ApoE and SNAP-25 Polymorphisms Predict the Outcome of Multidimensional Stimulation Therapy Rehabilitation in Alzheimer's Disease.

Background: Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder. Rate of decline and functional restoration in AD greatly depend on the capacity for neural plasticity within residual neural tissues; this is at least partially influenced by polymorphisms in genes that determine neural plasticity, including Apolipoprotein E4 (ApoE4) and synaptosomal-associated protein of 25 kDa (SNAP-25).

Objective: We investigated whether correlations could be detected between polymorphisms of ApoE4 and SNAP-25 and the outcome of a multidimensional rehabilitative approach, based on cognitive stimulation, behavioral, and functional therapy (multidimensional stimulation therapy [MST]).

Multiple inflammasome complexes are activated in autistic spectrum disorders.

Background: Inflammasomes are multimeric protein platforms involved in the regulation of inflammatory responses whose activity results in the production of proinflammatory cytokines. Because neuroinflammation is observed in autistic spectrum disorders (ASD), a neurologic condition of childhood resulting in a complex behavioural impairment, we analyzed the inflammasomes activity in ASD. Additionally we verified whether alterations of the gastrointestinal (GI) barriers might play a role in inflammasomes activation.

SNPs in FNDC5 (irisin) are associated with obesity and modulation of glucose and lipid metabolism in Saudi subjects.

Background: Irisin is a recently identified myokine that plays an important role in preventing obesity and insulin resistance. We investigated whether the common FNDC5 (irisin precursor) gene variants influence susceptibility to obesity and type 2 diabetes (T2D) and verified the impact of FNDC5 gene variants on serum irisin levels, glucose and lipid metabolism in a Saudi population.

Methods: Genomic DNA from 814 (394 T2DM and 414 controls) subjects were genotyped for the five common SNPs (rs3480A/G, rs1746661G/T, rs1298190A/G, rs726344A/G and rs1570569G/T) of the FNDC5 gene using the TaqMan genotyping assay.

Impact of vitamin D receptor polymorphisms in centenarians.

Vitamin D is a seco-sterol produced endogenously in the skin or obtained from certain foods. It exerts its action through binding to intracellular vitamin D receptor (VDR). Lately, the role of vitamin D has been revised regarding its potential advantage on delaying the process of aging.

The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer's disease.

Background: Interleukin-1 beta (IL-1β) and its key regulator, the inflammasome, are suspected to play a role in the neuroinflammation observed in Alzheimer's disease (AD); no conclusive data are nevertheless available in AD patients.

Results: mRNA for inflammasome components (NLRP1, NLRP3, PYCARD, caspase 1, 5 and 8) and downstream effectors (IL-1β, IL-18) was up-regulated in severe and MILD AD. Monocytes co-expressing NLRP3 with caspase 1 or caspase 8 were significantly increased in severe AD alone, whereas those co-expressing NLRP1 and NLRP3 with PYCARD were augmented in both severe and MILD AD.

The evolutionary history of genes involved in spoken and written language: beyond FOXP2.

Humans possess a communication system based on spoken and written language. Other animals can learn vocalization by imitation, but this is not equivalent to human language. Many genes were described to be implicated in language impairment (LI) and developmental dyslexia (DD), but their evolutionary history has not been thoroughly analyzed.

The mammalian complement system as an epitome of host-pathogen genetic conflicts.

The complement system is an innate immunity effector mechanism; its action is antagonized by a wide array of pathogens and complement evasion determines the virulence of several infections. We investigated the evolutionary history of the complement system and of bacterial-encoded complement-interacting proteins. Complement components targeted by several pathogens evolved under strong selective pressure in primates, with selection acting on residues at the contact interface with microbial/viral proteins.

Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy.

Introduction: Dendritic cells play a key role as initiators of T-cell responses, and even if tumour antigen-loaded dendritic cells can induce anti-tumour responses, their efficacy has been questioned, suggesting a need to enhance immunization strategies.

Matherials & Methods: We focused on the characterization of bone marrow-derived dendritic cells pulsed with whole tumour lysate (TAA-DC), as a source of known and unknown antigens, in a mouse model of breast cancer (MMTV-Ras). Dendritic cells were evaluated for antigen uptake and for the expression of MHC class I/II and costimulatory molecules and markers associated with maturation.

Extensive Positive Selection Drives the Evolution of Nonstructural Proteins in Lineage C Betacoronaviruses.

Unlabelled: Middle East respiratory syndrome-related coronavirus (MERS-CoV) spreads to humans via zoonotic transmission from camels. MERS-CoV belongs to lineage C of betacoronaviruses (betaCoVs), which also includes viruses isolated from bats and hedgehogs. A large portion of the betaCoV genome consists of two open reading frames (ORF1a and ORF1b) that are translated into polyproteins.

Synaptosomal Protein of 25 kDa (Snap25) Polymorphisms Associated with Glycemic Parameters in Type 2 Diabetes Patients.

A possible role of Snap25 polymorphisms in type 2 diabetes mellitus (T2DM) was evaluated by analyzing three SNPs within intron 1 in a region known to affect the gene expression in vitro. Genomic DNA from 1019 Saudi individuals (489 confirmed T2DM and 530 controls) was genotyped for SNPs rs363039, rs363043, and rs363050 in Snap25 using the TaqMan Genotyping Assay. Significantly higher levels of fasting glucose and HbA1c were detected in T2DM patients carrying the rs363050 (AG/GG) genotypes compared to the (AA) genotype (f = 4.

Mind-Reading Ability and Structural Connectivity Changes in Aging.

The Mind-Reading ability through the eyes is an important component of the affective Theory of Mind (ToM), which allows people to infer the other's mental state from the eye gaze. The aim of the present study was to investigate to which extent age-associated structural brain changes impact this ability and to determine if this association is related to executive functions in elderly subjects. For this purpose, Magnetic Resonance Imaging was used to determine both gray matter and white matter (WM) areas associated with aging.

Lack of evidence for a role of HHV-6 in the pathogenesis of Alzheimer's disease.

Background: Alzheimer's disease (AD), the most common form of dementia worldwide, is associated with impairment in the mechanisms of the clearing of amyloid-β within a scenario of neuroinflammation. The etiopathogenesis of the AD is unclear, but a role for viral infection is suspected to play a role in initiating the disease. We recently described a positive correlation between high titers of HSV-1-specific antibodies (Ab) and the volumes of brain regions typically affected in disease.

Short Communication: Immune Activation Is Present in HIV-1-Exposed Seronegative Individuals and Is Independent of Microbial Translocation.

Analyses of immune activation in HIV-exposed seronegative individuals (HESN) yielded discrepant results. To clarify this issue we performed an extensive investigation of immune parameters in HESN and, in particular, we analyzed in these individuals the possible presence of microbial translocation, the most widely accepted reason driving immune activation in HIV-infected patients. Results showed that immune activation, a skewing of T lymphocyte maturation, and increased responsiveness to lipopolysaccharide (LPS) characterize the HESN phenotype; this is not driven by alterations of the gastrointestinal barrier and microbial translocation.

The heptad repeat region is a major selection target in MERS-CoV and related coronaviruses.

Middle East respiratory syndrome coronavirus (MERS-CoV) originated in bats and spread to humans via zoonotic transmission from camels. We analyzed the evolution of the spike (S) gene in betacoronaviruses (betaCoVs) isolated from different mammals, in bat coronavirus populations, as well as in MERS-CoV strains from the current outbreak. Results indicated several positively selected sites located in the region comprising the two heptad repeats (HR1 and HR2) and their linker.

Variants in the CYP7B1 gene region do not affect natural resistance to HIV-1 infection.

Background: The genetic bases of natural resistance to HIV-1 infection remain largely unknown. Recently, two genome-wide association studies suggested a role for variants within or in the vicinity of the CYP7B1 gene in modulating HIV susceptibility. CYP7B1 is an appealing candidate for this due to its contribution to antiviral immune responses.

Immunomodulatory activity of pidotimod administered with standard antibiotic therapy in children hospitalized for community-acquired pneumonia.

Background: Several attempts to improve immune function in young children have been made and encouraging results have been collected with pidotimod (PDT), a synthetic dipeptide molecule that seems to have immunomodulatory activity on both innate and adaptive responses. Until now, the effects of PDT on the immune system have only been studied in vivo after long-term administration to evaluate whether its immunomodulatory activity might prevent the development of infections. This study was planned to evaluate the immunomodulatory activity of PDT administered together with standard antibiotic therapy in children hospitalized for community-acquired pneumonia (CAP).

Effective artifact removal in resting state fMRI data improves detection of DMN functional connectivity alteration in Alzheimer's disease.

Artifact removal from resting state fMRI data is an essential step for a better identification of the resting state networks and the evaluation of their functional connectivity (FC), especially in pathological conditions. There is growing interest in the development of cleaning procedures, especially those not requiring external recordings (data-driven), which are able to remove multiple sources of artifacts. It is important that only inter-subject variability due to the artifacts is removed, preserving the between-subject variability of interest-crucial in clinical applications using clinical scanners to discriminate different pathologies and monitor their staging.

Natural Selection at the Brush-Border: Adaptations to Carbohydrate Diets in Humans and Other Mammals.

Dietary shifts can drive molecular evolution in mammals and a major transition in human history, the agricultural revolution, favored carbohydrate consumption. We investigated the evolutionary history of nine genes encoding brush-border proteins involved in carbohydrate digestion/absorption. Results indicated widespread adaptive evolution in mammals, with several branches experiencing episodic selection, particularly strong in bats.

Positive selection underlies the species-specific binding of Plasmodium falciparum RH5 to human basigin.

Plasmodium falciparum, the causative agent of the deadliest form of malaria, is a member of the Laverania subgenus, which includes ape-infecting parasites. P. falciparum is thought to have originated in gorillas, although infection is now restricted to humans.

Paradoxical Expansion of Th1 and Th17 Lymphocytes in Rheumatoid Arthritis Following Infliximab Treatment: a Possible Explanation for a Lack of Clinical Response.

Purpose: The immunogenicity of anti-TNF-α drugs may affect their safety and efficacy. Infliximab (IFX), a chimeric monoclonal antibody, induces antibody formation in up to 60% of cases. Some studies have suggested the involvement of a Th1 response to TNFα blockers following immunization, but the triggering of Th17 responses has never been reported.

Indoleamine 2,3 Dioxygenase (IDO) Expression and Activity in Relapsing-Remitting Multiple Sclerosis.

Background: Interferon gamma (IFN-γ) production induces the transcription of indoleamine 2,3 dioxygenase (IDO) resulting in the reduction of T-cell activation and proliferation through the depletion of tryptophan and the elicitation of Treg lymphocytes. IDO was shown to be involved in the pathogenesis of autoimmune diseases; we investigated whether changes in IDO gene expression and activity could be indicative of onset of relapse in multiple sclerosis (MS) patients.

Methods: IDO and interferon-γ (IFN-γ) gene expression, serum IDO activity (Kynurenine/Tryptophan ratio) and serum neopterin concentration--a protein released by macrophages upon IFN-γ stimulation--were measured in 51 individuals: 36 relapsing remitting (RR)-MS patients (21 in acute phase--AMS, 15 in stable phase--SMS) and 15 healthy controls (HC).

MicroRNA-572 expression in multiple sclerosis patients with different patterns of clinical progression.

Background: Demyelination and failure of remyelination are core mechanisms in the pathogenesis of multiple sclerosis (MS); the factor(s) modulating these processes are still mostly unknown. MicroRNA 572 (miR-572) is deregulated in MS and is suggested to targets neural cell adhesion molecule (NCAM), a glycoprotein involved in CNS reparative mechanisms. The aim of this study is to analyze miR-572 in patients with different clinical phenotypes of MS.