New Genomic Techniques applied to food cultures: a powerful contribution to innovative, safe, and sustainable food products.

Nontransgenic New Genomic Techniques (NGTs) have emerged as a promising tool for food industries, allowing food cultures to contribute to an innovative, safe, and more sustainable food system. NGTs have the potential to be applied to microorganisms, delivering on challenging performance traits like texture, flavour, and an increase of nutritional value. This paper brings insights on how nontransgenic NGTs applied to food cultures could be beneficial to the sector, enabling food industries to generate innovative, safe, and sustainable products for European consumers.

Natalizumab Treatment Induces Proinflammatory CD4 T Cells Preferentially in the Integrin β7+ Compartment.

Background And Objectives: Natalizumab, a monoclonal humanized antibody targeting integrin α4, inhibits the transmigration of lymphocytes into the CNS by preventing the interaction of integrin α4β1 with V-CAM expressed on brain vascular endothelial cells. Although natalizumab treatment reduces the clinical relapse rate in patients with relapsing-remitting MS, its discontinuation after reactivation of the JC virus is associated with a rebound of the disease in 20% of patients. The mechanisms of this rebound are not elucidated, but natalizumab increases the frequencies of circulating CD4 T cells expressing proinflammatory cytokines as well as the proportion of circulating Th17/Th1 cells (Th1-like Th17 cells).

Tracing Founder Mutations in Circulating and Tissue-Resident Follicular Lymphoma Precursors.

Unlabelled: Follicular lymphomas (FL) are characterized by BCL2 translocations, often detectable in blood years before FL diagnosis, but also observed in aging healthy individuals, suggesting additional lesions are required for lymphomagenesis. We directly characterized early cooperating mutations by ultradeep sequencing of prediagnostic blood and tissue specimens from 48 subjects who ultimately developed FL. Strikingly, CREBBP lysine acetyltransferase (KAT) domain mutations were the most commonly observed precursor lesions, and largely distinguished patients developing FL (14/48, 29%) from healthy adults with or without detected BCL2 rearrangements (0/13, P = 0.

The Effect of Smoking on Long-term Gray Matter Atrophy and Clinical Disability in Patients with Relapsing-Remitting Multiple Sclerosis.

Background And Objectives: The relationship between smoking, long-term brain atrophy, and clinical disability in patients with multiple sclerosis (MS) is unclear. Here, we assessed long-term effects of smoking by evaluating MRI and clinical outcome measures after 10 years in smoking and nonsmoking patients with relapsing-remitting MS (RRMS).

Methods: We included 85 treatment-naive patients with RRMS with recent inflammatory disease activity who participated in a 10-year follow-up visit after a multicenter clinical trial of 24 months.

Serum neurofilament as a predictor of 10-year grey matter atrophy and clinical disability in multiple sclerosis: a longitudinal study.

Background: The predictive value of serum neurofilament light chain (sNfL) on long-term prognosis in multiple sclerosis (MS) is still unclear.

Objective: Investigate the relation between sNfL levels over a 2-year period in patients with relapsing-remitting MS, and clinical disability and grey matter (GM) atrophy after 10 years.

Methods: 85 patients, originally enrolled in a multicentre, randomised trial of ω-3 fatty acids, participated in a 10-year follow-up visit.

Low vitamin D, but not tobacco use or high BMI, is associated with long-term disability progression in multiple sclerosis.

Background: Low vitamin D levels, tobacco use and high body mass index (BMI) have been linked to adverse disease outcomes in multiple sclerosis (MS), but their influence on long-term disability progression remains unclear. Therefore, we explored whether these modifiable lifestyle factors were associated with 10-year clinical disability progression in patients with MS.

Methods: In this prospective study, a cohort of 88 patients with relapsing-remitting MS completed a randomized controlled study on ω-3 fatty acids between 2004 and 2008.

Live Biotherapeutic Products, A Road Map for Safety Assessment.

Recent developments in the understanding of the relationship between the microbiota and its host have provided evidence regarding the therapeutic potential of selected microorganisms to prevent or treat disease. According to Directive 2001/83/EC, in the European Union (EU), any product intended to prevent or treat disease is defined as a medicinal product and requires a marketing authorization by competent authorities prior to commercialization. Even if the pharmaceutical regulatory framework is harmonized at the EU level, obtaining marketing authorisations for medicinal products remains very challenging for Live Biotherapeutic Products (LBPs).

Antitumoral effect of maintained neutrophilia induced by rhG-CSF in a murine model of pancreatic cancer.

Although the protumoral functions of polymorphonuclear neutrophils are well known, some now-forgotten studies report antitumoral roles for these cells. The present work examines the antitumoral effect of maintained neutrophilia induced via the injection of recombinant human granulocyte colony stimulating factor (rhG-CSF, 100 μg/kg/day) in a Panc-1 subcutaneous xenograft murine model of pancreatic cancer. This treatment was compared with gemcitabine administration (120 mg/kg every two days) and a saline control (n = 6-7 mice per group).

An extended Moran process that captures the struggle for fitness.

When a new type of individual appears in a stable population, the newcomer is typically not advantageous. Due to stochasticity, the new type can grow in numbers, but the newcomers can only become advantageous if they manage to change the environment in such a way that they increase their fitness. This dynamics is observed in several situations in which a relatively stable population is invaded by an alternative strategy, for instance the evolution of cooperation among bacteria, the invasion of cancer in a multicellular organism and the evolution of ideas that contradict social norms.

Study of tumor growth indicates the existence of an "immunological threshold" separating states of pro- and antitumoral peritumoral inflammation.

Background: Peritumoral inflammation-a response mainly involving polimorphonuclear neutrophils-has traditionally been thought protumoral in its effects. In recent years, however, a number of studies have indicated that it may play an important antitumoral role. This discrepancy has been difficult to explain.

Scaling in complex systems: a link between the dynamics of networks and growing interfaces.

We consider growing interfaces as dynamical networks whose nodes are the discrete points of the interface and the edges the physical interactions among them. We map the points of the interface formed at each time into a graph by means of a visibility algorithm. As the corresponding interfaces grow, their visibility graphs change over time.

Mathematical modeling of tuberculosis bacillary counts and cellular populations in the organs of infected mice.

Background: Mycobacterium tuberculosis is a particularly aggressive microorganism and the host's defense is based on the induction of cellular immunity, in which the creation of a granulomatous structure has an important role.

Methodology: We present here a new 2D cellular automata model based on the concept of a multifunctional process that includes key factors such as the chemokine attraction of the cells; the role of innate immunity triggered by natural killers; the presence of neutrophils; apoptosis and necrosis of infected macrophages; the removal of dead cells by macrophages, which induces the production of foamy macrophages (FMs); the life cycle of the bacilli as a determinant for the evolution of infected macrophages; and the immune response.

Results: The results obtained after the inclusion of two degrees of tolerance to the inflammatory response triggered by the infection shows that the model can cover a wide spectrum, ranging from highly-tolerant (i.

Tumour cell lines HT-29 and FaDu produce proinflammatory cytokines and activate neutrophils in vitro: possible applications for neutrophil-based antitumour treatment.

There is evidence that polymorphonuclear neutrophils (PMNs) can exert severe antineoplastic effects. Cross-talk between tumour cells and endothelial cells (ECs) is necessary for the accumulation of PMN around a tumour. This work reports the ability of two PMN-sensitive, human, permanent cell lines-colorectal adenocarcinoma (HT-29) and pharyngeal squamous-cell carcinoma (FaDu) cells-to act as inflammatory foci.

Polymorphonuclear neutrophils and cancer: intense and sustained neutrophilia as a treatment against solid tumors.

Polymorphonuclear neutrophils (PMN) are the most abundant circulating immune cells and represent the first line of immune defense against infection. This review of the biomedical literature of the last 40 years shows that they also have a powerful antitumoral effect under certain circumstances. Typically, the microenvironment surrounding a solid tumor possesses many of the characteristics of chronic inflammation, a condition considered very favorable for tumor growth and spread.

The carbon monoxide-releasing molecule tricarbonyldichlororuthenium(II) dimer protects human osteoarthritic chondrocytes and cartilage from the catabolic actions of interleukin-1beta.

We have investigated the effects of a carbon monoxide-releasing molecule, tricarbonyldichlororuthenium(II) dimer (CORM-2), on catabolic processes in human osteoarthritis (OA) cartilage and chondrocytes activated with interleukin-1beta. In these cells, proinflammatory cytokines induce the synthesis of matrix metalloproteinases (MMPs) and aggrecanases, including members of a disintegrin and metalloproteinase with thrombospondin domain (ADAMTS) family, which may contribute to cartilage loss. CORM-2 down-regulated MMP-1, MMP-3, MMP-10, MMP-13, and ADAMTS-5 in OA chondrocytes, and it inhibited cartilage degradation.

[Limbic encephalitis--a diagnostic challenge].

Background: The etiology of limbic encephalitis (LE) is often autoimmune. Autoimmune LE is often paraneoplastic and should be suspected in patients with subacute confusional states. Subgroups of LE require different treatment, and the prognosis is variable; making the correct diagnosis is therefore essential for a good outcome.

Position-dependent expression of GADD45alpha in rat brain tumours.

Although the complex and multifactorial process of tumour growth has been extensively studied for decades, our understanding of the fundamental relationship between tumour growth dynamics and genetic expression profile remains incomplete. Recent studies of tumour dynamics indicate that gene expression in solid tumours would depend on the distance from the centre of the tumour. Since tumour proliferative activity is mainly localised to its external zone, and taking into account that generation and expansion of genetic mutations depend on the number of cell divisions, important differences in gene expression between central and peripheral sections of the same tumour are to be expected.

The effect of pressure on the growth of tumour cell colonies.

This paper describes some experiments on the manner in which external pressure affects cell colony growth in general, and tumour growth in particular. More precisely, our results show that cell colony borders growing under high-pressure conditions have geometrical and dynamical properties that are markedly different from those corresponding to growth under homeostatic, normal pressure conditions. These behaviours are characterized by means of the so-called dynamical exponents of each type of growth.

Clinical status and parasitic infection in a Wichí Aboriginal community in Salta, Argentina.

In a study, carried out in 2000, of the clinical and parasitological status of a Wichi Aboriginal community living in the suburbs of Tartagal, northern Salta, Argentina, 154 individuals were screened for parasitic infections. Ninety-five faecal samples were also obtained from the same population. Ninety-three percent of the subjects were positive for 1 or more of the parasites investigated by direct test and 70.

Pinning of tumoral growth by enhancement of the immune response.

Tumor growth is a surface phenomenon of the molecular beam epitaxy universality class in which diffusion at the surface is the determining factor. This Letter reports experiments performed in mice showing that these dynamics can, however, be changed. By stimulating the immune response, we induced strong neutrophilia around the tumor.

The universal dynamics of tumor growth.

Scaling techniques were used to analyze the fractal nature of colonies of 15 cell lines growing in vitro as well as of 16 types of tumor developing in vivo. All cell colonies were found to exhibit exactly the same growth dynamics-which correspond to the molecular beam epitaxy (MBE) universality class. MBE dynamics are characterized by 1), a linear growth rate, 2), the constraint of cell proliferation to the colony/tumor border, and 3), surface diffusion of cells at the growing edge.

Plasmidic extended-spectrum beta-lactamases in Vibrio cholerae O1 El Tor isolates in Argentina.

Since 1992 there have been seven major outbreaks of cholera in Argentina. Susceptibility analysis of 1,947 isolates (40% of reported cases) of Vibrio cholerae O1 biotype El Tor suggested the presence of extended-spectrum beta-lactamases (ESBLs) in 28 isolates. Because of their different susceptibility profiles, V.