Miracle-dz/UniFAR-FTUs huggingface dataset:
The Relevance of Insulin Action in the Dopaminergic System

The advances in medicine, together with lifestyle modifications, led to a rising life expectancy. Unfortunately, however, aging is accompanied by an alarming boost of age-associated chronic pathologies, including neurodegenerative and metabolic diseases. Interestingly, a non-negligible interplay between alterations of glucose homeostasis and brain dysfunction has clearly emerged. In particular, epidemiological studies have pointed out a possible association between Type 2 Diabetes (T2D) and Parkinson’s Disease (PD). Insulin resistance, one of the major hallmark for etiology of T2D, has a detrimental influence on PD, negatively affecting PD phenotype, accelerating its progression and worsening cognitive impairment. This review aims to provide an exhaustive analysis of the most recent evidences supporting the key role of insulin resistance in PD pathogenesis. It will focus on the relevance of insulin in the brain, working as pro-survival neurotrophic factor and as a master regulator of neuronal mitochondrial function and oxidative stress. Insulin action as a modulator of dopamine signaling and of alpha-synuclein degradation will be described in details, too. The intriguing idea that shared deregulated pathogenic pathways represent a link between PD and insulin resistance has clinical and therapeutic implications. Thus, ongoing studies about the promising healing potential of common antidiabetic drugs such as metformin, exenatide, DPP IV inhibitors, thiazolidinediones and bromocriptine, will be summarized and the rationale for their use to decelerate neurodegeneration will be critically assessed.
Temporal Variation in the Microbiome of Acropora Coral Species Does Not Reflect Seasonality

The coral microbiome is known to fluctuate in response to environmental variation and has been suggested to vary seasonally. However, most studies to date, particularly studies on bacterial communities, have examined temporal variation over a time frame of less than 1 year, which is insufficient to establish if microbiome variations are indeed seasonal in nature. The present study focused on expanding our understanding of long-term variability in microbial community composition using two common coral species, Acropora hyacinthus, and Acropora spathulata, at two mid-shelf reefs on the Great Barrier Reef. By sampling over a 2-year time period, this study aimed to determine whether temporal variations reflect seasonal cycles. Community composition of both bacteria and Symbiodiniaceae was characterized through 16S rRNA gene and ITS2 rDNA metabarcoding. We observed significant variations in community composition of both bacteria and Symbiodiniaceae among time points for A. hyacinthus and A. spathulata. However, there was no evidence to suggest that temporal variations were cyclical in nature and represented seasonal variation. Clear evidence for differences in the microbial communities found between reefs suggests that reef location and coral species play a larger role than season in driving microbial community composition in corals. In order to identify the basis of temporal patterns in coral microbial community composition, future studies should employ longer time series of sampling at sufficient temporal resolution to identify the environmental correlates of microbiome variation.
Mycobacterium tuberculosis Primary Infection and Dissemination: A Critical Role for Alveolar Epithelial Cells

Globally, tuberculosis (TB) has reemerged as a major cause of morbidity and mortality, despite the use of the Mycobacterium bovis BCG vaccine and intensive attempts to improve upon BCG or develop new vaccines. Two lacunae in our understanding of the Mycobacterium tuberculosis (M. tb)-host pathogenesis have mitigated the vaccine efforts; the bacterial-host interaction that enables successful establishment of primary infection and the correlates of protection against TB. The vast majority of vaccine efforts are based on the premise that cell-mediated immunity (CMI) is the predominating mode of protection against TB. However, studies in animal models and in humans demonstrate that post-infection, a period of several weeks precedes the initiation of CMI during which the few inhaled bacteria replicate dramatically and disseminate systemically. The “Trojan Horse” mechanism, wherein M. tb is phagocytosed and transported across the alveolar barrier by infected alveolar macrophages has been long postulated as the sole, primary M. tb:host interaction. In the current review, we present evidence from our studies of transcriptional profiles of M. tb in sputum as it emerges from infectious patients where the bacteria are in a quiescent state, to its adaptations in alveolar epithelial cells where the bacteria transform to a highly replicative and invasive phenotype, to its maintenance of the invasive phenotype in whole blood to the downregulation of invasiveness upon infection of epithelial cells at an extrapulmonary site. Evidence for this alternative mode of infection and dissemination during primary infection is supported by in vivo, in vitro cell-based, and transcriptional studies from multiple investigators in recent years. The proposed alternative mechanism of primary infection and dissemination across the alveolar barrier parallels our understanding of infection and dissemination of other Gram-positive pathogens across their relevant mucosal barriers in that barrier-specific adhesins, toxins, and enzymes synergize to facilitate systemic establishment of infection prior to the emergence of CMI. Further exploration of this M. tb:non-phagocytic cell interaction can provide alternative approaches to vaccine design to prevent infection with M. tb and not only decrease clinical disease but also decrease the overwhelming reservoir of latent TB infection.
Kidney Disease in HIV Infection

Antiretroviral therapy (ART) has significantly improved life expectancy of infected subjects, generating a new epidemiological setting of people aging withHuman Immunodeficiency Virus (HIV). People living with HIV (PLWH), having longer life expectancy, now face several age-related conditions as well as side effects of long-term exposure of ART. Chronic kidney disease (CKD) is a common comorbidity in this population. CKD is a relentlessly progressive disease that may evolve toward end-stage renal disease (ESRD) and significantly affect quality of life and risk of death. Herein, we review current understanding of renal involvement in PLWH, mechanisms and risk factors for CKD as well as strategies for early recognition of renal dysfunction and best care of CKD.
Increased Extracellular Osteopontin Levels in Normal Human Breast Tissue at High Risk of Developing Cancer and Its Association With Inflammatory Biomarkers in situ

Mammographic breast density is a strong independent risk factor for breast cancer (BC), but the molecular mechanisms behind this risk is yet undetermined and prevention strategies for these women are lacking. The anti-estrogen tamoxifen may reduce the risk of BC but this treatment is associated with severe side effects. Thus, other means for BC prevention, such as diet interventions, need to be developed. Osteopontin (OPN) is a major mediator of inflammation which is key in carcinogenesis. OPN may be cleaved by proteases in the tissue and cleaved OPN may in turn induce an inflammatory cascade in the extracellular microenvironment. We aimed to determine if extracellular OPN was altered in BC and in normal breast tissue with different densities and if tamoxifen or a diet of flaxseed could modify OPN levels. The study comprised 103 women; 13 diagnosed with BC, 42 healthy post-menopausal women with different breast densities at their mammography screen, and 34 post-menopausal women who added 25 g of ground flaxseed/day or were treated with tamoxifen 20 mg/day and were investigated before and after 6 weeks of exposure. Additionally, 10 premenopausal women who added flaxseed for one menstrual cycle and four who were investigated in two unexposed consecutive luteal phases of the menstrual cycle. Microdialysis was used to sample extracellular proteins in vivo in breast tissue and proteins were quantified using a multiplex proximity extension assay. We found that, similar to BC, extracellular in vivo OPN levels were significantly increased in dense breast tissue. Additionally, significant correlations were found between OPN and chemokine (C-X-C motif) ligand (CXCL)-1, −8, −9, −10, and −11, interleukin-6, vascular endothelial growth factor, matrix metalloproteinase (MMP)-1, −2, −3, 7, and −12 and urokinase-type plasminogen activator whereas no correlations were found with MMP-9, chemokine (C-C motif) ligand (CCL)-2, and −5. Estradiol did not affect OPN levels in breast tissue. None of the interventions altered OPN levels. The pro-tumorigenic protein OPN may indeed be a molecular target for BC prevention in women with increased breast density but other means than tamoxifen or flaxseed i.e., more potent anti-inflammatory approaches, need to be evaluated for this purpose.
Heterotrophic Bacteria Enhance the Aggregation of the Marine Picocyanobacteria Prochlorococcus and Synechococcus

Marine picocyanobacteria are ubiquitous primary producers across the world’s oceans, and play a key role in the global carbon cycle. Recent evidence stemming from in situ investigations have shown that picocyanobacteria are able to sink out of the euphotic zone to depth, which has traditionally been associated with larger, mineral ballasted cells. The mechanisms behind the sinking of picocyanobacteria remain a point of contention, given that they are too small to sink on their own. To gain a mechanistic understanding of the potential role of picocyanobacteria in carbon export, we tested their ability to form “suspended” (5–60 μm) and “visible” (ca. > 0.1 mm) aggregates, as well as their production of transparent exopolymer particles (TEP)—which are a key component in the formation of marine aggregates. Additionally, we investigated if interactions with heterotrophic bacteria play a role in TEP production and aggregation in Prochlorococcus and Synechococcus by comparing xenic and axenic cultures. We observed TEP production and aggregation in batch cultures of axenic Synechococcus, but not in axenic Prochlorococcus. Heterotrophic bacteria enhanced TEP production as well as suspended and visible aggregate formation in Prochlorococcus, while in Synechococcus, aggregation was enhanced with no changes in TEP. Aggregation experiments using a natural plankton community dominated by picocyanobacteria resulted in aggregation only in the presence of the ballasting mineral kaolinite, and only when Synechococcus were in their highest seasonal abundance. Our results point to a different export potential between the two picocyanobacteria, which may be mediated by interactions with heterotrophic bacteria and presence of ballasting minerals. Further studies are needed to clarify the mechanistic role of bacteria in TEP production and aggregation of these picocyanobacteria.
Precuneus-Dominant Degeneration of Parietal Lobe Is at Risk of Epilepsy in Mild Alzheimer's Disease

Introduction: Alzheimer's disease (AD) is the leading cause of cognitive decline. Epilepsy is a frequent comorbid condition of AD. While previous studies analyzed the risk factors of AD-related epileptic seizures, we still lack biomarkers of epilepsy in mild AD cases. Purpose: The aim of our study was to analyze the correlations between neuropsychology, cortical thickness, and brain volumetric measurements in mild Alzheimer patients with concomitant epileptic seizures. Materials and methods: We selected mild AD patients from our database to examine them with structural magnetic resonance imaging, 24 h electroencephalography, and detailed neuropsychology. We made the diagnosis of epilepsy based on epileptology data including neurophysiology. We retrospectively analyzed the neuropsychology pattern, clinical and epidemiologic features, cortical thickness, and volumetric values of mild AD patients with and without overt clinical seizures using covariance weighted general linear model. Results: We found epileptic seizures in 26% of mild AD patients. Patients with seizures performed worse in visuo-spatial scores than patients without (p = 0.003). Patients with seizures had smaller parietal thickness (p = 0.018), being associated to reduced thickness of left (p = 0.007), and right precunei (p = 0.005). The visuo-spatial performance positively and strongly correlated with the thickness of the parietal lobe (r = 0.67; p = 0.002) and with the volume of the precuneus (r = 0.612; p = 0.005). Conclusion: Epileptic seizures are common even in mild AD. We found that a prominent deficit in visuo-spatial skills is a red flag for epileptic seizures in the initial phase of AD, indicating the early involvement of parietal lobe in the neurodegenerative process. Because our findings suggest that the degeneration of precuneus is a sensitive marker of seizures associated to mild AD, clinicians need to pay special attention to the pattern of atrophy shown by structural MRI. Our results confirm previous data suggesting that epileptic seizures might be associated to a faster progressing type of AD with the early degeneration of posterior cortical areas.
Key Genetic Parameters for Population Management

Population management has the primary task of maximizing the long-term competitiveness of a breed. Breeds compete with each other for being able to supply consumer demands at low costs and also for funds from conservation programs. The competition for consumer preference is won by breeds with high genetic gain for total merit who maintained a sufficiently high genetic diversity, whereas the competition for funds is won by breeds with high conservation value. The conservation value of a breed could be improved by increasing its contribution to the gene pool of the species. This may include the recovery of its original genetic background and the maintenance of a high genetic diversity at native haplotype segments. The primary objective of a breeding program depends on the genetic state of the population and its intended usage. In this paper, we review the key genetic parameters that are relevant for population management, compare the methods for estimating them, derive the formulas for predicting their value at a future time, and clarify their usage in various types of breeding programs that differ in their main objectives. These key parameters are kinships, native kinships, breeding values, Mendelian sampling variances, native contributions, and mutational effects. Population management currently experiences a transition from using pedigree-based estimates to marker-based estimates, which improves the accuracies of these estimates and thereby increases response to selection. In addition, improved measures of the factors that determine the competitiveness of a breed and utilize auxiliary parameters, such as Mendelian sampling variances, mutational effects, and native kinships, enable to improve further upon historic recommendations for genetic population management.
Effects of Mortality Salience on Physiological Arousal

Making the inevitability of mortality salient makes people more defensive about their self-esteem and worldviews. Theoretical arguments and empirical evidence point to a mediating role of arousal in this defensive process, but evidence from physiological measurement studies is scarce and inconclusive. The present study seeks to draw a comprehensive picture of how physiological arousal develops over time in the mortality salience (MS) paradigm, and whether contemplating one’s mortality actually elicits more physiological arousal than reflecting on a death-unrelated aversive control topic. In a between-subjects design, participants were asked two open questions about their mortality or about dental pain. Cardiac, respiratory, and electrodermal indicators of arousal were measured both as participants provided written answers to the questions, and during a series of resting intervals surrounding the questions. A Bayes factor analysis indicated support for the hypothesis that the MS paradigm increases physiological arousal, both while answering the two open-ended questions and afterward. Regarding the MS versus dental pain comparison, the null hypothesis of no difference was supported for most analysis segments and signals. The results indicate that the arousal elicited by MS is not different from that elicited by dental pain salience. This speaks against the idea that worldview defense following MS occurs because MS produces higher physiological arousal. Of course, this finding does not rule the importance of other forms of arousal (i.e., subjective arousal) for MS effects.
Identification of candidate genes and miRNAs associated with neuropathic pain induced by spared nerve injury

Neuropathic pain (NP) is a complex, chronic pain condition caused by injury or dysfunction affecting the somatosensory nervous system. This study aimed to identify crucial genes and miRNAs involved in NP. Microarray data (access number GSE91396) were downloaded from the Gene Expression Omnibus (GEO). Murine RNA-seq samples from three brain regions [nucleus accumbens, (NAc); medial prefrontal cortex, (mPFC) and periaqueductal gray, (PAG)] were compared between the spared nerve injury (SNI) model and a sham surgery. After data normalization, differentially expressed RNAs were screened using the limma package and functional enrichment analysis was performed with Database for Annotation, Visualization and Integrated Discovery. The microRNA (miRNA/miR)-mRNA regulatory network and miRNA-target gene-pathway regulatory network were constructed using Cytoscape software. A total of 2,776 differentially expressed RNAs (219 miRNAs and 2,557 mRNAs) were identified in the SNI model compared with the sham surgery group. A total of two important modules (red and turquoise module) were found to be related to NP using weighed gene co-expression network analysis (WGCNA) for the 2,325 common differentially expressed RNAs in three brain regions. The differentially expressed genes (DEGs) in the miRNA-mRNA regulatory network were significantly enriched in 21 Gene Ontology terms and five pathways. A total of four important DEGs (CXCR2, IL12B, TNFSF8 and GRK1) and five miRNAs (miR-208a-5p, miR-7688-3p, miR-344f-3p, miR-135b-3p and miR-135a-2-3p) were revealed according to the miRNA-target gene-pathway regulatory network to be related to NP. Four important DEGs (CXCR2, IL12B, TNFSF8 and GRK1) and five miRNAs (miR-208a-5p, miR-7688-3p, miR-344f-3p, miR-135b-3p and miR-135a-2-3p) were differentially expressed in SNI, indicating their plausible roles in NP pathogenesis.
Psycho social risks noted by oncology workers related to their quality of life.

OBJECTIVE To analyze the relation between occupational psychosocial risks and quality of life related to health, felt by workers who work in oncology and palliative care units in a region of Chile. METHOD Cross-sectional analytical study of quantitative approach, in which 110 health workers participated. Research met the ethical requirements of E. Emanuel. RESULTS Participants perceive greater exposure to psychosocial risks in the dimension of psychological demands and double presence. On the other hand, they see better results in the physical health component (𝒙: 76.72; SD 9.75) versus the mental health component (𝒙: 71.13; SD 6.38). In addition, there are relations with statistical significance, between psychosocial risks and quality of life related to Health (p≤0.05). CONCLUSIONS This study shows that there the perception of psychosocial risks and quality of life are related, when considering the health of workers.
Inhibition of HTLV-1 Infection by HIV-1 First- and Second-Generation Integrase Strand Transfer Inhibitors

More than 10 million people worldwide are infected with the retrovirus human T-cell lymphotropic virus type 1 (HTLV-1). Infection phenotypes can range from asymptomatic to severe adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy. HTLV-1, like human immunodeficiency virus type 1 (HIV-1), is a blood-borne pathogen and viral infection happens in a similar fashion, with the major mode of transmission through breastfeeding. There is a strong correlation between time of infection and disease development, with a higher incidence of ATLL in patients infected during childhood. There is no successful therapeutic or preventative regimen for HTLV-1. It is therefore essential to develop therapies to inhibit transmission or block the onset/development of HTLV-1 associated diseases. Recently, we have seen the overwhelming success of integrase strand transfer inhibitors (INSTIs) in the treatment of HIV-1. Previously, raltegravir was shown to inhibit HTLV-1 infection. Here, we tested FDA-approved and two Phase II HIV-1 INSTIs in vitro and in a cell-to-cell infection model and show that they are highly active in blocking HTLV-1 infection, with bictegravir (EC50 = 0.30 ± 0.17 nM) performing best overall. INSTIs, in particular bictegravir, are more potent in blocking HTLV-1 transmission than tenofovir disproxil fumarate (TDF), an RT inhibitor. Our data suggest that HIV-1 INSTIs could present a good clinical strategy in HTLV-1 management and justifies the inclusion of INSTIs in clinical trials.
T Cells Control Chemokine Secretion by Keratinocytes

The massive infiltration of lymphocytes into the skin is a hallmark of numerous human skin disorders. By co-culturing murine keratinocytes with splenic T cells we demonstrate here that T cells affect and control the synthesis and secretion of chemokines by keratinocytes. While pre-activated CD8+T cells induce the synthesis of CXCL9 and CXCL10 in keratinocytes and keep in check the synthesis of CXCL1, CXCL5, and CCL20, keratinocytes dampen the synthesis of CCL3 and CCL4 in pre-activated CD8+T cells. One key molecule is IFN-γ that is synthesized by CD8+T cells under the control of NFATc1 and NFATc2. CD8+T cells deficient for both NFAT factors are unable to induce CXCL9 and CXCL10 expression. In addition, CD8+T cells induced numerous type I IFN-inducible “defense genes” in keratinocytes encoding the PD1 and CD40 ligands, TNF-α and caspase-1. The enhanced expression of type I IFN-inducible genes resembles the gene expression pattern at the dermal/epidermal interface in lichen planus, an inflammatory T lymphocyte-driven skin disease, in which we detected the expression of CXCL10 in keratinocytes in close vicinity to the infiltration front of T cells. These data reflect the multifaceted interplay of lymphocytes with keratinocytes at the molecular level.