Miracle-dz/UniFAR-FTUs huggingface dataset:
The Diagnosis and Blistering Mechanisms of Mucous Membrane Pemphigoid

Mucous membrane pemphigoid (MMP) is a mucous membrane-dominated autoimmune subepithelial blistering disease that is caused by autoantibodies against various autoantigens in basement membrane zone (BMZ) proteins, including collagen XVII (COL17). Clinicians face diagnostic problems in detecting circulating antibodies and targeted antigens in MMP. The diagnostic difficulties are mainly attributed to the low titers of MMP autoantibodies in sera and to heterogeneous autoantigens. Additionally, no unanimous diagnostic criteria have been drawn for MMP, which can result in delayed diagnoses or misdiagnoses. This review aims to integrate and present currently available data to clarify diagnostic strategies and to present diagnostic criteria for MMP. The ultimate blistering mechanism in MMP has not been elucidated, and such mechanism is especially obscure in COL17-type MMP. In bullous pemphigoid (BP), which is the most common autoimmune subepidermal blistering disease, some patients show oral lesion as well as predominant skin lesions. However, there is no fundamental explanation for the onset of oral lesions in BP. This article summarizes innovative research perspectives on the pathogenesis of oral lesions in pemphigoid. Finally, we propose a potential pathogenesis for COL17-type MMP.
Impairment of Dendrodendritic Inhibition in the Olfactory Bulb of APP/PS1 Mice

Olfactory dysfunction is an early event in Alzheimer’s disease (AD). However, the mechanism underlying the AD-related changes in the olfactory bulb (OB) remains unknown. Granule cells (GCs) in the OB regulate the activity of mitral cells (MCs) through reciprocal dendrodendritic synapses, which is crucial for olfactory signal processing and odor discrimination. Nevertheless, the relationships between the morphological and functional changes of dendrodendritic synapses, particularly the local field potentials (LFPs) as a consequence of olfactory disorders in patients with AD have not been investigated. Here, we studied the morphological and functional changes induced by dendrodendritic inhibition in GCs onto MCs in the OB of amyloid precursor protein (APP)/PS1 mice and age-matched control mice during aging, particular, we focused on the effects of olfactory disorder in the dendrodendritic synaptic structures and the LFPs. We found that olfactory disorder was associated with increased amyloid-β (Aβ) deposits in the OB of APP/PS1 mice, and those mice also exhibited abnormal changes in the morphology of GCs and MCs, a decreased density of GC dendritic spines and impairments in the synaptic interface of dendrodendritic synapses between GCs and MCs. In addition, the aberrant enhancements in the γ oscillations and firing rates of MCs in the OB of APP/PS1 mice were recorded by multi-electrode arrays (MEAs). The local application of a GABAAR agonist nearly abolished the aberrant increase in γ oscillations in the external plexiform layer (EPL) at advanced stages of AD, whereas a GABAAR antagonist aggravated the γ oscillations. Based on our findings, we concluded that the altered morphologies of the synaptic structures of GCs, the dysfunction of reciprocal dendrodendritic synapses between MCs and GCs, and the abnormal γ oscillations in the EPL might contribute to olfactory dysfunction in AD.
SqueezeMeta, A Highly Portable, Fully Automatic Metagenomic Analysis Pipeline

The improvement of sequencing technologies has allowed the generalization of metagenomic sequencing, which has become a standard procedure for analysing the structure and functionality of microbiomes. The bioinformatic analysis of the sequencing results poses a challenge because it involves many different complex steps. SqueezeMeta is a full automatic pipeline for metagenomics/metatranscriptomics, covering all steps of the analysis. SqueezeMeta includes multi-metagenome support allowing the co-assembly of related metagenomes and the retrieval of individual genomes via binning procedures. SqueezeMeta features several unique characteristics: Co-assembly procedure or co-assembly of unlimited number of metagenomes via merging of individual assembled metagenomes, both with read mapping for estimation of the abundances of genes in each metagenome. It also includes binning and bin checking for retrieving individual genomes. Internal checks for the assembly and binning steps inform about the consistency of contigs and bins. Also, the results are stored in a mySQL database, where they can be easily exported and shared, and can be inspected anywhere using a flexible web interface allowing the easy creation of complex queries. We illustrate the potential of SqueezeMeta by analyzing 32 gut metagenomes in a fully automatic way, allowing to retrieve several millions of genes and several hundreds of genomic bins. One of the motivations in the development of SqueezeMeta was producing a software capable to run in small desktop computers, thus being amenable to all users and all settings. We were also able to co-assemble two of these metagenomes and complete the full analysis in less than one day using a simple laptop computer, illustrating the capacity of SqueezeMeta to run without high-performance computing infrastructure. SqueezeMeta is a complete system covering all steps in the analysis of metagenomes and metatranscriptomes, capable to work even in scarcity of computational resources. It is therefore adequate for in-situ, real time analysis of metagenomes produced by nanopore sequencing. SqueezeMeta can be downloaded from https://github.com/jtamames/SqueezeMeta
Study the Longitudinal in vivo and Cross-Sectional ex vivo Brain Volume Difference for Disease Progression and Treatment Effect on Mouse Model of Tauopathy Using Automated MRI Structural Parcellation

Brain volume measurements extracted from structural MRI data sets are a widely accepted neuroimaging biomarker to study mouse models of neurodegeneration. Whether to acquire and analyze data in vivo or ex vivo is a crucial decision during the phase of experimental designs, as well as data analysis. In this work, we extracted the brain structures for both longitudinal in vivo and single-time-point ex vivo MRI acquired from the same animals using accurate automatic multi-atlas structural parcellation, and compared the corresponding statistical and classification analysis. We found that most gray matter structures volumes decrease from in vivo to ex vivo, while most white matter structures volume increase. The level of structural volume change also varies between different genetic strains and treatment. In addition, we showed superior statistical and classification power of ex vivo data compared to the in vivo data, even after resampled to the same level of resolution. We further demonstrated that the classification power of the in vivo data can be improved by incorporating longitudinal information, which is not possible for ex vivo data. In conclusion, this paper demonstrates the tissue-specific changes, as well as the difference in statistical and classification power, between the volumetric analysis based on the in vivo and ex vivo structural MRI data. Our results emphasize the importance of longitudinal analysis for in vivo data analysis.
Polarity Specific Effects of Cross-Hemispheric tDCS Coupled With Approach-Avoidance Training on Chocolate Craving

Transcranial Direct Current Stimulation (tDCS) over the Dorsolateral Prefrontal Cortex (DLPFC) has already been shown to decrease craving for food. However, it remains unclear whether a single session of tDCS combined with a cognitive bias modification (CBM) task may affect explicit and implicit measures of craving for chocolate. Fifty-one healthy volunteers (38 females; mean age: 22.12 ± 3.38) were randomly allocated to CBM training based on the Approach Avoidance task and either Sham, Right anodal-Left cathodal (RALC), or Left anodal-Right cathodal (LARC) tDCS. Results show that there was an increase in the explicit craving for chocolate, as assessed by the Visual Analog Scale [F(2, 46) = 3.239, p = 0.048], from the baseline to post-intervention. Participants which received LARC tDCS were explicitly self-reporting more craving for chocolate than those that received RALC tDCS (p = 0.023). Moreover, this effect was also observed on the implicit measure [F(2, 46) = 4.168, p = 0.022]. LARC tDCS significantly increased the implicit preference for chocolate when comparing to both RALC (p = 0.009) and Sham tDCS (p = 0.034). Previous studies have shown that RALC tDCS over the PFC is able to effectively decrease craving for food. Interestingly, the present data not only does not reproduce such result, but instead it suggests that LARC tDCS can actually increase the preference for chocolate. This result is compatible with recent models of brain laterality, in which cue craving seems to be more dependent on the left hemisphere. Thus, shifting the activity to the left hemisphere (while simultaneously reducing the activity over the homotopic region) may have led to this increased implicit as well as explicit preference for chocolate.
St. John’s Wort (Hypericum perforatum) Products – How Variable Is the Primary Material?

Background: Saint John’s wort (Hypericum perforatum L., HP) is commonly registered in Europe under the THR scheme (Traditional Herbal Registration) or licensed as a medicine. Nonetheless unregulated medical products and food supplements are accessible through the internet which are often of poor quality. The species’ natural distribution stretches through large regions of Europe to China and four subspecies have been distinguished. When compared to the European Pharmacopoeia reference, the presence of additional compounds was linked to so-called Chinese HP. Aim: In order to obtain an integrated picture of the entire chemoprofile, the chemical composition of HP materia prima was studied using a combination of techniques well-established in the relevant industries. The impact of phytogeographic factors on the materia prima can shed light on whether the variability of the final products is strongly influenced by these factors of whether they relate to poor processing, adulteration, or other factors linked to the processing of the material. Methods: Eighty-six Hypericum samples (77 H. perforatum) were collected from 14 countries. Most were authenticated and harvested in the wild; others came as roughly ground material from commercial cultivations, markets and pharmacies. The samples were analyzed using HPTLC and 1H-NMR-based principal component analysis (PCA). Results and Discussion: Limited chemical variability was found. Nonetheless, the typical fingerprint of Chinese HP was observed in each specimen from China. Additional compounds were also detected in some samples collected in Spain. Rutin is not necessarily present in the crude material. The variability previously found in the marketed products can be ascribed only partially to the geographical origin of harvested material, but mainly to the plant part harvested, closely related to harvesting techniques, processing and probably time of harvest. Conclusion: HP can be sourced in a consistent composition (and thus quality) from different geographical sources. However, chemical variability needs to be accounted for when evaluating what is considered authentic good material. Therefore, the processing and good practice are all stages of primary importance, calling for a better (self-)regulation and quality assurance along the value chain of an herbal medical product or botanical.
Molecular Characterization of Peroxisome Proliferator-Activated Receptor-Gamma Coactivator-1α (PGC1α) and Its Role in Mitochondrial Biogenesis in Blunt Snout Bream (Megalobrama amblycephala)

PGC1α is a transcriptional coactivator that plays key roles in mitochondrial biogenesis, so exploring its molecular characterization contributes to the understanding of mitochondrial function in cultured fish. In the present study, a full-length cDNA coding PGC1α was cloned from the liver of blunt snout bream (Megalobrama amblycephala) which covered 3741 bp with an open reading frame of 2646 bp encoding 881 amino acids. Sequence alignment and phylogenetic analysis revealed high conservation with other fish species, as well as other higher vertebrates. Comparison of the derived amino acid sequences indicates that, as with other fish, there is a proline at position 176 (RIRP) compared to a Thr in the mammalian sequences (RIRT). To investigate PGC1α function, three in vitro tests were carried out using primary hepatocytes of blunt snout bream. The effect of AMPK activity on the expression of PGC1α was determined by the culture of the hepatocytes with an activator (Metformin) or inhibitor (Compound C) of AMPK. Neither AMPK activation nor inhibition altered PGC1α expression. Knockdown of PGC1α expression in hepatocytes using small interfering RNA (si-RNA) was used to determine the role of PGC1α in mitochondrial biogenesis. No significant differences in the expression of NRF1 and TFAM, and mtDNA copy number were found between control and si-RNA groups. Also, hepatocytes were cultured with oleic acid, and the findings showed the significant reduction of mtDNA copy number in oleic acid group compared to control. Moreover, oleic acid down-regulated the expression of NRF1 and TFAM genes, while PGC1α expression remained unchanged. Our findings support the proposal that PGC1α may not play a role in mitochondrial biogenesis in blunt snout bream hepatocytes.
Efficient biosynthetic incorporation of tryptophan analogues, and spectroscopic characterization of tryptophan-analogue labelled LysM proteins

Tryptofaan toepassen in fluorescentiespectroscopie Dejan Petrovic verrichtte onderzoek naar de vraag hoe het aminozuur tryptofaan kan worden toegepast in fluorescentiespectroscopie, een onderzoeksmethode die in de laatste decennia belangrijk is geworden in de levenswetenschappen. Tryptofaan (Trp) heeft eigenschappen die maken dat het erg geschikt is voor het bestuderen van eiwitstructuren en eiwitdynamica. Deze eigenschappen kunnen in de praktijk echter alleen optimaal benut worden als gezuiverd eiwit met slechts 1 of 2 Trp-residuen gebruikt wordt. Een mogelijkheid om een mengsel van eiwitten m.b. v. fluorescentie te bestuderen is het vervangen van een specifieke Trp in een van de eiwitten door een Trp-analogon. Vanwege de aanwezigheid van een onnatuurlijk aminozuur worden deze eiwitten ook wel alloproteines genoemd. Een van de doelen van het promotieproject was te onderzoeken of Trp-analogon bevattende eiwitten gebruikt kunnen worden als moleculair herkenningselement in een biosensor. Daarnaast zijn een aantal nieuwe procedures ontwikkeld voor de productie van alloproteines. Tot nu toe was er geen gevoelige spectroscopische methode voorhanden om de interactie tussen LysM domeinen en de celwand direct te kunnen volgen. In hoofdstuk 2 wordt een fluorescentiemethode gepresenteerd waarmee deze interactie gevolgd kan worden. In hoofdstuk 3 wordt een Lactococcus lactis Trp auxotroof expressie systeem beschreven dat de biosynthetische inbouw van Trp-analoga met grotere substituenten mogelijk maakt. In hoofdstuk 4 worden experimentele data gepresenteerd over de emissietoestand van vrij 5HI en 5HW, en van 5HW ingebouwd in een eiwit. Hieruit blijkt dat in de meeste gevallen 1Lb de emissietoestand is. Echter, een eiwit vertoont zowel 1La en 1Lb emissie.
M3, a natural lignan xyloside, exhibits potent anticancer activity in HCT116 cells

4-O-(2′,3′,4′-tri-O-methyl-β-D-xylopyranosyl) diphyllin (M3) is a cytotoxic compound that was first isolated from the aerial parts of Phyllanthus taxodiifolius. The current study demonstrated that M3, a lignan xyloside, exhibits anticancer effects in a number of cancer cell lines by MTT test, including HCT116 cells. An association was identified between M3 treatment and the reduced proliferation of cancer cells; the half maximal inhibitory concentration (IC50) value of M3 ranged from 0.08 to 1.12 µM. Furthermore, M3 was revealed to exhibit a stronger antiproliferative effect by Annexin-V-FLUOS test compared with VP-16, another natural lignan used in cancer treatment. Notably, the IC50 value of M3 with MTT test in HCT116 cells was 0.08 µM. In addition, it was revealed that M3 could induce apoptosis in HCT116 cells in a caspase-3-dependent manner at a lower concentration compared with VP-16. Further analysis identified that the antiproliferation effect of M3 was associated with the promotion of microtubule depolymerization by CytoDYNAMIX Screen 03 Tubulin Polymerization assay. In summary, the current study demonstrated that M3 could inhibit proliferation and induce apoptosis in HCT116 cells, which supports a potential therapeutic application of M3 in cancer treatment, particularly in colon cancer.
miR-146a-5p targets interleukin-1 receptor-associated kinase 1 to inhibit the growth, migration, and invasion of breast cancer cells

MicroRNAs (miRNAs) are associated with the formation and progression of many types of cancers. In the present study, the aim was to elucidate the involvement of miR-146a-5p in the regulation of human breast cancer (BC) cell growth and invasion, as well as the mechanisms underlying its effects. Reverse transcription-quantitative polymerase chain reaction results revealed that miR-146a-5p was markedly downregulated in BC tissues relative to those of adjacent normal tissues. miR-146a-5p expression was also markedly downregulated in BC cells. Overexpression of miR-146a-5p significantly suppressed the proliferation, invasion and migration of BC MDA-MB-453 and MCF7 cells. Furthermore, the results indicated that miR-146a-5p downregulated the expression of interleukin-1 receptor-associated kinase 1 (IRAK1) by directly binding to its 3′-untranslated region in BC cells. Furthermore, IRAK1 expression was observed to be markedly upregulated and inversely correlated with miR-146a-5p expression in BC tissues. Mechanical studies indicated that restoring IRAK1 expression reversed the miR-146a-5p-induced inhibitory effects on proliferation and invasion of BC cells. In conclusion, miR-146a-5p may act as a tumor suppressor in BC by directly targeting IRAK1. These results highlighted the potential of miR-146a-5p as a novel therapeutic target for the treatment of BC.
Synchronous endometrioid endometrial and ovarian carcinomas are biologically related: A clinico-pathological and molecular (next generation sequencing) study of 22 cases

The criteria for distinction between independent primary tumors and metastasis from one site to the other in synchronous endometrioid endometrial and ovarian carcinoma (SEO) has been a matter of dispute for a long time. In our study we performed a comprehensive clinico-pathological and molecular analysis of 22 cases of SEO. Based on conventional clinico-pathological criteria the cases were classified as independent primary tumors (10 cases) and metastasis from one location to the other (12 cases). All tumors were analyzed by NGS with a panel of 73 genes (219 kbp). Clonal origin was confirmed in all cases by at least one shared mutation in PTEN, AKT1, PIK3CA, KRAS, TP53 and ARID1A. Two patients carried germline pathogenic mutation in cancer-predisposing genes BRCA1 or BARD1. Microsatellite instable phenotype was detected in 5/22 (22.7%) SEO, but in one case only in the endometrial tumor. In conclusion, our results showed that all 22 SEOs were clonally related, irrespectively of their clinico-pathological features. Even low grade and low stage tumors classified as independent primaries, according to the conventional morphological criteria, have a clonal origin. From the practical point of view, only the conventional morphological criteria should be used for the classification (staging) of these tumors. However, molecular profiling of these tumors may have prognostic and predictive meaning.
Effects of Sex and Breed on Meat Quality and Sensory Properties in Three-way Crossbred Pigs Sired by Duroc or by a Synthetic Breed Based on a Korean Native Breed

Abstract This study was conducted to determine the effects of breed and sex on meat quality and sensory properties of the loin in three-way crossbred pigs: Landrace× Yorkshire×Duroc (LYD) and Landrace×Yorkshire×Woori (LYW) black pig synthesized by Korean native breed. Carcass traits did not differ by breed. Carcass weight and backfat thickness were higher in castrates than in gilts (p<0.01). LYW showed significant high values in fat content, cooking loss, and water-holding capacity (WHC) than LYD (p<0.05). Redness and yellowness of the meat were higher in LYW than in LYD (p<0.01). Further, LYW had lower pH and shear force than LYD (p<0.001). Significant high scores in color and flavor were obtained in LYW or gilts compared to LYD or castrates by sensory panel, respectively (p<0.05). However, other sensory traits did not differ by breed or sex. Capric acid (C10:0) was higher in LYD than LYW (p<0.001). However, stearic acid (C18:0) and saturated fatty acid (SFA) contents were higher in LYW than LYD (p<0.05). Eicosenoic acid (C20:2) and the n6/n3 ratio were higher in gilts than in castrates, whereas SFA content was higher in castrates than in gilts. These results suggest that certain physicochemical qualities of meat and sensory properties are improved in LYW compared to LYD. This study could provide basic data on meat quality of crossbred pigs with Woori black pig as a terminal sire.
Tinnitus Treatment Using Noninvasive and Minimally Invasive Electric Stimulation: Experimental Design and Feasibility

Noninvasive transcranial or minimally invasive transtympanic electric stimulation may offer a desirable treatment option for tinnitus because it can activate the deafferented auditory nerve fibers while posing little to no risk to hearing. Here, we built a flexible research interface to generate and control accurately charge-balanced current stimulation as well as a head-mounted instrument capable of holding a transtympanic electrode steady for hours. We then investigated the short-term effect of a limited set of electric stimulation parameters on tinnitus in 10 adults with chronic tinnitus. The preliminary results showed that 63% of conditions of electric stimulation produced some degree of tinnitus reduction, with total disappearance of tinnitus in six subjects in response to at least one condition. The present study also found significant side effects such as visual, tactile, and even pain sensations during electric stimulation. In addition to masking and residual inhibition, neuroplasticity is likely involved in the observed tinnitus reduction. To translate the present electric stimulation into a safe and effective tinnitus treatment option, we need to optimize stimulation parameters that activate the deafferented auditory nerve fibers and reliably suppress tinnitus, with minimal side effects and tolerable sensations. Noninvasive or minimally invasive electric stimulation can be integrated with sound therapy, invasive cochlear implants, or other forms of coordinated stimulation to provide a systematic strategy for tinnitus treatment or even a cure.