 people with Lewy body dementia (including 13 Parkinson’s disease dementia and 18 dementia with Lewy bodies cases), 16 people with Alzheimer’s disease, and 23 healthy controls, we administered an attention task whilst they underwent functional 3 T MRI. Using hierarchical Bayesian estimation of a drift-diffusion model, we decomposed task performance into drift rate and decision boundary parameters. We tested the hypothesis that the drift rate—a measure of the quality of sensory evidence accumulation—is specifically impaired in Lewy body dementia, compared to Alzheimer’s disease. We further explored whether trial-by-trial variations in the drift rate related to activity within the default and dorsal attention networks, to determine whether altered activity in these networks was associated with slowed drift rates in Lewy body dementia. Our results revealed slower drift rates in the Lewy body dementia compared to the Alzheimer’s disease group, whereas the patient groups were equivalent for their decision boundaries. The patient groups were reduced relative to controls for both parameters. This highlights sensory evidence accumulation deficits as a key feature that distinguishes attention impairments in Lewy body dementia, consistent with impaired ability to efficiently process information from the environment to guide behaviour. We also found that the drift rate was strongly related to activity in the dorsal attention network across all three groups, whereas the Lewy body dementia group showed a divergent relationship relative to the Alzheimer’s disease and control groups for the default network, consistent with altered default network modulation being associated with impaired evidence accumulation. Together, our findings reveal impaired sensory evidence accumulation as a specific marker of attention problems in Lewy body dementia, which may relate to large-scale network abnormalities. By identifying impairments in a specific sub-process of attention, these findings will inform future exploratory and intervention studies that aim to understand and treat attention-related symptoms that are a key feature of Lewy body dementia.
Musical Expertise Is Associated with Improved Neural Statistical Learning in the Auditory Domain
Authors: Pesnot Lerousseau Jacques , Schön Daniele
Published: April 2021

It is poorly known whether musical training is associated with improvements in general cognitive abilities, such as statistical learning (SL). In standard SL paradigms, musicians have shown better performances than nonmusicians. However, this advantage could be due to differences in auditory discrimination, in memory or truly in the ability to learn sequence statistics. Unfortunately, these different hypotheses make similar predictions in terms of expected results. To dissociate them, we developed a Bayesian model and recorded electroencephalography (EEG). Our results confirm that musicians perform approximately 15% better than nonmusicians at predicting items in auditory sequences that embed either low or high-order statistics. These higher performances are explained in the model by parameters governing the learning of high-order statistics and the selection stage noise. EEG recordings reveal a neural underpinning of the musician’s advantage: the P300 amplitude correlates with the surprise elicited by each item, and so, more strongly for musicians. Finally, early EEG components correlate with the surprise elicited by low-order statistics, as opposed to late EEG components that correlate with the surprise elicited by high-order statistics and this effect is stronger for musicians. Overall, our results demonstrate that musical expertise is associated with improved neural SL in the auditory domain.

Significance statement

It is poorly known whether musical training leads to improvements in general cognitive skills. One fundamental cognitive ability, SL, is thought to be enhanced in musicians, but previous studies have reported mixed results. This is because such musician’s advantage can embrace very different explanations, such as improvement in auditory discrimination or in memory. To solve this problem, we developed a Bayesian model and recorded EEG to dissociate these explanations. Our results reveal that musical expertise is truly associated with an improved ability to learn sequence statistics, especially high-order statistics. This advantage is reflected in the electroencephalographic recordings, where the P300 amplitude is more sensitive to surprising items in musicians than in nonmusicians.
Design of Multidrug-Resistant Tuberculosis Treatment Regimens Based on DNA Sequencing
Authors: Grobbel Hans-Peter , Merker Matthias , Köhler Niklas , Andres Sönke , Hoffmann Harald , Heyckendorf Jan , Reimann Maja , Barilar Ivan , Dreyer Viola , Hillemann Doris , Kalsdorf Barbara , Kohl Thomas A , Sanchez Carballo Patricia , Schaub Dagmar , Todt Katharina , Utpatel Christian , Maurer Florian P , Lange Christoph , Niemann Stefan
Published: April 2021

Background

Comprehensive and reliable drug susceptibility testing (DST) is urgently needed to provide adequate treatment regimens for patients with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). We determined whether next-generation sequencing (NGS) analysis of Mycobacterium tuberculosis complex isolates and genes implicated in drug resistance can guide the design of effective MDR/RR-TB treatment regimens.

Methods

NGS-based genomic DST predictions of M. tuberculosis complex isolates from MDR/RR-TB patients admitted to a TB reference center in Germany between 1 January 2015 and 30 April 2019 were compared with phenotypic DST results of mycobacteria growth indicator tubes (MGIT). Standardized treatment algorithms were applied to design individualized therapies based on either genomic or phenotypic DST results, and discrepancies were further evaluated by determination of minimal inhibitory drug concentrations (MICs) using Sensititre MYCOTBI and UKMYC microtiter plates.

Results

In 70 patients with MDR/RR-TB, agreement among 1048 pairwise comparisons of genomic and phenotypic DST was 86.3%; 76 (7.2%) results were discordant, and 68 (6.5%) could not be evaluated due to the presence of polymorphisms with yet unknown implications for drug resistance. Importantly, 549 of 561 (97.9%) predictions of drug susceptibility were phenotypically confirmed in MGIT, and 27 of 64 (42.2%) false-positive results were linked to previously described mutations mediating a low or moderate MIC increase. Virtually all drugs (99.0%) used in combination therapies that were inferred from genomic DST were confirmed to be susceptible by phenotypic DST.

Conclusions

NGS-based genomic DST can reliably guide the design of effective MDR/RR-TB treatment regimens.
Efficacy and Safety of Tofacitinib Re-treatment for Ulcerative Colitis After Treatment Interruption: Results from the OCTAVE Clinical Trials
Authors: Panés Julian , Vermeire Séverine , Dubinsky Marla C , Loftus Edward V , Lawendy Nervin , Wang Wenjin , Salese Leonardo , Su Chinyu , Modesto Irene , Guo Xiang , Colombel Jean-Frederic
Published: April 2021

Background and Aims

Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. Here, we evaluate the efficacy and safety of tofacitinib re-treatment following treatment interruption in patients with ulcerative colitis.

Methods

Here, patients with clinical response to tofacitinib 10 mg b.d. induction therapy were randomised to receive placebo in OCTAVE Sustain. Those experiencing treatment failure after Week 8 of OCTAVE Sustain entered OCTAVE Open and re-initiated tofacitinib 10 mg b.d. [re-treatment subpopulation]; efficacy and safety data are presented up to Month 36 of OCTAVE Open.

Results

Median time to treatment failure following interruption was 169 (95% confidence interval [CI], 94.0–179.0) and 123 [95% CI, 91.0–168.0] days for induction remitters, and induction responders but non-remitters, respectively. Following re-treatment with tofacitinib, rates (non-responder imputation after a patient discontinued; latest observation carried forward imputation after a patient advanced to a subsequent study [NRI-LOCF]) of clinical response, remission, and endoscopic improvement were 74.0%, 39.0%, and 55.0% at Month 2, and 48.5%, 37.4%, and 42.4% at Month 36, respectively. Among induction remitters and induction responders but non-remitters, clinical response rates at Month 36 were 60.6% and 42.4% [NRI-LOCF], respectively. Efficacy was recaptured regardless of prior tumour necrosis factor inhibitor failure status. The safety profile of tofacitinib 10 mg b.d. re-treatment was consistent with the overall cohort and demonstrated no new safety risks associated with exposure of ≤36 months.

Conclusions

Median time to treatment failure was numerically higher in induction remitters versus induction responders but non-remitters. Following treatment interruption, efficacy was safely and successfully recaptured with tofacitinib 10 mg b.d. re-treatment in a substantial proportion of patients [ClinicalTrials.gov:NCT01458574;NCT01470612].
Long-term mortality in patients with ischaemic heart failure revascularized with coronary artery bypass grafting or percutaneous coronary intervention: insights from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)
Authors: Völz Sebastian , Redfors Björn , Angerås Oskar , Ioanes Dan , Odenstedt Jacob , Koul Sasha , Valeljung Inger , Dworeck Christian , Hofmann Robin , Hansson Emma , Venetsanos Dimitrios , Ulvenstam Anders , Jernberg Tomas , Råmunddal Truls , Pétursson Pétur , Fröbert Ole , Erlinge David , Jeppsson Anders , Omerovic Elmir
Published: April 2021

Aims 

To compare coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for treatment of patients with heart failure due to ischaemic heart disease.

Methods and results 

We analysed all-cause mortality following CABG or PCI in patients with heart failure with reduced ejection fraction and multivessel disease (coronary artery stenosis >50% in ≥2 vessels or left main) who underwent coronary angiography between 2000 and 2018 in Sweden. We used a propensity score-adjusted logistic and Cox proportional-hazards regressions and instrumental variable model to adjust for known and unknown confounders. Multilevel modelling was used to adjust for the clustering of observations in a hierarchical database. In total, 2509 patients (82.9% men) were included; 35.8% had diabetes and 34.7% had a previous myocardial infarction. The mean age was 68.1 ± 9.4 years (47.8% were >70 years old), and 64.9% had three-vessel or left main disease. Primary designated therapy was PCI in 56.2% and CABG in 43.8%. Median follow-up time was 3.9 years (range 1 day to 10 years). There were 1010 deaths. Risk of death was lower after CABG than after PCI [odds ratio (OR) 0.62; 95% confidence interval (CI) 0.41–0.96; P = 0.031]. The risk of death increased linearly with quintiles of hospitals in which PCI was the preferred method for revascularization (OR 1.27, 95% CI 1.17–1.38, P  trend < 0.001).

Conclusion 

In patients with ischaemic heart failure, long-term survival was greater after CABG than after PCI.
Salt reduction to prevent hypertension: the reasons of the controversy
Authors: He Feng J , Campbell Norm R C , Woodward Mark , MacGregor Graham A
Published: April 2021

There is a causal relationship between dietary salt intake and blood pressure. A reduction in salt intake from the current world average of ∼10 g/day to the WHO recommended level of <5 g/day, lowers blood pressure and reduces the risk of cardiovascular disease and all-cause mortality. However, a few cohort studies have claimed that there is a J-shaped relationship between salt intake and cardiovascular risk, i.e. both high and low salt intakes are associated with an increased risk. These cohort studies have several methodological problems, including reverse causality, and inaccurate and biased estimation of salt intake, e.g. from a single spot urine sample with formulas. Recent studies have shown that the formulas used to estimate salt intake from spot urine cause a spurious J-curve. Research with inappropriate methodology should not be used to refute the robust evidence on the enormous benefits of population-wide reduction in salt intake. Several countries, e.g. Finland, the UK, have successfully reduced salt intake, which has resulted in falls in population blood pressure and deaths from stroke and ischaemic heart disease. Every country should develop and implement a coherent, workable strategy to reduce salt intake. Even a modest reduction in salt intake across the whole population will lead to a major improvement in public health, along with huge cost-savings to the healthcare service.
Soil fungal diversity and community assembly: affected by island size or type?
Authors: Zheng Yong , Maitra Pulak , Gan Hui-Yun , Chen Liang , Li Shengchun , Tu Tieyao , Chen Lei , Mi Xiangcheng , Gao Cheng , Zhang Dianxiang , Guo Liang-Dong
Published: April 2021

Fungi have a huge biodiversity and play important roles in soil biogeochemical cycling in island ecosystems. Although island biogeography has been widely studied for macroorganisms, fungal community assembly in true islands and its relationship with island area are less documented. We examined soil fungal communities in 18 oceanic islands of two types (eight non-coral islands and 10 coral islands) using the Illumina MiSeq sequencing technique. Our results showed that fungal α-diversity (species richness) was substantially different among the oceanic islands, with a higher value in non-coral islands than in coral islands. Fungal α-diversity was significantly affected by soil potassium and magnesium (Mg) and plant communities in non-coral islands, whereas only soil Mg significantly affected it in coral islands. Soil fungal community composition was significantly different in the non-coral and coral islands and was influenced by soil property, plant community and spatial distance. The ecological stochasticity model showed that the fungal community assembly was mainly governed by deterministic processes regardless of island type. Fungal β-diversity, but not α-diversity, increased significantly with increasing island area. These findings have implications for the better prediction of soil fungal community dynamics in island systems and biodiversity conservation in fragmented habitats.
CONTROL OF FEMALE REPRODUCTION IN DROSOPHILA: GENETIC DISSECTION USING GYNANDROMORPHS
Authors: Szabad János , Fajszi Csaba
Published: April 2021

The sexual behavior of Drosophila melanogaster gynandromorphs was studied to analyze the relationship between different steps in the female reproductive pathway. It was assumed that, in some gynandromorphs, certain female functions are missing because the corresponding control sites (foci) are either composed of male tissue or did not develop. A given gynandromorph can show elements of both male and female reproductive pathways. None of the steps of the female reproductive pathway appeared to be dependent on any other, in contrast to male behavior where, for example, following of females is a prerequisite for attempted copulation. By correlating each of the behaviors with the genotype of the cuticle, we confirmed previous findings that the focus for the female sex appeal is located in the abdomen, but receptivity to copulation is controlled by a site in the head. Many of the gynandromorphs did not lay eggs, presumably because either the focus controlling egg transfer from the ovaries to the uterus or the one controlling egg deposition was composed of male tissue. Many of the nonovipositing gynandromorphs laid eggs while dying or could be induced to deposit eggs after implantation of hormone-producing glands or topical application of a juvenile hormone analog. Some of the noninseminated gynandromorphs laid eggs at the rate characteristic for inseminated females, suggesting that an oviposition focus (mapping in the head region) suppresses oviposition in virgin females, but not in gynandromorphs whose focus is composed of male tissue. Some of the inseminated gynandromorphs oviposited eggs at a low rate, possibly because the focus responsible for detection of insemination could not function properly. Some of the inseminated gynandromorphs laid unfertilized eggs, revealing the importance of the focus controlling sperm release from the seminal receptacle. Foci controlling egg transfer, egg deposition and sperm release are located in the thorax, according to mosaic fate mapping results and studies on the reproductive behavior of decapitated females. The location of egg deposition in the culture vial seems to be controlled by a brain site. Sexual behavior in Drosophila does not depend on the presence (or absence) of the ovary or germ line.
THE ROLE OF S. CEREVISIAE CELL DIVISION CYCLE GENES IN NUCLEAR FUSION
Authors: Dutcher Susan K , Hartwell Leland H
Published: April 2021

Forty temperature-sensitive cell division cycle (cdc) mutants of Saccharomyces cerevisiae were examined for their ability to complete nuclear fusion during conjugation in crosses to a CDC parent strain at the restrictive temperature. Most of the cdc mutant alleles behaved as the CDC parent strain from which they were derived, in that zygotes produced predominantly diploid progeny with only a small fraction of zygotes giving rise to haploid progeny (cytoductants) that signalled a failure in nuclear fusion. However, cdc4 mutants exhibited a strong nuclear fusion (karyogamy) defect in crosses to a CDC parent and cdc28, cdc34 and cdc37 mutants exhibited a weak karyogamy defect. For all four mutants, the karyogamy defect and the cell cycle defect cosegregated, suggesting that both defects resulted from a single lesion for each of these cdc mutants. Therefore, the cdc 4, 28, 34 and 37 gene products are required in both cell division and karyogamy.
POSITIVE REGULATION IN A EUKARYOTE, A STUDY OF THE uaY GENE OF ASPERGILLUS NIDULANS: I. CHARACTERIZATION OF ALLELES, DOMINANCE AND COMPLEMENTATION STUDIES, AND A FINE STRUCTURE MAP OF THE uaY - oxpA CLUSTER
Authors: Scazzocchio Claudio , Sdrin Nicholas , Ong Gloria
Published: April 2021

In this paper we characterize genetically a positive eukaryotic regulatory gene: the uaY gene of the ascomycete Aspergillus nidulans. Several steps in the uptake and degradation of purines are under the control of the uaY gene (summarized in Scazzocchio and Gorton 1977). In the present paper 12 uaY- mutations are characterized with respect to their inducibility for adenine deaminase, xanthine dehydrogenase (purine hydroxylase I) and urate oxidase and by the absence of the uric acid-xanthine permease scored in vivo by resistance to 2-thiouric acid. While 10 mutations are uniformly unleaky, two others are almost wild type for the induction of urate oxidase. A fine structure map of the uaY gene shows that the two "leaky" mutations are not clustered. The fine structure mapping unambiguously positions six uaY alleles and provides preliminary but interesting trends regarding the pattern of gene conversion in the uaY gene. The enzyme levels in all uaY-/uaY+ heterozygous diploids are intermediate between the corresponding uaY-/uaY- and uaY+/uaY+ homozygous diploids, suggesting that one functional copy of the uaY gene is able to mediate the complete induction of only one set of structural genes. No complementation was found between any two uaY- alleles. This establishes that the mutations showing either of the phenotypes are alleles in the same gene; it fails to provide evidence for intracistronic complementation. A mutation, oxpA5, causes resistance to the xanthine analogue oxypurinol (4, 6-dihydroxypyrazolo-(3, 4-d)-pyrimidine) and partial constitutivity of adenine deaminase, xanthine dehydrogenase (purine hydroxylase I) and urate oxidase. The constitutive phenotype is suppressed by mutations blocking the synthesis of intracellular inducers. The mutation is recessive and complements fully with the 11 uaY- mutations tested. It maps to the left of all 12 uaY mutations to which it has been crossed. The data indicate that both the resistance and constitutivity arise from one mutational event in a gene, oxpA, different from uaY and possibly adjacent to it. We propose that the oxpA gene codes for a protein involved in limiting the flow of inducers into the cell nucleus. Thus oxpA and uaY constitute a regulatory gene cluster, indicating that uaY is the regulatory gene.
PARALOG, A CONTROL MUTANT IN DROSOPHILA MELANOGASTER
Authors: Thierry-Mieg Danielle
Published: April 2021

The genetic properties of a pleiotropic mutant mapping at 1.4 ± 0.1 in band 3B3 or its adjacent interbands on the X chromosome are described. The mutation is expressed autonomously in germ line cells, where it is recessive and has antimorphic properties. At 29°, the mutation blocks oocyte differentiation, causing female sterility. At lower temperatures, it disturbs the maternal information in the egg; as a result, the progeny lack germ line cells (grandchildless phenotype) and exhibit defects of the cuticular pattern. The mutation is also expressed in somatic cells through zygotic interactions with neighboring regions, including 3A2, 3A3 (zeste), 3C1-2, 3C4 and 3C6-8 (Notch). We interpret the data by postulating that the expression of sets of dispersed genes might be controlled by the local topology of the chromosome, itself constrained by pairing of dispersed repeated elements. We call the mutation paralog.
AN ASSESSMENT OF ARSENATE SELECTION AS A METHOD FOR OBTAINING NONPHOTOSYNTHETIC MUTANTS OF CHLAMYDOMONAS
Authors: Spreitzer Robert J , Mets Laurens
Published: April 2021

It has been proposed that the absence of photosynthesis in Chlamydomonas reinhardii produces a relative arsenate resistance and that selection for arsenate resistance therefore serves as an enrichment for nonphotosynthetic mutants (Togasaki and Hudock 1972; Harris, Boynton and Gillham 1974). We have found that: 1. mutants selected for arsenate resistance are not substantially enriched for acetate-requiring mutants as compared with unselected cells; 2. none of the acetate-requiring mutants we obtained without arsenate selection are arsenate resistant; 3. the acetate-requiring mutants obtained following arsenate selection are all capable of CO2 fixation, suggesting that they do not have a major lesion in primary photosynthetic processes; 4. in most acetate-requiring mutants selected on arsenate medium, the arsenate-resistant and acetate-requiring characters segregate from one another during meiosis, indicating that these two characters arose independently. We conclude that if any enrichment is provided by selecting for arsenate resistance, it is for only a subclass of acetate requirers that are not obviously defective in photosynthesis.
LONG-TERM RESPONSE TO SELECTION I. RELATION TO BREEDING POPULATION SIZE, INTENSITY, AND ACCURACY WITH ADDITIVE GENE ACTION
Authors: Harris Dewey L
Published: April 2021

Dual CDC-6500 computers were used to simulate the probabilistic aspects of genetic selection and reproduction in random mating populations with additive gene action. These simulations involved either 10 or 20 replicates of 200 consecutive nonoverlapping generations for 72 combinations of breeding population sizes, mating ratios, selection intensities, and accuracies of genetic determination of quantitative phenotypes. The results demonstrate that at least some long-term responses can be characterized by modified exponential functions that, with increasing generations, approach asymptotically to limits whose expectations increase linearly with the inverse tangent of multiples of the expected initial responses. The multiplicative constants are greater for populations with large effective breeding population size than for those of smaller size. Agreement with and discrepancies from past theoretical results are discussed. The supposition is made that the general form of these equations will be retained for broader situations than those simulated, but probably not for nonadditive gene action.
TEMPERATURE-SENSITIVE, ASSEMBLY-DEFECTIVE FLAGELLA MUTANTS OF CHLAMYDOMONAS REINHARDTII
Authors: Adams G Mike W , Huang Bessie , Luck David J L
Published: April 2021

We describe an efficient selection procedure for the isolation of mutants of Chlamydomonas reinhardtii with temperature sensitive flagella defects, with final yields of up to 11% of the population being mutant. Several mutants, all showing an inability to maintain flagellar integrity at the restrictive temperature, are described. We have examined flagellar stability and reassembly at various temperatures in the mutants. Mapping data are provided for these, as well as for some previously described mutants.
A MUTATOR FACTOR IN A STRAIN OF DROSOPHILA MELANOGASTER: IDENTIFIED BY USE OF MUTATION, REVERSION RATES AND MALE RECOMBINATION
Authors: Scobie Nita N , Schaffer Henry E
Published: April 2021

A set of 1,000 "mutation accumulation" lines of Drosophila melanogaster, which originated from two different wild-type, lethal-bearing second chromosomes (Yamaguchi and Mukai 1974; Mukai and Cockerham 1977), was examined for evidence of a mutator factor by using the occurrence of recessive visible mutations and male recombination to identify its presence. The 1,000 lines were screened at approximately generation 240 for the presence of recessive visible mutations at twelve loci, by outcrossing to a balanced multiply marked second chromosome stock (Muller's "12ple" Bowling Green). Twenty-three lines were found to carry a visible mutation at one of the loci. Seventeen of these lines carried a mutation of either the dp or the vg locus. Mutations found in three lines, two at the dp locus and one at the vg locus, demonstrated instability as revertants to the wild type and were recovered and verified in these three cases. The three revertant lines, and three lines showing no reversion, were tested for their ability to induce male recombination. Male recombination was observed in the three lines in which revertants were recovered. Male and female sterility assays indicated conclusively that these "hybrid dysgenic" characteristics could not be used to identify lines potentially carrying mutator factors, whereas the consistent ability of the lines to induce high rates of reversion and male recombination was successful in determining that the "mutation accumulation lines" do possess mutator factors.
Recombination between small X chromosome duplications and the X chromosome in Caenorhabditis elegans.
Authors: Herman R K , Kari C K
Published: April 2021

Twelve new X chromosome duplications were identified and characterized. Eight are translocated to autosomal sites near four different telomeres, and four are free. Ten include unc-1(+), which in wild type is near the left end of the X chromosome, and two of these, mnDp72(X;IV) and mnDp73(X;f), extend rightward past dpy-3. Both mnDp72 and mnDp73 recombined with the one X chromosome in males in the unc-1-dpy-3 interval at a frequency 15- to 30-fold higher than was observed for X-X recombination in hermaphrodites in the same interval. Recombinant duplications and recombinant X chromosomes were both recovered. Recombination with the X chromosome in the unc-1-dpy-3 interval was also detected for five other unc-1(+) duplications, even though their right breakpoints lie within the interval. In hermaphrodites, mnDp72 and mnDp73 promoted meiotic X nondisjunction and recombined with an X chromosome in the unc-1-dpy-3 interval at frequencies comparable to that found for X-X recombination; mnDp72(X;IV) also promoted trisomy for chromosome IV. A mutation in him-8 IV was identified that severely reduced recombination between the two X chromosomes in hermaphrodites and between mnDp73 and the X chromosome in males. Recombination between the X chromosome and duplications of either the right end of the X or a region near but not including the left end was rare. We suggest that the X chromosome has one or more elements near its left end that promote meiotic chromosome pairing.
The rIIA gene of bacteriophage T4. II. Regulation of its messenger RNA synthesis.
Authors: Daegelen P , Brody E
Published: April 2021

When the rII genes are first introduced into cells which had been previously infected by T4 phage deleted for these genes, the kinetics of synthesis of rIIA and rIIB RNA are rapid and identical. We show that this rapid synthesis depends on a functional motA gene for rIIB, but not for rIIA, RNA synthesis. By primer-extension mapping of T4 messenger RNA, we find three promoters close to the rIIA gene. One of them is an early promoter just before the rIIA.1 gene; it is used under all conditions tested. Another is in the coding portion of the rIIA.1 gene; it is weak, primarily because of a 19-bp spacing between the -10 and -35 elements, and its use is stimulated by T4 functions. The third is a motA-dependent (middle) promoter which has an unusual CCCGCTT box at -33. We present results which suggest that none of these promoters is likely to be the site at which the motB and motC gene products exercise their major influence on rIIA RNA synthesis.
Chromosomal assignment of mutations by specific chromosome loss in the yeast Saccharomyces cerevisiae.
Authors: Wakem L P , Sherman F
Published: April 2021

Yeast 2-microns plasmids were integrated near the centromere of a different chromosome in each of 16 cir0 mapping strains of Saccharomyces cerevisiae. The specific chromosomes containing the integrated 2-microns plasmid DNA were lost at a high frequency after crossing the cir0 strains to cir+ strains. A recessive mutation in a cir+ strain can then be easily assigned to its chromosome using this set of mapping strains, since the phenotype of the recessive mutation will be manifested only in diploids having the integrated 2-microns plasmid and the unmapped mutation on homologous chromosomes.
The NXSM recombinant inbred strains of mice: genetic profile for 58 loci including the Mtv proviral loci.
Authors: Eicher E M , Lee B K
Published: April 2021

We report the construction of 17 recombinant inbred (RI) strains of mice derived from the progenitor strains NZB/BINRe and SM/J and the typing of this RI strain set, designated NXSM, for 58 loci distributed on 16 autosomes and the X chromosome. Two backcrosses involving NZB/BINJ and SM/J were constructed to confirm chromosomal assignments and determine gene orders suggested from NXSM RI strain data. From these results we recommend that chromosomal assignments and gene orders suggested from analyses of RI strain sets be confirmed using data obtained by other means. We also typed NZB/BINJ and SM/J for mammary tumor proviral (Mtv) loci. Both strains share three previously described Mtv loci: Mtv-7, Mtv-14 and Mtv-17. In addition, NZB/BINJ contains the previously described Mtv-3 and Mtv-9 loci and two new Mtv proviral loci: Mtv-27 located on chromosome (Chr) 1 and Mtv-28 located on the X chromosome. SM/J contains the previously described loci Mtv-6 and Mtv-8. Four LTR, mink cell focus-forming murine leukemia viral loci were identified and mapped: Ltrm-1 on Chr 12, Ltrm-2 on Chr 16, Ltrm-3 on Chr 5, and Ltrm-4 on Chr 13. The Tgn locus was positioned proximal to the Ly-6 locus on Chr 15.