Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of a Polymer-coated Urea Based Diet on the Performance of Lactating Dairy Cows

Abstract Pinos-Rodríguez, J.M. , López, S. , Bárcena, R. , González-Muñoz, S.S. , García, J.C. and Jasso, Y. 2010. Effect of a polymer-coated urea based diet on the performance of lactating dairy cows. J. Appl. Anim. Res., 37: 201–205. The aims of this study were to determine: 1) nitrogen (N) release of a polymer-coated urea (PCU), 2) effects of PCU on the in vitro dry matter degradation (IVDMD) of a diet for lactating cows and 3) effects of addition of PCU (1%) to the diet on milk production of dairy cows. The N release of urea, PCU and soybean meal (SBM) were evaluated under in vitro conditions for 12 h. N release of PCU was lower than urea, but higher as compared to SBM. TVDMD of the diet with or without PCU was similar. The PCU increased the in vitro ammonia N and volatile fatty acids concentration. Milk yield, fat-corrected milk and components were not affected by PCU. Thus PCU did not affect production and quality of milk in dairy cows.
Adaptor Template Oligo-Mediated Sequencing (ATOM-Seq): A versatile and ultra-sensitive UMI-based NGS library preparation technology, for use with cfDNA and cfRNA

Liquid biopsy testing utilising Next Generation Sequencing (NGS) is rapidly moving towards clinical adoption for personalised oncology. However, before NGS can fulfil its potential any novel testing approach must identify ways of reducing errors, allowing for separating true low-frequency mutations from procedural artefacts, and be designed to improve upon current technologies while also avoiding their limitations. Popular NGS technologies typically utilise two approaches; PCR and ligation, which have known limitations and seem to have reached a development plateau with only small, stepwise improvements being made. To maximise the ultimate utility of liquid biopsy testing we have developed a highly versatile approach to NGS: Adaptor Template Oligo Mediated Sequencing (ATOM-Seq). ATOM-Seq’s strengths and versatility avoid the major limitations of both PCR- and ligation-based approaches. This technology is ligation free, simple, efficient, flexible, and streamlined, and offers novel advantages that make it perfectly suited for use on highly challenging clinical material. Using reference materials, we demonstrate detection of known SNVs at allele frequencies of 0.1% using as little as 20 ng of DNA, as well as the ability to detect fusions from RNA. We illustrate ATOM-Seq’s suitability for clinical testing by showing high concordance rates between paired cfDNA and FFPE clinical samples.
Transplantation of organic surface horizons of boreal soils into warmer regions alters microbiology but not the temperature sensitivity of decomposition

Changes in soil carbon, the largest terrestrial carbon pool, are critical for the global carbon cycle, atmospheric CO2 levels and climate. Climate warming is predicted to be most pronounced in the northern regions and therefore the large soil carbon pool residing in boreal forests will be subject to larger global warming impact than soil carbon pools in the temperate or the tropical forest. A major uncertainty in current estimates of the terrestrial carbon balance is related to decomposition of soil organic matter (SOM). We hypothesized that when soils are exposed to warmer climate the structure of the ground vegetation will change much more rapidly than the dominant tree species. This change will alter the quality and amount of litter input to the soil and induce changes in microbial communities, thus possibly altering the temperature sensitivity of SOM decomposition. We transferred organic surface soil sections from the northern borders of the boreal forest zone to corresponding forest sites in the southern borders of the boreal forest zone and studied the effects of warmer climate after an adaptation period of 2 years. The results showed that initially ground vegetation and soil microbial community structure and community functions were different in northern and southern forest sites and that 2 years of exposure to warmer climate was long enough to cause changes in these ecological indicators. The rate of SOM decomposition was approximately equally sensitive to temperature irrespective of changes in vegetation or microbial communities in the studied forest sites. However, as temperature sensitivity of the decomposition increases with decreasing temperature regime, the proportional increase in the decomposition rate in northern latitudes could lead to significant carbon losses from the soils.
Viscoelastic relaxation of collagen networks provides a self-generated directional cue during collective migration

There is growing evidence that the physical properties of the cellular environment can impact cell migration. However, it is not currently understood how active physical remodeling of the network by cells affects their migration dynamics. Here, we study collective migration of small clusters of cells on deformable collagen-1 networks. Combining theory and experiments, we find that cell clusters, despite displaying no apparent internal polarity, migrate persistently and generate asymmetric collagen gradients during migration. We find that persistent migration can arise from viscoelastic relaxation of collagen networks, and reducing the viscoelastic relaxation time by chemical crosslinking leads to a reduction in migration persistence. Single cells produce only short range network deformations that relax on shorter timescales, which leads to lower migration persistence. This physical model provides a mechanism for self-generated directional migration on viscoelastic substrates in the absence of internal biochemical cues.
Lipid lowering and antioxidant potential of Asparagus racemosus in hyperlipidemic rats

Background: Atherosclerosis is associated with hyperlipidemia which is a major risk factor for coronary artery disease. Therefore, treatment of hyperlipidemia is one of the major approaches to decrease the atherogenic process. Many studies revealed that Asparagus racemosus (AR) possesses hypolipidemic and antioxidant potential, but results were not consistent. Therefore, the present study was undertaken to investigate lipid lowering and antioxidant potential of AR root powder in hyperlipidemic rats. Methods: Hyperlipidemia was induced in normal rats by including 0.75 gm% cholesterol and 1.5 gm% bile salt in normal diet and these rats were used for the experiments. Dried root powder of Asparagus racemosus was administered as feed supplement at 5 gm% and 10 gm% dose levels to the hyperlipidemic rats. Plasma lipid profile, malondialdehyde, ascorbic acid, catalase and superoxide dismutase were estimated using standard methods. Statistical analysis was done by one way analysis of variance (ANOVA). Results: Feed supplementation with 5 gm% and 10 gm% Asparagus racemosus resulted in a significant decrease in plasma cholesterol, LDL and significant increase in HDL. But there were no significant decrease in triglycerides and VLDL. The feed supplementation increased activities of catalase, superoxide dismutase and ascorbic acid content increased significantly in both the experimental groups (5 and 10 gm% supplemented groups). But there was no significant change in the concentration of malondialdehyde in these groups. Conclusions: The present study demonstrated that addition of Asparagus racemosus root powder at 5 gm% and 10 gm% level as feed supplement reduces the plasma lipid levels and also acts as an antioxidant.
GAN-based anomaly detection in multi-modal MRI images

Generative adversarial networks (GANs) are known to be a powerful tool in order to correct image aberrations, and even predict entirely synthetic images. We describe and demonstrate a method to use GANs trained from multi-modal magnetic resonance images as a 3-channel input. The training of the generative network was performed using only healthy images together with pseudo-random irregular masks. The dataset consisted of just 20 people. The resulting model was then used to detect anomalies real patient images in which the anomaly was a tumour. The search was performed using no prior knowledge of the tumour location, if indeed a tumour was present. Resulting accuracies are observed to vary significantly on the size of the anomaly. The area under the receiver operator characteristic curve is observed to be greater than 0.75 for anomaly sizes greater than 4 cm2.
Widespread retention of ohnologs in key developmental gene families following whole genome duplication in arachnopulmonates

Whole genome duplications (WGD) have occurred multiple times in the evolution of animals, including in the lineages leading to vertebrates, teleosts, horseshoe crabs and arachnopulmonates. These dramatic genomic events initially produce a wealth of new genetic material, which is generally followed by extensive gene loss. It appears that developmental genes such as homeobox genes, signalling pathway components and microRNAs, however, tend to be more frequently retained in duplicate following WGD (ohnologs). These not only provide the best evidence for the occurrence of WGD, but an opportunity to study its evolutionary implications. Although these genes are relatively well studied in the context of vertebrate WGD, genomic and transcriptomic data for independent comparison in other groups are scarce, with patchy sampling of only two of the five extant arachnopulmonate orders. To improve our knowledge of developmental gene repertoires, and their evolution since the arachnopulmonate WGD, we sequenced embryonic transcriptomes from two additional spider species and two whip spider species and surveyed them for three important gene families: Hox, Wnt and frizzled. We report extensive retention of ohnologs in all four species, further supporting the arachnopulmonate WGD hypothesis. Thanks to improved sampling we were able to identify patterns of likely ohnolog retention and loss within spiders, including apparent differences between major clades. The two amblypygid species have larger ohnolog repertoires of these genes than both spiders and scorpions; including the first reported duplicated Wnt1/wg, the first Wnt10 recovered in an arachnid, and broad retention of frizzled genes. These insights shed light on the evolution of the enigmatic whip spiders, highlight the importance of the comparative approach within lineages, and provide substantial new transcriptomic data for future study.
Stimulus dependence of directed information exchange between cortical layers in macaque V1

Perception and cognition require the integration of feed-forward sensory information with feedback signals. Feed-forward and feedback signals have been associated with specific cortical laminae and specific oscillatory frequencies. We used stimuli of different sizes to isolate spectral signatures of feedforward and feedback signals, and their effect on communication between layers in primary visual cortex of male macaque monkeys. Small stimuli, centered on the neurons’ receptive fields elicited broad band gamma frequency oscillations predominantly in the superficial layers. These Granger causal originated in upper layer 4 and lower supragranular layers, in line with existing feed-forward models of oscillatory responses. However, large stimuli extending into the far surround of neurons’ receptive fields, generated strong narrow band gamma oscillatory activity across cortical layers. They Granger causal arose in layer 5, were conveyed through layer 6 to superficial layers, and violated existing models of feedback spectral signatures. Equally surprising, with large stimuli, alpha band oscillatory activity arose predominantly in granular and supragranular layers, and communicated in a feed-forward direction. This shows that oscillations in specific frequency bands can be dynamically modulated to serve feedback and feed-forward communication and are not restricted to specific cortical layers in V1
Aversion encoded in the subthalamic nucleus

Activation of the subthalamic nucleus (STN) is associated with the stopping of ongoing behavior via the basal ganglia. However, we recently observed that optogenetic STN excitation induced a strong jumping/escaping behavior. We hypothesized that STN activation is aversive. To test this, place preference was assessed. Optogenetic excitation of the STN caused potent place aversion. Causality between STN activation and aversion has not been demonstrated previously. The lateral habenula (LHb) is a critical hub for aversion. Optogenetic stimulation of the STN indeed caused firing of LHb neurons, but with delay, suggesting the involvement of a polysynaptic circuit. To unravel a putative pathway, the ventral pallidum (VP) was investigated. VP receives projections from the STN and in turn projects to the LHb. Optogenetic excitation of STN-VP terminals caused firing of VP neurons and induced aversive behavior. This study identifies the STN as critical hub for aversion, potentially mediated via an STN-VP-LHb pathway.
Crowdsourcing Machine Intelligence Solutions to Accelerate Biomedical Science: Lessons learned from a machine intelligence ideation contest to improve the prediction of 3D domain swapping

Machine intelligence methods, including natural language processing, computer vision, machine vision, artificial intelligence, and deep learning approaches, are rapidly evolving and play an essential role in biomedicine. Machine intelligence methods could help to accelerate image analyses aid in building complex models capable of interpretation beyond cognitive limitations and statistical assumptions in biomedicine. However, irrespective of the democratization via accessible computing and software modules, machine intelligence handiness is scarce in the setting of a traditional biomedical research laboratory. In such a context, collaborations with bioinformatics and computational biologists may help. Further, the biomedical diaspora could also seek help from the expert communities using a crowdsourcing website that hosts machine intelligence competitions. Machine intelligence competitions offer a vast pool of seasoned data scientists and machine intelligence experts to develop solutions through competition portals. An alternate approach to improve the adoption of machine intelligence in biomedicine is to offer machine intelligence competitions as part of scientific meetings. In this paper, we discuss a structured methodology employed to develop the machine intelligence competition as part of an international bioinformatics conference. The competition leads to developing a novel method through crowdsourcing to solve a challenging problem in biomedicine – predicting probabilities of proteins that undergo 3D domain swapping. As a biomedical science conference focused on computational methods, the competition received multiple entries that ultimately helped improve the predictive modeling of 3D domain swapping using sequence information.
Expression attenuation as a mechanism of robustness to gene duplication in protein complexes

Gene duplication is ubiquitous and a major driver of phenotypic diversity across the tree of life, but its immediate consequences are not fully understood. Deleterious effects would decrease the probability of retention of duplicates and prevent their contribution to long term evolution. One possible detrimental effect of duplication is the perturbation of the stoichiometry of protein complexes. Here, we measured the fitness effects of the duplication of 899 essential genes in the budding yeast using high-resolution competition assays. At least ten percent of genes caused a fitness disadvantage when duplicated. Intriguingly, the duplication of most protein complex subunits had small to non-detectable effects on fitness, with few exceptions. We selected four complexes with subunits that had an impact on fitness when duplicated and measured the impact of individual gene duplications on their protein-protein interactions. We found that very few duplications affect both fitness and interactions. Furthermore, large complexes such as the 26S proteasome are protected from gene duplication by attenuation of protein abundance. Regulatory mechanisms that maintain the stoichiometric balance of protein complexes may protect from the immediate effects of gene duplication. Our results show that a better understanding of protein regulation and assembly in complexes is required for the refinement of current models of gene duplication.
Quantitative assessment of localized growth rates and gene expression patterns in Pseudomonas aeruginosa biofilms

Gene expression in biofilms is dependent on bacterial responses to the local environmental conditions. Most techniques for studying bacterial gene expression in biofilms characterize average values over the entire population. Here, we describe the use of laser capture microdissection microscopy (LCMM) combined with multiplex quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) to isolate and quantify RNA transcripts from small groups of cells at spatially resolved sites within biofilms. The approach was first tested and analytical parameters determined for Pseudomonas aeruginosa containing an IPTG-inducible gene for the green fluorescent protein (gfp). The results show that amounts of gfp mRNA were greatest in the top zones of the biofilms, and that gfp mRNA levels correlated with the zone of active GFPfluorescence. The method was then used to quantify transcripts from wild-type P. aeruginosa biofilms for a housekeeping gene, acpP; the 16S rRNA; and two genes 24 regulated by quorum-sensing, phzA1 and aprA. The results demonstrated that the amount of acpP mRNA was greatest in the top 30 μm of the biofilm, with little or no mRNA for this gene at the base of the biofilms. In contrast, 16S rRNA amounts were relatively uniform throughout biofilm strata. Using this strategy, the RNA amounts of individual genes are determined, and therefore results are dependent on both gene expression and the half-life of transcripts. Therefore, the uniform amount of rRNA throughout the biofilms is likely due to the stability of the rRNA within ribosomes. Levels of aprA mRNA showed stratification, with the greatest amounts localized to the upper 30 μm zone. The results demonstrate that mRNA levels for individual genes are not uniformly distributed throughout biofilms, but may vary by orders of magnitude over small distances. The LCMM/qRT-PCR technique can be used to resolve and quantify this RNA variability at high spatial resolution.
Gene Duplication and Gene Loading

During the early evolution of life, gene duplication, the production of two copies of a DNA sequence, allowed the rapid diversification of enzymatically catalyzed reactions and an increase in genome size, providing also material for the invention of new enzymatic properties and complex regulatory and developmental patterns. A duplication may involve (i) a part of a gene, (ii) a whole gene, (iii) DNA stretches including two or more genes involved in the same or in different metabolic pathways, (iv) entire operons, (v) a part of a chromosome, (vi) an entire chromosome, and finally (vii) the whole genome. Therefore, any DNA sequence may undergo a duplication event(s), but the fate of the replicate depends on whether it provides an evolutionary advantage to the host cell. Two hypotheses on the origin and evolution of metabolic pathways exist. The first one, the Horowitz retrograde hypothesis, predicts that an entire metabolic route was assembled by successive duplications of an ancestral gene in a backward fashion, starting with the synthesis of the final product, then the penultimate pathway intermediate, and so on down the pathway to the initial precursor. The patchwork hypothesis is based on the duplication(s) of ancestral gene(s) leading to the progressive increasing of specificity of low-specific enzymes, which then may be recruited to catalyze similar reactions in different metabolic pathways or sequential steps in the same route.
Investigation of cell nucleus heterogeneity

Nucleus deformation has been shown to play a key role in cell mechanotransduction and migration. Therefore, it is of wide interest to accurately characterize nucleus mechanical behavior. In this study we present the first computational investigation of the in-situ deformation of a heterogeneous cell nucleus. A novel methodology is developed to accurately reconstruct a three-dimensional finite element spatially heterogeneous model of a cell nucleus from confocal microscopy z-stack images of nuclei stained for nucleus DNA. The relationship between spatially heterogeneous distributions microscopic imaging-derived greyscale values, shear stiffness and resultant shear strain is explored through the incorporation of the reconstructed heterogeneous nucleus into a model of a chondrocyte embedded in a PCM and cartilage ECM. Externally applied shear deformation of the ECM is simulated and computed intra-nuclear strain distributions are directly compared to corresponding experimentally measured distributions. Simulations suggest that the nucleus is highly heterogeneous in terms of its mechanical behaviour, with a sigmoidal relationship between experimentally measure greyscale values and corresponding local shear moduli (μn). Three distinct phases are identified within the nucleus: a low stiffness phase (0.17 kPa ≤ μn ≤ 0.63 kPa) corresponding to mRNA rich interchromatin regions; an intermediate stiffness phase (1.48 kPa ≤ μn ≤ 2.7 kPa) corresponding to euchromatin; a high stiffness phase (3.58 kPa ≤ μn ≤ 4.0 kPa) corresponding to heterochromatin. Our simulations indicate that disruption of the nucleus envelope associated with lamin-A/C depletion significantly increases nucleus strain in regions of low DNA concentration. A phenotypic shift of chondrocytes to fibroblast-like cells, a signature for osteoarthritic cartilage, results in a 35% increase in peak nucleus strain compared to control. The findings of this study may have broad implications for the current understanding of the role of nucleus deformation in cell mechanotransduction.
The maintenance of polygenic sex determination depends on the dominance of fitness effects which are predictive of the role of sexual antagonism

In species with polygenic sex determination, multiple male- and/or female-determining loci on different proto-sex chromosomes segregate as polymorphisms within populations. The extent to which these polymorphisms are stable equilibria is not yet resolved. Previous work demonstrated that polygenic sex determination is most likely to be maintained as a stable polymorphism when the proto-sex chromosomes have opposite (sexually antagonistic) fitness effects in males and females. However, these models usually consider polygenic sex determination systems with only two proto-sex chromosomes, or they do not broadly consider the dominance of the variants under selection. To address these shortcomings, I used forward population genetic simulations to identify selection pressures that can maintain polygenic sex determination under different dominance scenarios in a system with more than two proto-sex chromosomes (modeled after the house fly). I found that overdominant fitness effects of male-determining proto-Y chromosomes in males are more likely to maintain polygenic sex determination than dominant, recessive, or additive fitness effects. I also found that additive fitness effects that maintain polygenic sex determination have the strongest signatures of sexually antagonistic selection, but there is also some evidence for sexually antagonism when fitness effects of proto-Y chromosomes are dominant or recessive. More generally, these results suggest that the expected effect of sexually antagonistic selection on the maintenance of genetic variation in natural populations will depend on whether the alleles are sex-linked and the dominance of their fitness effects.