Distinct blood and visceral adipose tissue regulatory T cell and innate lymphocyte profiles characterize obesity and colorectal cancer

Visceral adipose tissue (VAT) is a main site where metabolic and immunologic processes interplay to regulate, at local and systemic level, the inflammatory status and immune response. Obesity-associated inflammation and immune dysfunctions are inextricably linked to tumor but, in spite of intense efforts, the mechanisms underpinning this asso- ciation remain elusive. In this report, we characterized the profile of VAT-associated and circulating innate lymphocyte and regulatory T (T reg ) cell subsets underlying inflammatory conditions, such as obesity and colorectal cancer (CRC). Analysis of NK, NKT-like, γδ T, and T reg cell populations in VAT and blood of healthy lean subjects revealed that CD56 hi NK and OX40 + T reg cells are more abundant in VAT with respect to blood. Conversely, CD56 dim NK and total T reg cells are most present in the circulation, while γδ T lymphocytes are uniformly distributed in the two compartments. Interestingly, a reduced frequency of circulating activated T reg cells, and a concomitant preferential enrichment of OX40- expressing T reg cells in VAT, were selectively observed in obese (Ob) subjects, and directly correlated with body mass index. Likewise, CRC patients were characterized by a specific enrichment of VAT-associated NKT-like cells. In addition, Ob and CRC-affected individuals shared a significant reduction of the V γ 9V δ 2/ γδ T cell ratio at systemic level. The alterations in the relative proportions of T reg and NKT-like cells in VAT were found to correlate with the content of pro- and anti-inflammatory polyunsaturated fatty acids (PUFA), respectively. Overall, these results provide evidence for distinct alterations of the immune cell repertoire in the periphery with respect to the VAT microenvironment that uniquely characterize or are shared by different inflammatory conditions, such as obesity and CRC, and suggest that VAT PUFA composition may represent one of the factors that contribute to shape the immune phenotypes

A Condenser to Recover Organic Volatile Compounds during Vinification

Volatile compounds are lost during grape must fermentation owing to escaping carbon dioxide, which ultimately affects the wine\u2019s aroma. An innovative condensation device was designed to trap organic volatile compounds that would otherwise be lost. Trials were performed on Sangiovese and Syrah grapes and involved continuous condensation of vapor (condensed fractions, CFs) escaping from fermentation tanks. Daily measurements were taken of the ethanol content and volatile compound composition of CFs. An average of 1.3g of CF per kilogram of fermenting must was recovered, corresponding to a theoretical yield of condensed product of about 0.37%. Mean ethanol content was about 24% by volume, while the total organic volatile compound concentration was about 1200 mg L 121. Predominant compounds were alcohols and esters of secondary origin, with four compounds (ethyl octanoate, 1-propanol, ethyl acetate, and 2, 3-butanediol) accounting for more than 88% of the final concentration. The CF volatile profile changed as a function of fermentation time. CFs were added back to their respective wines for sensory evaluation and were statistically shown to be detectable at a rate of 1\u2030

Comparison between two filtration techniques for red wines

Filtration is a separation operation used in oenology to provide microbiological stabilization and limpidity of wines. Currently, in Tuscany filter-presses are the most common devices. However, they show some drawbacks in terms of required workforce and wine losses. Further, the process can\u2019t be automated. Probably, in next future the cross-flow microfiltration, i.e. the most popular filtration system in biotechnology, food industry, and large wine estates, will replace the traditional filter-press system. However, especially in Tuscany, this method has low diffusion mainly due to the small average farms size, which cannot afford the high purchasing costs. The aim of this work is the comparison between the two above-mentioned filtration techniques in terms of operative parameters and economic costs, at working-scale. The comparisons were made using about 13000 l of Sangiovese wine produced in San Casciano Val di Pesa (FI), Italy. The effects of the two filtration techniques on wine quality were evaluated in terms of chemical and physical profiles by comparing several parameters before and after the two treatments. Also, the main operative parameters, such as operation time, energy, water, and material consumption were recorded and the break-even point of the two filtration techniques has been assessed. The results show a comparable effect of the two techniques in terms of physical and chemical parameters of the treated wines. The cross-flow microfiltration system is convenient beyond 438000 l of processed wine. Moreover, the lower variable costs, especially the required labour, make this kind of filtration more convenient than the traditional filter-press system

Optical Diffraction Tomography and Raman Confocal Microscopy for the Investigation of Vacuoles Associated with Cancer Senescent Engulfing Cells

Wild-type p53 cancer therapy-induced senescent cells frequently engulf and degrade neighboring ones inside a massive vacuole in their cytoplasm. After clearance of the internalized cell, the vacuole persists, seemingly empty, for several hours. Despite large vacuoles being associated with cell death, this process is known to confer a survival advantage to cancer engulfing cells, leading to therapy resistance and tumor relapse. Previous attempts to resolve the vacuolar structure and visualize their content using dyes were unsatisfying for lack of known targets and ineffective dye penetration and/or retention. Here, we overcame this problem by applying optical diffraction tomography and Raman spectroscopy to MCF7 doxorubicin-induced engulfing cells. We demonstrated a real ability of cell tomography and Raman to phenotype complex microstructures, such as cell-in-cells and vacuoles, and detect chemical species in extremely low concentrations within live cells in a completely label-free fashion. We show that vacuoles had a density indistinguishable to the medium, but were not empty, instead contained diluted cell-derived macromolecules, and we could discern vacuoles from medium and cells using their Raman fingerprint. Our approach is useful for the noninvasive investigation of senescent engulfing (and other peculiar) cells in unperturbed conditions, crucial for a better understanding of complex biological processes

Metaprogetto per Case della Comunità e Ospedali di Comunità. Criteri di progettazione architettonico-funzionale e organizzativi [Meta 2 e 3].

A seguito della Pandemia di COVID-19, che ha evidenziato le significative criticità del SSN, il Governo ha approvato il PNRR per rilanciarne l'economia e promuovere al contempo salute, sostenibilità e innovazione digitale. Nello specifico M6C1 prevede l’introduzione delle Case di Comunità (CdC), Ospedali di Comunità (OdC) e Centrali Operative Territoriali (COT) con l’intento di rafforzare le prestazioni sanitarie erogate sul territorio e l’assistenza domiciliare dando un forte impulso alla telemedicina e, assicurare un’efficace integrazione con tutti i servizi socio-sanitari. Oltre alla disamina del DM 77, per l’elaborazione delle strategie generali delle CdC, OdC e COT, lo studio è stato articolato in tre fasi: • una conoscitiva in cui è stato analizzato l’attuale panorama nazionale e internazionale riguardante il tema della rete sanitaria territoriale, con la definizione di Best Practice; • una di indagine in cui sono state analizzate tutte le normative attuative Nazionali e Regionali; • una propositiva di elaborazione finale in cui vengono elaborati gli input provenienti dalle prime due fasi per lo sviluppo del Metaprogetto. Per la definizione del Metaprogetto delle CdC, OdC e COT, a partire dal DM 77 e le indicazioni regionali è stato desunto il quadro funzionale per elaborare il programma spaziale corredato dei layout funzionali più significativi. I diversi servizi sono stati organizzati per macro-aree funzionali e, in sequenza, la definizione per ciascuna di esse di un quadro sinottico nel quale siano riportati l’approccio prestazionale e le caratteristiche ambientali, dimensionali, ecc. Nello specifico le diverse funzioni sono state così classificate in: • macro-aree omogenee per tipologia di funzione da erogare (servizi sanitari, cure primarie, ecc.); • a ciascuna macro-area corrispondono diverse aree funzionali che sono state strutturate per dare indicazioni metaprogettuali atte ad ottimizzarne il funzionamento interno in termini di layout spaziale, di sistema delle relazioni funzionali e spaziali; • infine ciascuna area funzionale, è stata caratterizzata da diverse unità ambientali. Lo studio condotto ha l’intento di supportare la programmazione di queste strutture in relazione al bacino di utenza e al loro dimensionamento. Nella realizzazione delle seguenti strutture sarà necessario definire la localizzazione valutando la possibilità di insediarle all’interno di poli ospedalieri esistenti oppure in presidi autonomi esistenti oppure di nuova costruzione

Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination

Upon recruitment to active enhancers and promoters, RNA polymerase II (Pol II) generates short non-coding transcripts of unclear function. The mechanisms that control the length and the amount of ncRNAs generated by cis-regulatory elements are largely unknown. Here, we show that the adaptor protein WDR82 and its associated complexes actively limit such non-coding transcription. WDR82 targets the SET1 H3K4 methyltransferases and the nuclear protein phosphatase 1 (PP1) complexes to the initiating Pol II. WDR82 and PP1 also interact with components of the transcriptional termination and RNA processing machineries. Depletion of WDR82, SET1, or the PP1 subunit required for its nuclear import caused distinct but overlapping transcription termination defects at highly expressed genes and active enhancers and promoters, thus enabling the increased synthesis of unusually long ncRNAs. These data indicate that transcription initiated from cis-regulatory elements is tightly coordinated with termination mechanisms that impose the synthesis of short RNAs

Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation.

Cohesin is important for 3D genome organization. Nevertheless, even the complete removal of cohesin has surprisingly little impact on steady-state gene transcription and enhancer activity. Here we show that cohesin is required for the core transcriptional response of primary macrophages to microbial signals, and for inducible enhancer activity that underpins inflammatory gene expression. Consistent with a role for inflammatory signals in promoting myeloid differentiation of hematopoietic stem and progenitor cells (HPSCs), cohesin mutations in HSPCs led to reduced inflammatory gene expression and increased resistance to differentiation-inducing inflammatory stimuli. These findings uncover an unexpected dependence of inducible gene expression on cohesin, link cohesin with myeloid differentiation, and may help explain the prevalence of cohesin mutations in human acute myeloid leukemia