Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue

Previous work indicated that lysine-specific demethylase 1 (Lsd1) can positively regulate the oxidative and thermogenic capacities of white and beige adipocytes. Here we investigate the role of Lsd1 in brown adipose tissue (BAT) and find that BAT- selective Lsd1 ablation induces a shift from oxidative to glycolytic metabolism. This shift is associated with downregulation of BAT-specific and upregulation of white adipose tissue (WAT)-selective gene expression. This results in the accumulation of di- and triacylglycerides and culminates in a profound whitening of BAT in aged Lsd1- deficient mice. Further studies show that Lsd1 maintains BAT properties via a dual role. It activates BAT-selective gene expression in concert with the transcription factor Nrf1 and represses WAT-selective genes through recruitment of the CoREST complex. In conclusion, our data uncover Lsd1 as a key regulator of gene expression and metabolic function in BAT

The histone code reader Spin1 controls skeletal muscle development

While several studies correlated increased expression of the histone code reader Spin1 with tumor formation or growth, little is known about physiological functions of the protein. We generated Spin1(M5) mice with ablation of Spin1 in myoblast precursors using the Myf5-Cre deleter strain. Most Spin1(M5) mice die shortly after birth displaying severe sarcomere disorganization and necrosis. Surviving Spin1(M5) mice are growth-retarded and exhibit the most prominent defects in soleus, tibialis anterior, and diaphragm muscle. Transcriptome analyses of limb muscle at embryonic day (E) 15.5, E16.5, and at three weeks of age provided evidence for aberrant fetal myogenesis and identified deregulated skeletal muscle (SkM) functional networks. Determination of genome-wide chromatin occupancy in primary myoblast revealed direct Spin1 target genes and suggested that deregulated basic helix-loop-helix transcription factor networks account for developmental defects in Spin1(M5) fetuses. Furthermore, correlating histological and transcriptome analyses, we show that aberrant expression of titin-associated proteins, abnormal glycogen metabolism, and neuromuscular junction defects contribute to SkM pathology in Spin1(M5) mice. Together, we describe the first example of a histone code reader controlling SkM development in mice, which hints at Spin1 as a potential player in human SkM disease

Human campylobacteriosis related to the consumption of raw milk sold by vending machines in Italy: quantitative risk assessment based on official controls over four years

open18noA quantitative risk assessment (RA) model was developed to describe the risk of campylobacteriosis linked to consumption of raw milk sold in vending machines in Italy. Exposure assessment was based on the official microbiological records of raw milk samples from vending machines monitored by the regional Veterinary Authorities from 2008 to 2011, microbial growth during storage, destruction experiments, consumption frequency of raw milk, serving size, consumption preference and age of consumers. The differential risk considered milk handled under regulation conditions (4°C throughout all phases) and the worst time-temperature field handling conditions detected. Two separate RA models were developed, one for the consumption of boiled milk and the other for the consumption of raw milk, and two different dose-response (D-R) relationships were considered. The RA model predicted no human campylobacteriosis cases per year either in the best (4°C) storage conditions or in the case of thermal abuse in case of boiling raw milk, whereas in case of raw milk consumption the annual estimated campylobacteriosis cases depend on the dose-response relationships used in the model (D-R I or D-R II), the milk time-temperature storage conditions, consumer behaviour and age of consumers, namely young (with two cut-off values of ≤5 or ≤6 years old for the sensitive population) versus adult consumers. The annual estimated cases for young consumers using D-R II for the sensitive population (≤5 years old) ranged between 1013.7/100,000 population and 8110.3/100,000 population and for adult consumers using D-R I between 79.4/100,000 population and 333.1/100,000 population. Quantification of the risks associated with raw milk consumption is necessary from a public health perspective and the proposed RA model represents a useful and flexible tool to perform future RAs based on local consumer habits to support decision-making on safety policies. Further educational programmes for raw milk consumers or potential raw milk consumers are required to encourage consumers to boil milk to reduce the associated risk of illness.openFederica Giacometti; Paolo Bonilauri; Simonetta Amatiste; Norma Arrigoni; Manila Bianchi; Marina Nadia Losio; Stefano Bilei; Giuseppe Cascone; Damiano Comin; Paolo Daminelli; Lucia Decastelli; Giuseppe Merialdi; Renzo Mioni; Angelo Peli; Annalisa Petruzzelli; Franco Tonucci; Silvia Piva; Andrea Serraino.Federica Giacometti; Paolo Bonilauri; Simonetta Amatiste; Norma Arrigoni; Manila Bianchi; Marina Nadia Losio; Stefano Bilei; Giuseppe Cascone; Damiano Comin; Paolo Daminelli; Lucia Decastelli; Giuseppe Merialdi; Renzo Mioni; Angelo Peli; Annalisa Petruzzelli; Franco Tonucci; Silvia Piva; Andrea Serraino

The relationship between plasma amino acids and circulating albumin and haemoglobin in postabsorptive stroke patients.

BackgroundThis retrospective study had two main aims: (1) to document possible correlations between plasma Amino Acids (AAs) and circulating Albumin (Alb) and Haemoglobin (Hb); and (2) to identify which AAs were predictors of Alb and Hb.MethodsThe study considered 125 stroke subjects (ST) (61.6% males; 65.6 +/- 14.9 years) who met the eligibility criteria (absence of co morbidities associated with altered plasma AAs and presence of plasma AAs determined after overnight fasting). Fifteen matched healthy subjects with measured plasma AAs served as controls.ResultsThe best correlations of Alb were with tryptophan (Trp) and histidine (His) (r = + 0.53; p ConclusionsThe study shows that the majority of plasma AAs were positively correlated with Alb and Hb. The best predictors of circulating Alb and Hb were the levels of tryptophan and glutamine, respectively

Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

Previous work indicated that lysine-specific demethylase 1 (Lsd1) can positively regulate the oxidative and thermogenic capacities of white and beige adipocytes. Here we investigate the role of Lsd1 in brown adipose tissue (BAT) and find that BAT-selective Lsd1 ablation induces a shift from oxidative to glycolytic metabolism. This shift is associated with downregulation of BAT-specific and upregulation of white adipose tissue (WAT)-selective gene expression. This results in the accumulation of di- and triacylglycerides and culminates in a profound whitening of BAT in aged Lsd1-deficient mice. Further studies show that Lsd1 maintains BAT properties via a dual role. It activates BAT-selective gene expression in concert with the transcription factor Nrf1 and represses WAT-selective genes through recruitment of the CoREST complex. In conclusion, our data uncover Lsd1 as a key regulator of gene expression and metabolic function in BAT

Mycobacterium avium paratuberculosis in Italy: commensal or emerging human pathogen?

Specific bacterial infections or alterations of the gut microbiota likely trigger immuno-pathological phenomena associated with Crohn's disease and ulcerative colitis. Mycobacterium avium subspecies paratuberculosis is a candidate etiological agent of Crohn's disease. Definitive causal connection between Mycobacterium avium subspecies paratuberculosis infection and Crohn's disease has not been demonstrated

Inflammation and rehabilitation outcomes in patients with nontraumatic intracranial haemorrhage

Systemic inflammation and its impact on rehabilitation for patients with non-traumatic haemorrhagic injury (HBI) sequelae has not yet been adequately documented