Exploring Responses to Art in Adolescence: A Behavioral and Eye-Tracking Study

Adolescence is a peculiar age mainly characterized by physical and psychological changes that may affect the perception of one''s own and others'' body. This perceptual peculiarity may influence the way in which bottom-up and top-down processes interact and, consequently, the perception and evaluation of art. This study is aimed at investigating, by means of the eye-tracking technique, the visual explorative behavior of adolescents while looking at paintings. Sixteen color paintings, categorized as dynamic and static, were presented to twenty adolescents; half of the images represented natural environments and half human individuals; all stimuli were displayed under aesthetic and movement judgment tasks. Participants'' ratings revealed that, generally, nature images are explicitly evaluated as more appealing than human images. Eye movement data, on the other hand, showed that the human body exerts a strong power in orienting and attracting visual attention and that, in adolescence, it plays a fundamental role during aesthetic experience. In particular, adolescents seem to approach human-content images by giving priority to elements calling forth movement and action, supporting the embodiment theory of aesthetic perception.     

Rapid and Efficient Conversion of Integration-Free Human Induced Pluripotent Stem Cells to GMP-Grade Culture Conditions

Data suggest that clinical applications of human induced pluripotent stem cells (hiPSCs) will be realized. Nonetheless, clinical applications will require hiPSCs that are free of exogenous DNA and that can be manufactured through Good Manufacturing Practice (GMP). Optimally, derivation of hiPSCs should be rapid and efficient in order to minimize manipulations, reduce potential for accumulation of mutations and minimize financial costs. Previous studies reported the use of modified synthetic mRNAs to reprogram fibroblasts to a pluripotent state. Here, we provide an optimized, fully chemically defined and feeder-free protocol for the derivation of hiPSCs using synthetic mRNAs. The protocol results in derivation of fully reprogrammed hiPSC lines from adult dermal fibroblasts in less than two weeks. The hiPSC lines were successfully tested for their identity, purity, stability and safety at a GMP facility and cryopreserved. To our knowledge, as a proof of principle, these are the first integration-free iPSCs lines that were reproducibly generated through synthetic mRNA reprogramming that could be putatively used for clinical purposes.     

Risk of Obstructive Sleep Apnea with Daytime Sleepiness Is Associated with Liver Damage in Non-Morbidly Obese Patients with Nonalcoholic Fatty Liver Disease

Background

A high prevalence of obstructive sleep apnea syndrome (OSAS) has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD), but few studies have evaluated OSAS in non-morbidly obese NAFLD patients.

Aims

To determine the prevalence of risk for OSAS with or without daytime sleepiness in non-morbidly obese patients with NAFLD and evaluate the association with the severity of liver damage.

Methods

We considered 159 consecutive patients with histological NAFLD and body mass index (BMI) <35 Kg/m², and 80 controls without ultrasonographic steatosis matched for age, sex, and BMI. OSAS risk was determined by positivity for Berlin questionnaire (BQ), and daytime sleepiness by the Sleepness Epworth Scale (ESS). Liver damage was evaluated according to the NAFLD activity score.

Results

In NAFLD patients, BQ alone was positive in 39 (25%), ESS in 8 (5%), and both in 13 (8%, OSAS with sleepines); p = ns vs. controls without steatosis. In NAFLD patients at risk for OSAS with (but not in those without) sleepiness, we observed a higher prevalence of nonalcoholic steatohepatitis (NASH; 11/13, 85% vs. 72/146, 49%; p = 0.018), and of clinically significant fibrosis (stage>1; 9/13, 69% vs. 39/146, 27%; p = 0.003). At multivariate logistic regression analysis, OSAS with sleepiness was strongly associated with NASH and fibrosis>1 independently of known clinical risk factors such as age, gender, BMI, diabetes, and ALT levels (OR 7.1, 95% c.i. 1.7–51, p = 0.005 and OR 14.0, 95% c.i. 3.5–70, p = 0.0002, respectively).

Conclusions

A proportion of NAFLD patients without severe obesity is at risk for OSAS with daytime sleepiness, which is associated with the severity of liver damage independently of body mass and other cofactors.     

Class I Major Histocompatibility Complex,the Trojan Horse for Secretion of Amyloidogenic β2-Microglobulin

To form extracellular aggregates, amyloidogenic proteins bypass the intracellular quality control, which normally targets unfolded/aggregated polypeptides. Human D76N β₂-microglobulin (β₂m) variant is the prototype of unstable and amyloidogenic protein that forms abundant extracellular fibrillar deposits. Here we focus on the role of the class I major histocompatibility complex (MHCI) in the intracellular stabilization of D76N β₂m. Using biophysical and structural approaches, we show that the MHCI containing D76N β₂m (MHCI₇₆) displays stability, dissociation patterns, and crystal structure comparable with those of the MHCI with wild type β₂m. Conversely, limited proteolysis experiments show a reduced protease susceptibility for D76N β₂m within the MHCI₇₆ as compared with the free variant, suggesting that the MHCI has a chaperone-like activity in preventing D76N β₂m degradation within the cell. Accordingly, D76N β₂m is normally assembled in the MHCI and circulates as free plasma species in a transgenic mouse model.     

Thriving at high hydrostatic pressure: the example of ammonoids (extinct cephalopods)

Ammonoids are a group of extinct mollusks belonging to the same class of the living genus Nautilus (cephalopoda). In both Nautili and ammonoids, the (usually planospiral) shell is divided into chambers separated by septa that, during their lifetime, are filled with gas at atmospheric pressure. The intersection of septa with the external shell generates a curve called the suture line, which in living and most fossil Nautili is fairly uncomplicated. In contrast, suture lines of ancient ammonoids were gently curved and during the evolution of the group became highly complex, in some cases so extensively frilled as to be considered as fractal curves. Numerous theories have been put forward to explain the complexity of suture ammonoid lines. Calculations presented here lend support to the hypothesis that complex suture lines aided in counteracting the effect of the external water pressure. Additionally, it is suggested that complex suture lines diminished shell shrinkage caused by water pressure, and thus aided in improving buoyancy. Understanding the reason for complex sutures in ammonoids represents an important issue in paleobiology with potential applications to the problem of the resistance of hollow mechanical structures subjected to high pressure.     

Sister chromatid exchange (SCE) for the first time in Casertana pig breed

Lymphocyte cell cultures from 30 Casertana pigs (13 males and 17 females), reared in southern Italy, underwent the sister chromatid exchange (SCE) test. The Casertana pig is an endangered native breed from the region of Campania, raised chiefly half-wild. In the 1500 cells we studied, the mean SCE was 6.32+/-2.92 and SCE frequency did not follow a Poisson distribution. A higher mean value of SCE cell(-1) was found in the older group (SCE cell(-1)=6.68+/-2.95) compared with the younger (SCE cell(-1)=5.94+/-2.84), the difference being statistically significant (P<0.01). To our knowledge, this is the first investigation in a representative sample of Italian pig breed using the SCE test. Furthermore, this is the first report where the differences found in the mean SCE values were related to age in domestic species.     

Redox regulation of cellular stress response in neurodegenerative disorders

There is increasing evidence that reactive oxygen species (ROS) are not only toxic but play an important role in cellular signaling and in the regulation of gene expression. A number of biochemical and physiologic stimuli, such as perturbation in redox status, expression of misfolded proteins, altered glyc(osyl)ation and glucose deprivation, overloading of products of polyunsaturated fatty acid peroxidation (Hydroxynonenals, HNE) or cholesterol oxidation and decomposition, can disrupt redox homeostasis, impose stress and subsequently lead to accumulation of unfolded or misfolded proteins in brain cells. Alzheimer's (AD), Parkinson's (PD), Huntington's disease (HD), Amyothrophic lateral sclerosis (ALS) and Friedreich ataxia (FRDA) are major neurological disorders associated with production of abnormal proteins and, as such, belong to the so called "protein conformational diseases". The Central Nervous System has evolved highly specific signaling pathways called the unfolded protein response to cope with the accumulation of unfolded or misfolded proteins. Recent discoveries of the mechanisms of cellular stress signaling have led to major new insights into the diverse processes that are regulated by cellular stress response. Thus, the pathogenic dysfunctional aggregation of proteins in non-native conformations is associated with metabolic derangements and excessive production of ROS. The brain response to detect and control metabolic or oxidative stress is accomplished by a complex network of "longevity assurance processes" integrated to the expression of genes termed vitagenes. Heat shock proteins are a highly conserved system responsible for the preservation and repair of correct protein conformation. Heme oxygenase-1, a inducible and redox-regulated enzyme, is currently considered as having an important role in cellular antioxidant defense. A neuroprotective effect, due to its heme degrading activity, and tissue-specific antioxidant effects due to its products CO and biliverdin, this latter being further reduced by biliverdin reductase in bilirubin is an emerging concept. There is a current interest in dietary compounds that can inhibit, retard or reverse the multi-stage pathophysiology of Alzheimer disease, with a chronic inflammatory response, brain injury and beta-amyloid associated pathology. Curcumin and ferulic acid, two powerful antioxidants, the first from the curry spice turmeric and the second a major constituent of fruit and vegetables, have emerged as strong inducers of the heat shock response. Food supplementation with curcumin and ferulic acid is considered a nutritional approach to reduce oxidative damage and amyloid pathology in Alzheimer disease. This review summarizes the complex regulation of cellular stress signaling and its relevance to human physiology and disease.     

Follistatin induction by nitric oxide through cyclic GMP: a tightly regulated signaling pathway that controls myoblast fusion

The mechanism of skeletal myoblast fusion is not well understood. We show that endogenous nitric oxide (NO) generation is required for myoblast fusion both in embryonic myoblasts and in satellite cells. The effect of NO is concentration and time dependent, being evident only at the onset of differentiation, and direct on the fusion process itself. The action of NO is mediated through a tightly regulated activation of guanylate cyclase and generation of cyclic guanosine monophosphate (cGMP), so much so that deregulation of cGMP signaling leads to a fusion-induced hypertrophy of satellite-derived myotubes and embryonic muscles, and to the acquisition of fusion competence by myogenic precursors in the presomitic mesoderm. NO and cGMP induce expression of follistatin, and this secreted protein mediates their action in myogenesis. These results establish a hitherto unappreciated role of NO and cGMP in regulating myoblast fusion and elucidate their mechanism of action, providing a direct link with follistatin, which is a key player in myogenesis.     

Synthesis and NMR characterization of new hyaluronan-based NO donors

Nitric oxide (NO) and hyaluronic acid (HA), two species widely different in terms of molecular complexity and biological competence, are both known to play an important role in the wound healing process. To combine the properties of HA and NO, we synthesized new NO-donors based on hyaluronic acid derivatives exhibiting a controlled NO-release under physiological conditions (in vitro tests). Since two molecules of NO can form a covalent bond with secondary amines to yield structures, named NONO-ates, able to release NO in solution, we used spermidine bound to HA as the NO-linker. The HA-spermidine derivative was obtained by controlled HA amidation in aqueous media, activating the biopolymer carboxylate groups with a water soluble carbodiimide. The resulting derivative, soluble in water, was fully characterized by high field 1H and 13C NMR spectroscopy. The amount of grafting of spermidine on HA was determined by integration of suitable 1H NMR signals. In addition, cross-linked derivatives of HA were synthesized by the Ugi's four-component reaction using formaldehyde, cyclohexylisocyanide, and spermidine. The HA-spermidine networks were characterized by 13C CP-MAS NMR spectroscopy. The degree of cross-linking of the networks was also determined. Finally, the release of NO from the swollen hydrogels freshly saturated with NO, in contact with aqueous media, was monitored by means of UV spectrophotometric measurements.