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Summary The intestinal epithelium serves as an essential barrier to the outside world and is maintained by functionally distinct populations of rapidly cycling intestinal stem cells (CBC ISCs) and slowly cycling, reserve ISCs (r-ISCs). Because disruptions in the epithelial barrier can result from pathological activation of the immune system, we sought to investigate the impact of inflammation on ISC behavior during the regenerative response. In a murine model of αCD3 antibody-induced small-intestinal inflammation, r-ISCs proved highly resistant to injury, while CBC ISCs underwent apoptosis. Moreover, r-ISCs were induced to proliferate and functionally contribute to intestinal regeneration. Further analysis revealed that the inflammatory cytokines interferon gamma and tumor necrosis factor alpha led to r-ISC activation in enteroid culture, which could be blocked by the JAK/STAT inhibitor, tofacitinib. These results highlight an important role for r-ISCs in response to acute intestinal inflammation and show that JAK/STAT-1 signaling is required for the r-ISC regenerative response., Graphical Abstract, Highlights • Reserve intestinal stem cells (r-ISCs) enter the cell cycle following inflammation • Activated r-ISCs proliferate and contribute to intestinal regeneration • Cytokine-stimulated JAK/STAT-1 signaling is required for r-ISC activation, Richmond et al. demonstrate that, following intestinal inflammatory injury, reserve intestinal stem cells (r-ISCs) exit quiescence and contribute to intestinal regeneration. In contrast, crypt base columnar ISCs undergo apoptosis and show a reduced lineage contribution in the immediate recovery period. JAK/STAT-1 signaling is required for r-ISC activation during the early recovery period following inflammatory injury.

Clostridium difficile toxin B (TcdB) is a critical virulence factor that causes diseases associated with C. difficile infection. Here we carried out CRISPR-Cas9-mediated genome-wide screens and identified the members of the Wnt receptor frizzled family (FZDs) as TcdB receptors. TcdB binds to the conserved Wnt-binding site known as the cysteine-rich domain (CRD), with the highest affinity towards FZD1, 2 and 7. TcdB competes with Wnt for binding to FZDs, and its binding blocks Wnt signalling. FZD1/2/7 triple-knockout cells are highly resistant to TcdB, and recombinant FZD2-CRD prevented TcdB binding to the colonic epithelium. Colonic organoids cultured from FZD7-knockout mice, combined with knockdown of FZD1 and 2, showed increased resistance to TcdB. The colonic epithelium in FZD7-knockout mice was less susceptible to TcdB-induced tissue damage in vivo. These findings establish FZDs as physiologically relevant receptors for TcdB in the colonic epithelium.

Tra il 1954 e il 1955 intercorre uno scambio di lettere tra lo storico dell’arte Francesco Arcangeli e il collezionista milanese Alfredo Costa che possedeva un Noli me tangere di Pontormo (ora in collezione privata a Busto Arsizio) e alcuni dipinti di Boldini. Arcangeli è intenzionato a scrivere un articolo sulla tavola del maestro toscano e pubblicarlo sulla rivista «Paragone», fondata da Roberto Longhi. Il progetto però fallisce, forse a causa dell’inadeguatezza dell’apparato fotografico approntato per la pubblicazione. Between 1954 and 1955, Francesco Arcangeli exchanges letters with the Milanese collector Alfredo Costa, who owned a Noli me tangere by Pontormo (now in Busto Arsizio, private collection) and some paintings by Boldini. Arcangeli discusses the opportunity to write an article about the painting of the Tuscan master and to publish it in RobertoLonghi's review «Paragone». The project fails maybe because of the inadequacy of the photographic material., Concorso. Arti e lettere, VI - Intorno ad alcuni carteggi del '900

Background: In obesity, the addition of mass loading of the chest wall by adipose tissue decreases compliance, but its ventilation does not seem to be a limiting factor to physical performance. Plasma K+ and lactic acid are considered important determinants of ventilation during exercise. Obesity is characterized by insulin resistance. Objectives: The aim of this study was to assess ventilatory adaptations to sustained effort and the effects of lactic acid and potassium in young obese subjects. Methods: Twelve obese subjects with a body mass index of 40 (mean age 27 years, 6 males) and 12 normal subjects with a body mass index of 22 (aged 28 years, 6 males) performed a progressive cycloergometric test with increases of 20 W every 4 min to exhaustion while minute ventilation, oxygen consumption, carbon dioxide production, end-tidal oxygen pressure, and end-tidal carbon dioxide pressure were measured. Blood samples were collected at the end of every step to determine plasma K+. Lactic acid was measured at rest, 40, 80, 120 W and peak exercise (or only at peak exercise if Results: Obese subjects had lower insulin sensitivity (0.318 vs. 0.345, p < 0.01). Peak exercise was not significantly different between both groups (125 W in the obese group vs. 137 W in the control group), but the ventilatory threshold was at lower power output in the obese group compared to the controls (76 vs. 107 W, p < 0.05). Ventilation increased less in the obese group but oxygen saturation of hemoglobin remained within normal limits up to exhaustion in both groups. Ventilation was appropriate for the CO2 increase but less appropriate for the increased O2 consumption. Both K+ and lactic acid increased less in the obese group. Conclusions: In our obese subjects, ventilation was not a limiting factor during exercise. Its lower increase may be due, in addition to the characteristics of their chest walls, to insulin resistance which may limit the increase in lactic acid during effort, and to the hypertrophy of muscle fibers previously noted, which may be linked to a lower increase in plasma K+ during physical exercise.

Leptin values are higher in obesity. Physical exercise reduces fat mass (FM) and decreases leptin levels. Intensity of physical training seems to play a role in reducing circulating leptin. In 16 obese subjects (8 men and 8 women, age 38.6±3.9 years, BMI 35.9±1.8 kg/m(2)), leptin was sampled before and after 4 weeks of controlled training. Eight subjects (4 men and 4 women) performed an aerobic training schedule (Group A), the remainders an aerobic training program with a bout of work beyond the anaerobic threshold (AT) (Group B). Training determined a reduction in leptin levels in both groups, which was significant in Group A (12.2 vs. 27.8 μg/l, p

The present study describes a project carried out in the Center for SIDS/ALTE of the Pediatric Clinic of Varese, targeted to deliver and provide parents with a movies on PBLS titled "A Minute for Life". The impact on the parent was evaluated by applying a questionnaire.The movie "A Minute for Life" was given to 308 parents (122 fathers, mean age 35.2 and 186 mothers, mean age 28.4). All parents completed a questionnaire based on 4 parameters: 1. clarity of the content presented; 2. anxiety felt while watching the movie clip 3. reassurance related to their ability to review other times the movie; 4. the perception of its usefulness.Regarding the clarity of content, the results provide evidence that 231 parents (75% of the sample) rated him "very clear", while 77 subjects (25%) considered it "quite clear". On the possibility of being able to have at home, 277 parents (90% of subjects) believed it would be very reassuring to see it back Home. According to 231 parents (75% of the sample) the vision of the movie does not convey anxiety, while 77 of them (25% of subjects) felt slightly concerned in relation to vision. With regard to the overall assessment of the movie, all parents (308, 100% of the sample) agreed about its extreme usefulness.Our study opens the way for further prospective studies regarding the appropriateness and usefulness of the movie. It's also important to consider the release of the movie to all new parents and the possibility of giving first aid courses open to all those who want to be able to act with promptness and expertise if and when necessary.

Two trials, conducted in two locations in Italy over 4 years with Chardonnay grapevines trained to GDC, Pergola or Casarsa systems and grafted onto 6 rootstocks (SO4, Kober 5BB, Teleki 5C, 8B, 140Ru and 1103P), provided vine yield and pruning weight data to study a practical and reliable method for assessing genotypic stability. Commonly used stability statistics, like indices based on coefficients of variation and regression, were estimated. When the deviations from regression of genotype performances on the environmental index were large, biological response of rootstocks to different environments was better fitted by double regression analysis based on Verma's coefficients. The unpredictable part of the response in regression approach was quantified by Wricke's ecovalence index. The results confirmed that the use of more than one statistical procedure is necessary in the selection of stable genotypes. Genotype × environment interactions were partitioned into four components (variability, ecovalence, linear response or deviation from linear response, environmental sensitivity). The use of a graphical representation of the four components was easy to use and appropriate for grouping genotypes of greater and lesser stability. Rootstocks Teleki 5C and 8B were identified as stable for grape yield, while high yielding genotypes (SO4 and 1103 P) were judged as unstable. 140Ru and Kober 5BB were detected as stable for yield of pruning wood.

It is demonstrated that aerobic exercise plays an important role in weight loss programs for obesity by increasing 24 h metabolic rate. While aerobic exercise can result in health and fitness benefits in obese subjects, also independently of weight loss, not completely clear are the effects of bouts of hard exercise on metabolic outcomes. The aim of this study was to test the hypothesis that short-term aerobic activity with anaerobic bouts might result in a greater improvement in the management of obesity than aerobic activity alone. We studied 16 obese subjects (eight men) during a progressive cycloergometric test up to exhaustion, before and after 4 weeks of two different training schedules (6 days/week). Insulin and glycaemia, non-esterified fatty acids (NEFA) and lactic acid were sampled. Group A (eight subjects, four men) performed an aerobic cycle workout; Group B (eight subjects, four men) performed a 25 min aerobic workout followed by 5 min of anaerobic workout. All the subjects maintained their individual eating habits. The post-training test showed a decrease in AUCs NEFA in Group A (p

International audience; Background. Growth hormone (GH) is normally sensitive to physical exercise. Intensity and duration of exercise, fitness as well as age, all can influence GH response to exercise. In obesity, GH secretion is decreased both in basal conditions and in response to exercise. Objective. To analyse the dynamics of GH response to a progressive cycloergometric test conducted up to exhaustion in adult normal subjects and obese patients, after a reconditioning program at different workloads. Design and methods. We studied 8 lean subjects (4 males, mean age 34.3 yrs, range 26-47 yrs, mean BMI 22.1 kg/m2). GH was sampled at baseline and during the last 30 s of each power output increase. Anaerobic threshold (AT) was detected by the V-slope method. The same test was carried out in 16 obese subjects (7 males, mean age 39.1 yrs, range 20-59 yrs, mean BMI 35.8 kg/m2) and repeated after a 4-week reconditioning program consisting of aerobic workout (Group A, 8 subjects, 3 males, mean age 40.5 yrs, range 22-59 yrs, mean BMI 33.6 kg/m2), and aerobic plus anaerobic work (group B, 8 subjects, 4 males, mean age 37.6 yrs, range 20-56 yrs, mean BMI 38.0 kg/m2) for 6 days/wk, with no dietary restrictions. Results. Mean exercise peak occurred at higher intensity in controls (140 vs. 110 W, pConclusions. Our results confirm the blunted GH response to exercise in obese adults when compared to lean counterparts. With obesity, aerobic training poorly increases the GH response beyond AT while supplemental anaerobic workload appears to increase GH response beyond AT. These observations may have implications for prescription of physical exercise, which is one of the recommendations in the management of obesity.

“Delitto al voto”. Evoluzione e contraddizioni del sistema politico e del processo elettorale in Guatemala. Una missione di monitoraggio elettorale, Altre Modernità, N° 2 (2009): Letterature e migrazioni

In future, it is conceivable that satellite antennas will need to target a single house. Meeting this requirement, antennas that are larger and lighter must be designed. Example of antennas able to radiate narrow beams are reflector antennas and antenna arrays. Printed reflectarrays combine advantages of both reflectors and printed arrays. They consist in arrays of printed patches, generally of rectangular shape, that re-radiate the illuminating power from a primary feed horn back into space. As the elements have different positions, and the field that propagates from the feed to the patches covers different path lengths, it becomes necessary to adjust the phase of single elements to compensate the different path lengths. We analyze a configuration obtained by varying the length of a stub, the position of the elements and their relative orientation. Moreover, in order to compensate the frequency shift of individual elements introduced by the presence of the stubs, the dimensions of the patches are varied, too. Since the bandwidth of this kind of radiator is it particularly critical issue, a frequency response analysis of the genetically optimized configuration has also been performed.

POU domain proteins interact positively or negatively with steroid hormone receptors, depending on the precise array of these and other factors assembled on target gene promoters. Octamer transcription factor 1 (Oct-1), a ubiquitous POU factor, is implicated in androgen induction of the mouse sex-limited protein (Slp) gene based on protein-DNA interaction studies. However, direct evidence for a role of Oct-1 in the hormone response has been difficult to obtain. Brain 1 (Brn-1), another POU factor, is more tissue-specific, expressing in brain and also in kidney, which is a major site of Slp synthesis. We compared the interaction of the androgen receptor (AR) with Oct-1 and Brn-1 to reveal the more likely candidate for regulation of Slp. In transfection, addition of either Oct-1 or Brn-1 reduced AR activation, regardless of the presence of an octamer-like sequence in the enhancer, suggesting interference was indirect. However, when the octamer-like element was changed to a consensus octamer site, Brn-1, but not Oct-1, strongly enhanced androgen activation. This correlated with Brn-l's preference for the consensus octamer sequence in DNA binding assays. Direct interaction of AR with glutathione-S-transferase-(GST)-fused Oct-1 was DNA-dependent, while Brn-l-AR association was not. Chimeric Brn-1 and Oct-1 POU domains demonstrated that the DNA-dependent AR interaction relied on the origin of the POU homeodomain. However, in the context of full-length Brn-1 and Oct-1 chimeric proteins, the POU homedomain was not sufficient to confer the distinct behaviors of these factors in vivo, but instead revealed the importance of an N-terminal transactivation domain in Brn-1. These results demonstrate that functional interaction of Oct-1 and Brn-1 with AR is determined by the precise sequence of the octamer binding site, and by differential interaction of the POU factors with AR and other components of the transcriptional machinery.

Printed reflectarrays try to combine the advantages of both reflectors and printed arrays (see e.g. [l]) and consist in arrays of printed patches, illuminated by a primary feed horn, that re-radiate the illuminating power back into the space. Since the elements have different positions, the field that propagates from the feed to the patches covers different path lengths and therefore the contributions to the total re-radiated field coming from the different patches are not in phase. So it becomes necessary to adjust the phase of the single element to compensate the different path lengths and this may be obtained using at least one of the following different possible techniques: adding to the patches suitable differentlength transmission lines [2, 31, varying the size of the radiating elements [4], rotating the elements to different angles or finally varying the dielectric constant of the material below the radiator itself. Here we chose to combine the first two options together

Background Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice are relatively resistant to this pathogen. This intrinsic species-specific difference in EHEC infection limits the translation of murine research to human. Furthermore, studying the mechanisms underlying this differential susceptibility is a difficult problem due to complex in vivo interactions between the host, pathogen, and disparate commensal microbial communities. Results We utilize organ-on-a-chip (Organ Chip) microfluidic culture technology to model damage of the human colonic epithelium induced by EHEC infection, and show that epithelial injury is greater when exposed to metabolites derived from the human gut microbiome compared to mouse. Using a multi-omics approach, we discovered four human microbiome metabolites—4-methyl benzoic acid, 3,4-dimethylbenzoic acid, hexanoic acid, and heptanoic acid—that are sufficient to mediate this effect. The active human microbiome metabolites preferentially induce expression of flagellin, a bacterial protein associated with motility of EHEC and increased epithelial injury. Thus, the decreased tolerance to infection observed in humans versus other species may be due in part to the presence of compounds produced by the human intestinal microbiome that actively promote bacterial pathogenicity. Conclusion Organ-on-chip technology allowed the identification of specific human microbiome metabolites modulating EHEC pathogenesis. These identified metabolites are sufficient to increase susceptibility to EHEC in our human Colon Chip model and they contribute to species-specific tolerance. This work suggests that higher concentrations of these metabolites could be the reason for higher susceptibility to EHEC infection in certain human populations, such as children. Furthermore, this research lays the foundation for therapeutic-modulation of microbe products in order to prevent and treat human bacterial infection., Microbiome, 7 (1), ISSN:2049-2618

Here we describe a method for fabricating a primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The primary epithelial cells are expanded as 3D organoids, dissociated, and cultured on a porous membrane within a microfluidic device with human intestinal microvascular endothelium cultured in a parallel microchannel under flow and cyclic deformation. In the Intestine Chip, the epithelium forms villi-like projections lined by polarized epithelial cells that undergo multi-lineage differentiation similar to that of intestinal organoids, however, these cells expose their apical surfaces to an open lumen and interface with endothelium. Transcriptomic analysis also indicates that the Intestine Chip more closely mimics whole human duodenum in vivo when compared to the duodenal organoids used to create the chips. Because fluids flowing through the lumen of the Intestine Chip can be collected continuously, sequential analysis of fluid samples can be used to quantify nutrient digestion, mucus secretion and establishment of intestinal barrier function over a period of multiple days in vitro. The Intestine Chip therefore may be useful as a research tool for applications where normal intestinal function is crucial, including studies of metabolism, nutrition, infection, and drug pharmacokinetics, as well as personalized medicine., Scientific Reports, 8 (1), ISSN:2045-2322