Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflammasome Meets Centrosome: Understanding the Emerging Role of Centrosome in Controlling Inflammasome Activation

Inflammasomes are multi-protein platforms that are assembled in response to microbial and danger signals to activate proinflammatory caspase-1 for production of active form of IL-1β and induction of pyroptotic cell death. Where and how an inflammasome is assembled in cells has remained controversial. While the endoplasmic reticulum, mitochondria and Golgi apparatus have been reported to be associated with inflammasome assembly, none of these sites seems to match the morphology, number and size of activated inflammasomes that are microscopically observable as one single perinuclear micrometer-sized punctum in each cell. Recently, emerging evidence shows that NLRP3 and pyrin inflammasomes are assembled, activated and locally regulated at the centrosome, the major microtubule organizing center in mammalian cells, elegantly accounting for the singularity, size and perinuclear location of activated inflammasomes. These new exciting findings reveal the previously unappreciated importance of the centrosome in controlling inflammasome assembly and activation as well as inflammasome-related diseases.
Integrated Analysis of Metabolomics and Transcriptomics for Assessing Effects of Fish Meal and Fish Oil Replacement on the Metabolism of Rainbow Trout (Oncorhynchus mykiss)

Reducing dependency on dietary fish meal (FM) and fish oil (FO) is extremely important for the sustainable development of the aquaculture industry. However, the metabolic consequences and mechanisms underlying the replacement of dietary FM and FO by terrestrial proteins (TPs) and lipids remain unclear. To reveal the effects of replacing dietary FM and/or FO on the metabolic changes, the integrated analysis of metabolomics and transcriptomics were employed to evaluate the changes in metabolites and genes of rainbow trout (Oncorhynchus mykiss) feeding different experimental diets. Four diets were formulated for the 84-day duration of the experiment: control group (FMFO), FM and vegetable oil (FMVO), terrestrial protein and FO (TPFO), and terrestrial protein and vegetable oil (TPVO). Integrated metabolomic and transcriptomic analyses revealed the significant difference in the metabolic pathways of O. mykiss among the three replacement schemes, i.e., single replacement of dietary FM by TP, single replacement of dietary FO by VO, and combined replacement of FM by TP and FO by VO. The combined replacement of FM and FO by TP and VO, respectively, disturbed immune function, energy metabolism, cellular protein biosynthesis capacity, and lipid metabolism of O. mykiss. The reduction of antioxidant capacity was only observed in individuals feeding diets with replacement of FM by TP. Furthermore, as soon as the dietary FM and/or FO were reduced, cellular protein biosynthesis ability was suppressed and accompanied by higher energy consumption in response to fluctuations of dietary quality, resulting in reduced growth performance. Interestingly, adenylosuccinate and adenosine monophosphate involved in purine metabolism were induced by both individual and combined replacement of FM and FO by TPs and lipids, respectively. It suggested that these two metabolites might be potential biomarkers for O. mykiss fed diets with reduction of FM and/or FO. This study constitutes a new understanding of the molecular and metabolic mechanisms of O. mykiss in response to the replacement of dietary FM and/or FO by TP and/or VO, respectively, and built a theoretical basis for further improvement of aquafeed formulation and sustainable development of aquaculture.
Streptococcus agalactiae Infects Glial Cells and Invades the Central Nervous System via the Olfactory and Trigeminal Nerves

Streptococcus agalactiae causes neonatal meningitis and can also infect the adult central nervous system (CNS). S. agalactiae can cross the blood-brain barrier but may also reach the CNS via other paths. Several species of bacteria can directly invade the CNS via the olfactory and trigeminal nerves, which extend between the nasal cavity and brain and injury to the nasal epithelium can increase the risk/severity of infection. Preterm birth is associated with increased risk of S. agalactiae infection and with nasogastric tube feeding. The tubes, also used in adults, can cause nasal injuries and may be contaminated with bacteria, including S. agalactiae. We here investigated whether S. agalactiae could invade the CNS after intranasal inoculation in mice. S. agalactiae rapidly infected the olfactory nerve and brain. Methimazole-mediated model of nasal epithelial injury led to increased bacterial load in these tissues, as well as trigeminal nerve infection. S. agalactiae infected and survived intracellularly in cultured olfactory/trigeminal nerve- and brain-derived glia, resulting in cytokine production, with some differences between glial types. Furthermore, a non-capsulated S. agalactiae was used to understand the role of capsule on glial cells interaction. Interestingly, we found that the S. agalactiae capsule significantly altered cytokine and chemokine responses and affected intracellular survival in trigeminal glia. In summary, this study shows that S. agalactiae can infect the CNS via the nose-to-brain path with increased load after epithelial injury, and that the bacteria can survive in glia.
Optimal Dietary Crude Protein in Commercial Feeds for Shrimp and Halophytes in Marine Aquaponic Biofloc Systems

Formulated diets for animals is the primary source of nutrients in aquaponic systems that need to maintain beneficial bacteria as well as for plants. Dietary protein is one of the expensive macronutrients in fish diets, especially when fishmeal is used, and it is the source of nitrogen (N) for other biotic components. Biofloc has the potential to serve as the supplement diet for shrimp and reduce the need of expensive protein. However, it is not clear if low dietary protein will be adequate to support the three organisms (animals, plants, and bacteria) in an aquaponic system operated with biofloc technology. The aim of the present study was to investigate the effect of shrimp feed with different protein concentrations (30, 35, or 40%) on water quality and the growth performance of Pacific whiteleg shrimp (Litopenaeus vannamei) and three edible halophytic plants (Atriplex hortensis, Salsola komarovii, and Plantago coronopus) in biofloc-based marine aquaponics. The experiment was conducted for 12 weeks, the plants were harvested and seedlings transplanted every 4 weeks. Dietary protein content did not influence shrimp growth in the current study, indicating that feeds with lower protein concentrations can be used in biofloc-based marine aquaponic systems. During the early and mid-stages of cultivation, plants grew better when supplied diets with higher protein concentration, whereas no differences were observed for later harvests. Hence, for maximum production with mature systems or in the scenario of high concentration of nitrate, providing a higher protein concentration feed in the early stages of system start-up, and switching to a lower protein concentration feed in later stages of cultivation was recommended.
Reliability of Isokinetic Strength Assessments of Knee and Hip Using the Biodex System 4 Dynamometer and Associations With Functional Strength in Healthy Children

Background This study aimed to analyze the reliability of concentric isokinetic strength assessments (knee and hip) using the Biodex System 4 in healthy children and assess the association with functional strength tests (sit-to-stand [STS], lateral-step-up [LSU]). Methods 19 children (6–12 years) were included. Knee and hip flexion and extension, and hip abduction and adduction were tested at 60 and 90°/s. Results Relative and absolute reliability at 60°/s tended to show better results compared to those at 90°/s. Intra class correlations (ICCs) of knee flexion and extension at 60°/s were good (0.79–0.89). For hip flexion, extension, abduction and adduction at 60°/s ICCs were moderate to good (0.53–0.83). The smallest detectable change (SDC) values (expressed in %) were highly variable. The SDC% for knee flexion and extension and hip abduction at 60°/s were around 50%. Positive associations were found between hip extension and abduction isokinetic strength and the STS test. Conclusion Concentric isokinetic strength assessments in healthy children using the Biodex System 4 were found reliable for knee flexion and extension and hip abduction. Limited associations were found between concentric isokinetic strength tests and functional strength tests.
Modulation of Cross-Language Activation During Bilingual Auditory Word Recognition: Effects of Language Experience but Not Competing Background Noise

Previous research has shown that as the level of background noise increases, auditory word recognition performance drops off more rapidly for bilinguals than monolinguals. This disproportionate bilingual deficit has often been attributed to a presumed increase in cross-language activation in noise, although no studies have specifically tested for such an increase. We propose two distinct mechanisms by which background noise could cause an increase in cross-language activation: a phonetically based account and an executive function-based account. We explore the evidence for the phonetically based account by comparing cognate facilitation effects for three groups of native English listeners (monolinguals, late (L2) learners of Spanish, and heritage Spanish speakers) and four noise conditions (no noise, speech-shaped noise, English two-talker babble, and Spanish two-talker babble) during an auditory lexical decision task in English. By examining word recognition in the dominant language, the role of language control mechanisms is minimized, and by examining three different types of competing noise, the role of energetic vs. informational masking can be assessed. Contrary to predictions, we find no evidence that background noise modulates cross-language activation; cognate facilitation is constant across the four noise conditions. Instead, several indices of word recognition performance are found to correlate with aspects of linguistic experience: (1) The magnitude of the cognate facilitation effect is correlated with heritage listeners’ self-ratings of Spanish proficiency; (2) Overall noise deficits are marginally larger for heritage listeners with lower English vocabulary scores; (3) Heritage listeners’ Spanish self-ratings predict their magnitude of informational masking; (4) For all bilinguals, the degree of masking incurred in both English and Spanish two-talker babble is correlated with self-reported daily exposure to Spanish; and (5) The degree of masking incurred by Spanish babble is correlated with Spanish vocabulary knowledge. The results enrich our understanding of auditory word recognition in heritage speakers in particular and provide evidence that informational masking is most subject to modulation due to variation in linguistic experience. It remains to be seen whether cross-language activation is modulated by noise when the target language is the less dominant one.
Optimal Experimental Design Based on Two-Dimensional Likelihood Profiles

Dynamic behavior of biological systems is commonly represented by non-linear models such as ordinary differential equations. A frequently encountered task in such systems is the estimation of model parameters based on measurement of biochemical compounds. Non-linear models require special techniques to estimate the uncertainty of the obtained model parameters and predictions, e.g. by exploiting the concept of the profile likelihood. Model parameters with significant uncertainty associated with their estimates hinder the interpretation of model results. Informing these model parameters by optimal experimental design minimizes the additional amount of data and therefore resources required in experiments. However, existing techniques of experimental design either require prior parameter distributions in Bayesian approaches or do not adequately deal with the non-linearity of the system in frequentist approaches. For identification of optimal experimental designs, we propose a two-dimensional profile likelihood approach, providing a design criterion which meaningfully represents the expected parameter uncertainty after measuring data for a specified experimental condition. The described approach is implemented into the open source toolbox Data2Dynamics in Matlab. The applicability of the method is demonstrated on an established systems biology model. For this demonstration, available data has been censored to simulate a setting in which parameters are not yet well determined. After determining the optimal experimental condition from the censored ones, a realistic evaluation was possible by re-introducing the censored data point corresponding to the optimal experimental condition. This provided a validation that our method is feasible in real-world applications. The approach applies to, but is not limited to, models in systems biology.
Transcriptional Landscape of Cotton Fiber Development and Its Alliance With Fiber-Associated Traits

Cotton fiber development is still an intriguing question to understand fiber commitment and development. At different fiber developmental stages, many genes change their expression pattern and have a pivotal role in fiber quality and yield. Recently, numerous studies have been conducted for transcriptional regulation of fiber, and raw data were deposited to the public repository for comprehensive integrative analysis. Here, we remapped > 380 cotton RNAseq data with uniform mapping strategies that span ∼400 fold coverage to the genome. We identified stage-specific features related to fiber cell commitment, initiation, elongation, and Secondary Cell Wall (SCW) synthesis and their putative cis-regulatory elements for the specific regulation in fiber development. We also mined Exclusively Expressed Transcripts (EETs) that were positively selected during cotton fiber evolution and domestication. Furthermore, the expression of EETs was validated in 100 cotton genotypes through the nCounter assay and correlated with different fiber-related traits. Thus, our data mining study reveals several important features related to cotton fiber development and improvement, which were consolidated in the “CottonExpress-omics” database.
Memory B Cells Induced by Sputnik V Vaccination Produce SARS-CoV-2 Neutralizing Antibodies Upon Ex Vivo Restimulation

The development of effective vaccines against SARS-CoV-2 remains a global health priority. Despite extensive use, the effects of Sputnik V on B cell immunity need to be explored in detail. We performed comprehensive profiling of humoral and B cell responses in a cohort of vaccinated subjects (n = 22), and demonstrate that Sputnik vaccination results in robust B cell immunity. We show that B memory cell (MBC) and antibody responses to Sputnik V were heavily dependent on whether the vaccinee had a history of SARS-CoV-2 infection or not. 85 days after the first dose of the vaccine, ex vivo stimulated MBCs from the vast majority of Sputnik V vaccinees produced antibodies that robustly neutralized the Wuhan Spike-pseudotyped lentivirus. MBC-derived antibodies from all previously infected and some of the naïve vaccine recipients could also cross-neutralize Beta (B.1.351) variant of SARS-CoV-2. Virus-neutralizing activity of MBC-derived antibodies correlated well with that of the serum antibodies, suggesting the interplay between the MBC and long-lived plasma cell responses. Thus, our in-depth analysis of MBC responses in Sputnik V vaccinees complements traditional serological approaches and may provide important outlook into future B cell responses upon re-encounter with the emerging variants of SARS-CoV-2.
Detecting Tuberculosis-Consistent Findings in Lateral Chest X-Rays Using an Ensemble of CNNs and Vision Transformers

Research on detecting Tuberculosis (TB) findings on chest radiographs (or Chest X-rays: CXR) using convolutional neural networks (CNNs) has demonstrated superior performance due to the emergence of publicly available, large-scale datasets with expert annotations and availability of scalable computational resources. However, these studies use only the frontal CXR projections, i.e., the posterior-anterior (PA), and the anterior-posterior (AP) views for analysis and decision-making. Lateral CXRs which are heretofore not studied help detect clinically suspected pulmonary TB, particularly in children. Further, Vision Transformers (ViTs) with built-in self-attention mechanisms have recently emerged as a viable alternative to the traditional CNNs. Although ViTs demonstrated notable performance in several medical image analysis tasks, potential limitations exist in terms of performance and computational efficiency, between the CNN and ViT models, necessitating a comprehensive analysis to select appropriate models for the problem under study. This study aims to detect TB-consistent findings in lateral CXRs by constructing an ensemble of the CNN and ViT models. Several models are trained on lateral CXR data extracted from two large public collections to transfer modality-specific knowledge and fine-tune them for detecting findings consistent with TB. We observed that the weighted averaging ensemble of the predictions of CNN and ViT models using the optimal weights computed with the Sequential Least-Squares Quadratic Programming method delivered significantly superior performance (MCC: 0.8136, 95% confidence intervals (CI): 0.7394, 0.8878, p < 0.05) compared to the individual models and other ensembles. We also interpreted the decisions of CNN and ViT models using class-selective relevance maps and attention maps, respectively, and combined them to highlight the discriminative image regions contributing to the final output. We observed that (i) the model accuracy is not related to disease region of interest (ROI) localization and (ii) the bitwise-AND of the heatmaps of the top-2-performing models delivered significantly superior ROI localization performance in terms of mean average precision [mAP@(0.1 0.6) = 0.1820, 95% CI: 0.0771,0.2869, p < 0.05], compared to other individual models and ensembles. The code is available at https://github.com/sivaramakrishnan-rajaraman/Ensemble-of-CNN-and-ViT-for-TB-detection-in-lateral-CXR.
Mesenchymal Stem Cells Exposed to Persistently High Glucocorticoid Levels Develop Insulin-Resistance and Altered Lipolysis: A Promising In Vitro Model to Study Cushing’s Syndrome

Background In Cushing’s syndrome (CS), chronic glucocorticoid excess (GC) and disrupted circadian rhythm lead to insulin resistance (IR), diabetes mellitus, dyslipidaemia and cardiovascular comorbidities. As undifferentiated, self-renewing progenitors of adipocytes, mesenchymal stem cells (MSCs) may display the detrimental effects of excess GC, thus revealing a promising model to study the molecular mechanisms underlying the metabolic complications of CS. Methods MSCs isolated from the abdominal skin of healthy subjects were treated thrice daily with GCs according to two different regimens: lower, circadian-decreasing (Lower, Decreasing Exposure, LDE) versus persistently higher doses (Higher, Constant Exposure, HCE), aimed at mimicking either the physiological condition or CS, respectively. Subsequently, MSCs were stimulated with insulin and glucose thrice daily, resembling food uptake and both glucose uptake/GLUT-4 translocation and the expression of LIPE, ATGL, IL-6 and TNF-α genes were analyzed at predefined timepoints over three days. Results LDE to GCs did not impair glucose uptake by MSCs, whereas HCE significantly decreased glucose uptake by MSCs only when prolonged. Persistent signs of IR occurred after 30 hours of HCE to GCs. Compared to LDE, MSCs experiencing HCE to GCs showed a downregulation of lipolysis-related genes in the acute period, followed by overexpression once IR was established. Conclusions Preserving circadian GC rhythmicity is crucial to prevent the occurrence of metabolic alterations. Similar to mature adipocytes, MSCs suffer from IR and impaired lipolysis due to chronic GC excess: MSCs could represent a reliable model to track the mechanisms involved in GC-induced IR throughout cellular differentiation.
Practical Model to Optimize the Strategy of Adjuvant Postmastectomy Radiotherapy in T1-2N1 Breast Cancer With Modern Systemic Therapy

Purpose The effect of adjuvant irradiation after mastectomy in early-stage breast cancer patients remains controversial. The present study aims to explore the clinical benefit obtained from adjuvant radiotherapy among post-mastectomy pT1-2N1 breast cancer patients who received adjuvant modern systemic therapy. Methods Medical records of consecutive patients with pT1-2N1 breast cancer who received mastectomy in our institution between January 2009 and December 2016 were retrospectively reviewed. High-risk features consist of patient age, number of positive lymph nodes, T stage, and Ki67 index, which were developed previously at our institution using early-stage breast cancer patients after mastectomy without adjuvant radiotherapy. Differences of survival and local recurrence were compared between no-postmastectomy radiotherapy (PMRT) and PMRT group according to number of risk factors. The time-to-event curves were calculated by the Kaplan–Meier methods and compared by the log-rank test. Propensity score matching (PSM) was performed to reduce the imbalances in patient characteristics. Results A total of 548 patients were enrolled (no-PMRT: 259 and PMRT: 289). After a median follow-up of 69 months, the 5-year rate of DFS, BCSS, and LRR in the overall cohort was 90.2%, 97.4%, and 3.6%, respectively. PMRT did not significantly improve DFS, BCSS, and LRRFS in the whole cohort. Patients were divided into low-risk (with no or one risk factor) and high-risk (with two or more risk factors) groups. According to the univariable and multivariable analysis, high-risk group (HR = 1.81, 95% CI 1.11–2.98, p = 0.02) was demonstrated as an independent risk factor for DFS. For the high-risk group, PMRT significantly improved DFS from 81.4% to 91.9% and BCSS from 95.5% to 98.6% and decreased the 5-year rate of LRR from 5.6% to 1.4%, respectively (p < 0.01, p = 0.05, and p = 0.06). However, no survival benefit from PMRT was observed in the low-risk group in terms of DFS, BCSS, and LRR (p = 0.45, p = 0.51, and p = 0.99, respectively). In multivariate analysis, PMRT remained an independent prognostic factor for DFS (HR = 0.50, 95% CI 0.24–1.00, p = 0.05) in the high-risk group. After PSM analysis, the survival benefit of PMRT was sustained in high-risk patients. Conclusion PMRT significantly improved DFS in high-risk pT1-2N1 breast cancer patients, but not in low-risk patients. Independent validation of our scoring system is recommended.
How Arsenic, an Inorganic Pollutant, is Involved in the Physiology of Biomolecular Condensates in the Cell

The existence of membrane-less organelles in the cells has been known for a relatively long time. Of the membrane-less organelles, stress granules, processing bodies, and PML-NBs have been intensively investigated in relation to arsenic. The membrane-less organelles, which concentrate biomolecules (proteins, nucleic acids), have recently been shown to self-organize by means of phase separation/transition. These biomolecular condensates (membrane-less organelles) can provide local enhancement of the efficiency of specific reactions. The biomolecular condensates have attracted dramatic attention over the last decade because highly organized biochemical complexes in the cell have long been understood by the membrane-dependent compartmentalization. In this mini review, we highlight the initiation of phase separation for each biomolecular condensate in which arsenic could be involved. We further reflect on the adequacy of the arsenic-dependent ROS levels for the formation of biomolecular condensates. These perspectives led us to re-evaluate the biological action of arsenic from a biophysical and bio-rheological point of view.