Miracle-dz/UniFAR-FTUs huggingface dataset:
Nested tandem duplications of the gene Melanoma antigen recognized by T-cells (Mlana) underlie the sexual dimorphism locus in domestic pigeons

Birds have classic examples of exaggerated sexually dimorphic traits, including colors. Sexes among the wild rock dove and its derived domestic breeds, however, are quite indistinguishable and sex can only be ascertained through genotyping or egg laying and successful hatching of eggs. Yet, the pigeon fancy has discovered sexually dimorphic traits and harnessed some of these traits in some auto-sexing breeds. Early genetics pioneers characterized the sex-linked Stipper locus and showed it to be linked to the pigeon Z linked B-locus (Tyrp1). The alleles of the Stipper locus have variable dominance relative to wild-type (more severe alleles are incompletely dominant, less severe alleles are reportedly fully dominant), characterized by a continuum of lightening in homozygotes and increased variegation in heterozygotes corresponding with severity. We leveraged this positional information and population structure among breeds in a candidate gene approach to identify the genetic mechanism of de novo pigeon sex dichromatism. A large tandem duplication (77 kb) centered on the gene Melanoma antigen recognized by T cells (Mlana) is completely associated with alleles of the Stipper locus. Copy number of the 77 kb genetic lesion was not correlated with allele severity suggesting that other mechanisms, including epigenetic regulation could underlie both allele severity and degree of variegation.
Studies of top quark properties in CMS

In this article, recent studies of top quark properties in CMS are presented. The discussed analyses are measurements of the charge asymmetry, CP violation and jet mass, all carried out in final states of $\textrm{t}\bar{\textrm{t}}$ production with one or two leptons. The data were recorded with the CMS detector in the years 2016 to 2018.
Functional Disruption of the Tomato Putative Ortholog of HAWAIIAN SKIRT Results in Facultative Parthenocarpy, Reduced Fertility and Leaf Morphological Defects

A number of plant microRNAs have been demonstrated to regulate developmental processes by integrating internal and environmental cues. Recently, the Arabidopsis thaliana F-box protein HAWAIIAN SKIRT (HWS) gene has been described for its role in miRNA biogenesis. We have isolated in a forward genetic screen a tomato (Solanum lycopersicum) line mutated in the putative ortholog of HWS. We show that the tomato hws-1 mutant exhibits reduction in leaflet serration, leaflet fusion, some degree of floral organ fusion, and alteration in miRNA levels, similarly to the original A. thaliana hws-1 mutant. We also describe novel phenotypes for hws such as facultative parthenocarpy, reduction in fertility and flowering delay. In slhws-1, the parthenocarpy trait is influenced by temperature, with higher parthenocarpy rate in warmer environmental conditions. Conversely, slhws-1 is able to produce seeds when grown in cooler environment. We show that the reduction in seed production in the mutant is mainly due to a defective male function and that the levels of several miRNAs are increased, in accordance with previous HWS studies, accounting for the abnormal leaf and floral phenotypes as well as the altered flowering and fruit development processes. This is the first study of HWS in fleshy fruit plant, providing new insights in the function of this gene in fruit development.
Anuran diversity in and around historic Joysagar Tank of Sivasagar district, Assam

The present study is on the anuran diversity in and around the Ahom kings’ historic Joysagar tank of Sivasagar District, Assam. 12 species of anurans were enlisted belonging to 5 families and 10 genera. The most dominant family is Dicroglossidae and the most common and abundant species was Duttaphrynus melanostictus. Species diversity index, richness and evenness were also estimated for the study area.
LGR5 controls extracellular matrix production by stem cells in the developing intestine

The Lgr5 receptor is a marker of intestinal stem cells (ISCs) that regulates Wnt/b-catenin signaling. In this study, phenotype analysis of knockin/knockout Lgr5-eGFP-IRES-Cre and Lgr5-DTReGFP embryos revealed that Lgr5 deficiency during Wnt-mediated cytodifferentiation results in amplification of ISCs and early differentiation into Paneth cells, which can be counteracted by in utero treatment with the Wnt inhibitor LGK974. Conditional ablation of Lgr5 postnatally, but not in adults, altered stem cell fate towards the Paneth lineage. Together, these in vivo studies suggest that Lgr5 is part of a feedback loop to adjust the Wnt tone in ISCs. Moreover, transcriptome analyses revealed that fetal ISCs generate their own extracellular matrix components, a property lost in adult ISCs, which adopt a definitive epithelialized phenotype and an inflammatory response signature. Absence of Lgr5 in fetal ISCs resulted in reduced extracellular matrix production and accelerated ISC maturation, indicating that Lgr5 regulates the ISC niche. Finally, evidences are provided that Rspondin 2 negatively regulates the pool of ISCs in organoids via Lgr5, revealing a sophisticated regulatory process for Wnt signaling in ISC.
Detection of stress resistance genes in transgenic maize by multiplex and touchdown polymerase chain reaction

M. A. Bannikova © 2015 M. A. Bannikova; Published by the Institute of Molecular Biology and Genetics, NAS of Ukraine on behalf of Biopolymers and Cell. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited Molecular and Cell Biotechnologies ISSN 0233-7657 Biopolymers and Cell. 2015. Vol. 31. N 5. P. 362–370 doi: http://dx.doi. org/10.7124/bc.0008F8
A Rare Opportunist, Morganella morganii, Decreases Severity of Polymicrobial Catheter-Associated Urinary Tract Infection

Catheter-associated urinary tract infections (CAUTIs) are common hospital-acquired infections and frequently polymicrobial, which complicates effective treatment. However, few studies experimentally address the consequences of polymicrobial interactions within the urinary tract, and the clinical significance of polymicrobial bacteriuria is not fully understood. ABSTRACT Catheter-associated urinary tract infections (CAUTIs) are common hospital-acquired infections and frequently polymicrobial, which complicates effective treatment. However, few studies experimentally address the consequences of polymicrobial interactions within the urinary tract, and the clinical significance of polymicrobial bacteriuria is not fully understood. Proteus mirabilis is one of the most common causes of monomicrobial and polymicrobial CAUTI and frequently cocolonizes with Enterococcus faecalis, Escherichia coli, Providencia stuartii, and Morganella morganii. P. mirabilis infections are particularly challenging due to its potent urease enzyme, which facilitates formation of struvite crystals, catheter encrustation, blockage, and formation of urinary stones. We previously determined that interactions between P. mirabilis and other uropathogens can enhance P. mirabilis urease activity, resulting in greater disease severity during experimental polymicrobial infection. Our present work reveals that M. morganii acts on P. mirabilis in a contact-independent manner to decrease urease activity. Furthermore, M. morganii actively prevents urease enhancement by E. faecalis, P. stuartii, and E. coli. Importantly, these interactions translate to modulation of disease severity during experimental CAUTI, predominantly through a urease-dependent mechanism. Thus, products secreted by multiple bacterial species in the milieu of the catheterized urinary tract can directly impact prognosis.
Designing of a mini-core that effectively represents 3004 diverse accessions of rice

Genetic diversity provides foundation for plant breeding and genetic research. As part of the 3K Rice Genome Project, over 3000 rice genomes were recently sequenced. We added four Indian rice accessions to it and made original panel of 3004 accessions. However, large set of germplasms are difficult to preserve and evaluate. Construction of core and mini-core collections is an efficient method for managing genetic resources. This study aims to designing of mini-core comprised of 520 accessions representing original panel. The designed mini-core captured most of the SNPs and represented all phenotypes and geographical regions. The mini-core was validated using different statistical analyses and had representation from all major groups including japonica, indica, aus/boro and aromatic/basmati. GWAS analyses with mini-core panel efficiently reproduced the marker-traits association identified among original 3004 panel. Expression analysis of trait-associated genes highlights the relevance of such mini-core panel. Haplotype analysis could also validate our mini-core panel. Apart from mini-core, we identified few regional and varietal specific marker-trait associations which were not evident in original panel. In this era of large-scale sequencing projects, such a strategy of designing mini-core will be very useful. One-sentence summary Designing of mini-core as manageable association panel that efficiently mirroring the large and diverse collection of 3004 rice accessions.
Study of the transcriptional function of cyclin D1 in leukemia

Leukemia is a type of cancer that starts in blood-forming tissue, such as the bone marrow. It causes the production of large numbers of abnormal blood cells that end up entering into the bloodstream. 1 Within the different types of leukemia, Mantle Cell Lymphoma (MCL) is the one with the worst prognosis due to the short survival average of a patient, which is close to three years. This tumor is characterized by the over-expression of Cyclin D1, a protein that helps control cell division. MCL is also characterized by the binding of this protein to certain regions of DNA involved in the regulation of DNA-damage response (DDR). The presented study aims to identify similarities between the gene expression regulated by Cyclin D1 in lymphomas and the gene expression in DNA damage. That knowledge will allow the exploration of essential mechanisms of carcinogenesis and help in the identification of genes that could be an interesting therapeutic target in the process of tumor progression. Additionally, new biomarkers that could be used in early diagnosis can be found. With the addition of Machine Learning algorithms to the biology analysis pipeline, this project explores new ways to improve the traditional methodologies and boost the identification of significantly enriched genes that will serve the purposes mentioned above. The result of such a pipeline is the accurate selection of genes correlated with Cyclin D1, involved in MCL and DDR, and its posterior analysis and identification of significantly enriched gene sets. As a conclusion, the results obtained in this study suggested that targeting of Notch pathway and studying potential common mechanisms of hypoxia and apoptosis resistance would be of great interest for possible future studies on treatments of MCL.
New additions to the CRISPR toolbox: CRISPR-CLONInG and CRISPR-CLIP

CRISPR proven to be one of the most versatile protein of our time, predominantly as a precision genome engineering tool. Here, two additional usages to the ever-expanding repertoire of CRISPR’s application are demonstrated for procuration of donor DNA template, an indispensable component for facilitating precision genome editing. (i) CRISPR-CLONInG (CRISPR-Cutting & Ligation Of Nucleic acid In vitro via Gibson) is devised as a promising digestion tool to enable efficient cut-and-paste of DNA sequences to construct donor templates (dsDNA and AAV vectors) via Gibson Assembly. Cas9 was used to cut out undesired DNA segment from existing plasmid with complex sequences, rendering vector backbone suited for facilitating Gibson Assembly to ligate multiple DNA fragments without cloning scars and incorrect insert orientation. (ii) CRISPR-CLIP (CRISPR-Clipped Long ssDNA via Incising Plasmid) is devised as a DNA clipping tool to efficiently procure long single-stranded DNA (lssDNA) up to 2.2 kbase from donor-carrying plasmid that can be supplied as a donor template for genome editing in mouse zygotes via Easi-CRISPR. I utilized two different Cas types, namely Cpf1 and Cas9n (D10A mutant nickase of Cas9) to create two types of incisions on the respective ends of the lssDNA cassette junctions on the plasmid, yielding three independent single-stranded DNA units of different sizes eligible for strand separation treatment, followed by target strand clip-out through gel extraction. The acquired lssDNA donor was directly retrieved from plasmid without using restriction enzymes or involvement of DNA polymerase-based steps, hence not only retains sequence fidelity but carries virtually no restriction on sequence composition, further mitigating limitations on current Easi-CRISPR method. In addition, by placing an universal add-on DNA-tag sequences of Cpf1-Cas9 duo PAM on the plasmid at two sites flanking the lssDNA cassette, the devising of CRISPR-CLIP can be further simplified and applicable to construct lssDNA template targeting any genomic sequences. Altogether, the two CRISPR-based methods presented herein offer solutions to overcome technical challenges frequently encountered in procuring donor DNA for genome editing.
immuneSIM: tunable multi-feature simulation of B- and T-cell receptor repertoires for immunoinformatics benchmarking

Summary B- and T-cell receptor repertoires of the adaptive immune system have become a key target for diagnostics and therapeutics research. Consequently, there is a rapidly growing number of bioinformatics tools for immune repertoire analysis. Benchmarking of such tools is crucial for ensuring reproducible and generalizable computational analyses. Currently, however, it remains challenging to create standardized ground truth immune receptor repertoires for immunoinformatics tool benchmarking. Therefore, we developed immuneSIM, an R package that allows the simulation of native-like and aberrant synthetic full length variable region immune receptor sequences. ImmuneSIM enables the tuning of the immune receptor features: (i) species and chain type (BCR, TCR, single, paired), (ii) germline gene usage, (iii) occurrence of insertions and deletions, (iv) clonal abundance, (v) somatic hypermutation, and (vi) sequence motifs. Each simulated sequence is annotated by the complete set of simulation events that contributed to its in silico generation. immuneSIM permits the benchmarking of key computational tools for immune receptor analysis such as germline gene annotation, diversity and overlap estimation, sequence similarity, network architecture, clustering analysis, and machine learning methods for motif detection. Availability The package is available via https://github.com/GreiffLab/immuneSIM and will also be available at CRAN (submitted). The documentation is hosted at https://immuneSIM.readthedocs. io. Contact victor.greiff@medisin.uio. no, sai.reddy@ethz.ch
Assessing the impact of high-throughput sequencing strategy and model complexity on ABC-inferred demographic history in mussels

Genome-scale diversity data are increasingly available in a variety of biological systems, and can be used to reconstruct the past evolutionary history of species divergence. However, extracting the full demographic information from these data is not trivial and requires inferential methods that account for the diversity of coalescent histories throughout the genome. Here, we evaluate the potential and limitations of one such approach. We reexamine a well-known system of mussel sister species, using the coding joint site frequency spectrum (jSFS), in an approximate Bayesian computation (ABC) framework. We first assess the best sampling strategy (number of: individuals, loci, and classes in the jSFS), and show that the number of individuals and loci have little effect on model selection. In contrast, different decompositions of the joint site frequency spectrum strongly affect the results: including classes of low and high frequency shared polymorphisms can more effectively reveal recent migration events. We then take advantage of the flexibility of the ABC to compare more realistic models of speciation including variation in migration rates through time (i.e. periodic connectivity) and across genes (i.e. genome-wide heterogeneity in migration rates). We show that these models consistently outperform the simpler alternatives. This argues that methods that are restricted to simpler models may fail to reconstruct the true speciation history.
It takes two (Las1 HEPN Endoribonuclease Motifs) to cut the RNA right

Las1 is an essential endoribonuclease that is well-conserved across eukaryotes and a newly established member of the HEPN (higher eukaryotes and prokaryotes nucleotide-binding) nuclease family. HEPN nucleases participate in diverse RNA cleavage pathways and share a short HEPN nuclease motif important for RNA cleavage. While most HEPN nucleases participate in stress activated RNA cleavage pathways, Las1 plays a fundamental role in processing the pre-ribosomal RNA. Underscoring the significance of Las1 function, mutations to the LAS1L gene have been associated with neurological dysfunction. Two juxtaposed Las1 HEPN nuclease motifs create its composite nuclease active site, however the roles of the individual HEPN residues are poorly defined. Here we show through a combination of in vivo and in vitro studies that both Las1 HEPN nuclease motifs are required for nuclease activity and fidelity. Through in-depth sequence analysis and systematic mutagenesis, we define the consensus Las1 HEPN nuclease motif and uncover its canonical and specialized elements. Using reconstituted Las1 HEPN-HEPN’chimeras, we define the molecular requirements for RNA cleavage. Intriguingly, both copies of the Las1 HEPN motif are necessary for nuclease specificity revealing that both HEPN motifs participate in coordinating the RNA within the active site. Taken together, our work reveals critical information about HEPN nuclease function and establishes that HEPN nucleases can be re-wired to cleave alternative RNA substrates.
Role of β-Cryptoxanthin as an Antioxidant and Its Ability to Bind with Transferrin

The potential nutraceutical benefits of carotenoids, which are versatile bioactive compounds, have been of great interest recently for its applications as dietary supplements. Carotenoids are red-orange coloured pigments which absorb light in the wavelength region of 400-550 nm. They are produced by plants, bacteria, algae and fungi and are abundantly distributed in the nature. In this study, our focus is on beta-cryptoxanthin (β-CRX), a yellow colored pro-vitamin A xanthophyll which is extracted from a previously isolated bacterium Kocuria marina DAGII grown in Brain Heart Infusion and sub-cultured in low cost dairy waste like whey and incubated at 25°C and 150 rpm for 5 days. The extracted beta-cryptoxanthin showed good radical scavenging activity and played a role in inhibition of lipid oxidation. Transferrin is a glycoprotein which plays a significant role in the mobilisation of iron in the body. It has two receptors TfR1 and TfR2 amongst which TfR1 binds to the iron-loaded transferrin. In cases of secondary hemochromatosis, HFE protein competes with transferrin to bind to TfR1 which leads to iron built up which is detrimental to the human body. Beta-cryptoxanthin was found to bind to Transferrin with a binding energy of -8.2 kcal/mol.
Histone Acetyltransferase-Dependent Pathways Mediate Upregulation of NADPH Oxidase 5 in Human Macrophages under Inflammatory Conditions: A Potential Mechanism of Reactive Oxygen Species Overproduction in Atherosclerosis

Histone acetylation plays a major role in epigenetic regulation of gene expression. Monocyte-derived macrophages express functional NADPH oxidase 5 (Nox5) that contributes to oxidative stress in atherogenesis. The mechanisms of Nox5 regulation are not entirely elucidated. The aim of this study was to investigate the expression pattern of key histone acetyltransferase subtypes (p300, HAT1) in human atherosclerosis and to determine their role in mediating the upregulation of Nox5 in macrophages under inflammatory conditions. Human nonatherosclerotic and atherosclerotic tissue samples were collected in order to determine the expression of p300 and HAT1 isoforms, H3K27ac, and Nox5. In vitro determinations were done on human macrophages exposed to lipopolysaccharide in the absence or presence of histone acetyltransferase inhibitors. Western blot, immunohistochemistry, immunofluorescence, real-time PCR, transfection, and chromatin immunoprecipitation assay were employed. The protein levels of p300 and HAT1 isoforms, H3K27ac, and Nox5 were found significantly elevated in human atherosclerotic specimens. Immunohistochemistry/immunofluorescence staining revealed that p300, HAT1, H3K27ac, H3K9ac, and Nox5 proteins were colocalized in the area of CD45+/CD68+ immune cells and lipid-rich deposits within human atherosclerotic plaques. Lipopolysaccharide induced the levels of HAT1, H3K27ac, H3K9ac, and Nox5 and the recruitment of p300 and HAT1 at the sites of active transcription within Nox5 gene promoter in cultured human macrophages. Pharmacological inhibition of histone acetyltransferase significantly reduced the Nox5 gene and protein expression in lipopolysaccharide-challenged macrophages. The overexpression of p300 or HAT1 enhanced the Nox5 gene promoter activity. The histone acetyltransferase system is altered in human atherosclerosis. Under inflammatory conditions, HAT subtypes control Nox5 overexpression in cultured human macrophages. The data suggest the existence of a new epigenetic mechanism underlying oxidative stress in atherosclerosis.
Specific nanoscale synaptic reshuffling and control of short-term plasticity following NMDAR- and P2XR-dependent Long-Term Depression

Long-Term Potentiation (LTP) and Long-Term Depression (LTD) of excitatory synaptic transmission are considered as cellular basis of learning and memory. These two forms of synaptic plasticity have been mainly attributed to global changes in the number of synaptic AMPA-type glutamate receptor (AMPAR) through a regulation of the diffusion/trapping balance at the PSD, exocytosis and endocytosis. While the precise molecular mechanisms at the base of LTP have been intensively investigated, the ones involved in LTD remains elusive. Here we combined super-resolution imaging technique, electrophysiology and modeling to describe the various modifications of AMPAR nanoscale organization and their effect on synaptic transmission in response to two different LTD protocols, based on the activation of either NMDA receptors or P2X receptors. While both type of LTD are associated with a decrease in synaptic AMPAR clustering, only NMDAR-dependent LTD is associated with a reorganization of PSD-95 at the nanoscale. This change increases the pool of diffusive AMPAR improving synaptic short-term facilitation through a post-synaptic mechanism. These results demonstrate that specific dynamic reorganization of synapses at the nanoscale during specific LTD paradigm allows to improve the responsiveness of depressed synapses.