Fibroblast autofluorescence in connective tissue disorders: a future tool for clinical and differential diagnosis?

Marfan syndrome (MFS) is an inherited disorder of connective tissue due to mutations in FBN1 (90%) and TGFBR1 and TGFBR2 (5 to 10%) genes. Clinical and differential diagnosis is difficult because of the inter- and intrafamiliar marked heterogeneity and the variable onset age of clinical manifestations. Among the disorders, in differential diagnosis, thoracic aortic aneurysm (TAA) and Ullrich scleroatonic muscular dystrophy (UCMD) are reported. We evaluate the possibility of utilizing autofluorescence (AF) analysis as a diagnostic tool in the clinical and/or differential diagnosis of MFS and related disorders and in the investigation of the molecular mechanisms involved. Both multispectral imaging autofluorescence microscopy (MIAM) and autofluorescence microspectroscopy (AMS) have been used to characterize AF emission of fibroblasts from patients affected by inherited connective tissue disorders. Our preliminary results show significant differences in AF emission between normal and pathological fibroblasts, suggesting possible improvement in diagnostics of connective tissue disorders by AF analysis

α-Synuclein Aggregates with β-Amyloid or Tau in Human Red Blood Cells: Correlation with Antioxidant Capability and Physical Exercise in Human Healthy Subjects

Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1–42 (Aβ), and tau, in both brain and peripheral tissue. In addition to homo-oligomers, the role of α-syn interactions with Aβ or tau has gradually emerged. The altered protein accumulation has been related to both oxidative stress and physical activity; nevertheless, no correlation among the presence of peripheral α-syn hetero-aggregates, antioxidant capacity, and physical exercise has been discovered as of yet. Herein, the content of α-syn, Aβ, tau, and of their heterocomplexes was determined in red blood cells (RBCs) of healthy subjects (sedentary and athletes). Such parameters were related to the extent of the antioxidant capability (AOC), a key marker of oxidative stress in aging-related pathologies, and to physical exercise, which is known to play an important preventive role in NDs and to modulate oxidative stress. Tau content and plasma AOC toward hydroxyl radicals were both reduced in older or sedentary subjects; in contrast, α-syn and Aβ accumulated in elderly subjects and showed an inverse correlation with both hydroxyl AOC and the level of physical activity. For the first time, α-syn heterocomplexes with Aβ or tau were quantified and demonstrated to be inversely related to hydroxyl AOC. Furthermore, α-syn/Aβ aggregates were significantly reduced in athletes and inversely correlated with physical activity level, independent of age. The positive correlation between antioxidant capability/physical activity and reduced protein accumulation was confirmed by these data and suggested that peripheral α-syn heterocomplexes may represent new indicators of ND-related protein misfolding

α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson's Disease Patients and Correlate with Disease Severity

Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1-42(Aβ1-42) and tau, in both brain and peripheral tissues. In addition to oligomers, the role of the interactions of α-syn with Aβ or tau has gradually emerged. Nevertheless, despite intensive research, NDs have no accepted peripheral markers for biochemical diagnosis. In this respect, Red Blood Cells (RBCs) are emerging as a valid peripheral model for the study of aging-related pathologies. Herein, a small cohort (N= 28) of patients affected by Parkinson's disease (PD) and age-matched controls were enrolled to detect the content of α-syn (total and oligomeric), Aβ1-42and tau (total and phosphorylated) in RBCs. Moreover, the presence of α-syn association with tau and Aβ1-42was explored by co-immunoprecipitation/western blotting in the same cells, and quantitatively confirmed by immunoenzymatic assays. For the first time, PD patients were demonstrated to exhibit α-syn heterocomplexes with Aβ1-42and tau in peripheral tissues; interestingly, α-syn-Aβ1-42concentrations were increased in PD subjects with respect to healthy controls (HC), and directly correlated with disease severity and motor deficits. Moreover, total-α-syn levels were decreased in PD subjects and inversely related to their motor deficits. Finally, an increase of oligomeric-α-syn and phosphorylated-tau was observed in RBCs of the enrolled patients. The combination of three parameters (total-α-syn, phosphorylated-tau and α-syn-Aβ1-42concentrations) provided the best fitting predictive index for discriminating PD patients from controls. Nevertheless further investigations should be required, overall, these data suggest α-syn hetero-aggregates in RBCs as a putative tool for the diagnosis of PD

The Observed and Predicted Spatial Distribution of Milky Way Satellite Galaxies

We review evidence that the census of Milky Way satellites similar to those known may be incomplete at low latitude due to obscuration and in the outer halo due to a decreasing sensitivity to dwarf satellites with distance. We evaluate the possible impact that incompleteness has on comparisons with substructure models by estimating corrections to the known number of dwarfs using empirical and theoretical models. If we assume that the true distribution of Milky Way satellites is uniform with latitude, then we estimate a 33% incompleteness in the total number of dwarfs due to obscuration at low latitude. Similarly, if we suppose that the radial distribution of Milky Way satellites matches that of M31, or that of the oldest sub-halos or the most massive sub-halos in a simulation, we estimate a total number of Milky Way dwarfs ranging from 1 -- 3 times the known population. Although the true level of incompleteness is quite uncertain, the fact that our extrapolations yield average total numbers of MW dwarfs that are realistically 1.5 -- 2 times the known population, shows that incompleteness needs to be taken seriously when comparing to models of dwarf galaxy formation. Interestingly, the radial distribution of the oldest sub-halos in a Lambda+CDM simulation of a Milky Way-like galaxy possess a close match to the observed distribution of M31's satellites, which suggests that reionization may be an important factor controlling the observability of sub-halos. We also assess the prospects for a new SDSS search for Milky Way satellites to constrain the possible incompleteness in the outer halo.Comment: 9 pages, 7 figures. Replaced with MNRAS accepted versio

High Risk of Unexpected Late Fetal Death in Monochorionic Twins Despite Intensive Ultrasound Surveillance: A Cohort Study

BACKGROUND: The rationale for fetal surveillance in monochorionic twin pregnancies is timely intervention to prevent the increased fetal/perinatal morbidity and mortality attributed to twin–twin transfusion syndrome and intrauterine growth restriction. We investigated the residual risk of fetal death after viability in otherwise uncomplicated monochorionic diamniotic twin pregnancies. METHODS AND FINDINGS: We searched an electronic database of 480 completed monochorionic pregnancies that underwent fortnightly ultrasound surveillance in our tertiary referral fetal medicine service between 1992 and 2004. After excluding pregnancies with twin–twin transfusion syndrome, growth restriction, structural abnormalities, or twin reversed arterial perfusion sequence, and monoamniotic and high-order multiple pregnancies, we identified 151 uncomplicated monochorionic diamniotic twin pregnancies with normal growth, normal liquor volume, and normal Doppler studies on fortnightly ultrasound scans. Ten unexpected intrauterine deaths occurred in seven (4.6%) of 151 previously uncomplicated monochorionic diamniotic pregnancies, within 2 wk of a normal scan, at a median gestational age of 34(+1) wk (weeks(+days); range 28(+0) to 36(+3)). Two of the five cases that underwent autopsy had features suggestive of acute late onset twin–twin transfusion syndrome, but no antenatal indicators of transfusional imbalance or growth restriction, either empirically or in a 1:3 gestation-matched case–control comparison. The prospective risk of unexpected antepartum stillbirth after 32 wk was 1/23 monochorionic diamniotic pregnancies (95% confidence interval 1/11 to 1/63). CONCLUSION: Despite intensive fetal surveillance, structurally normal monochorionic diamniotic twin pregnancies without TTTS or IUGR are complicated by a high rate of unexpected intrauterine death. This prospective risk of fetal death in otherwise uncomplicated monochorionic diamniotic pregnancies after 32 wk of gestation might be obviated by a policy of elective preterm delivery, which now warrants evaluation

Bacterial Diversity and Bioremediation Potential of the Highly Contaminated Marine Sediments at El-Max District (Egypt, Mediterranean Sea)

Coastal environments worldwide are threatened by the effects of pollution, a risk particularly high in semienclosed basins like the Mediterranean Sea that is poorly studied from bioremediation potential perspective especially in the Southern coast. Here, we investigated the physical, chemical, and microbiological features of hydrocarbon and heavy metals contaminated sediments collected at El-Max bay (Egypt). Molecular and statistical approaches assessing the structure of the sediment-dwelling bacterial communities showed correlations between the composition of bacterial assemblages and the associated environmental parameters. Fifty strains were isolated on mineral media supplemented by 1% crude oil and identified as a diverse range of hydrocarbon-degrading bacteria involved in different successional stages of biodegradation. We screened the collection for biotechnological potential studying biosurfactant production, biofilm formation, and the capability to utilize different hydrocarbons. Some strains were able to grow on multiple hydrocarbons as unique carbon source and presented biosurfactant-like activities and/or capacity to form biofilm and owned genes involved in different detoxification/degradation processes. El-Max sediments represent a promising reservoir of novel bacterial strains adapted to high hydrocarbon contamination loads. The potential of the strains for exploitation for in situ intervention to combat pollution in coastal areas is discussed

Exploring the Properties of the M31 Halo Globular Cluster System

Following on from our discovery of a significant population of M31 outer halo globular clusters (GCs), and updates to the Revised Bologna Catalogue of M31 GCs, we investigate the GC system of M31 out to an unprecedented radius (~120kpc). We derive various ensemble properties, including the magnitude, colour and metallicity distributions, as well as the GC number density profile. One of our most significant findings is evidence for a flattening in the radial GC number density profile in the outer halo. Intriguingly, this occurs at a galactocentric radius of ~2 degrees (~30 kpc) which is the radius at which the underlying stellar halo surface density has also been shown to flatten. The GCs which lie beyond this radius are remarkably uniform in terms of their blue (V-I)o colours, consistent with them belonging to an ancient population with little to no metallicity gradient. Structural parameters are also derived for a sample of 13 newly-discovered extended clusters (ECs) and we find the lowest luminosity ECs have magnitudes and sizes similar to Palomar-type GCs in the Milky Way halo. We argue that our findings provide strong support for a scenario in which a significant fraction of the outer halo GC population of M31 has been accreted.Comment: Accepted to MNRAS. Contains 13 pages, 11 figure

Effetto dell’inositolo nelle donne con ovaio micropolicistico

Il primo approccio a donne affette da sindrome dell’ovaio policistico in ricerca di prole prevede una correzione della sindrome metabolica come tentativo primario di ristabilire una attività ovulatoria spontanea. Tra le nuove molecole a disposizione la combinazione Myo-Inositolo e acido folico ha portato numerosi benefici a queste pazienti, sia in termini di ripristino dell’ovulazione spontanea e di miglioramento dell sindrome metabolica sia in termini di maturità e competenza ovocitaria in donne sottoposte ad induzione dell’ovulazione per Procreazione Medicalmente Assistita