Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipopolysaccharide Preconditioning Augments Phagocytosis of Malaria-Parasitized Red Blood Cells by Bone Marrow-Derived Macrophages in the Liver, Thereby Increasing the Murine Survival after Plasmodium yoelii Infection

Malaria remains a grave concern for humans, as effective medical countermeasures for Plasmodium infection have yet to be developed. Phagocytic clearance of parasitized red blood cells (pRBCs) by macrophages is an important front-line innate host defense against Plasmodium infection. ABSTRACT Malaria remains a grave concern for humans, as effective medical countermeasures for Plasmodium infection have yet to be developed. Phagocytic clearance of parasitized red blood cells (pRBCs) by macrophages is an important front-line innate host defense against Plasmodium infection. We previously showed that repeated injections of low-dose lipopolysaccharide (LPS) prior to bacterial infection, called LPS preconditioning, strongly augmented phagocytic/bactericidal activity in murine macrophages. However, whether LPS preconditioning prevents murine Plasmodium infection is unclear. We investigated the protective effects of LPS preconditioning against lethal murine Plasmodium infection, focusing on CD11bhigh F4/80low liver macrophages, which are increased by LPS preconditioning. Mice were subjected to LPS preconditioning by intraperitoneal injections of low-dose LPS for 3 consecutive days, and 24 h later, they were intravenously infected with pRBCs of Plasmodium yoelii 17XL. LPS preconditioning markedly increased the murine survival and reduced parasitemia, while it did not reduce tumor necrosis factor (TNF) secretions, only delaying the peak of plasma gamma interferon (IFN-γ) after Plasmodium infection in mice. An in vitro phagocytic clearance assay of pRBCs showed that the CD11bhigh F4/80low liver macrophages, but not spleen macrophages, in the LPS-preconditioned mice had significantly augmented phagocytic activity against pRBCs. The adoptive transfer of CD11bhigh F4/80low liver macrophages from LPS-preconditioned mice to control mice significantly improved survival after Plasmodium infection. We conclude that LPS preconditioning stimulated CD11bhigh F4/80low liver macrophages to augment the phagocytic clearance of pRBCs, which may play a central role in resistance against Plasmodium infection.
Impact on reproductive performance and body condition in a small limpet parasitized by a large castrator pea crab

Parasitic castrators utilize the energy reserves that the host allocates on reproduction resulting in sterilization of the host. However, whether other processes (e.g., growth) are also impaired depends on the balance between the castrator's energy requirements and the available resources that the castrated host does not use in reproduction. We investigated whether the castrator pea crab Calytraeotheres garthi alters body condition, reproductive performance, and occurrence of copulation in its limpet host Bostrycapulus odites. For this purpose, we examined the anatomy of the ovary, the seminal receptacles, and the body condition of parasitized and unparasitized limpets. The histology of the female gonad of parasitized limpets revealed the ovarian tubules are smaller and characterized by a greater proportion of intertubular and intratubular free space compared with non‐parasitized individuals. The body condition of female limpets from all sizes (during summer) and those larger than ~16 mm (during spring and autumn) were impacted by the pea crab. These results are in contrast to that previously reported in the comparatively larger limpet species Crepidula cachimilla, in which the same pea crab species does not alter or even increase the host body weight. We concluded this pea crab species could drastically impair its host's reproduction and body condition although deleterious effects are species‐specific and likely depend on limpet body size. The histology of seminal receptacles revealed an uncommon disposition of spermatozoa (i.e., excessive debris and acrosomes detached from epithelium) in seminal receptacles of some parasitized limpets. However, this analysis failed to determine whether sperm derived from present matings or previous pea crab infection. Further studies are needed to address whether pea crabs interfere with the mating behavior of limpets and if the alterations in sperm disposition are a consequence of castration.
Reexamination of N-terminal domains of Syntaxin-1 in vesicle fusion from central murine synapses.

Syntaxin-1 (STX1) and Munc18-1 are two requisite components of synaptic vesicular release machinery, so much so synaptic transmission cannot proceed in their absence. They form a tight complex through two major binding modes: through STX1's N-peptide and through STX's closed conformation driven by its Habc- domain. However, physiological roles of these two reportedly different binding modes in synapses are still controversial. Here we characterized the roles of STX1's N-peptide, Habc-domain, and open conformation with and without N-peptide deletion using our STX1-null mouse model system and exogenous reintroduction of STX1A mutants. We show, on the contrary to the general view, that the Habc-domain is absolutely required and N-peptide is dispensable for synaptic transmission. However, STX1A's N-peptide plays a regulatory role, particularly in the Ca2+-sensitivity and the short-term plasticity of vesicular release, whereas STX1's open-conformation governs the vesicle fusogenicity. Strikingly, we also show neurotransmitter release still proceeds when the two interaction modes between STX1A and Munc18-1 are presumably intervened, necessitating a refinement of the conceptualization of STX1A-Munc18-1 interaction.
Causal Relationship between the Right Auditory Cortex and Speech-Evoked Envelope-Following Response: Evidence from Combined Transcranial Stimulation and Electroencephalography

Abstract Speech-evoked envelope-following response (EFR) reflects brain encoding of speech periodicity that serves as a biomarker for pitch and speech perception and various auditory and language disorders. Although EFR is thought to originate from the subcortex, recent research illustrated a right-hemispheric cortical contribution to EFR. However, it is unclear whether this contribution is causal. This study aimed to establish this causality by combining transcranial direct current stimulation (tDCS) and measurement of EFR (pre- and post-tDCS) via scalp-recorded electroencephalography. We applied tDCS over the left and right auditory cortices in right-handed normal-hearing participants and examined whether altering cortical excitability via tDCS causes changes in EFR during monaural listening to speech syllables. We showed significant changes in EFR magnitude when tDCS was applied over the right auditory cortex compared with sham stimulation for the listening ear contralateral to the stimulation site. No such effect was found when tDCS was applied over the left auditory cortex. Crucially, we further observed a hemispheric laterality where aftereffect was significantly greater for tDCS applied over the right than the left auditory cortex in the contralateral ear condition. Our finding thus provides the first evidence that validates the causal relationship between the right auditory cortex and EFR.
Outcomes of 25-gauge pars plana vitrectomy for cytomegalovirus retinitis-related retinal detachment

Purpose: The purpose of this study is to evaluate the anatomical and functional outcomes of 25-gauge (G) pars plana vitrectomy (PPV) in patients with cytomegalovirus retinitis (CMVR)-related rhegmatogenous retinal detachment (RRD). Methods: Single-center retrospective consecutive case series of patients who underwent 25-G PPV for CMVR-related RRD repair with a minimum follow-up of 3 months. Complete anatomic success was defined as the complete attachment of retina including the periphery. Best-corrected visual acuity (BCVA) of ≥20/400 was defined as functional success. Results: Sixteen eyes of 15 patients were included in the study. Eleven patients were human immunodeficiency virus positive, three patients had hematological malignancies, and one patient suffered from dyskeratosis congenita. The mean follow-up was 20.5 ± 17.4 months (range 3–60 months). Complete anatomical success was seen in 15 eyes (93.75%). One eye had a residual inferior detachment with attached macula. Silicone oil was used as tamponade in 15 eyes and C3F8 gas in one eye. The mean change in BCVA was statistically significant, preoperative LogMAR BCVA was 2.05 ± 0.94 while the final follow-up postoperative LogMAR BCVA was 1.03 ± 0.61 (P < 0.001). Thirteen eyes (81.25%) had final BCVA ≥20/400. Conclusion: Microincision vitrectomy surgery can achieve excellent retinal reattachment rates in post-CMVR RRDs without significant intraoperative and postoperative complications. The visual outcome varies depending on the status of the optic disc and macula. Majority of the patients maintained functional vision.
Whole-exome sequencing identifies multiple pathogenic variants in a large South Indian family with primary open-angle glaucoma

Purpose: To identify the pathogenic variants associated with primary open-angle glaucoma (POAG) using whole-exome sequencing (WES) data of a large South Indian family. Methods: We recruited a large five-generation South Indian family (n = 84) with a positive family history of POAG (n = 19). All study participants had a comprehensive ocular evaluation. We performed WES for 16 samples (nine POAG and seven unaffected controls) since Sanger sequencing of the POAG candidate genes (MYOC, OPTN, and TBK1) showed no genetic variation. We used an in-house pipeline for prioritizing the pathogenic variants based on their segregation among the POAG individual. Results: We identified one novel and five low-frequency pathogenic variants with consistent co-segregation in all affected individuals. The variant c.G3719A in RPGR-interacting domain of RPGRIP1 that segregated heterozygously with the six POAG cases is distinct from variants causing photoreceptor dystrophies, reported affecting the RPGR protein complex signaling in primary cilia. The cilia in trabecular meshwork (TM) cells has been reported to mediate the intraocular pressure (IOP) sensation. Furthermore, we identified a novel c.A1295G variant in Rho guanine nucleotide exchange factors Gene 40 (ARHGEF40) and a likely pathogenic variant in the RPGR gene, suggesting that they may alter the RhoA activity essential for IOP regulation. Conclusion: Our study supports that low-frequency pathogenic variants in multiple genes and pathways probably affect Primary Open Angle Glaucoma's pathogenesis in the large South Indian family. Furthermore, it requires larger case-controls to perform family-based association tests and to strengthen our analysis.
Development and comprehensive evaluation of a new spring-steel-driven glove for grasping assistance during activities of daily living

Millions of people suffer from a decline in grip strength and hand function due to conditions such as chronic disease, injuries, and aging. Hand function decline results in difficulties with performing activities of daily living, where grasping, lifting, and releasing objects are essential. There is an increasing demand for assistive gloves to enhance users’ hand function and improve their independence. This paper presents the design of a new bidirectional lightweight assistive glove and demonstrates its capabilities through comprehensive experiments using human subjects. The developed glove can provide adequate power augmentation for grasping and releasing objects due to its simple yet effective design using spring steel strips and linear actuators. The glove directly transfers assistive forces to users’ fingertips without any complex intermediate mechanism, and its low weight of 196 g promotes its usability. The rigorous experiment design provided a thorough assessment of the developed glove by accounting for both parameters of size and weight of objects and by including subjects with different hand sizes. To quantify the glove’s performance, the subjects’ muscle activity, their finger and thumb joints’ trajectories, and their grasping forces while using the glove were investigated. The glove could generate the necessary grasping forces to assist with lifting common-household objects. The subjects’ muscle activity significantly decreased when using the glove for object manipulation. The trajectories of the index finger and thumb joints when using the glove were dependent on the size of objects similar to natural unassisted grasping. The obtained results demonstrate the glove’s ability for grip power augmentation of individuals with declining hand strength.
Urokinase plasminogen activator mediates changes in human astrocytes modeling fragile X syndrome

The function of astrocytes intertwines with the extracellular matrix, whose neuron and glial cell‐derived components shape neuronal plasticity. Astrocyte abnormalities have been reported in the brain of the mouse model for fragile X syndrome (FXS), the most common cause of inherited intellectual disability, and a monogenic cause of autism spectrum disorder. We compared human FXS and control astrocytes generated from human induced pluripotent stem cells and we found increased expression of urokinase plasminogen activator (uPA), which modulates degradation of extracellular matrix. Several pathways associated with uPA and its receptor function were activated in FXS astrocytes. Levels of uPA were also increased in conditioned medium collected from FXS hiPSC‐derived astrocyte cultures and correlated inversely with intracellular Ca2+ responses to activation of L‐type voltage‐gated calcium channels in human astrocytes. Increased uPA augmented neuronal phosphorylation of TrkB within the docking site for the phospholipase‐Cγ1 (PLCγ1), indicating effects of uPA on neuronal plasticity. Gene expression changes during neuronal differentiation preceding astrogenesis likely contributed to properties of astrocytes with FXS‐specific alterations that showed specificity by not affecting differentiation of adenosine triphosphate (ATP)‐responsive astrocyte population. To conclude, our studies identified uPA as an important regulator of astrocyte function and demonstrated that increased uPA in human FXS astrocytes modulated astrocytic responses and neuronal plasticity.
Age patterns of intra‐pair DNA methylation discordance in twins: Sex difference in epigenomic instability and implication on survival

Aging is a biological process linked to specific patterns and changes in the epigenome. We hypothesize that age‐related variation in the DNA methylome could reflect cumulative environmental modulation to the epigenome which could impact epigenomic instability and survival differentially by sex. To test the hypothesis, we performed sex‐stratified epigenome‐wide association studies on age‐related intra‐pair DNA methylation discordance in 492 twins aged 56–80 years. We identified 3084 CpGs showing increased methylation variability with age (FDR < 0.05, 7 CpGs with p < 1e‐07) in male twins but no significant site found in female twins. The results were replicated in an independent cohort of 292 twins aged 30–74 years with 37% of the discovery CpGs successfully replicated in male twins. Functional annotation showed that genes linked to the identified CpGs were significantly enriched in signaling pathways, neurological functions, extracellular matrix assembly, and cancer. We further explored the implication of discovery CpGs on individual survival in an old cohort of 224 twins (220 deceased). In total, 264 CpGs displayed significant association with risk of death in male twins. In female twins, 175 of the male discovery CpGs also showed non‐random correlation with mortality. Intra‐pair comparison showed that majority of the discovery CpGs have higher methylation in the longer‐lived twins suggesting that loss of DNA methylation during aging contributes to increased risk of death which is more pronounced in male twins. In conclusion, age‐related epigenomic instability in the DNA methylome is more evident in males than in females and could impact individual survival and contribute to sex difference in human lifespan.
Differential interaction with TREM2 modulates microglial uptake of modified Aβ species

Rare coding variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2) confer an increased risk for Alzheimer's disease (AD) characterized by the progressive accumulation of aggregated forms of amyloid β peptides (Aβ). Aβ peptides are generated by proteolytic processing of the amyloid precursor protein (APP). Heterogeneity in proteolytic cleavages and additional post‐translational modifications result in the production of several distinct Aβ variants that could differ in their aggregation behavior and toxic properties. Here, we sought to assess whether post‐translational modifications of Aβ affect the interaction with TREM2. Biophysical and biochemical methods revealed that TREM2 preferentially interacts with oligomeric Aβ, and that phosphorylation of Aβ increases this interaction. Phosphorylation of Aβ also affected the TREM2 dependent interaction and phagocytosis by primary microglia and in APP transgenic mouse models. Thus, TREM2 function is important for sensing phosphorylated Aβ variants in distinct aggregation states and reduces the accumulation and deposition of these toxic Aβ species in preclinical models of Alzheimer's disease.
A simple computational method to estimate stance velocity in running.

Running dynamical analyses typically approximate a runner's stance velocity as the average stride cycle velocity (the average running speed). That approximation necessarily overestimates stance velocity and biases subsequent results. Stance velocities are crucial in kinetic spring-mass analyses of running, where approximation of a runner's impact angle and calculation of leg stiffness require that input. Here, a new method is presented to approximate a runner's stance velocity via measurement of contact and flight times with the runner's average speed, leg length or height, and mass. This method accurately estimated stance velocities of simulated spring-mass systems across typical running speeds of 3.5-5.5 m/s (r>0.99) and more accurately estimated impact angles of simulations and leg stiffnesses. The method also accurately estimated peak horizontal vertical ground reaction forces across speeds (r=0.82), but the bias magnitude increased with speed. Robustness of the new method was further tested for runners at 2.5, 3.5, and 4.5 m/s, and the new method provided steeper impact angles than those from traditional estimates and correspondingly higher leg stiffnesses, analogous to the observations in the simulation models. Horizontal ground reaction force estimates were weakly correlated in braking and propulsion. They were improved by a corrective algorithm, but the intra- and inter-individual variation persisted. The directionality and magnitude of angle and stiffness estimates in the human runners were similar to simulations, suggesting the new method more accurately modeled runners' spring-mass characteristics by using an accurate approximation of stance velocity. The new method can improve traditional kinetic analyses of running where stance velocity recordings are not captured with kinematic recordings and extend opportunities for accurate field-based analyses with limited measurement sources.
Streptococcus pyogenes TrxSR Two-Component System Regulates Biofilm Production in Acidic Environments

Bacteria form biofilms for their protection against environmental stress and produce virulence factors within the biofilm. Biofilm formation in acidified environments is regulated by a two-component system, as shown by studies on isogenic mutants of the sensor protein of the two-component regulatory system in Streptococcus pyogenes. ABSTRACT Bacteria form biofilms for their protection against environmental stress and produce virulence factors within the biofilm. Biofilm formation in acidified environments is regulated by a two-component system, as shown by studies on isogenic mutants of the sensor protein of the two-component regulatory system in Streptococcus pyogenes. In this study, we found that the LiaS histidine kinase sensor mediates biofilm production and pilus expression in an acidified environment through glucose fermentation. The liaS isogenic mutant produced biofilms in a culture acidified by hydrochloric acid but not glucose, suggesting that the acidified environment is sensed by another protein. In addition, the trxS isogenic mutant could not produce biofilms or activate the mga promoter in an acidified environment. Mass spectrometry analysis showed that TrxS regulates M protein, consistent with the transcriptional regulation of emm, which encodes M protein. Our results demonstrate that biofilm production during environmental acidification is directly under the control of TrxS.
An Efficient Numerical Approach for Transient Simulation of Multiphase Flow Behavior in Centrifuges

In this study, a developed numerical approach for spatial and time resolved simulations of the separation process in a tube centrifuge and some numerical results are presented. The back coupling of the dispersed and sedimented particles is realized by locally defined viscosity functions. The open source computation software OpenFOAM was used to simulate the turbulent multiphase flow within the centrifuge. The numerical investigations show the crucial influence of the growing sediment onto the flow conditions and of the rheological behavior of the sediment onto the sediment shape.
Impact of eugenol on in vivo model of 6-hydroxydopamine-induced oxidative stress

Abstract Oxidative stress is involved in many pathological disturbs, such as neurodegenerative disorders. Eugenol (Eug) is a phenolic compound with antioxidant and neuroprotective activities. Then, this study was conducted to investigate the potential neuroprotective effects of Eug on oxidative stress model induced by 6-hydroxydopamine (6-OHDA) in rats. First, the in vivo oxidative stress model was performed by intrastriatal injection (int.) of 6-OHDA (21 µg), followed by the treatment of Eug (0.1, 1, and 10 mg/kg/7 d) per os (p.o.). On the 7 d, behavioral tests were performed. On the 8 d, all the animals were euthanasied and their cerebral areas were excised for neurochemical and transcriptional analyses. The results showed that the treatment with Eug promoted neuroprotective effects on in vivo through reducing of oxidative stress and modulation of genes related to antioxidant activity. Furthermore, animals treated with Eug demonstrated returning of behavioral performance and body weight gain to normal conditions. Thus, this study reports the neuroprotective effects of Eug against oxidative stress induced by 6-OHDA in rats.