Caveolae-Mediated internalization of extracellular HIV-1 tat fusion proteins visualized in real time

n/

Bacterial composition, genotoxicity, and cytotoxicity of fecal samples from individuals consuming omnivorous or vegetarian diets

This study analyzes the composition of viable fecal bacteria and gut toxicology biomarkers of 29 healthy volunteers, who followed omnivorous, lacto-ovo-vegetarian, or vegan diets. In particular, the research was focused on the prevalence of some representative viable bacteria from the four dominant phyla (Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria) commonly present in human feces, in order to evaluate the relationship between microorganisms selected by the habitual dietary patterns and the potential risk due to fecal water (FW) genotoxicity and cytotoxicity, considered as biomarkers for cancer risk and protective food activity. The relative differences of viable bacteria among dietary groups were generally not statistically significant. However, compared to omnivores, lacto-ovo-vegetarians showed low levels of total anaerobes. Otherwise, vegans showed total anaerobes counts similar to those of omnivores, but with lower number of bifidobacteria and the highest levels of bacteria from the Bacteroides-Prevotella genera. FW genotoxicity of lacto-ovo-vegetarians resulted significantly lower either in relation to that of omnivores and vegans. Lacto-ovo-vegetarians also showed the lowest levels of cytotoxicity, while the highest were found for vegans. These results highlighted that lacto-ovo-vegetarian diet was particularly effective in a favorable modulation of microbial activity, thus contributing to a significant reduction of the genotoxic and cytotoxic risk in the gut

Talent development in young cross-country skiers: longitudinal analysis of anthropometric and physiological characteristics

Introduction: Very little is known about talent development and selection processes in young cross-country skiers. Aim: (1) to analyze the effect of age on anthropometric and physiological parameters in medium-to-high level cross-country skiers during the late teenage period; (2) to describe parameters' trend in selected talents after the late teenage period; (3) to define which characteristics during the late teenage period could discriminate against further talent selection. Method: We found 14 male (M) and nine (F) athletes in our database, identified as talents by regional teams during the late teenage period, who performed the same diagonal-stride roller-skiing incremental test to exhaustion at 17 and 18 years old. Of these, four M and three F teenagers performed four further evaluations, and were selected by the national team. Age effect during the late teenage period was verified on anthropometric and physiological parameters measured at maximal intensity (MAX), first (VT1), and second (VT2) ventilatory thresholds, and 3\ub0 and 6\ub0 of treadmill incline. An observational analysis allowed to evaluate parameters' trend after the late teenage period in selected athletes, and to determine possible characteristics early discriminating further selection. Results: During the late teenage period, height, weight, and BMI was still raising in M as well as V'O2 at VT2 and 6\ub0 of treadmill incline (all P > 0.05). In F, mass-scaled V'O2 MAX increased while heart rate (HR) at MAX and VT2 decreased (all P > 0.05). Since the late teenage period, all selected males showed maximal ventilation volumes, absolute V'O2 at MAX, VT1, and VT2 that were within or above the 75th percentile of their group; the same was found in selected females for mass-scaled V'O2 MAX, VT1, and VT2 time. After the late teenage period, all selected athletes showed an increasing trend for VT2 time, while a decreasing trend for sub-maximal energetic cost, %V'O2 and HR. Discussion: During the late teenage period, males are still completing their maturation process. Since the late teenage period, some physiological parameters seem good indicators to early discriminate for further talents. A progressive increase in skiing efficiency was demonstrated in developing talents of both sexes after the late teenage period

Cell membrane lipid rafts mediate caveolar endocytosis of HIV-1 Tat fusion proteins.

The transactivator protein of human immunodeficiency virus type 1 Tat has the unique property of mediating the delivery of large protein cargoes into the cells when present in the extracellular milieu. Here we show that Tat fusion proteins are internalized by the cells through a temperature-dependent endocytic pathway that originates from cell membrane lipid rafts and follows caveolar endocytosis. These conclusions are supported by the study of the slow kinetics of the internalization of Tat endosomes, by their resistance to nonionic detergents, the colocalization of internalized Tat with markers of caveolar endocytosis, and the impairment of the internalization process by drugs that disrupt lipid rafts or disturb caveolar trafficking. These results are of interest for all those who exploit Tat as a vehicle for transcellular protein delivery

Assessment of Corneal Fluorescein Staining in Different Dry Eye Subtypes Using Digital Image Analysis

To describe a new objective technique of digital image analysis for the quantification and the morphological characterization of corneal staining in the setting of dry eye disease (DED), and to apply it to distinguish Sj\uf6gren syndrome (SS) from ocular graft versus-host disease (oGVHD)

A model of N-terminal Cyclin T1 based on FRET experiments

Human Cyclin T1 is the cyclin partner of kinase CDK9 in the positive transcription elongation factor b (P-TEFb). P-TEFb is recruited by Tat, the transactivator of the human immunodeficiency virus type 1 (HIV-1), to the viral promoter by direct interactions between Tat, Cyclin T1 and thecis-acting transactivation-responsive region (TAR) present at the 5′-end of each viral mRNA. At present, no structural data for Cyclin T1 are available. Here, we build a structural model of an N-terminus portion of Cyclin T1 (aa 27–263) based on the X-ray structure of Cyclin H. The model is compared with site directed mutagenesis data from the literature and validated by fluorescence resonance energy transfer (FRET) using Tat as a probe in living cells. This model provides a first step towards the structural characterization of the CDK9–CycT1–Tat-TAR complex, which is crucial for HIV-1 replication and may constitute a promising target for pharmaceutical intervention

Post-exercise cardiac autonomic and cardiovascular responses to heart rate-matched and work rate-matched hypoxic exercise

PURPOSE: This study investigated the effect of performing hypoxic exercise at the same heart rate (HR) or work rate (WR) as normoxic exercise on post-exercise autonomic and cardiovascular responses.METHODS: Thirteen men performed three interval-type exercise sessions (5*5-min; 1-min recovery): normoxic exercise at 80% of the WR at the first ventilatory threshold (N), hypoxic exercise (FiO2=14.2%) at the same WR as N (H-WR) and hypoxic exercise at the same HR as N (H-HR). Autonomic and cardiovascular assessments were conducted before and after exercise, both at rest and during active squat-stand manoeuvres (SS).RESULTS: Compared to N, H-WR elicited a higher HR response (83% vs 75%HRmax, p<0.001) and H-HR a reduced exercise WR (-21.1\ub19.3%, p<0.001). Cardiac parasympathetic indices were reduced 15min after exercise and recovered within 60min in N and H-HR, but not after H-WR (p<0.05). H-WR altered cardiac baroreflex sensitivity (cBRS) both at rest and during SS (specifically in the control of blood pressure fall during standing phases) in the first 60min after the exercise bout (p<0.05). Post-exercise hypotension (PEH) did not occur in H-HR (p>0.05) but lasted longer in H-WR than in N (p<0.05).CONCLUSIONS: Moderate HR-matched hypoxic exercise mimicked post-exercise autonomic responses of normoxic exercise without resulting in significant PEH. This may relate to the reduced WR and the limited associated mechanical/metabolic strain. Conversely, WR-matched hypoxic exercise impacted upon post-exercise autonomic and cardiovascular responses, delaying cardiac autonomic recovery, temporarily decreasing cBRS and evoking prolonged PEH

Beyond BRCA1 and BRCA2: deleterious variants in DNA repair pathway genes in italian families with breast/ovarian and pancreatic cancers

The 5-10% of breast/ovarian cancers (BC and OC) are inherited, and germline pathogenic (P) variants in DNA damage repair (DDR) genes BRCA1 and BRCA2 explain only 10-20% of these cases. Currently, new DDR genes have been related to BC/OC and to pancreatic (PC) cancers, but the prevalence of P variants remains to be explored. The purpose of this study was to investigate the spectrum and the prevalence of pathogenic variants in DDR pathway genes other than BRCA1/2 and to correlate the genotype with the clinical phenotype. A cohort of 113 non-BRCA patients was analyzed by next-generation sequencing using a multigene panel of the 25 DDR pathways genes related to BC, OC, and PC. We found 43 unique variants in 18 of 25 analyzed genes, 14 classified as P/likely pathogenic (LP) and 28 as variants of uncertain significance (VUS). Deleterious variants were identified in 14% of index cases, whereas a VUS was identified in 20% of the probands. We observed a high incidence of deleterious variants in the CHEK2 gene, and a new pathogenic variant was detected in the RECQL gene. These results supported the clinical utility of multigene panel to increase the detection of P/LP carriers and to identify new actionable pathogenic gene variants useful for preventive and therapeutic approaches

CVD-graphene/graphene flakes dual-films as advanced DSSC counter electrodes

The use of graphene-based electrodes is burgeoning in a wide range of applications, including solar cells, light emitting diodes, touch screens, field-effect transistors, photodetectors, sensors and energy storage systems. The success of such electrodes strongly depends on the implementation of effective production and processing methods for graphene. In this work, we take advantage of two different graphene production methods to design an advanced, conductive oxide- and platinum-free, graphene-based counter electrode for dye-sensitized solar cells (DSSCs). In particular, we exploit the combination of a graphene film, produced by chemical vapor deposition (CVD) (CVD-graphene), with few-layer graphene (FLG) flakes, produced by liquid phase exfoliation. The CVD-graphene is used as charge collector, while the FLG flakes, deposited atop by spray coating, act as catalyst for the reduction of the electrolyte redox couple (i.e., I3-/I-- and Co+2/+3). The as-produced counter electrodes are tested in both I3-/I-- and Co+2/+3-based semitransparent DSSCs, showing power conversion efficiencies of 2.1% and 5.09%, respectively, under 1 SUN illumination. At 0.1 SUN, Co+2/+3-based DSSCs achieve a power conversion efficiency as high as 6.87%. Our results demonstrate that the electrical, optical, chemical and catalytic properties of graphene-based dual films, designed by combining CVD-graphene and FLG flakes, are effective alternatives to FTO/Pt counter electrodes for DSSCs for both outdoor and indoor applications

John Latham’s cosmos and mid-century representation

The conceptual artist John Latham (1921 – 2006) is sometimes cast as disconnected to the currents of British visual culture. Latham’s idiosyncratic cosmology based upon time and events and incorporating human creativity rather than matter and energy is used to distinguish this disconnection. However, this paper argues that his work can be seen as closely related to that of other mid-century cultural producers who were engaged with alternative cosmic speculations, and part of a broader shift in the register of representation. Papers from the Latham digital archive help make this case