Alpha synuclein post translational modifications: potential targets for Parkinson’s disease therapy?

Parkinson’s disease (PD) is the most common neurodegenerative disorder with motor symptoms. The neuropathological alterations characterizing the brain of patients with PD include the loss of dopaminergic neurons of the nigrostriatal system and the presence of Lewy bodies (LB), intraneuronal inclusions that are mainly composed of alpha-synuclein (α-Syn) fibrils. The accumulation of α-Syn in insoluble aggregates is a main neuropathological feature in PD and in other neurodegenerative diseases, including LB dementia (LBD) and multiple system atrophy (MSA), which are therefore defined as synucleinopathies. Compelling evidence supports that α-Syn post translational modifications (PTMs) such as phosphorylation, nitration, acetylation, O-GlcNAcylation, glycation, SUMOylation, ubiquitination and C-terminal cleavage, play important roles in the modulation α-Syn aggregation, solubility, turnover and membrane binding. In particular, PTMs can impact on α-Syn conformational state, thus supporting that their modulation can in turn affect α-Syn aggregation and its ability to seed further soluble α-Syn fibrillation. This review focuses on the importance of α-Syn PTMs in PD pathophysiology but also aims at highlighting their general relevance as possible biomarkers and, more importantly, as innovative therapeutic targets for synucleinopathies. In addition, we call attention to the multiple challenges that we still need to face to enable the development of novel therapeutic approaches modulating α-Syn PTMs

Role of Quantum Confinement in Luminescence Efficiency of Group IV Nanostructures

Experimental results obtained previously for the photoluminescence efficiency (PL$_{eff}$) of Ge quantum dots (QDs) are theoretically studied. A $\log$-$\log$ plot of PL$_{eff}$ versus QD diameter ($D$) resulted in an identical slope for each Ge QD sample only when $E_{G}\sim (D^2+D)^{-1}$. We identified that above $D\approx$ 6.2 nm: $E_{G}\sim D^{-1}$ due to a changing effective mass (EM), while below $D\approx$ 4.6 nm: $E_{G}\sim D^{-2}$ due to electron/ hole confinement. We propose that as the QD size is initially reduced, the EM is reduced, which increases the Bohr radius and interface scattering until eventually pure quantum confinement effects dominate at small $D$

Kit Radicaux Libres, a Biological Application for Monitoring Oxidative Stress in Pigs

Kit Radicaux Libres (KRL) test is a biological application, successfully applied on humans, helpful for the study of the total antiradical activity. In the present work, the first objective was to test on a subset of pig blood samples in order to determine the maximum time of storage able to provide reliable results. Blood samples were collected from 46 piglets and determinations were carried out on the blood samples after three h from collection (T1) and thereafter at 24 (T2) and 48 (T3) h. Successively blood samples from 313 piglets (171 castrated males and 142 females) were collected and analysed in order to determine reference intervals. Results are expressed as half-haemolysis time (HT50 in min), that is a reference point for blood susceptibility to free radical attack. Our findings showed that for samples analysed at T1 and T2 there were no significant changes but significantly increased values (P<0.05) were obtained when samples were analysed after 48 h from collection, underlining biological and analytical interference due to the hemolysis of the samples. The reference values found in the subjects, expressed as ET AL50 were 46.6-68.7 min (males) and 52.5-86.8 min (females) in RBC, 59.8-93.6 min (males) and 70.5-113.0 (females) in whole blood. In conclusion, a prolonged time (till +48 h) caused haemolysis, therefore the use of freshly collected blood is strictly recommended. The reference values obtained are considered to represent valid reference ranges for healthy pigs starting after weaning to 175 days of age under modern husbandry conditions

What are we losing? Are the personality traits of Italian autochthonous cows different from those of cosmopolitan breeds?

Objective: This study assessed personality traits in five cattle breeds (Bos taurus), two cosmopolitan (Holstein Friesian and Brown Swiss) and three endangered Italian autochthonous (Varzese, Rendena, and Modenese). Our aim was to provide an evaluation of the personality dimensions obtained by our questionnaire in order to compare some Italian autochthonous breeds with the cosmopolitan one. Our choice fell upon the comparison of the Varzese, the Modenese, the Rendena, the Brown Swiss, and the Holstein Friesian because the genetic selection at the base of the typical attitudes has induced different characteristics, and as a consequence, detectable differences in personality can be expected between the populations. Materials and methods: A personality questionnaire was completed by milkers/owners for each subject involved in this study. The milking staff involved in the study have been working with cows for over 20 years; they have experience with numerous breeds, and therefore, can be considered expert evaluators since they certainly have an appreciation of the full range of cow behavior. Results: The milkers\u2019 assessments analysis found breed differences in dairy cattle, showing that certain personality traits are more marked in certain breeds in terms of curiosity, friendliness to milkers, and responses to unknown people. Conclusion: This pilot survey shows the usefulness of questionnaires in cattle personality studies, highlighting some peculiarity of the endangered breeds

Direct Estimate of Cirrus Noise in Herschel Hi-GAL Images

In Herschel images of the Galactic plane and many star forming regions, a major factor limiting our ability to extract faint compact sources is cirrus confusion noise, operationally defined as the "statistical error to be expected in photometric measurements due to confusion in a background of fluctuating surface brightness". The histogram of the flux densities of extracted sources shows a distinctive faint-end cutoff below which the catalog suffers from incompleteness and the flux densities become unreliable. This empirical cutoff should be closely related to the estimated cirrus noise and we show that this is the case. We compute the cirrus noise directly, both on Herschel images from which the bright sources have been removed and on simulated images of cirrus with statistically similar fluctuations. We connect these direct estimates with those from power spectrum analysis, which has been used extensively to predict the cirrus noise and provides insight into how it depends on various statistical properties and photometric operational parameters. We report multi-wavelength power spectra of diffuse Galactic dust emission from Hi-GAL observations at 70 to 500 microns within Galactic plane fields at l= 30 degrees and l= 59 degrees. We find that the exponent of the power spectrum is about -3. At 250 microns, the amplitude of the power spectrum increases roughly as the square of the median brightness of the map and so the expected cirrus noise scales linearly with the median brightness. Generally, the confusion noise will be a worse problem at longer wavelengths, because of the combination of lower angular resolution and the rising power spectrum of cirrus toward lower spatial frequencies, but the photometric signal to noise will also depend on the relative spectral energy distribution of the source compared to the cirrus.Comment: 4 pages (in journal), 3 figures, Astronomy and Astrophysics, accepted for publication 13 May 201

Neonatal mortality in dogs : prognostic value of Doppler ductus venosus waveform evaluation - Preliminary results

Aim: To define the prognostic value of Doppler ultrasonographic morphology of ductus venosus (DV) waveform on canine neonatal mortality. Materials and Methods: Fifty-four healthy pregnant bitches underwent fetal ultrasonographic assessment. The DV waveforms were classified as diphasic (dDVw) or triphasic (tDVw) and compared with neonatal mortality. Results: Ninety-three fetuses were evaluated. Twenty fetuses belonged to litters with neonatal mortality, in which tDVw was observed. Seven fetuses belonged to litters without neonatal mortality, in which tDVw was observed. Fifty-eight fetuses belonged to litters without neonatal mortality, in which only dDVw was observed. Eight fetuses belonged to litters with neonatal mortality, in which only dDVw was observed. The correlation between tDVw and neonatal mortality was statistically significant (odds ratio [OR], 20.7; p<0.0001). Considering only pregnancies with one or two fetuses with the same DV waveform: Two fetuses with tDVw belonged to litters with neonatal mortality; 1 foetus with tDVw belonged to litter without neonatal mortality and 26 fetuses showed dDVw without neonatal mortality. The correlation between tDVw and neonatal mortality even in litters up to two pups was statistically significant (OR, 88.3; p=0.01). Conclusion: Echo-Doppler assessment of DV is feasible in canine fetuses, and the presence tDVw seems to be related to neonatal mortality

Methylphenidate Analogues as a New Class of Potential Disease-Modifying Agents for Parkinson’s Disease: Evidence from Cell Models and Alpha-Synuclein Transgenic Mice

Parkinson’s disease (PD) is characterized by dopaminergic nigrostriatal neurons degeneration and Lewy body pathology, mainly composed of α-synuclein (αSyn) fibrillary aggregates. We recently described that the neuronal phosphoprotein Synapsin III (Syn III) participates in αSyn pathology in PD brains and is a permissive factor for αSyn aggregation. Moreover, we reported that the gene silencing of Syn III in a human αSyn transgenic (tg) mouse model of PD at a pathological stage, manifesting marked insoluble αSyn deposits and dopaminergic striatal synaptic dysfunction, could reduce αSyn aggregates, restore synaptic functions and motor activities and exert neuroprotective effects. Interestingly, we also described that the monoamine reuptake inhibitor methylphenidate (MPH) can recover the motor activity of human αSyn tg mice through a dopamine (DA) transporter-independent mechanism, which relies on the re-establishment of the functional interaction between Syn III and α-helical αSyn. These findings support that the pathological αSyn/Syn III interaction may constitute a therapeutic target for PD. Here, we studied MPH and some of its analogues as modulators of the pathological αSyn/Syn III interaction. We identified 4-methyl derivative I-threo as a lead candidate modulating αSyn/Syn III interaction and having the ability to reduce αSyn aggregation in vitro and to restore the motility of αSyn tg mice in vivo more efficiently than MPH. Our results support that MPH derivatives may represent a novel class of αSyn clearing agents for PD therapy

Allele *2 of the HS1,2A enhancer of the Ig regulatory region associates with rheumatoid arthritis

Objective: To investigate the role of the HS1.2 enhancer polymorphisms as a new candidate marker for rheumatoid arthritis (RA) and to define the possible association with autoantibody positivity and clinical outcome. Methods: Genomic DNA was obtained from two cohorts of patients with RA (100 with early RA (ERA) and 114 with longstanding RA (LSRA)) and from 248 gender-matched controls from the same geographical area. Clinical and immunological characteristics were recorded for all the patients. Results: The percentage of the 2/2 genotype was higher In patients with ERA (27.0%), and In patients with LSRA (34.2%), than In controls (14.9%) (ERA: OR = 2.11 (95% Cl 1.20 to 3.70) vs controls; LSRA: OR = 2.96 (95% Cl 1.76 to 5.00) vs controls). A lower representation of allele *3 was present In patients with ERA (2.0%) than In controls (6.0%; OR = 0.32 (95% Cl 0.11 to 0.91)). No significant associations were found between polymorphisms and autoantibodies positivity. Conclusion: The HS1.2A allele *2 associates with early and longstanding RA

Do personality traits diverge in different communally housed captive penguin species?

Research into animal personality has grown over the last decade as its relevance to animal health and welfare has become more apparent. Personality has been used also for aspects of captive management, including decreasing stress, increasing positive health outcomes, successful breeding also in terms of infant survival. For wildlife management, determining inter-species differences in the personality traits of communally housed animals could be of great help to optimize the use of resources, in order to improve animal welfare. In group-living species, integrated decisions made by individuals result in collective behaviors which may, in turn, influence interactions between individuals and shape the resulting social system. There is evidence that animal groups may exhibit coordinated behavior and make collective decisions based on simple interaction rules. It has been described that in a flock or a colony, birds tend to exhibit behavioral synchrony, maintaining similar behavior at approximately the same time throughout the group, and also wild penguins have exhibited within-group synchrony. In this study we have considered three species of penguins, housed together at RZSS Edinburgh Zoo, Scotland, UK. The exhibit houses a colony of Gentoo penguins (Pygoscelis papua), a bachelor group of King penguins (Aptenodytes patagonicus) and a small colony of Northern rockhopper penguins (Eudyptes moseleyi). In a mixed species enclosure, animals are far more intermingled than they would be in the wild and have a limited area in which to maintain different territories. A keeper questionnaire (coding method) was used to produce personality profiles for each penguin. A multivariate analysis (Multiple Factor Analysis) on the mean values of the variables was used to analyze the data. The quantitative variables were all the measured characteristics; gender and species were included as qualitative variables. Results outlined a distinct personality in each animal, distinguishing each species in personality traits. The three species are almost sharply separated in the multidimensional space. In Gentoo and in Northern rockhopper penguins the prevailing components include some aggressiveness, fear, and insecurity. King penguins seem to be the \u201cmildest\u201d species, with components related to activity, playfulness, friendliness, and curiosity. We advocate that a deeper understanding of each animal\u2019s personality and behavior can offer practical help to zoological institutions to facilitate daily husbandry, animal welfare, tailor training or enrichment and ultimately increase reproductive success

Erectile dysfunction is common among men with acromegaly and is associated with morbidities related to the disease

Background: The prevalence of erectile dysfunction (ED) and its correlates in men with acromegaly has never been investigated. Aim: To evaluate sexual function in men with acromegaly. Methods: Multicenter-based, retrospective analysis of a non-selected series of 57 acromegalic subjects (mean age: 52.7 14.2 years) was performed. Acromegalic subjects reporting ED (n = 24) were compared with matched ED- patients without acromegaly or pituitary disease (con- trols), selected from a cohort of more than 4000 subjects enrolled in the Flrence Sexual Medicine and Andrology Unit. Patients were interviewed using SIEDY structured interview, a 13-item tool for the assessment of ED-related morbidities. Several clinical and biochemical parameters were taken. Penile colour-Doppler ultrasound (PCDU) was performed in a subgroup of 37 acromegalic subjects. Results: ED was reported by 42.1% of acromegalic sub- jects. After adjusting for age and testosterone, acromegalic subjects with ED had a higher prevalence of hypertension, and more often reported an impairment of sleep-related erections and a longer smoking habit. Accordingly, acro- megaly-associated ED was characterized by a higher organic component and worse PCDU parameters. No rela- tionship between ED and testosterone levels or other acro- megaly-related parameters was found. However, acromegalic subjects with severe ED reported a longer dis- ease duration. In a case-control analysis, comparing acromegalic subjects with ED-matched-controls free from acromegaly (1:5 ratio), acromegalic men had a worse ED problem and a higher organic component of ED, as derived from SIEDY score. In line with these data, acrome- galic patients with ED had a higher prevalence of major adverse cardiovascular events (MACE) history at enrol- ment and lower PCDU parameters. Conclusions: Subjects with complicated acromegaly are at an increased risk of developing ED, especially those with cardiovascular morbidities. Our data suggest including a sexual function evaluation in routine acromegaly follow- up