Miracle-dz/UniFAR-FTUs huggingface dataset:
Is Community Relevance Enough? Civic and Science Identity Impact of Microbiology CUREs Focused on Community Environmental Justice

Course-based undergraduate research experiences (CUREs) often involve a component where the outcomes of student research are broadly relevant to outside stakeholders. We wanted to see if building courses around an environmental justice issue relevant to the local community would impact students’ sense of civic engagement and appreciation of the relevance of scientific research to the community. In this quasi-experimental study, we assessed civic engagement and scientific identity gains (N = 98) using pre- and post-semester surveys and open-ended interview responses in three different CUREs taught simultaneously at three different universities. All three CURES were focused on an environmental heavy metal pollution issue predominantly affecting African–Americans in Birmingham, Alabama. While we found increases in students’ sense of science efficacy and identity, our team was unable to detect meaningful changes in civic engagement levels, all of which were initially quite high. However, interviews suggested that students were motivated to do well in their research because the project was of interest to outside stakeholders. Our observations suggest that rather than directly influencing students’ civic engagement, the “broadly relevant” component of our CUREs engaged their pre-existing high levels of engagement to increase their engagement with the material, possibly influencing gains in science efficacy and science identity. Our observations are consistent with broader community relevance being an important component of CURE success, but do not support our initial hypothesis that CURE participation would influence students’ attitudes toward the civic importance of science.
The PTI to ETI Continuum in Phytophthora-Plant Interactions

Phytophthora species are notorious pathogens of several economically important crop plants. Several general elicitors, commonly referred to as Pathogen-Associated Molecular Patterns (PAMPs), from Phytophthora spp. have been identified that are recognized by the plant receptors to trigger induced defense responses in a process termed PAMP-triggered Immunity (PTI). Adapted Phytophthora pathogens have evolved multiple strategies to evade PTI. They can either modify or suppress their elicitors to avoid recognition by host and modulate host defense responses by deploying hundreds of effectors, which suppress host defense and physiological processes by modulating components involved in calcium and MAPK signaling, alternative splicing, RNA interference, vesicle trafficking, cell-to-cell trafficking, proteolysis and phytohormone signaling pathways. In incompatible interactions, resistant host plants perceive effector-induced modulations through resistance proteins and activate downstream components of defense responses in a quicker and more robust manner called effector-triggered-immunity (ETI). When pathogens overcome PTI—usually through effectors in the absence of R proteins—effectors-triggered susceptibility (ETS) ensues. Qualitatively, many of the downstream defense responses overlap between PTI and ETI. In general, these multiple phases of Phytophthora-plant interactions follow the PTI-ETS-ETI paradigm, initially proposed in the zigzag model of plant immunity. However, based on several examples, in Phytophthora-plant interactions, boundaries between these phases are not distinct but are rather blended pointing to a PTI-ETI continuum.
The effect of hemicylindrical disruptors on the cell free layer thickness in animal blood flows inside microchannels

Abstract Blood-side resistance to oxygen transport in extracorporeal membrane blood oxygenators (MBO) depends on fluid mechanics governing the laminar flow in very narrow channels, particularly the hemodynamics controlling the cell free layer (CFL) built-up at solid/blood interfaces. The CFL thickness constitutes a barrier to oxygen transport from the membrane towards the erythrocytes. Interposing hemicylindrical CFL disruptors in animal blood flows inside rectangular microchannels, surrogate systems of MBO mimicking their hemodynamics, proved to be effective in reducing (ca. 20%) such thickness (desirable for MBO to increase oxygen transport rates to the erythrocytes). The blockage ratio (non-dimensional measure of the disruptor penetration into the flow) increase is also effective in reducing CFL thickness (ca. 10–20%), but at the cost of risking clot formation (undesirable for MBO) for disruptors with penetration lengths larger than their radius, due to large residence times of erythrocytes inside a low-velocity CFL formed at the disruptor/wall edge.
A Multi-Agent Based Approach to Short Message Service (SMS) Normalization System

SMS language is characterized by fashion and user’s creativity but needs a transformation to proper English words or spelling to formulate natural language and text processing activities. The proposed application, Web Information Retrieval System Architecture Based on SMS (WIRSABoSMS), normalizes SMS language to retain its original syntactic structure. The concept of mobile agents in web technology was introduced as a medium to achieving Short Message Service (SMS) normalization. SMS normalization was carried out with the adoption of multi-agent technology, as agents are involved in character search, sort, and compare of the strings written in SMS form into its parental orthography. This architecture was designed based on web information retrieval system (IRS) in order to achieve SMS normalization. BLEU (bilingual evaluation understudy) was used to evaluate the quality of text. BLEU scores compare the human judgment with that of the machine translation using two set of corpora. The outcome of syntactic text message normalization recorded an average of 90% performance (for the corpus collected from researchers) when compared with the similar test conducted with human judgment using BLEU scores metric in an health-related domain.
Human serum albumin (HSA) adsorption with chitosan microspheres

In this study, chitosan microspheres were prepared and characterized for adsorption of human serum albumin (HSA) as affinity sorbent. The chitosan microspheres were obtained with a “suspension crosslinking technique” in the size range of 30–700 μm by using a crosslinker, i.e., glutaraldehyde. The chitosan microspheres used in HSA adsorption studies were having the average size of 170 ± 81 μm. Adsorption medium pH and the initial HSA concentration in the adsorption medium were changed as 4.0–7.0 and 0.5–2.0 mg HSA/mL, respectively, to investigate the HSA adsorption capacity of chitosan microspheres. Maximum HSA adsorption (i.e., 11.35 mg HSA/g chitosan microspheres) was obtained at pH 5.0 and 1.5 mg HSA/mL of the initial HSA concentration in the adsorption medium was obtained as the saturation value for HSA adsorption. A very common dye ligand, i.e., Cibacron Blue F3GA was attached to the chitosan microspheres to increase the HSA adsorption capacity. Actually, the HSA adsorption capacity was increased up to 15.35 mg HSA/g chitosan microspheres in the case of Cibacron Blue F3GA attached to chitosan microspheres used. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 3035–3039, 2002
Receptor-gated IL-2 delivery by an anti-human IL-2 antibody activates regulatory T cells in three different species

CD25-biased human IL-2 complexes stimulate regulatory T cells in freshly isolated human T cells ex vivo and in mice and rhesus macaques in vivo. Antibody hits the sweet spot A promising approach for the treatment of autoimmunity is the activation of immunosuppressive cells called regulatory T cells. These cells can be expanded with interleukin-2, but the same cytokine can also activate other T cells, negating the regulatory T cells’ protective effects. Karakus et al. identified an antibody against interleukin-2 that specifically promotes its binding to a form of the interleukin-2 receptor highly expressed on regulatory T cells. The authors examined the detailed mechanism underlying this antibody’s activity and then demonstrated its ability to activate human regulatory T cells ex vivo and those from mice and nonhuman primates in vivo. Stimulation of regulatory T (Treg) cells holds great promise for the treatment of autoimmune, chronic inflammatory, and certain metabolic diseases. Recent clinical trials with low-dose interleukin-2 (IL-2) to expand Treg cells led to beneficial results in autoimmunity, but IL-2 immunotherapy can activate both Treg cells and pathogenic T cells. Use of IL-2 receptor α (IL-2Rα, CD25)–biased IL-2/anti–IL-2 antibody complexes improves IL-2 selectivity for Treg cells; however, the mechanism of action of such IL-2 complexes is incompletely understood, thus hampering their translation into clinical trials. Using a cell-based and dynamic IL-2R platform, we identified a particular anti-human IL-2 antibody, termed UFKA-20. When bound to UFKA-20, IL-2 failed to stimulate cells expressing IL-2Rβ (CD122) and IL-2Rγ (CD132), unless these cells also expressed high amounts of CD25. CD25 allowed IL-2/UFKA-20 complexes to bind, and binding to CD25 in the presence of CD122 and CD132 was followed by rapid dissociation of UFKA-20 from IL-2, delivery of IL-2 to CD122 and CD132, and intracellular signaling. IL-2/UFKA-20 complexes efficiently and preferentially stimulated CD4+ Treg cells in freshly isolated human T cells ex vivo and in mice and rhesus macaques in vivo. The crystal structure of the IL-2/UFKA-20 complex demonstrated that UFKA-20 interfered with IL-2 binding to CD122 and, to a lesser extent, also CD25. Together, we translated CD25-biased IL-2 complexes from mice to nonhuman primates and extended our mechanistic understanding of how CD25-biasing anti-human IL-2 antibodies work, which paves the way to clinical trials of CD25-biased IL-2 complexes.
Bayesian inference of transcriptional branching identifies regulators of early germ cell development in humans

During embryonic development, cells undertake a series of fate decisions to form a complete organism comprised of various cell types, epitomising a branching process. A striking example of branching occurs in humans around the time of implantation, when primordial germ cells (PGCs), precursors of sperm and eggs, and somatic lineages are specified. Due to inaccessibility of human embryos at this stage of development, understanding the mechanisms of PGC specification remains difficult. The integrative modelling of single cell transcriptomics data from embryos and appropriate in vitro models should prove to be a useful resource for investigating this system, provided that the cells can be suitably ordered over a developmental axis. Unfortunately, most methods for inferring cell ordering were not designed with structured (time series) data in mind. Although some probabilistic approaches address these limitations by incorporating prior information about the developmental stage (capture time) of the cell, they do not allow the ordering of cells over processes with more than one terminal cell fate. To investigate the mechanisms of PGC specification, we develop a probabilistic pseudotime approach, branch-recombinant Gaussian process latent variable models (B-RGPLVMs), that use an explicit model of transcriptional branching in individual marker genes, allowing the ordering of cells over developmental trajectories with arbitrary numbers of branches. We use first demonstrate the advantage of our approach over existing pseudotime algorithms and subsequently use it to investigate early human development, as primordial germ cells (PGCs) and somatic cells diverge. We identify known master regulators of human PGCs, and predict roles for a variety of signalling pathways, transcription factors, and epigenetic modifiers. By concentrating on the earliest branched signalling events, we identified an antagonistic role for FGF receptor (FGFR) signalling pathway in the acquisition of competence for human PGC fate, and identify putative roles for PRC1 and PRC2 in PGC specification. We experimentally validate our predictions using pharmacological blocking of FGFR or its downstream effectors (MEK, PI3K and JAK), and demonstrate enhanced competency for PGC fate in vitro, whilst small molecule inhibition of the enzymatic component of PRC1/PRC2 reveals reduced capacity of cells to form PGCs in vitro. Thus, B-RGPLVMs represent a powerful and flexible data-driven approach for dissecting the temporal dynamics of cell fate decisions, providing unique insights into the mechanisms of early embryogenesis. Scripts relating to this analysis are available from: https://github.com/cap76/PGCPseudotime
The prevalence and distribution in genomes of low-complexity, amyloid-like, reversible, kinked segment (LARKS), a common structural motif in amyloid-like fibrils

Membraneless Organelles (MLOs) are vital and dynamic reaction centers in cells that organize metabolism in the absence of a membrane. Multivalent interactions between protein Low-Complexity Domains (LCDs) contribute to MLO organization. Our previous work used computational methods to identify structural motifs termed Low-complexity Amyloid-like Reversible Kinked Segments (LARKS) that can phase-transition to form hydrogels and are common in human proteins that participate in MLOs. Here we searched for LARKS in proteomes of six model organisms: Homo sapiens, Drosophila melanogaster, Plasmodium falciparum, Saccharomyces cerevisiae, Mycobacterium tuberculosis, and Escherichia coli. We find LARKS are abundant in M. tuberculosis, D. melanogaster, and H. sapiens, but not in S. cerevisiae or P. falciparum. Abundant LARKS require high glycine content, which enables kinks to form in LARKS as is illustrated in the known LARKS-rich amyloid structures of TDP43, FUS, and hnRNPA2, three proteins that participate in MLOs. These results support the idea of LARKS as an evolved structural motif and we offer the LARKSdb webserver which permits users to search for LARKS in their protein sequences of interest.
Alzheimer’s Aβ assembly binds sodium pump and blocks endothelial NOS activity via ROS-PKC pathway

Amyloid β-protein (Aβ) may contribute to worsening of Alzheimer’s disease (AD) through vascular dysfunction, but the actual molecular mechanisms remain controversial. Using ex-vivo blood vessels and primary endothelial cells derived from human brain microvessels, we revealed that patient-derived Aβ assemblies, termed amylospheroids (ASPD), exist on the microvascular surface in patient brains and inhibit vasorelaxation through binding to the α3 subunit of sodium, potassium-ATPase (NAKα3) on endothelial cells. Interestingly, NAKα3 also serves as the toxic target of ASPD in neurons. ASPD elicit neurodegeneration through calcium overload, while ASPD suppress vasorelaxation by inhibiting nitric oxide (NO) production. ASPD-NAKα3 interaction on cerebrovascular endothelial cells disturbs the NO release by inactivating endothelial NO synthase through mitochondrial reactive oxygen species and protein kinase C. The findings suggest that ASPD may dually contribute to neuronal and vascular pathologies through binding to NAKα3. Thus, blocking the ASPD-NAKα3 interaction may be a useful target for AD therapy.
Finite element analysis of DNA supercoiling

A DNA polymer with hundreds or thousands of base pairs is modeled as a thin elastic rod. To find the equilibrium configurations and associated elastic energies as a function of linking number difference (ΔLk), a finite element scheme based on Kirchhoff’s rod theory is newly formulated so as to be able to treat self‐contact. The numerical results obtained here agree well with those already published, both analytical and numerical, but a much more detailed picture emerges of the several equilibrium states which can exist for a given ΔLk. Of particular interest is the discovery of interwound states having odd integral values of the writhing number and very small twist energy. The existence of a noncircular cross section, inhomogeneous elastic constants, intrinsic curvature, and sequence‐dependent bending and twisting can all be readily incorporated into the new formalism.
Predicting Social Exclusion: A Study of Linguistic Ostracism in Social Networks

Ostracism is a community-level phenomenon, shared by most social animals, including humans. Its detection plays a crucial role for the individual, with possible evolutionary consequences for the species. Considering (1) its bound with communication and (2) its social nature, we hypothesise the combination of (a) linguistic and (b) community-level features to have a positive impact on the automatic recognition of ostracism in human online communities. We model an English linguistic community through Reddit data and we analyse the performance of simple classification algorithms. We show how models based on the combination of (a) and (b) generally outperform the same architectures when fed by (a) or (b) in isolation.1
CHILab @ HaSpeeDe 2: Enhancing Hate Speech Detection with Part-of-Speech Tagging (short paper)

The present paper describes two neural network systems used for Hate Speech Detection tasks that make use not only of the pre-processed text but also of its Partof-Speech (PoS) tag. The first system uses a Transformer Encoder block, a relatively novel neural network architecture that arises as a substitute for recurrent neural networks. The second system uses a Depth-wise Separable Convolutional Neural Network, a new type of CNN that has become known in the field of image processing thanks to its computational efficiency. These systems have been used for the participation to the HaSpeeDe 2 task of the EVALITA 2020 workshop with CHILab as the team name, where our best system, the one that uses Transformer, ranked first in two out of four tasks and ranked third in the other two tasks. The systems have also been tested on English, Spanish and German languages.
Importance of test-retest reliability for promoting fMRI based screening and interventions in major depressive disorder

Proponents of personalized medicine have promoted neuroimaging evaluation and treatment of major depressive disorder in three areas of clinical application: clinical prediction, outcome evaluation, and neurofeedback. Whereas psychometric considerations such as test-retest reliability are basic precursors to clinical adoption for most clinical instruments, they are often not considered for neuroimaging assessments. As an example, we consider functional magnetic resonance imaging (fMRI) of depression, a common and particularly well validated mechanistic technology for understanding disorder and guiding treatment. In this article, we review work on test-retest reliability for depression fMRI studies. We find that basic psychometrics have not been regularly attended to in this domain. For instance, no fMRI neurofeedback study has included measures of test-retest reliability despite the implicit assumption that brain signals are stable enough to train. We consider several factors that could be useful to aid clinical translation including 1) attending to how the BOLD response is parameterized, 2) identifying and promoting regions or voxels with stronger psychometric properties 3) accounting for within-individual changes (e.g., in symptomatology) across time and 4) focusing on tasks and clinical populations that are relevant for the intended clinical application. We apply these principles to published prognostic and neurofeedback data sets. The broad implication of this work is that attention to psychometrics is important for clinical adoption of mechanistic assessment, is feasible, and may improve the underlying science.
Surprising phenotypic diversity of cancer-associated mutations of Gly 34 in the histone H3 tail

Sequencing of cancer genomes has identified recurrent somatic mutations in histones, termed oncohistones, which are frequently poorly understood. Previously we showed that fission yeast expressing only the H3.3G34R mutant identified in aggressive pediatric glioma had reduced H3K36 trimethylation and acetylation, increased genomic instability and replicative stress, and defective homology-dependent DNA damage repair (Yadav et al., 2017). Here we show that surprisingly distinct phenotypes result from G34V (also in glioma) and G34W (giant cell tumors of bone) mutations, differentially affecting H3K36 modifications, subtelomeric silencing, genomic stability, sensitivity to irradiation, alkylating agents, hydroxyurea and influencing DNA repair. In cancer, only one of thirty alleles encoding H3 is mutated. Whilst co-expression of wild-type H3 rescues most G34 mutant phenotypes, G34R causes dominant hydroxyurea sensitivity and homologous recombination defects, and dominant subtelomeric silencing. Together, these studies demonstrate the complexity associated with different substitutions at even a single residue in H3 and highlight the utility of genetically tractable systems for their analysis.
Leptospira interrogans triosephosphate isomerase: exploring the structural determinants of stability, high reaction rate and specificity

Leptospires are zoonotic pathogens that cause significant socio-economic burden in developing countries, world-wide. The pathogenic species Leptospira interrogans (Li) is an important and interesting target for investigating the enzymes essential to its metabolic needs and adaptations. We cloned and expressed triosephosphate isomerase (LiTIM), a central metabolic flux regulator of Li, in AA200, E. coli TIM null strain. LiTIM was obtained as an active dimer (D-GAP→DHAP kcat = 1740 s−1 and Km (D-GAP) = 0.21 mM, at 25 °C) with mid-transition concentrations, Cm, 0.8 mM and 2.6 mM, respectively, for guanidine hydrochloride and urea induced equilibrium unfolding. We report the high resolution X-ray structures of LiTIM in apo and substrate (DHAP) bound forms. Our analysis highlights key features of TIM that regulate the mode of substrate binding and transition state stabilization and thus play a decisive role in attainment of high proficiency for the isomerisation reaction while avoiding the elimination reaction. Unexpected differences in the effect of temperature on stability and activity were observed for the three mesophilic pathogenic TIMs viz. from Li, Plasmodium falciparum (Pf) and Trypanosoma brucei (Tb). LiTIM and TbTIM (Tm = 46.5 °C) were more susceptible to unfolding and precipitation compared to PfTIM (Tm = 67 °C). In contrast, the initial (or zero point) activity of PfTIM rises till 50 °C and saturates unlike LiTIM and TbTIM which show a rise till 55 °C and 60 °C, respectively. These observations could be rationalized by sequence comparison and examination of the structures of the three TIMs.