Miracle-dz/UniFAR-FTUs huggingface dataset:
Current State of Carbohydrate Recognition and C-Type Lectin Receptors in Pneumocystis Innate Immunity

Pneumocystis jirovecii is one of the most common fungal pathogens in immunocompromised individuals. Pneumocystis jirovecii pneumonia (PJP) causes a significant host immune response that is driven greatly by the organism’s cell wall components including β-glucans and major surface glycoprotein (Msg). These ligands interact with a number of C-type lectin receptors (CLRs) leading to downstream activation of proinflammatory signaling pathways. This minireview provides a brief overview summarizing known CLR/Pneumocystis interactions.
The Borderline Bias in Explicit Emotion Interpretation

Atypical emotion interpretation has been widely reported in individuals with borderline personality disorder (iBPD); however, empirical studies reported mixed results so far. We suggest that discrepancies in observations of emotion interpretation by iBPD can be explained by biases related to their fear of rejection and abandonment, i.e., the three moral emotions of anger, disgust, and contempt. In this study, we hypothesized that iBPD would show a higher tendency to correctly interpret these three displays of social rejection and attribute more negative valence. A total of 28 inpatient iBPDs and 28 healthy controls were asked to judge static and dynamic facial expressions in terms of emotions, valence, and self-reported arousal evoked by the observed faces. Our results partially confirmed our expectations. The iBPD correctly interpreted the three unambiguous moral emotions. Contempt, a complex emotion with a difficulty in recognizing facial expressions, was recognized better by iBPD than by healthy controls. All negative emotions were judged more negatively by iBPD than by controls, but no difference was observed in the neutral or positive emotion. Alexithymia and anxiety trait and state levels were controlled in all analyses.
Genoarchitectonic Compartmentalization of the Embryonic Telencephalon: Insights From the Domestic Cat

The telencephalon develops from the alar plate of the secondary prosencephalon and is subdivided into two distinct divisions, the pallium, which derives solely from prosomere hp1, and the subpallium which derives from both hp1 and hp2 prosomeres. In this first systematic analysis of the feline telencephalon genoarchitecture, we apply the prosomeric model to compare the expression of a battery of genes, including Tbr1, Tbr2, Pax6, Mash1, Dlx2, Nkx2-1, Lhx6, Lhx7, Lhx2, and Emx1, the orthologs of which alone or in combination, demarcate molecularly distinct territories in other species. We characterize, within the pallium and the subpallium, domains and subdomains topologically equivalent to those previously described in other vertebrate species and we show that the overall genoarchitectural map of the E26/27 feline brain is highly similar to that of the E13.5/E14 mouse. In addition, using the same approach at the earlier (E22/23 and E24/25) or later (E28/29 and E34/35) stages we further analyze neurogenesis, define the timing and duration of several developmental events, and compare our data with those from similar mouse studies; our results point to a complex pattern of heterochronies and show that, compared with the mouse, developmental events in the feline telencephalon span over extended periods suggesting that cats may provide a useful animal model to study brain patterning in ontogenesis and evolution.
Chlorogenic Acid-Induced Gut Microbiota Improves Metabolic Endotoxemia

Background Coffee can regulate glucose homeostasis but the underlying mechanism is unclear. This study investigated the preventive and therapeutic effects of chlorogenic acid (CGA), a polyphenol that is found in coffee, on obesity and obesity-related metabolic endotoxemia. Method Male 4-week-old C57BL/6 mice were fed either normal chow or a high-fat diet or 20 weeks and half the mice in each group were gavaged with CGA. Oral glucose tolerance tests (OGTTs) and insulin tolerance tests (ITTs) were performed. Markers of inflammation and intestinal barrier function were assayed. The composition of the gut microbiota was analyzed by 16S rRNA high-throughput pyrosequencing. The role of CGA-altered microbiota in metabolic endotoxemia was verified by fecal microbiota transplantation. Results CGA protected against HFD-induced weight gain, decreased the relative weight of subcutaneous and visceral adipose, improved intestinal barrier integrity, and prevented glucose metabolic disorders and endotoxemia (P <0.05). CGA significantly changed the composition of the gut microbiota and increased the abundance of short chain fatty acid (SCFA)-producers (e.g., Dubosiella, Romboutsia, Mucispirillum, and Faecalibaculum) and Akkermansia, which can protect the intestinal barrier. In addition, mice with the CGA-altered microbiota had decreased body weight and fat content and inhibited metabolic endotoxemia. Conclusion CGA-induced changes in the gut microbiota played an important role in the inhibition of metabolic endotoxemia in HFD-fed mice.
Bus Technology Meta-Analysis

This paper analyzes data obtained from international studies that compared natural gas, diesel, and hybrid technologies for buses to determine differences in particulate matter (PM10), nitrogen oxides (NOx), nonmethane hydrocarbon (NMHC), carbon monoxide (CO), greenhouse gas, and air toxic emissions. The results presented here are for 90-passenger 12-m buses. Two types of comparisons were made: technology and fuel. The comparison revealed that buses using ultra-low-sulfur diesel (ULSD) with diesel particulate filters (DPF) and buses using compressed natural gas (CNG) with oxidation catalysts (OC) had the lowest emissions of PM10 and CO; CNG with OC had lower NOx and greenhouse gases emissions, while ULSD with DPF had lower NMHC emissions. Posttreatment technologies are presented as a low-cost option to reduce emissions. Hybrid diesel buses were found to be the technology that has the lowest emissions for most of the studied pollutants.
Body Image in BRCA-Positive Young Women Following Bilateral Risk-Reducing Mastectomy: A Review of the Literature

Background/Significance: The presence of a breast cancer (BRCA) gene mutation increases a woman’s lifetime risk of developing breast cancer. Bilateral risk-reducing mastectomy is a proactive treatment option which lowers that risk. However, breast removal can create a change in physical appearance. It is unclear if BRCA-positive women undergoing this surgery in young adulthood, a life stage where intimate relationships, families, and careers are being established, have the same experience with body image as women in later stages of life. Purpose: The aim of this literature review is to assess how bilateral risk-reducing mastectomy impacts body image in young BRCA-positive women less than 40 years of age, with no history of breast cancer. Methods: Database searches were performed, yielding 402 results. Studies were considered if participants had an increased lifetime breast cancer risk/BRCA-positive diagnosis and history of bilateral risk-reducing mastectomy, body image was evaluated, and mean age was less than 40 years. A total of three qualitative studies and three quantitative studies were identified as relevant for this review. Results: A dearth of information exists on body image in young women following bilateral risk-reducing mastectomy. It was found in this review that some women experienced a decline in body image following surgery, while in others body image was maintained or improved. Conclusion: Understanding factors that impact body image following this risk-reducing surgery will allow clinicians to support this unique population. Open and informative discussion should be encouraged with young women considering, or who have undergone, bilateral risk-reducing mastectomy.
Generative Model of Brain Microbleeds for MRI Detection of Vascular Marker of Neurodegenerative Diseases

Cerebral microbleeds (CMB) are increasingly present with aging and can reveal vascular pathologies associated with neurodegeneration. Deep learning-based classifiers can detect and quantify CMB from MRI, such as susceptibility imaging, but are challenging to train because of the limited availability of ground truth and many confounding imaging features, such as vessels or infarcts. In this study, we present a novel generative adversarial network (GAN) that has been trained to generate three-dimensional lesions, conditioned by volume and location. This allows one to investigate CMB characteristics and create large training datasets for deep learning-based detectors. We demonstrate the benefit of this approach by achieving state-of-the-art CMB detection of real CMB using a convolutional neural network classifier trained on synthetic CMB. Moreover, we showed that our proposed 3D lesion GAN model can be applied on unseen dataset, with different MRI parameters and diseases, to generate synthetic lesions with high diversity and without needing laboriously marked ground truth.
Radiolabeled Monoclonal Antibody Against Colony-Stimulating Factor 1 Receptor Specifically Distributes to the Spleen and Liver in Immunocompetent Mice

Macrophages can promote tumor development. Preclinically, targeting macrophages by colony-stimulating factor 1 (CSF1)/CSF1 receptor (CSF1R) monoclonal antibodies (mAbs) enhances conventional therapeutics in combination treatments. The physiological distribution and tumor uptake of CSF1R mAbs are unknown. Therefore, we radiolabeled a murine CSF1R mAb and preclinically visualized its biodistribution by PET. CSF1R mAb was conjugated to N-succinyl-desferrioxamine (N-suc-DFO) and subsequently radiolabeled with zirconium-89 (89Zr). Optimal protein antibody dose was first determined in non-tumor-bearing mice to assess physiological distribution. Next, biodistribution of optimal protein dose and 89Zr-labeled isotype control was compared with PET and ex vivo biodistribution after 24 and 72 h in mammary tumor-bearing mice. Tissue autoradiography and immunohistochemistry determined radioactivity distribution and tissue macrophage presence, respectively. [89Zr]Zr-DFO-N-suc-CSF1R-mAb optimal protein dose was 10 mg/kg, with blood pool levels of 10 ± 2% injected dose per gram tissue (ID/g) and spleen and liver uptake of 17 ± 4 and 11 ± 4%ID/g at 72 h. In contrast, 0.4 mg/kg of [89Zr]Zr-DFO-N-suc-CSF1R mAb was eliminated from circulation within 24 h; spleen and liver uptake was 126 ± 44% and 34 ± 7%ID/g, respectively. Tumor-bearing mice showed higher uptake of [89Zr]Zr-DFO-N-suc-CSF1R-mAb in the liver, lymphoid tissues, duodenum, and ileum, but not in the tumor than did 89Zr-labeled control at 72 h. Immunohistochemistry and autoradiography showed that 89Zr was localized to macrophages within lymphoid tissues. Following [89Zr]Zr-DFO-N-suc-CSF1R-mAb administration, tumor macrophages were almost absent, whereas isotype-group tumors contained over 500 cells/mm2. We hypothesize that intratumoral macrophage depletion by [89Zr]Zr-DFO-N-suc-CSF1R-mAb precluded tumor uptake higher than 89Zr-labeled control. Translation of molecular imaging of macrophage-targeting therapeutics to humans may support macrophage-directed therapeutic development.
Noise generated in switched capacitor networks

It is shown that the noise generated in a passive first-order switched-capacitor lowpass filter has its origin in the thermal noise of the m.o. s. transistors' on-resistance. The spectral description of this noise at the output of the filter is given. The measurements made on a discrete laboratory model show good correspondence with the analytical results and confirm the noise model established.
HSDFinder: A BLAST-Based Strategy for Identifying Highly Similar Duplicated Genes in Eukaryotic Genomes

Gene duplication is an important evolutionary mechanism capable of providing new genetic material for adaptive and nonadaptive evolution. However, bioinformatics tools for identifying duplicate genes are often limited to the detection of paralogs in multiple species or to specific types of gene duplicates, such as retrocopies. Here, we present a user-friendly, BLAST-based web tool, called HSDFinder, which can identify, annotate, categorize, and visualize highly similar duplicate genes (HSDs) in eukaryotic nuclear genomes. HSDFinder includes an online heatmap plotting option, allowing users to compare HSDs among different species and visualize the results in different Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional categories. The external software requirements are BLAST, InterProScan, and KEGG. The utility of HSDFinder was tested on various model eukaryotic species, including Chlamydomonas reinhardtii, Arabidopsis thaliana, Oryza sativa, and Zea mays as well as the psychrophilic green alga Chlamydomonas sp. UWO241, and was proven to be a practical and accurate tool for gene duplication analyses. The web tool is free to use at http://hsdfinder.com. Documentation and tutorials can be found via the GitHub: https://github.com/zx0223winner/HSDFinder.
T Cell-Mediated Autoimmunity in Glaucoma Neurodegeneration

Glaucoma as the leading neurodegenerative disease leads to blindness in 3.6 million people aged 50 years and older worldwide. For many decades, glaucoma therapy has primarily focused on controlling intraocular pressure (IOP) and sound evidence supports its role in delaying the progress of retinal ganglial cell (RGC) damage and protecting patients from vision loss. Meanwhile, accumulating data point to the immune-mediated attack of the neural retina as the underlying pathological process behind glaucoma that may come independent of raised IOP. Recently, some scholars have suggested autoimmune aspects in glaucoma, with autoreactive T cells mediating the chief pathogenic process. This autoimmune process, as well as the pathological features of glaucoma, largely overlaps with other neurodegenerative diseases in the central nervous system (CNS), including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. In addition, immune modulation therapy, which is regarded as a potential solution for glaucoma, has been boosted in trials in some CNS neurodegenerative diseases. Thus, novel insights into the T cell-mediated immunity and treatment in CNS neurodegenerative diseases may serve as valuable inspirations for ophthalmologists. This review focuses on the role of T cell-mediated immunity in the pathogenesis of glaucoma and discusses potential applications of relevant findings of CNS neurodegenerative diseases in future glaucoma research.
Size Isn't Everything: The Effects of Size and Brightness of Retroreflective Materials on Nighttime Conspicuity

To increase their level of conspicuity, emergency response personnel wear Personal Protective Equipment (PPE) with retroreflective materials. That is, retroreflective materials increase the probability that oncoming motorists will see them. The goal of the current study was to provide empirical evidence regarding the relative nighttime conspicuity of conventional-trim retroreflective patterned garments (which have retroreflective material concentrated on specific portions of the garment) and area-retroreflective patterned garments (which have retroreflective material distributed evenly across the surface area of the garments). The question of interest was whether trim and area-reflective garments that reflect the same amount of light (i.e., equal RI values) provide equivalent conspicuity. At night, subjects seated in the passenger seat of cars approaching a live simulated roadway accident scene attempted to detect and recognize a human form in the road. Across three different levels of RI, the results demonstrate that when area reflective and trim garments reflect the same overall amount of light, area reflective garments provide lower levels of conspicuity than do conventional trim garments. These results suggest that, under the conditions of the current study, the brightness per unit area of retroreflective material needs to be considered rather than simply considering the total brightness of the garment independent of the size of the retroreflective surface-area.
Whole-Brain Reconstruction of Neurons in the Ventral Pallidum Reveals Diverse Projection Patterns

The ventral pallidum (VP) integrates reward signals to regulate cognitive, emotional, and motor processes associated with motivational salience. Previous studies have revealed that the VP projects axons to many cortical and subcortical structures. However, descriptions of the neuronal morphologies and projection patterns of the VP neurons at the single neuron level are lacking, thus hindering the understanding of the wiring diagram of the VP. In this study, we used recently developed progress in robust sparse labeling and fluorescence micro-optical sectioning tomography imaging system (fMOST) to label mediodorsal thalamus-projecting neurons in the VP and obtain high-resolution whole-brain imaging data. Based on these data, we reconstructed VP neurons and classified them into three types according to their fiber projection patterns. We systematically compared the axonal density in various downstream centers and analyzed the soma distribution and dendritic morphologies of the various subtypes at the single neuron level. Our study thus provides a detailed characterization of the morphological features of VP neurons, laying a foundation for exploring the neural circuit organization underlying the important behavioral functions of VP.
Oxoglutarate dehydrogenase coordinates myofibril growth by maintaining amino acid homeostasis

Myofibrils are long intracellular cables specific to muscles, composed mainly of actin and myosin filaments. The actin and myosin filaments are organized into repeated units called sarcomeres, which form the myofibril cables. Muscle contraction is achieved by the simultaneous shortening of sarcomeres and for a highly coordinated contraction to occur all sarcomeres should have the same size. Muscles have evolved a variety of ways to ensure sarcomere homogeneity, one example being the controlled oligomerization of Zasp proteins that sets the diameter of the myofibril. To understand how Zasp proteins effect myofibril growth, we looked for Zasp-binding proteins at the Z-disc. We found that the E1 subunit of the oxoglutarate dehydrogenase complex is recruited to the Z-disc by Zasp52 and is required to sustain myofibril growth. By making specific mutants, we show that its enzymatic activity is important for myofibril growth, and that the other two subunits of the complex are also required for myofibril formation. Using super resolution microscopy, we revealed the overall organization of the complex at the Z-disc. Then, using metabolomic analysis, we uncovered an amino acid balance defect affecting protein synthesis, that we also confirmed by genetic tools. In summary, we show that Zasp controls the local amino acid pool responsible for myofibril growth by recruiting the OGDH complex to the Z-disc.
Single Molecule Analysis of differential functional mechanisms of MtRecG while being exposed to variants of stalled replication-fork

Helicases are motor proteins involved in multiple activities to carry out manipulation of the nucleic acids for efficient gene regulation. In case of roadblocks that can lead the replication machinery to get halted, a complex molecular surveillance system utilizing helicases as its key player ensures the halted fork to resume its duplication process. RecG, belonging to the category of Superfamily-2 plays a vital role in rescuing different kinds of stalled fork. Here, through adoption of single-molecule techniques we have attempted to probe the DNA unwinding features by RecG and tried to capture several stages of genetic rearrangement. An elevated processivity of RecG has been observed for the kinds of stalled fork where progression of lagging daughter strand is ahead than that of the leading strand. Through precise alteration of its function in terms of unwinding, depending upon the substrate DNA, RecG catalyzes the formation of Holliday junction from a stalled fork DNA. In summary, we have featured that RecG adopts asymmetric mode of locomotion to unwind the lagging daughter strand to facilitate Holliday junction creation which acts as a suitable intermediate for recombinational repair pathway.
The 3D architecture of the pepper (Capsicum annum) genome and its relationship to function and evolution

The architecture of topologically associating domains (TADs) varies across plant genomes. Understanding the functional consequences of this diversity requires insights into the pattern, structure, and function of TADs. Here, we present a comprehensive investigation of the 3D genome organization of pepper (Capsicum annuum) and its association with gene expression and genomic variants. We report the first chromosome-scale long-read genome assembly of pepper and generate Hi-C contact maps for four tissues. The contact maps indicate that 3D structure varies somewhat across tissues, but generally the genome was segregated into subcompartments that were correlated with transcriptional state. In addition, chromosomes were almost continuously spanned by TADs, with the most prominent found in large genomic regions that were rich in retrotransposons. A substantial fraction of TAD boundaries were demarcated by chromatin loops, suggesting loop extrusion is a major mechanism for TAD formation; many of these loops were bordered by genes, especially in highly repetitive regions, resulting in gene clustering in three dimensional space. Integrated analysis of Hi-C profiles and transcriptomes showed that change in 3D chromatin structures (e.g. subcompartments, TADs, and loops) was not the primary mechanism contributing to differential gene expression between tissues, but chromatin structure does play a role in transcription stability. TAD boundaries were significantly enriched for breaks of synteny and depletion of sequence variation, suggesting that TADs constrain patterns of genome structural evolution in plants. Together, our work provides insights into principles of 3D genome folding in large plant genomes and its association with function and evolution.
The anti-angiogenic compound dimethyl fumarate inhibits the serine synthesis pathway and increases glycolysis in endothelial cells

A pathological and persistent angiogenesis is observed in several diseases like retinopathies, diabetes, psoriasis and cancer. Dimethyl fumarate, an ester from the Krebs cycle intermediate fumarate, is approved as a drug for the treatment of psoriasis and multiple sclerosis, and its anti-angiogenic activity has been reported in vitro and in vivo. However, it is not known whether dimethyl fumarate is able to modulate endothelial cell metabolism, considered an essential feature for the angiogenic switch. By means of different experimental approximations, including proteomics, isotope tracing and metabolomics experimental approaches, in this work we studied the possible role of dimethyl fumarate in endothelial cell energetic metabolism. We demonstrate for the first time that dimethyl fumarate promotes glycolysis and diminishes cell respiration, which could be a consequence of a down-regulation of serine and glycine synthesis through inhibition of PHGDH activity in endothelial cells. This new target can open a new field of study regarding the mechanism of action of dimethyl fumarate.