Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of New, Functionally Relevant Mutations in the Coding Regions of the Human Fos and Jun Proto-Oncogenes in Rheumatoid Arthritis Synovial Tissue

In rheumatoid arthritis (RA), the expression of many pro-destructive/pro-inflammatory proteins depends on the transcription factor AP-1. Therefore, our aim was to analyze the presence and functional relevance of mutations in the coding regions of the AP-1 subunits of the fos and jun family in peripheral blood (PB) and synovial membranes (SM) of RA and osteoarthritis patients (OA, disease control), as well as normal controls (NC). Using the non-isotopic RNAse cleavage assay, one known polymorphism (T252C: silent; rs1046117; present in RA, OA, and NC) and three novel germline mutations of the cfos gene were detected: (i) C361G/A367G: Gln121Glu/Ile123Val, denoted as “fos121/123”; present only in one OA sample; (ii) G374A: Arg125Lys, “fos125”; and (iii) C217A/G374A: Leu73Met/Arg125Lys, “fos73/125”, the latter two exclusively present in RA. In addition, three novel somatic cjun mutations (604–606ΔCAG: ΔGln202, “jun202”; C706T: Pro236Ser, “jun236”; G750A: silent) were found exclusively in the RA SM. Tansgenic expression of fos125 and fos73/125 mutants in NIH-3T3 cells induced an activation of reporter constructs containing either the MMP-1 (matrix metalloproteinase) promoter (3- and 4-fold, respectively) or a pentameric AP-1 site (approximately 5-fold). Combined expression of these two cfos mutants with cjun wildtype or mutants (jun202, jun236) further enhanced reporter expression of the pentameric AP-1 construct. Finally, genotyping for the novel functionally relevant germline mutations in 298 RA, 288 OA, and 484 NC samples revealed no association with RA. Thus, functional cfos/cjun mutants may contribute to local joint inflammation/destruction in selected patients with RA by altering the transactivation capacity of AP-1 complexes.
Characterization of Bacterial Microbiota Composition along the Gastrointestinal Tract in Rabbits

Simple Summary Each animal hosts a large community of bacteria, protozoa, fungi, and algae that colonize every surface of the body. The microbiota is defined as the complex microbial community that inhabits a specific anatomic region of animals and interacts with it, developing symbiotic relationships. In this regard, the intestinal microbiota has a vital impact on metabolism, digestive activity, immune development, resistance to infections, health, and welfare of the host. Therefore, knowing its characteristics is important for understanding its action in these specific functions. This study provides a comprehensive map of the most common bacterial communities that colonize different parts of the rabbit gastrointestinal tract (stomach, duodenum, jejunum, ileus, caecum, and colon) while using a modern methodological approach and comparing it with the studies that have been conducted to date on other animal species and human beings. It could be the starting point for further research on gut microbiota modulation with the ultimate goal to promote the health and welfare, in order to prevent or treat gastrointestinal diseases, decrease antibiotic use, and increase the productive performance of rabbit. Abstract The microbiota is extremely important for the animal’s health, but, to date, knowledge on the intestinal microbiota of the rabbit is very limited. This study aimed to describe bacterial populations that inhabit the different gastrointestinal compartments of the rabbit: stomach, duodenum, jejunum, ileum, caecum, and colon. Samples of the luminal content from all compartments of 14 healthy New White Zealand rabbits were collected at slaughter and analyzed using next generation 16S rRNA Gene Sequencing. The findings uncovered considerable differences in the taxonomic levels among the regions of the digestive tract. Firmicutes were the most abundant phylum in all of the sections (45.9%), followed by Bacteroidetes in the large intestine (38.9%) and Euryarchaeota in the foregut (25.9%). Four clusters of bacterial populations were observed along the digestive system: (i) stomach, (ii) duodenum and jejunum, (iii) ileum, and (iv) large intestine. Caecum and colon showed the highest richness and diversity in bacterial species, while the highest variability was found in the upper digestive tract. Knowledge of the physiological microbiota of healthy rabbits could be important for preserving the health and welfare of the host as well as for finding strategies to manipulate the gut microbiota in order to also promote productive performance.
MicroRNAs: An Update of Applications in Forensic Science

MicroRNAs (miRNAs) are a class of non-coding RNAs containing 18–24 nucleotides that are involved in the regulation of many biochemical mechanisms in the human body. The level of miRNAs in body fluids and tissues increases because of altered pathophysiological mechanisms, thus they are employed as biomarkers for various diseases and conditions. In recent years, miRNAs obtained a great interest in many fields of forensic medicine given their stability and specificity. Several specific miRNAs have been studied in body fluid identification, in wound vitality in time of death determination, in drowning, in the anti-doping field, and other forensic fields. However, the major problems are (1) lack of universal protocols for diagnostic expression testing and (2) low reproducibility of independent studies. This review is an update on the application of these molecular markers in forensic biology.
Study of Water in Dough Using Nuclear Magnetic Resonance

ABSTRACT The amount and state of water play an important role in the preparation and properties of wheat flour doughs and their products. A new method for presentation and analysis of relaxation time measurements of protons in dough is described in this article. This new method acknowledges a continuous probability distribution of protons having different relaxation times in heterogeneous systems such as dough, which is dramatically different from the conventional discrete methods that rely on prior assumptions of a number of discrete relaxation components. In the present study, pulsed proton nuclear magnetic resonance was used to study the relaxation characteristics of dough systems at moisture levels of 12–45%. The relaxation curves obtained using a 90-degree pulse (Onepulse) sequence and the Carr-Purcell-Meiboom-Gill pulse sequence were analyzed using a multiexponential discrete model and a continuum model. The discrete model produced three fractions of protons relaxing in three different time domains.
Recent Advances on the Anticancer Properties of Saffron (Crocus sativus L.) and Its Major Constituents

Cancer is the second leading cause of death globally with an estimated 9.6 million deaths in 2018 and a sustained rise in its incidence in both developing and developed countries. According to the WHO, about 1 in 6 deaths is due to cancer. Despite the emergence of many pioneer therapeutic options for patients with cancer, their efficacy is still time-limited and noncurative. Thus, continuous intensive screening for superior and safer drugs is still ongoing and has resulted in the detection of the anticancer properties of several phytochemicals. Among the spices, Crocus sativus L. (saffron) and its main constituents, crocin, crocetin, and safranal, have attracted the interest of the scientific community. Pharmacological experiments have established numerous beneficial properties for this brilliant reddish-orange dye derived from the flowers of a humble crocus family species. Studies in cultured human malignant cell lines and animal models have demonstrated the cancer prevention and antitumor activities of saffron and its main ingredients. This review provides an insight into the advances in research on the anticancer properties of saffron and its components, discussing preclinical data, clinical trials, and patents aiming to improve the pharmacological properties of saffron and its major ingredients.
Response to Letter to the Editor from Dalan: “Vitamin D Supplementation for Prevention of Type 2 Diabetes Mellitus: To D or Not to D?”

Response to Letter to the Editor from Dalan: “Vitamin D Supplementation for Prevention of Type 2 Diabetes Mellitus: To D or Not to D? ” Anastassios G. Pittas, Rolf Jorde, Tetsuya Kawahara, and Bess Dawson-Hughes Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center, Boston, Massachusetts 02111, USA; Institute of Clinical Medicine, UiT The Arctic University of Norway, 9037 Tromsø, Norway; and Division of Internal Medicine, Kokura Medical Association Health Testing Center, Kitakyushu, Japan
Accelerometric Assessment of Postural Balance in Children: A Systematic Review

The correct development of postural control in children is fundamental to ensure that they fully reach their psychomotor capacities. However, this capacity is one of the least studied in the clinical and academic scope regarding children. The objective of this study was to analyze the degree of implementation of accelerometry as an evaluation technique for postural control in children and how it is being used. Methods: A systematic search was conducted in PubMed, SpringerLink, SportsDiscus, Medline, Scopus, and Web of Science with the following terms: balance, postural control, children, kids, accelerometry, and accelerometer. Results: The search generated a total of 18 articles. Two groups of studies were differentiated: those which exclusively included healthy individuals (n = 5) and those which included children with pathologies (n = 13). Accelerometry is being used in children mainly to assess the gait and static balance, as well as to identify the differences between healthy children and children with developmental disorders. Conclusions: Accelerometry has a discrete degree of implementation as an evaluation tool to assess postural control. It is necessary to define a systematic method for the evaluation of postural control in pediatrics, in order to delve into the development of this capacity and its alterations in different neurodevelopmental disorders.
Comparison of proteomic profiles from the testicular tissue of males with impaired and normal spermatogenesis

ABSTRACT In this study, we aimed to explore the potential differences in proteomic profiles from the testicular tissue of azoospermatic men with impaired spermatogenesis and normal spermatogenesis. Isobaric tags for relative and absolute quantitation (iTRAQ) labeled technology and LC-MS/MS technology were used to identify differentially expressed proteins. Potential functions of differentially expressed proteins were predicted using gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG). Immunohistochemistry (IHC) and western blot (WB) were used to verify the differentially expressed proteins. A protein–protein interaction (PPI) network was built to outline the regulatory network of differentially expressed proteins. A total of 3,945 proteins were identified in men with normal and impaired spermatogenesis. Of these, 116 proteins were differentially expressed in men with impaired spermatogenesis: 39 were upregulated and 77 were downregulated. Furthermore, we found that these differentially expressed proteins were mainly involved in the cellular component, which may be mainly associated with the spliceosome, ribosome, and thyroid hormone synthesis signaling pathways. The spliceosome- and ribosome-associated proteins YBX1, FBL, and HNRNPU were downregulated. And the proteomic profile of testicular tissue in men with impaired spermatogenesis is different from that of men with normal spermatogenesis. For this reason, differentially expressed proteins such as YBX1, FBL and HNRNPU might be involved in the pathology of spermatogenesis dysfunction. Abbreviations: iTRAQ: Isobaric tags for relative and absolute quantitation;GO: Gene ontology; KEGG: Kyoto encyclopedia of genes and genomes; IHC: Immunohistochemistry; WB: Western blot; PPI: Protein–protein interaction; ICSI: Intracytoplasmic sperm injection; BP: Biological process; CC: Cellular components; MF: Molecular function; snoRNA: Small nucleolar RNA; snRNA: Small nuclear RNA; LC-MS/MS: Liquid chromatography and MS/MS analysis; BSA: Bovine serum albumin; SD: Spermatogenic dysfunction; micro-TESE: Testicular microscopic sperm extraction
Fake It ‘Till You Make It—The Pursuit of Suitable Membrane Mimetics for Membrane Protein Biophysics

Membrane proteins evolved to reside in the hydrophobic lipid bilayers of cellular membranes. Therefore, membrane proteins bridge the different aqueous compartments separated by the membrane, and furthermore, dynamically interact with their surrounding lipid environment. The latter not only stabilizes membrane proteins, but directly impacts their folding, structure and function. In order to be characterized with biophysical and structural biological methods, membrane proteins are typically extracted and subsequently purified from their native lipid environment. This approach requires that lipid membranes are replaced by suitable surrogates, which ideally closely mimic the native bilayer, in order to maintain the membrane proteins structural and functional integrity. In this review, we survey the currently available membrane mimetic environments ranging from detergent micelles to bicelles, nanodiscs, lipidic-cubic phase (LCP), liposomes, and polymersomes. We discuss their respective advantages and disadvantages as well as their suitability for downstream biophysical and structural characterization. Finally, we take a look at ongoing methodological developments, which aim for direct in-situ characterization of membrane proteins within native membranes instead of relying on membrane mimetics.
Direct Neuronal Reprogramming of Common Marmoset Fibroblasts by ASCL1, microRNA-9/9*, and microRNA-124 Overexpression

The common marmoset (Callithrix jacchus) has attracted considerable attention, especially in the biomedical science and neuroscience research fields, because of its potential to recapitulate the complex and multidimensional phenotypes of human diseases, and several neurodegenerative transgenic models have been reported. However, there remain several issues as (i) it takes years to generate late-onset disease models, and (ii) the onset age and severity of phenotypes can vary among individuals due to differences in genetic background. In the present study, we established an efficient and rapid direct neuronal induction method (induced neurons; iNs) from embryonic and adult marmoset fibroblasts to investigate cellular-level phenotypes in the marmoset brain in vitro. We overexpressed reprogramming effectors, i.e., microRNA-9/9*, microRNA-124, and Achaete-Scute family bHLH transcription factor 1, in fibroblasts with a small molecule cocktail that facilitates neuronal induction. The resultant iNs from embryonic and adult marmoset fibroblasts showed neuronal characteristics within two weeks, including neuron-specific gene expression and spontaneous neuronal activity. As directly reprogrammed neurons have been shown to model neurodegenerative disorders, the neuronal reprogramming of marmoset fibroblasts may offer new tools for investigating neurological phenotypes associated with disease progression in non-human primate neurological disease models.
Polystyrene Biodegradation by Tenebrio molitor Larvae: Identification of Generated Substances Using a GC-MS Untargeted Screening Method

A GC-MS method has been applied to screen and evaluate the generation of chemical compounds during the biodegradation of polystyrene (PS) with Tenebrio molitor larvae. Several resulting compounds have been identified, including trimers 2,4,6-triphenyl-1-hexene and 1,3,5-triphenylcyclohexane, the volatiles acetophenone and cumyl alcohol, and 2,4-di-tert butylphenol, a non-intentionally added substance (NIAS) present in the plastic material. The PS monomers styrene and α-methyl styrene were also identified in the extracts. Bioactive molecules present in the biomass of the studied insects were identified, such as the free fatty acids myristic, palmitic, and oleic acid. Undecanoic acid was also found, but in lower mass fractions. Finally, biochemically formatted amides resulting from their respective fatty acids were identified, namely tetradecanamide, hexadecanamide and oleamide. The formation of all these substances seems to suggest enzymatic and biochemical activity occurring during the biodegradation of PS, and their amounts varied throughout the experience. The overall degradation rate of PS resulted in a 13% rate, which highlights the potential of biorecycling using these insects.
The Role of Methemoglobin and Carboxyhemoglobin in COVID-19: A Review

Following the outbreak of a novel coronavirus (SARS-CoV-2) associated with pneumonia in China (Corona Virus Disease 2019, COVID-19) at the end of 2019, the world is currently facing a global pandemic of infections with SARS-CoV-2 and cases of COVID-19. Since severely ill patients often show elevated methemoglobin (MetHb) and carboxyhemoglobin (COHb) concentrations in their blood as a marker of disease severity, we aimed to summarize the currently available published study results (case reports and cross-sectional studies) on MetHb and COHb concentrations in the blood of COVID-19 patients. To this end, a systematic literature research was performed. For the case of MetHb, seven publications were identified (five case reports and two cross-sectional studies), and for the case of COHb, three studies were found (two cross-sectional studies and one case report). The findings reported in the publications show that an increase in MetHb and COHb can happen in COVID-19 patients, especially in critically ill ones, and that MetHb and COHb can increase to dangerously high levels during the course of the disease in some patients. The medications given to the patient and the patient’s glucose-6-phospate dehydrogenase (G6PD) status seem to be important factors determining the severity of the methemoglobinemia and carboxyhemoglobinemia. Therefore, G6PD status should be determined before medications such as hydroxychloroquine are administered. In conclusion, MetHb and COHb can be elevated in COVID-19 patients and should be checked routinely in order to provide adequate medical treatment as well as to avoid misinterpretation of fingertip pulse oximetry readings, which can be inaccurate and unreliable in case of elevated MetHb and COHb levels in the blood.
5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology

L-5-hydroxytryptophan (5-HTP) is both a drug and a natural component of some dietary supplements. 5-HTP is produced from tryptophan by tryptophan hydroxylase (TPH), which is present in two isoforms (TPH1 and TPH2). Decarboxylation of 5-HTP yields serotonin (5-hydroxytryptamine, 5-HT) that is further transformed to melatonin (N-acetyl-5-methoxytryptamine). 5-HTP plays a major role both in neurologic and metabolic diseases and its synthesis from tryptophan represents the limiting step in serotonin and melatonin biosynthesis. In this review, after an look at the main natural sources of 5-HTP, the chemical analysis and synthesis, biosynthesis and microbial production of 5-HTP by molecular engineering will be described. The physiological effects of 5-HTP are discussed in both animal studies and human clinical trials. The physiological role of 5-HTP in the treatment of depression, anxiety, panic, sleep disorders, obesity, myoclonus and serotonin syndrome are also discussed. 5-HTP toxicity and the occurrence of toxic impurities present in tryptophan and 5-HTP preparations are also discussed.
Possible Association of Periodontal Disease and Macular Degeneration: A Case-Control Study

Oral pathogens have been identified in bioptic specimens from Age-Related Macular Degeneration (ARMD) patients, and alveolar bone loss has been related to ARMD. Therefore, the possible association between ARMD and periodontal disease was investigated in the present case-control study, evaluating clinical and radiographic periodontal parameters, primarily, in cases vs. controls and, secondarily, in relation to ARMD risk factors, in cases, to highlight a possible pathogenic link between the disorders. Forty ARMD cases and 40 non-ARMD controls, matched for age (±3 years) and gender and homogeneous for ARMD risk factors, therefore comparable, underwent full-mouth periodontal charting, panoramic radiograph, and medical data, including ARMD risk factors, collection. Statistical analysis was conducted using the language R. Comparisons between groups were made using both traditional t-tests and Yuen’s test with bootstrap calibration. Enrolled subjects were ≥55 years old, and 50 females and 30 males were equally distributed among the two groups. No statistically significant difference was found in clinical and radiographic periodontal parameters in cases vs. controls. In the case group, no differences were found when relating the periodontal parameters to ARMD risk factors, except for Clinical Attachment Level values that were statistically significantly higher in hypertensive ARMD subjects. A possible association between periodontal disease and ARMD may be hypothesized in hypertensive ARMD subjects, with hypertension as a possible pathogenic link between the disorders.
Improvement of Executive Function after Short-Term Administration of an Antioxidants Mix Containing Bacopa, Lycopene, Astaxanthin and Vitamin B12: The BLAtwelve Study

During the last few years increasing interest has been focused on antioxidants as potentially useful agents in the prevention of the onset and progression of cognitive dysfunction. In this randomized, double-blind, controlled, parallel arm study, the effects of daily consumption of an antioxidant mix on cognitive function in healthy older adults were evaluated. After a 1 week run-in period, 80 subjects aged 60 years or more, and with no evidence of cognitive dysfunction, were randomly allocated to a mix of four bioactive compounds (bacopa, lycopene, astaxanthin, and vitamin B12) or matched placebo, taken orally once a day for 8 weeks. The primary objective of the study was to evaluate the changes in trial making test (TMT) scores from baseline to 8 weeks of treatment, analyzed in the following hierarchical order: TMT-B, TMT-A, and TMT-B minus TMT-A. TMT-B increased in the control group (+3.46 s) and decreased in the active group (−17.63 s). The treatment difference was −21.01 s in favor of the active group (95% C.I. −26.80 to −15.2, p < 0.0001). The decrease in TMT-A was significantly higher in the active group (−6.86 s) than in the control group (−0.37 s). TMT-B minus TMT-A increased in the control group (+3.84 s) and decreased in the active group (−10.46 s). The increase in letter fluency in the verbal fluency test (VFT) was also significantly higher in the active group and statistically significant (+5.28 vs. +1.07 words; p < 0.001). Our findings provide encouraging evidence that regular dietary supplementation with bacopa, lycopene, astaxanthin, and vitamin B12 may be an effective dietary approach for counteracting cognitive changes associated with brain aging.