Miracle-dz/UniFAR-FTUs huggingface dataset:
Vaginal Immunization to Elicit Primary T-Cell Activation and Dissemination

Primary T-cell activation at mucosal sites is of utmost importance for the development of vaccination strategies. T-cell priming after vaginal immunization, with ovalbumin and CpG oligodeoxynucleotide adjuvant as model vaccine formulation, was studied in vivo in hormone-synchronized mice and compared to the one induced by the nasal route. Twenty-four hours after both vaginal or nasal immunization, antigen-loaded dendritic cells were detected within the respective draining lymph nodes. Vaginal immunization elicited a strong recruitment of antigen-specific CD4+ T cells into draining lymph nodes that was more rapid than the one observed following nasal immunization. T-cell clonal expansion was first detected in iliac lymph nodes, draining the genital tract, and proliferated T cells disseminated towards distal lymph nodes and spleen similarly to what observed following nasal immunization. T cells were indeed activated by the antigen encounter and acquired homing molecules essential to disseminate towards distal lymphoid organs as confirmed by the modulation of CD45RB, CD69, CD44 and CD62L marker expression. A multi-type Galton Watson branching process, previously used for in vitro analysis of T-cell proliferation, was applied to model in vivo CFSE proliferation data in draining lymph nodes 57 hours following immunization, in order to calculate the probabilistic decision of a cell to enter in division, rest in quiescence or migrate/die. The modelling analysis indicated that the probability of a cell to proliferate was higher following vaginal than nasal immunization. All together these data show that vaginal immunization, despite the absence of an organized mucosal associated inductive site in the genital tract, is very efficient in priming antigen-specific CD4+ T cells and inducing their dissemination from draining lymph nodes towards distal lymphoid organs.
Protection Enhances Community and Habitat Stability: Evidence from a Mediterranean Marine Protected Area

Rare evidences support that Marine Protected Areas (MPAs) enhance the stability of marine habitats and assemblages. Based on nine years of observation (2001–2009) inside and outside a well managed MPA, we assessed the potential of conservation and management actions to modify patterns of spatial and/or temporal variability of Posidonia oceanica meadows, the lower midlittoral and the shallow infralittoral rock assemblages. Significant differences in both temporal variations and spatial patterns were observed between protected and unprotected locations. A lower temporal variability in the protected vs. unprotected assemblages was found in the shallow infralittoral, demonstrating that, at least at local scale, protection can enhance community stability. Macrobenthos with long-lived and relatively slow-growing invertebrates and structurally complex algal forms were homogeneously distributed in space and went through little fluctuations in time. In contrast, a mosaic of disturbed patches featured unprotected locations, with small-scale shifts from macroalgal stands to barrens, and harsh temporal variations between the two states. Opposite patterns of spatial and temporal variability were found for the midlittoral assemblages. Despite an overall clear pattern of seagrass regression through time, protected meadows showed a significantly higher shoot density than unprotected ones, suggesting a higher resistance to local human activities. Our results support the assumption that the exclusion/management of human activities within MPAs enhance the stability of the structural components of protected marine systems, reverting or arresting threat-induced trajectories of change.
Role of Galectins in Tumors and in Clinical Immunotherapy

Galectins are glycan-binding proteins that contain one or two carbohydrate domains and mediate multiple biological functions. By analyzing clinical tumor samples, the abnormal expression of galectins is known to be linked to the development, progression and metastasis of cancers. Galectins also have diverse functions on different immune cells that either promote inflammation or dampen T cell-mediated immune responses, depending on cognate receptors on target cells. Thus, tumor-derived galectins can have bifunctional effects on tumor and immune cells. This review focuses on the biological effects of galectin-1, galectin-3 and galectin-9 in various cancers and discusses anticancer therapies that target these molecules.
Early adversity and internalizing symptoms in adolescence: Mediation by individual differences in latent trait cortisol

Abstract Research suggests that early adversity places individuals at risk for psychopathology across the life span. Guided by concepts of allostasis and allostatic load, the present study examined whether early adversity contributes to the development of subsequent internalizing symptoms through its association with traitlike individual differences in hypothalamic–pituitary–adrenal axis regulation. Early adolescent girls (n = 113; M age = 12.30 years) provided saliva samples at waking, 30 min postwaking, and bedtime over 3 days (later assayed for cortisol). Objective contextual stress interviews with adolescents and their mothers were used to assess the accumulation of nine types of early adversity within the family environment. Greater early adversity predicted subsequent increases in internalizing symptoms through lower levels of latent trait cortisol. Traitlike individual differences in hypothalamic–pituitary–adrenal axis activity may be among the mechanisms through which early adversity confers risk for the development of psychopathology.
Structural characterization of As-MIF and hJAB1 during the inhibition of cell-cycle regulation

The biological activities of macrophage migration inhibitory factor (MIF) might be mediated through a classical receptor- mediated or non-classical endocytic pathway. JAB1 (C-Jun activation domain-binding protein-1) promotes the degradation of the tumor suppressor, p53, and the cyclin-dependent kinase inhibitor, p27. When MIF and JAB1 are bound to each other in various intracellular sites, MIF inhibits the positive regulatory effects of JAB1 on the activity of AP-1. The intestinal parasite, Anisakis simplex, has an immunomodulatory effect. The molecular mechanism of action of As-MIF and human JAB1 are poorly understood. In this study, As-MIF and hJAB1 were expressed and purified with high solubility. The structure of As-MIF and hJAB1 interaction was modeled by homology modeling based on the structure of Ace-MIF. This study provides evidence indicating that the MIF domain of As-MIF interacts directly with the MPN domain of hJAB1, and four structure-based mutants of As-MIF and hJAB1 disrupt the As-MIF-hJAB1 interaction.
Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications

Despite advances in diagnosis and new treatments such as targeted therapies, breast cancer (BC) is still the most prevalent tumor in women worldwide and the leading cause of death. The principal obstacle for successful BC treatment is the acquired or de novo resistance of the tumors to the systemic therapy (chemotherapy, endocrine, and targeted therapies) that patients receive. In the era of personalized treatment, several studies have focused on the search for biomarkers capable of predicting the response to this therapy; microRNAs (miRNAs) stand out among these markers due to their broad spectrum or potential clinical applications. miRNAs are conserved small non-coding RNAs that act as negative regulators of gene expression playing an important role in several cellular processes, such as cell proliferation, autophagy, genomic stability, and apoptosis. We reviewed recent data that describe the role of miRNAs as potential predictors of response to systemic treatments in BC. Furthermore, upon analyzing the collected published information, we noticed that the overexpression of miR-155, miR-222, miR-125b, and miR-21 predicts the resistance to the most common systemic treatments; nonetheless, the function of these particular miRNAs must be carefully studied and further analyses are still necessary to increase knowledge about their role and future potential clinical uses in BC.
Moderate Intense Physical Activity Depends on Selected Metabolic Equivalent of Task (MET) Cut-Off and Type of Data Analysis

Background Accelerometry data are frequently analyzed without considering whether moderate-to-vigorous physical activities (MVPA) were performed in bouts of >10 minutes as defined in most physical activity guidelines. We aimed i) to quantify MVPA by using different commonly-applied physical activity guidelines, ii) to investigate the effect of bouts versus non-bouts analysis, and iii) to propose and validate a MVPA non-bouts cut-point to classify (in-) active subjects. Methods Healthy subjects (n=110;62±6yrs) and patients with Chronic Obstructive Pulmonary Disease (COPD) (n=113;62±5yrs) wore an activity monitor for 7 days. Three Metabolic Equivalent of Task (MET) cut-offs and one individual target (50% VO2 reserve) were used to define MVPA. First, all minutes of MVPA were summed up (NON-BOUTS). Secondly, only minutes performed in bouts of >10 minutes continuous activity were counted (BOUTS). Receiver operating characteristic (ROC) curve analyses were used to propose and (cross-) validate new MVPA non-bout cut-points based on the criterion of 30 minutes MVPA per day (BOUTS). Likelihood ratios (sensitivity/[1-specificity]) were used to express the association between the proposed MVPA non-bout target and the MVPA bout target of 30 min*day-1. Results MVPA was variable across physical activity guidelines with lowest values for age-specific cut-offs. Selecting a METs cut-point corresponding to 50% VO2 reserve revealed no differences in MVPA between groups. MVPA’s analyzed in BOUTS in healthy subjects were 2 to 4 fold lower than NON-BOUTS analyses and this was even 3 to 12 fold lower in COPD. The MVPA non-bouts cut-point of 80 min*day-1 using a 3 METs MVPA threshold delivered positive likelihood ratios of 5.1[1.5-19.6] (healthy subjects) and 2.3[1.6-3.3] (COPD). Conclusion MVPA varies upon the selected physical activity guideline/targets and bouts versus non-bouts analysis. Accelerometry measured MVPA non-bouts target of 80 min*day-1, using a 3 METs MVPA threshold, is associated to the commonly-used MVPA bout target of 30 min*day-1.
Young Adults’ Risk Perceptions of Various Tobacco Products Relative to Cigarettes

Objectives. Tobacco product risk perceptions may influence whether individuals use those products instead of or in addition to regular cigarettes. This study aimed to explore risk perceptions of various tobacco products relative to traditional cigarettes with young adults, a group with higher rates of tobacco use. Method. We examined risk perception responses among a nationally representative sample of young adults (age 18-34 years; n = 2,871, including tobacco and non–tobacco users) from the 2011 National Young Adult Health Survey. Results. Most (57.8%) respondents believed that e-cigarettes were less risky than cigarettes. Respondents were more likely to rate combustible products hookah (24.5%) and cigars (13.9%) as being less risky compared to noncombustible snus (10%) and other smokeless tobacco (SLT) products (7.1%) relative to cigarettes. Few (2.5%) rated menthol cigarettes as less risky. For e-cigarettes, hookah, and SLT, less risky beliefs were significantly higher among ever or current versus never product users. Between 22% and 33% of all respondents believed that SLT, snus, menthol cigarettes, and cigars were more risky than cigarettes, but differences in this belief between current and nonusers of these products were small and insignificant. Younger young adults were more likely to rate e-cigarettes and hookah as being “less risky” and rate cigars and SLT as being “more risky” than older young adults. Conclusion. The public’s views of comparative tobacco risk perceptions vary widely by tobacco product type and age-group. While “less risky” perceptions may be associated with product use, perceptions that products are “more risky” than cigarettes may not necessarily dissuade people from their use.
Severe Community-Acquired Pneumonia due to Acinetobacter baumannii in North America: Case Report and Review of the Literature

Abstract Acinetobacter baumannii is a rare but emerging cause of fulminant community-acquired pneumonia (CAP-AB). We describe a patient from a rural area who developed acute respiratory distress syndrome and septic shock. We describe risk factors and characteristics of this syndrome and review published cases of CAP-AB from North America.
Hair Restoration in Androgenetic Alopecia: Looking Beyond Minoxidil, Finasteride and Hair Transplantation

Patterned hair loss (PHL) is one of the most commonly encountered problems for dermatologists. PHL at an early age is often cosmetically unacceptable, tends to be persistent and inflicts a profound negative impact on one’s quality of life. Androgenetic alopecia (AGA) affects both genders in a distinctive pattern of hair loss from the scalp (MPHL for male PHL and FPHL or female PHL). The etiopathogenesis of AGA is complex, so far the major factor emphasized to be involved has been the undesirable androgen metabolism at the hair follicle level. In this review article, we shall dwell upon the relatively newly understood pathophysiological factors behind the genesis of AGA apart from the hormonal factors like the Wnt/β-catenin pathway, follicular micro-inflammation, prostaglandin imbalance, loss of extracellular matrix and oxidative stress. Based on the sound understanding of these factors we will be elaborating upon therapies for treatment of AGA beyong minoxidil, finasteride and hair transplantation. Amongst the therapeutic options discussed include topical 5alpha reductase (AR) inhibitors like finasteride, oral 5AR inhibitor – dual receptor antagonist dutasteride, botanical 5AR inhibitors, oral anti-androgens and estrogens for FPHL like spiranolactone, drospirenone etc. Wnt/β-catenin activators like topical valproic acid, hair stem cell based therapies, prostaglandin based therapies, tetrapeptides, nutritional and anti-oxidants and many more.
Allostery at opioid receptors: modulation with small molecule ligands

Opioid receptors are 7‐transmembrane domain receptors that couple to heterotrimeric G proteins. The endogenous ligands for opioid receptors are peptides which bind to the orthosteric site on the receptors. The μ‐opioid receptor is the target for opioid analgesics, while the δ‐opioid receptor has been suggested as a target for pain management, migraine and depression. Similarly, κ‐opioid receptors are involved in pain and depression and nociceptin receptors in pain and mood behaviours. However, exogenous orthosteric ligands for opioid receptors cause a myriad of on‐target side effects. Recently, selective allosteric ligands for μ‐ and δ‐opioid receptors have been described. These compounds bind to a site on the receptor distinct from the orthosteric site. Occupation of this allosteric site leads to modulation of orthosteric ligand binding affinity and/or efficacy. Allosteric modulators may be positive, negative or silent (neutral) (PAMs, NAMs or SAMs respectively). PAMs may have in vivo activity by enhancing the activity of exogenous drugs or endogenous opioid peptides. Enhancing endogenous opioid peptide activity maintains the temporal and spatial distribution of these molecules but improves, and potentially qualitatively changes, activity at their cognate receptors which could limit side effects compared with traditional opioid drugs. In this review, we describe the rationale and promise for the development of allosteric modulators for opioid receptors, the discovery of selective allosteric modulators, the identification of potential allosteric sites on opioid receptors and the mode of action of the modulators.
Risk Assessment for Metals and PAHs by Mediterranean Seafood

Fish is a very important food because of its high nutritional value. Fish consumption is largely recommended in all countries, so quality and safety of seafood are becoming of great concern. Especially in Mediterranean Sea, where many pollutants, as metals and Polycyclic Aromatic Hydrocarbons (PAHs), are often relieved also in high concentrations, seafood safety has to be checked by a methodologically rigorous risk assessment. So we propose in this paper a stagesrisk assessment methodology to estimate the seafood potential risk for human health and point-out critical topics in order to support fish advisories.
Biological Signals Identification by a Dynamic Recurrent Neural Network: from Oculomotor Neural Integrator to Complex Human Movements and Locomotion

The recent advances in the application of artificial neural networks in the biological field have been inspired by the functional organization of real biological structures (Draye et al.,1997a; Anastasio & Gad, 2007). The fascination exerted by the oculomotor system upon both engineers and neuroscientists have played an important role in this issue. In particular, since the definitive evidence of the existence of a neural integrator in the brainstem (Cheron et al., 1986a; Cannon & Robinson, 1987; Robinson, 1989 for a review) performing mathematical integration of the eye velocity into eye position signals, numerous artificial networks have been developed allowing a better understanding of the fundamental question of how the brain control movement. Such bio-mimetic strategy has recently permitted to elaborate different dynamic recurrent neural networks (DRNN) specifically dedicated to the command of humanoid robot (Tani et al., 2008). Hierarchical neuralinspired modules have also been proposed forming cascades of forward dynamics models (Jordan & Rumelhart, 1992; Kawato et al., 1987; Tani, 2003) in which top-down and bottomup influences allowed generating behavioural primitives. This Chapter describes the main steps performed in the development of our DRNN from the neural integrator models to those applied in the field of human movement control.
Birefringence of ZnP2-D48 and Characteristics of Ме-ZnP2 Diodes

Spatial dispersion in ZnP2-D48 has been studied. The spectral dependences of the refractive index nс (Е||с, k||a), nа (Е||а, k||с) and nb (E||b, k||c) had been determined. ZnP2-D48 crystals are isotropic at λо=612nm wavelength, in case of crossed polarizators a transmittance maximum is observed. It was shown that the dispersion is positive nc(Е||с,k||a), nа (Е||а,k||с) > nb(E||b,k||c) in λ>λ0 region, the dispersion is negative nс (Е||с,k||a) at λ<λ0, and n=nс –nb =0 at λ=λ0. The LIV characteristics of Me- ZnP2-D48 diodes had been studied at different temperatures, the temperature dependences of the “imperfection” factor δ for different Schottky barriers. Capacitance voltage characteristics of Ме- ZnP2-D48 photodiodes obtained by electrochemical deposition of metal and by thermo-chemical spraying in vacuum had been studied. The dependence of diffusion potential ФВ on the work function of the metal ξm(С) has been revealed. The influence of birefringence and gyration on spectral characteristics of p-n photodiodes and Schottky diodes had been revealed. The ability of controlling photodiodes’ characteristics was obtained using the gyration particularities in ZnP2-D48 crystals.
Synchrotron radiation X-ray fluorescence analysis of Fe, Zn and Cu in mice brain associated with Parkinson’s disease

The contents and distributions of metal elements in the brain are closely related to neurodegenerative diseases.In this study, we examined Fe, Cu and Zn contents in the brain section associated with Parkinson‘s disease(PD)using synchrotron radiation X-ray fluorescence(SRXRF). PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-terahydropyridine(MPTP) was used for the elemental analysis(e.g., Fe, Cu and Zn) in the substantia nigra pars compacta(SNpc) region of mice brain tissue samples. We found that mice in the MPTP group had higher contents of Fe, Cu and Zn in the SNpc than the control group. After treating the PD mice with rapamycin, the contents of Fe, Cu and Zn were reduced, the dopamine neurons and motor function were rescued correspondingly. The results prompted that the SRXRF provided an ideal method for tracing and analyzing the metal elements in the brain section to assess the pathological changes of PD model and the therapeutic effect of drugs.
Biomarkers: A Critical Update

Periodontitis is a group of inflammatory diseases that affect the connective tissue attachment and supporting bone around the teeth. Early diagnosis and treatment of progressive periodontitis is important because of the irreversible nature of this disease. Biochemical mediators in oral fluids like saliva and gingival crevicular fluid (GCF) are highly beneficial in the determination of current periodontal status. This article highlights recent advances in the use of biomarker-based disease diagnostics that focus on the identification of active periodontal disease from GCF, and saliva.
Oxidative Stress in Parkinson's Disease

Parkinson's disease (PD) is a common adult‐onset neurodegenerative disorder. Typically PD is a sporadic neurological disorder, and over time affected patients see their disability growing and their quality of life declining. Oxidative stress has been hypothesized to be linked to both the initiation and the progression of PD. Preclinical findings from both in vitro and in vivo experimental models of PD suggest that the neurodegenerative process starts with otherwise healthy neurons being hit by some etiological factors, which sets into motion a cascade of deleterious events. In these models initial molecular alterations in degenerating dopaminergic neurons include increased formation of reactive oxygen species, presumably originating from both inside and outside the mitochondria. In the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model of PD, time‐course experiments suggest that oxidative stress is an early event that may directly kill some of the dopaminergic neurons. In this model it seems that oxidative stress may play a greater role in the demise of dopaminergic neurons indirectly by activating intracellular, cell death‐related, molecular pathways. As the neurodegenerative process evolves in the MPTP mouse model, indices of neuroinflammation develop, such as microglial activation. The latter increases the level of oxidative stress to which the neighboring compromised neurons are subjected to, thereby promoting their demise. However, these experimental studies have also shown that oxidative stress is not the sole deleterious factor implicated in the death of dopaminergic neurons. Should a similar multifactorial cascade underlie dopaminergic neuron degeneration in PD, then the optimal therapy for this disease may have to rely on a cocktail of agents, each targeting a different critical component of this hypothesized pathogenic cascade. If correct, this may be a reason why neuroprotective trials using a single agent, such as an antioxidant, have thus far generated disappointing results.