Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein ubiquitylation is essential for the schizont to merozoite transition in Plasmodium falciparum blood-stage development

Ubiquitylation is a common post translational modification of eukaryotic proteins and in the human malaria parasite, Plasmodium falciparum (Pf) overall ubiquitylation increases in the transition from intracellular schizont to extracellular merozoite stages in the asexual blood stage cycle. Here, we identify specific ubiquitylation sites of protein substrates in three intracellular parasite stages and extracellular merozoites; a total of 1464 sites in 546 proteins were identified (data available via ProteomeXchange with identifier PXD014998). 469 ubiquitylated proteins were identified in merozoites compared with only 160 in the preceding intracellular schizont stage, indicating a large increase in protein ubiquitylation associated with merozoite maturation. Following merozoite invasion of erythrocytes, few ubiquitylated proteins were detected in the first intracellular ring stage but as parasites matured through trophozoite to schizont stages the extent of ubiquitylation increased. We identified commonly used ubiquitylation motifs and groups of ubiquitylated proteins in specific areas of cellular function, for example merozoite pellicle proteins involved in erythrocyte invasion, exported proteins, and histones. To investigate the importance of ubiquitylation we screened ubiquitin pathway inhibitors in a parasite growth assay and identified the ubiquitin activating enzyme (UBA1 or E1) inhibitor MLN7243 (TAK-243) to be particularly effective. This small molecule was shown to be a potent inhibitor of recombinant PfUBA1, and a structural homology model of MLN7243 bound to the parasite enzyme highlights avenues for the development of P. falciparum specific inhibitors. We created a genetically modified parasite with a rapamycin-inducible functional deletion of uba1; addition of either MLN7243 or rapamycin to the recombinant parasite line resulted in the same phenotype, with parasite development blocked at the late schizont stage. These results indicate that the intracellular target of MLN7243 is UBA1, and this activity is essential for the final differentiation of schizonts to merozoites. The ubiquitylation of many merozoite proteins and their disappearance in ring stages are consistent with the idea that ubiquitylation leads to their destruction via the proteasome once their function is complete following invasion, which would allow amino acid recycling in the period prior to the parasite’s elaboration of a new food vacuole.
TGF-β, WNT, AND FGF SIGNALING PATHWAYS DURING AXOLOTL TAIL REGENERATION AND FORELIMB BUD DEVELOPMENT

OF DISSERTATION TGF-β, WNT, AND FGF SIGNALING PATHWAYS DURING AXOLOTL TAIL REGENERATION AND FORELIMB BUD DEVELOPMENT Tgf-β, Wnt, and Fgf signaling pathways are required for many developmental processes. Here, I investigated the requirement of these signaling pathways during tail regeneration and limb development in the Mexican axolotl (Ambystoma mexicanum). Using small chemical inhibitors during tail regeneration, I found that the Tgf-β signaling pathway was required from 0-24 and 48-72 hours post tail amputation (hpa), the Wnt signaling pathway was required from 0-120 hpa, and the Fgf signaling pathway was required from 0-12hpa. Tgf-β1 was upregulated after amputation and thus may mediate Tgf-β signaling pathway during tail regeneration. Both Smadmediated and non-Smad mediated Tgf-β signaling were activated as early as 1hpa. Smad-mediated Tgf-β signaling via activated pSmad2 and pSmad3, and via phosphorylated Erk and Akt. Two different Tgf-β signaling pathway inhibitors, SB505124 and Naringenin, differentially regulated pSmad2, pSmad3, p-Erk, and pAkt, while SB505124 and Naringenin both inhibited tail regeneration; only SB505124 reduced cell proliferation. Wnt/β-Catenin signaling was increased and was enhanced by Wnt-C59. Disruption of the Wnt signaling pathway directly or indirectly activated Erk and Akt signaling. Disruption of the Fgf signaling pathway decreased p-Erk and increased p-Akt. All three signaling pathways affected cell proliferation and mitosis during tail regeneration. The Wnt pathway inhibitor Wnt-C59 prevented forelimb bud outgrowth. The critical window for Wnt signaling regulating forelimb bud outgrowth was approximately developmental stage 40-42. Wnt signaling ligand Wnt3a and tight junction protein Zo-1 were expressed in the epidermis of the forelimb bud and both were downregulated by Wnt-C59. Moreover, both Wnt and Fgf signaling pathways affected cell proliferation and mitosis of mesodermal cells during forelimb bud outgrowth. Overall, my results show that Tgf-β, Wnt, and Fgf signaling pathways are required for axolotl tail regeneration. All three pathways affect Erk and Akt signaling and guide cell proliferation and mitosis. The Wnt signaling pathway is required for forelimb bud outgrowth, and it appears to regulate expression of Wnt3a and Zo1, and control cell proliferation and mitosis of mesodermal cells underlying the forelimb epidermis. These data enrich understanding of signaling network dynamics that underlie tissue regeneration and vertebrate limb development.
Aberrant KIF20A Expression Is Associated with Adverse Clinical Outcome and Promotes Tumor Progression in Prostate Cancer

Purpose KIF20A is essential in the process of spindle assembly and cytokinesis regulation. The role of KIF20A during tumorigenesis and tumor development has been well studied in several cancers. But the association between the KIF20A clinical role and prostate cancer (PCa) has not been reported yet. In this study, we investigated its potential prognostic effect and its role in progression of prostate cancer. Methods Real-time quantitative polymerase chain reaction and Western blots were used to investigate the KIF20A transcription and translation levels in 7 pairs of fresh PCa tissue and adjacent normal prostate tissue. Immunohistochemistry (IHC) was used to investigate the KIF20A protein level in 114 PCa tissue samples. Bioinformatics analysis was performed to analyze the effect of KIF20A in oncologic prognosis in PCa patients. MTT assay, transwell assay, and colony formation assay in vitro and tumor formation assay in vivo were performed to evaluate the biological behavior of KIF20A in prostate cancer. Results KIF20A was significantly elevated in tumor tissue compared with normal prostate tissue at both the mRNA and the protein level. High expression of KIF20A at the protein level was correlated with adverse clinicopathological features. Bioinformatics analysis showed that the high KIF20A expression group has a poor biochemical recurrence- (BCR-) free survival. Knocking down KIF20A suppressed the proliferation, migration, and invasion of the prostate cancer cell both in vitro and in vivo. Conclusions Our data demonstrated that the high expression of KIF20A was associated with poor clinical outcome and targeting KIF20A could reduce proliferation, migration, and invasion of the prostate cancer cell, indicating that KIF20A might be a potential prognostic and therapeutic target for PCa patients.
BWGS: A R package for genomic selection and its application to a wheat breeding programme

We developed an integrated R library called BWGS to enable easy computation of Genomic Estimates of Breeding values (GEBV) for genomic selection. BWGS relies on existing R-libraries, all freely available from CRAN servers. The two main functions enable to run 1) replicated random cross validations within a training set of genotyped and phenotyped lines and 2) GEBV prediction, for a set of genotyped-only lines. Options are available for 1) missing data imputation, 2) markers and training set selection and 3) genomic prediction with 15 different methods, either parametric or semi-parametric. The usefulness and efficiency of BWGS are illustrated using a population of wheat lines from a real breeding programme. Adjusted yield data from historical trials (highly unbalanced design) were used for testing the options of BWGS. On the whole, 760 candidate lines with adjusted phenotypes and genotypes for 47 839 robust SNP were used. With a simple desktop computer, we obtained results which compared with previously published results on wheat genomic selection. As predicted by the theory, factors that are most influencing predictive ability, for a given trait of moderate heritability, are the size of the training population and a minimum number of markers for capturing every QTL information. Missing data up to 40%, if randomly distributed, do not degrade predictive ability once imputed, and up to 80% randomly distributed missing data are still acceptable once imputed with Expectation-Maximization method of package rrBLUP. It is worth noticing that selecting markers that are most associated to the trait do improve predictive ability, compared with the whole set of markers, but only when marker selection is made on the whole population. When marker selection is made only on the sampled training set, this advantage nearly disappeared, since it was clearly due to overfitting. Few differences are observed between the 15 prediction models with this dataset. Although non-parametric methods that are supposed to capture non-additive effects have slightly better predictive accuracy, differences remain small. Finally, the GEBV from the 15 prediction models are all highly correlated to each other. These results are encouraging for an efficient use of genomic selection in applied breeding programmes and BWGS is a simple and powerful toolbox to apply in breeding programmes or training activities.
Examination of the Myokine Response in Pregnant and Non-pregnant Women Following an Acute Bout of Moderate-Intensity Walking

Background It is recommended that women accumulate 150-min of weekly moderate-intensity physical activity (MPA) when pregnant. Engaging in regular physical activity (PA) confers many health benefits to both the mother and the fetus. However, the molecular mechanisms by which these health benefits are bestowed are not well understood. One potential factor that may be contributing to the observed benefits is myokines, which are small peptides secreted by skeletal muscles. In the non-pregnant population, myokines are believed to be involved in the molecular mechanisms resulting from PA. The objective of this study was to characterize and compare the myokine profile of pregnant and non-pregnant women, after an acute bout of MPA. Methods Pregnant (n = 13) and non-pregnant (n = 17) women were recruited from the Ottawa region to undergo a treadmill walking session at moderate-intensity (40–60% heart rate reserve). Pre- and post-exercise serum samples were taken, and a set of 15 myokines were analyzed although only 10 were detected. IL-6 was analyzed using a high-sensitivity assay, while FGF21, EPO, BDNF, Fractalkine, IL-15, SPARC, FABP-3, FSTL-1, and oncostatin were analyzed using various multiplex assays. Results The pregnant and non-pregnant groups did not differ in terms of age, height, non/pre-pregnancy weight, BMI, and resting heart rate. Baseline levels of EPO and oncostatin were higher in the pregnant group while FGF21 was higher in the non-pregnant group. Circulating levels of three myokines, FGF21, EPO, and IL-15 significantly increased in response to the acute exercise in the pregnant group. Non-pregnant women exhibited an increase in three myokines, FABP-3, FSTL-1, and oncostatin, while one myokine, EPO, decreased post-exercise. SPARC, fractalkine and BDNF were shown to increase post-exercise regardless of pregnancy status while the response for BDNF was more pronounced in the non-pregnant group. Conclusion This is the first study examining myokine response following an acute bout of PA in pregnancy. Moderate intensity PA, which is recommended during pregnancy, elicited an increase in four myokines post-compared to pre-exercise in the pregnant group. Further research is warranted to understand the role of myokines in pregnancy.
The complete chloroplast genome of Streblus indicus

Abstract The first complete chloroplast genome sequences of Streblus indicus were reported in this study. The cpDNA of S. indicus is 159,853 bp in length, contains a large single copy region (LSC) of 88,950 bp and a small single copy region (SSC) of 19,313 bp, which were separated by a pair of inverted repeat (IR) regions of 25,795 bp. The genome contains 129 genes, including 84 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. The overall GC content of the whole genome is 36.1%. Phylogenetic analysis of 14 chloroplast genomes within the family Moraceae shows that S. indicus clustered in a unique clade.
Revisiting Feature Selection with Data Complexity

The identification of biomarkers or predictive features that are indicative of a specific biological or disease state is a major research topic in biomedical applications. Several feature selection(FS) methods ranging from simple univariate methods to recent deep-learning methods have been proposed to select a minimal set of the most predictive features. However, there still lacks the answer to the question of “which method to use when”. In this paper, we study the performance of feature selection methods with respect to the underlying datasets’ statistics and their data complexity measures. We perform a comparative study of 11 feature selection methods over 27 publicly available datasets evaluated over a range of number of selected features using classification as the downstream task. We take the first step towards understanding the FS method’s performance from the viewpoint of data complexity. Specifically, we (empirically) show that as regard to classification, the performance of all studied feature selection methods is highly correlated with the error rate of a nearest neighbor based classifier. We also argue about the non-suitability of studied complexity measures to determine the optimal number of relevant features. While looking closely at several other aspects, we also provide recommendations for choosing a particular FS method for a given dataset.
Constructing and Forgetting Temporal Context in the Human Cerebral Cortex

How does information from seconds earlier affect neocortical responses to new input? Here, we used empirical measurements and computational modeling to study the integration and forgetting of prior information. We found that when two groups of participants heard the same sentence in a narrative, preceded by different contexts, the neural responses of each group were initially different, but gradually fell into alignment. We observed a hierarchical gradient: sensory cortices aligned most quickly, followed by mid-level regions, while higher-order cortical regions aligned last. In some higher order regions, responses to the same sentence took more than 10 seconds to align. What kinds of computations can explain this hierarchical organization of contextual alignment? Passive linear integration models predict that regions which are slower to integrate new information should also be slower to forget old information. However, we found that higher order regions could rapidly forget prior context. The data were better captured by a model composed of hierarchical autoencoders in time (HAT). In HAT, cortical regions maintain a temporal context representation which is actively integrated with input at each moment, and this integration is gated by prediction error. These data and models suggest that sequences of information are combined throughout the cortical hierarchy using an active and gated integration process.
Early pathological signs in young dysf−/−
 mice are improved by halofuginone

Dysferlinopathies are a non-lethal group of late-onset muscular dystrophies. Here, we evaluated the fusion ability of primary myoblasts from young dysf−/− mice and the muscle histopathology prior to, and during early stages of disease onset. The ability of primary myoblasts of 5-weekold dysf−/− mice to form large myotubes was delayed compared to their wild-type counterparts, as evaluated by scanning electron microscopy. However, their fusion activity, as reflected by the presence of actin filaments connecting several cells, was enhanced by the antifibrotic drug halofuginone. Early dystrophic signs were already apparent in 4-week-old dysf−/− mice; their collagen level was double that in wild-type mice and continued to rise until 5 months of age. Continuous treatment with halofuginone from 4 weeks to 5 months of age reduced muscle fibrosis in a phosphorylated-Smad3 inhibition-related manner. Halofuginone also enhanced myofiber hypertrophy, reduced the percentage of centrally nucleated myofibers, and increased muscle performance. Together, the data suggest an inhibitory effect of halofuginone on the muscle histopathology at very early stages of dysferlinopathy, and better generation of force and muscle performance. These results offer new opportunities for early pharmaceutical treatment in dysferlinopathies with favorable outcomes at later stages of life.
Proteomic analysis reveals the recruitment of intrinsically disordered regions to stress granules

Heat-stress triggers the formation of condensates known as stress granules (SGs), which store non-translating mRNA and stalled translation initiation complexes. To gain a better understanding of SGs, we identified yeast proteins that sediment after heat-shock by mass spectrometry. Heat-regulated proteins are biased toward a subset of abundant proteins that are significantly enriched in intrinsically disordered regions (IDRs). SG localization of over 80 heat-regulated proteins was confirmed using microscopy, including 32 proteins that were not known previously to localize to SGs. We find that several IDRs are sufficient to mediate SG recruitment. Moreover, the diffusive exchange of IDRs within SGs, observed via FRAP, can be highly dynamic while other components remain immobile. Lastly, we showed that the IDR of the Ubp3 deubiquitinase is critical for SG formation. This work confirms that IDRs play an important role in cellular compartmentalization upon stress, can be sufficient for SG incorporation, can remain dynamic in vitrified SGs, and play a vital role during heat-stress. Summary The authors provide an in-depth proteomic study of yeast heat stress granule (SG) proteins. They identified intrinsic disordered regions (IDRs) as one of the main features shared by these proteins and demonstrated IDRs can be sufficient for SG recruitment.
Using population receptive field models to elucidate spatial integration in high-level visual cortex

While spatial information and biases have been consistently reported in high-level face regions, the functional contribution of this information toward face recognition behavior is unclear. Here, we propose that spatial integration of information plays a critical role in a hallmark phenomenon of face perception: holistic processing, or the tendency to process all features of a face concurrently rather than independently. We sought to gain insight into the neural basis of face recognition behavior by using a voxelwise encoding model of spatial selectivity to characterize the human face network using both typical face stimuli, and stimuli thought to disrupt normal face perception. We mapped population receptive fields (pRFs) using 3T fMRI in 6 participants using upright as well as inverted faces, which are thought to disrupt holistic processing. Compared to upright faces, inverted faces yielded substantial differences in measured pRF size, position, and amplitude. Further, these differences increased in magnitude along the face network hierarchy, from IOGto pFusand mFus-faces. These data suggest that pRFs in high-level regions reflect complex stimulusdependent neural computations that underlie variations in recognition performance.
Morphological and molecular identification of Pfenderius heterocaeca (Trematode: Paramphistomoidea) from Sumatran elephant (Elephas maximus sumatranus)

Background and Aim: Paramphistomiasis is common in tropical countries such as Indonesia and affects livestock and various endemic wild animals such as Sumatran elephants. However, the specific species of paramphistomoid worm that causes paramphistomiasis are rarely reported. The study aims at identifying paramphistomoid worm that infects Sumatran elephants. Materials and Methods: Flukes were collected from the feces of five semi-captive Sumatran elephants that lived at Tegal Yoso Elephant Response Unit in Way Kambas National Park, in 2018, after treatment of oxyclozanide 1 g at the dose of approximately 5-8 mg/kg of body weight. Eight paramphistomoid worms were flattened and stained in Semichon’s carmine for morphological identification, and five other worms were used for molecular identification at second internal transcribed spacer (ITS-2) of ribosomal deoxyribonucleic acid sequence. Results: Forty-five flukes were collected from five Sumatran elephants in Lampung, Indonesia. Eight paramphistomoid worms were morphologically identified as Pfenderius heterocaeca and five isolates did not show any variation in ITS-2. Phylogenetic analysis showed that there was a close genetic relationship between our sample and Chiorchis fabaceus that had a family similar to the samples. Conclusion: Based on the morphological and molecular characteristics, the paramphistomoids found in Sumatran elephant on Way Kambas National Park are P. heterocaeca.
Density dependence on multiple spatial scales maintains spatial variation in both abundance and traits

Population density affects fitness through various processes, such as mate finding and competition. The fitness of individuals in a population can in turn affect its density, making population density a key quantity linking ecological and evolutionary processes. Density effects are, however, rarely homogeneous. Different life-history processes can be affected by density over different spatial scales. In birds, for example, competition for food may depend on the number of birds nesting in the direct vicinity, while competition for nesting sites may occur over larger areas. Here we investigate how the effects of local density and of density in nearby patches can jointly affect the emergence of spatial variation in abundance as well as phenotypic diversification. We study a two-patch model that is described by coupled ordinary differential equations. The patches have no intrinsic differences: they both have the same fitness function that describes how an individual’s fitness depends on density in its own patch as well as the density in the other patch. We use a phase-space analysis, combined with a mathematical stability analysis to study the long-term behaviour of the system. Our results reveal that the mutual effect that the patches have on each other can lead to the emergence and long-term maintenance of a low and a high density patch. We then add traits and mutations to the model and show that different selection pressures in the high and low density patch can lead to diversification between these patches. Via eco-evolutionary feedbacks, this diversification can in turn lead to changes in the long-term population densities: under some parameter settings, both patches reach the same equilibrium density when mutations are absent, but different equilibrium densities when mutations are allowed. We thus show how, even in the absence of differences between patches, interactions between them can lead to differences in long-term population density, and potentially to trait diversification.