Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Physico-chemical and sensory characteristics of Spanish goat cheeses

In this study the physico-chemical characteristics, secondary proteolysis (nitrogen fractions) and sensory properties (odour, taste and texture) of 18 cheeses made with pasteurised goat milk by several producers in Castilla-La Mancha, Spain, was made. The cheeses were heterogeneous in their physico-chemical properties. Differences among cheeses were only significant (P< 0.05) for dry matter (DM), water activity (a(w)), NaCl and nitrogen fractions. These results,suggest that proteolysis was generally not very intense. The cheeses were broadly similar to other Spanish goat cheeses in their physico-chemical characteristics. Principal Component Analysis (PCA) of sensory properties showed that the attributes that contributed most to the cheeses differentiation were odour descriptors (goat milk odour, brine odour and butter odour) and textural attributes: hardness, pastiness, humidity, friability and adhesiveness. Sensory analysis proved to be a valuable tool for grouping cheeses: these goat cheeses may be classified as full-fat to extra-fat, and as semi-cured to cured cheeses.Peer reviewe

Comparative study of methods for the determination of proteolytic activity in lactic acid bacteria and selection of an autochthonous starter to manufacture Manchego cheese

The acidifying and proteolytic activity of 18 isolates of Lactococcus and Lactobacillus isolated from artisanal and industrial Manchego cheeses were studied in order to know which of them presented the best activities to be employed in the manufacture of this cheese. Of the two methods used to evaluate the proteolytic activity, Folin-Ciocalteau and opthaldehyde (oPA) methods, the latter gave higher values and showed a higher discriminating capacity with important differences for the values obtained for Lc. lactis subsp. lactis isolates. Of all the isolates studied, the Lactococcus lactis subp. lactis (Lc 8) showed the highest acidifying (0.79 % lactic acid) and proteolytic (2.19 mmol Gly/L) activity and could be selected as a starter culture for Manchego cheese manufacture.Peer reviewe

Comparison of microflora, chemical and sensory characteristics of artisanal Manchego cheeses from two dairies

It is widely accepted that cheeses, although manufactured according to the regulations of the Appellation of Origins, show important differences in the sensory attributes mainly due to the milk used (raw or pasteurised). This paper reports on comparison of changes in the microflora and chemical parameters related with proteolytic and lipolytic processes that occurred throughout eight months ripening in artisanal Manchego cheeses manufactured in two dairies. The results obtained indicate few chemical or microbiological differences between the cheeses from the two dairies; there were, however, differences in the proteolysis and lipolysis that gave rise to small but important sensory differences between cheeses from both dairies. Odour attributes contributed most to the differentiation of cheeses from both dairies.This research was supported by the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Acción Estratégica “Conservación de recursos genéticos de interés agroalimentario” del Plan Nacional de Investigación Científica, Desarrollo e Innovación tecnológica (I + D + I). Proyect Reference RM01-003. I. Sanchez and S. Seseña were supported by grants from the Castilla-La Mancha Regional Government.Peer reviewe

Phenotypic and genotypic characterization of lactobacilli isolated from Spanish goat cheeses

Lactic acid bacteria from 18 Spanish goat cheeses produced by seven dairies were isolated to evaluate the genetic diversity of this bacterial community. 136 representative isolates were characterized by phenotyping and Randomly Amplified Polymorphic DNA (RAPD-PCR) analysis. Ten species were identified with predominance of Lactobacillus paracasei subsp. paracasei. The presence of L. curvatus, L. pentosus, L. cellobiosus and L. rhamnosus has not hitherto been reported in Spanish goat cheeses. A high degree of genetic diversity was found for L. paracasei subsp. paracasei, L. curvatus and L. plantarum. Some of the identified strains displayed strong acidifying and proteolytic capacities.This research project was financed by the Consejería de Agricultura y Medio Ambiente de la Junta de Comunidades de Castilla–La Mancha. (Castilla–La Mancha Regional Government, Department of Agriculture and the Environment). I. Sanchez and S. Seseña were supported by grants from the Castilla–La Mancha Regional Government.Peer reviewe

Genetic diversity, dynamics, and activity of Lactobacillus community involved in traditional processing of artisanal Manchego cheese

A total of 248 strains of predominant lactobacilli isolated during the manufacture and ripening of artisanal Manchego cheeses obtained from two dairies were obtained and the genetic diversity of 197 investigated using random amplified polymorphic DNA (RAPD-PCR). 51 isolates could not be lysed and were therefore not genotyped. Forty-two distinct RAPD patterns, grouped in six major clusters at a similarity level of 54%, were obtained. Phenotypic characterization of isolates enabled their assignment to the species L. plantarum, L. brevis, L. paracasei subsp. paracasei, L. fermentum, L. pentosus, L. acidophilus and L. curvatus. In samples from both dairies, the species L. plantarum, L. brevis and L. paracasei subsp. paracasei dominated during ripening. Three genotypes showed excellent physiological characteristics and were therefore proposed as adjunct cultures for Manchego cheese manufacture.This research was supported by the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Acción Estratégica “Conservación de recursos genéticos de interés agroalimentario” del Plan Nacional de Investigación Científica, Desarrollo e Innovación tecnológica (I+D+I). Proyect Reference RM01-003. I. Sanchez and S. Seseña were supported by grants from the Castilla-La Mancha Regional Government.Peer reviewe

Ozone modified hypothalamic signaling enhancing thermogenesis in the TDP-43A315T transgenic model of Amyotrophic Lateral Sclerosis

Abstract Amyotrophic lateral sclerosis (ALS), a devastating progressive neurodegenerative disease, has no effective treatment. Recent evidence supports a strong metabolic component in ALS pathogenesis. Indeed, metabolic abnormalities in ALS correlate to disease susceptibility and progression, raising additional therapeutic targets against ALS. Ozone (O3), a natural bioactive molecule, has been shown to elicit beneficial effects to reduce metabolic disturbances and improved motor behavior in TDP-43A315T mice. However, it is fundamental to determine the mechanism through which O3 acts in ALS. To characterize the association between O3 exposure and disease-associated weight loss in ALS, we assessed the mRNA and protein expression profile of molecular pathways with a main role in the regulation of the metabolic homeostasis on the hypothalamus and the brown adipose tissue (BAT) at the disease end-stage, in TDP-43A315T mice compared to age-matched WT littermates. In addition, the impact of O3 exposure on the faecal bacterial community diversity, by Illumina sequencing, and on the neuromuscular junctions (NMJs), by confocal imaging, were analysed. Our findings suggest the effectiveness of O3 exposure to induce metabolic effects in the hypothalamus and BAT of TDP-43A315T mice and could be a new complementary non-pharmacological approach for ALS therapy