Essential Tremor (ET) is one of the most common neurological disorders. In most instances ET is inherited as an autosomal dominant trait with age-related penetrance (virtually complete in advanced ...age); however, ET genetics remains elusive. The current study aims to identify possibly pathogenic genetic variants in a group of well-characterized ET families.
34 individuals from 14 families with dominant ET were clinically evaluated and studied by whole exome sequencing studies (after excluding trinucleotide expansion disorders).
Most patients had pure ET. In 4 families, exome studies could identify a genetic variant potentially able to significantly alter the protein structure (CADD >20, REVEL score > 0.25), shared by all the affected individuals (in CAMTA1, FUS, MYH14, SGCE genes). In another family there were two variants in dominant genes (PCDH9 and SQSTM1). Moreover, an interrupted “intermediate” trinucleotide expansion in ATXN1 (“SCA1”) was identified in a further family with pure ET.
Combining our observations together with earlier reports, we can conclude that ET genes confirmed in at least two families to date include CAMTA1 and FUS (reported here), as well as CACNA1G, NOTCH2NLC and TENM4. Most cases of familial ET, inherited with an autosomal dominant inheritance, may result from “mild” variants of many different genes that, when affected by more harmful genetic variants, lead to more severe neurological syndromes (still autosomal dominant). Thus, ET phenotype may be the “mild”, incomplete manifestation of many other dominant neurogenetic diseases. These findings further support evidence of genetic heterogeneity for such disease(s).
Author's keywords: cerebellar ataxias, movement disorders, neurogenetics, rare neurological disorders, tremor.
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•Essential Tremor (ET) is one of the most common genetic disorders.•In 6 families a genetic variant was identified.•ET may result from “mild” variants of many different genes.•ET is the incomplete manifestation of other dominant neurogenetic diseases.•ET genes confirmed in ≥2 families now include CAMTA1, FUS, CACNA1G, NOTCH2NLC, TENM4.
This study investigates the stereospecific distribution of fatty acids across the triacylglycerol molecules in breast milk obtained at three different periods of lactation. Fatty acids were ...distributed within the three
sn
-positions of the glycerol backbone in a highly specific pattern; the shorter fatty acids tend toward the
sn
-2 and
sn
-3 positions of the glycerol molecule, whereas the longer chain fatty acids are more in the
sn
-1 and
sn
-3 position. Significant differences in fatty acid composition occurred between lactation times, but factors affecting the fatty acids content do not alter their regiospecific fatty acyl profile, although the quantities in each position can be changed. This suggests that the fatty acids regiodistribution profile in human milk related to the optimal infant growth should be used as a standard for the preparation of infant formulas.
► A novel GC method predicting the roasted coffee composition (Arabica/Robusta) of blends based on two components. ► The method was validated on coffees blends from the Italian market and no ...statistically significant differences were found. ► The method is useful to ensure the validation of certified roasted coffee blends in routine analysis. ► No need to calculate the response factors, no need to quantify the GC components, no need to add internal standards.
Since the price of Arabica is currently more than twice higher than Robusta, a rapid and reliable method for the determination of the roasted coffee blend composition is fundamental for the authentication of commercial blends used for the Italian Espresso coffee. A GC-FID method based on the ratio between the integrated peak areas of kahweol (K) divided by the sum of K and 16-O-methylcafestol (16MCF) was developed. No internal/external standard was used. Moreover, the quantitation of the unsaponifiable compounds is not necessary, as well as the calculation of any response factors. The percentage of Robusta in 34 samples of coffee blends with known composition, and in 48 samples of pure varieties was used to build a cubic polynomial function with R2=0.998. The roasting conditions did not affect the results. Considering eight commercial blends (ranging 0–90% Robusta), no significant difference (two-tailed P=0.817) was registered between the claimed and the predicted composition.
Acute lethal and sublethal toxicity of the imidazolinone imazethapyr (IMZT)-based commercial formulation herbicide Pivot H® (10.59% IMZT) was evaluated on Hypsiboas pulchellus tadpoles. Whereas ...mortality was used as the end point for lethality, frequency of micronuclei (MNs) and other nuclear abnormalities as well as DNA single-strand breaks evaluated by the single cell gel electrophoresis assay were employed to test genotoxicity. Behavioral, growth, developmental, and morphological abnormalities were also employed as sublethal end points. Mortality studies revealed equivalent LC50 (96h) values of 1.49mg/L (confidence limit, 1.09–1.63) and 1.55mg/L (confidence limit, 1.51–1.60) IMZT for Gosner stage (GS) 25 and GS36, respectively. Behavioral changes, i.e., irregular swimming and immobility, as well as a decreased frequency of keratodonts were observed. The herbicide increased the frequency of MNs in circulating erythrocytes of tadpoles exposed for 48h to the highest concentration assayed (1.17mg/L). However, regardless of the concentration of the herbicide assayed, an enhanced frequency of MNs was observed in tadpoles exposed for 96h. The herbicide was able to induce other nuclear abnormalities, i.e., blebbed and notched nuclei, only when tadpoles were exposed for 96h. In addition, we observed that exposure to IMZT within the 0.39–1.17mg/L range increased the genetic damage index in treatments lasting for both 48 and 96h. This study represents the first evidence of acute lethal and sublethal effects exerted by IMZT on amphibians. Finally, our findings highlight the properties of this herbicide that jeopardize nontarget living species exposed to IMZT.
•Lethality and genotoxicity of imazethapyr were used as endpoints in H. pulchellus.•Imazethapyr-based formulations induced DNA primary lesions in blood cells.•First evidence of genotoxicity exerted by imazethapyr-based formulations on tadpoles.
Acute lethal and sublethal toxicity of the pirimicarb-based commercial formulation Aficida® were evaluated on Boana pulchella tadpoles. Whereas mortality was used as end point for lethality, ...frequency of micronuclei and other nuclear abnormalities as well as alterations in the frequency of erythroblasts in circulating blood as biomarkers for genotoxicity and cytotoxicity, respectively. Swimming, growth, developmental and morphological abnormalities were also employed as sublethal end points. Results show that the species is within the 13th percentile of the distribution of acute sensitivity of species to pirimicarb for aquatic vertebrates. Results revealed values of 23.78 and 101.45mg/L pirimicarb as LC5096h for GS25 and GS36 tadpoles, respectively. The most evident effects were related with the swimming activity with NOEC and LOEC values within the 0.005–0.39mg/L pirimicarb concentration range. Aficida® induced DNA damage at the chromosomal level by increasing micronuclei frequency and other nuclear abnormalities, i.e., lobbed and notched nuclei and binucleated cells. Cellular cytotoxicity was found after Aficida® treatment. The presence of abdominal oedemas in exposed organisms and thus flotation response of organisms could be proposed as a new sensitive exposure parameter. The multiple end point assessment approach used allowed a complete understanding the multi level of effects occurring by exposure to pirimicarb, at least in B. pulchella.
•Pirimicarb-based formulation Aficida® jeopardizes anuran tadpoles.•Acute lethal and sublethal toxicity of Aficida® were evaluated on Boana pulchella.•The LC5096h for GS25 and GS36 tadpoles were 60.95 and 260.02mg/L Aficida®, respectively.•Flotation of organisms is proposed as a new sensitive biomarker.•Aficida® induced DNA damage at the chromosomal level.
Bed-rest experiments are designed for investigation on catabolic effects of hypokinetic conditions and/or for microgravity simulation in on-ground aerospace research. Bed-rest effects include a ...reduction in fat-free mass and muscle mass. Urea and creatinine are catabolites of endogenous protein and of muscular energetic metabolism which are excreted mainly by the kidney. The study investigated on urea, creatinine, and kidney function during bed-rest.
Twenty healthy young men underwent a 7-day adaptation period (day-6 to day-0) and a 35-day bed-rest experiment (day1 to day35) during normocaloric diet. Urine were collected from day-3 to day0 (baseline) and from day1 to day35. Blood samples and anthropometrical data were collected at day0 (baseline) and bed-rest days 7, 14, 21, 28, and 35.
Bed-rest reduced plasma volume, weight, fat-free mass, and muscle mass (P<0.001). During bed-rest there was a transient increase in plasma and urinary urea, a decrease in plasma creatinine, and no change in urinary creatinine. The overall integral of changes from day0 to day35 was on average +101.7 mg/dL for plasma urea (95%CI = +43.4/+159.9), +82.2 g/24 h for urinary urea (95%CI = +55.8/+108.7), -2.5 mg/dL for plasma creatinine (95%CI = -3.1/-1.9). Bed-rest reduced plasma cistatyn C also, which was used as mass-independent marker of glomerular filtration rate (-13.1%, P<0.05). Correlations with final reduction in fat-free mass and muscle mass were significant for the overall integral of changes in urinary urea from day0 to day35 (R = 0.706, P<0.001) and for early changes in urinary urea and plasma urea from day0 to day7 (R = 0.566, P = 0.009 and R = 0.715, P<0.001, respectively).
Study results shows that urea is a marker of catabolic conditions secondary to hypokinetic conditions.
Previous studies reported that some species of the family Ceratophryidae are able to produce sounds during premetamorphic tadpole stages. We have now determined the effects of the ...cholinesterase-inhibiting insecticide chlorpyrifos (CPF) on sounds emitted by tadpoles of Ceratophrys ornata. Tadpoles were exposed individually in order to evaluate the progression of effects. Effects on sound production were complemented with common ecotoxicological endpoints (mortality, behavior, abnormalities and growth inhibition). C. ornata was found to be more sensitive than other native (= 67%, 50%) and non-native species (= 75%, 100%) considering lethal and sublethal endpoints, respectively. Effects on sounds appear along with alterations in swimming, followed by the presence of mild, then severe abnormalities and finally death. Therefore, sound production may be a good biomarker since it anticipates other endpoints that are also affected by CPF. Ceratophrys ornata is a promising new model species in ecotoxicology.
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•First investigation using C. ornata to assess the effects of a pollutant.•Environmentally-relevant concentrations of chlorpyrifos are disrupting key behaviors.•Tadpole sounds may be a good biomarker since it anticipates other endpoints.•The species is more sensitive than other native and most non-native species.
Environmentally-relevant chlorpyrifos concentrations are disrupting key behaviors in C. ornata, including sound emission and locomotion.
In the present study, we assessed for the first time the changes in the antioxidant capacity, total phenolic content, and polyphenolic composition of interspecific hybrid palm oil extracted from ...Elaeis oleifera × Elaeis guineensis (O × G, Coari × La Mé cultivar) during the fruit ripening process 18, 20, 22, and 24 weeks after anthesis. A progressive decrease (p < 0.05) of phenolic content occurred during fruit development together with marked changes in polyphenol profiles. Significant negative correlations were established between antioxidant activity measured by TEAC (R = −0.954; p < 0.05) and ORAC (R = −0.745; p < 0.05) and the fruit ripening stage, while a positive correlation between total phenolic content was found using either the TEAC assay or the ORAC assay. The highest DPPH radical scavenging activity was also obtained with oils extracted at 18 WAA. These results highlight that O × G fruits of early ripeness represent a better source of phenolic compounds and may provide extracts with higher antioxidant activities when hybrid palm oil is aimed to be used as a functional ingredient for the development of food or food products with antioxidant properties.
Understanding the subjective meaning of a visual query, by converting it into numerical parameters that can be extracted and compared by a computer, is the paramount challenge in the field of ...intelligent image retrieval, also referred to as the ¿semantic gap¿ problem. In this paper, an innovative approach is proposed that combines a relevance feedback (RF) approach with an evolutionary stochastic algorithm, called particle swarm optimizer (PSO), as a way to grasp user's semantics through optimized iterative learning. The retrieval uses human interaction to achieve a twofold goal: 1) to guide the swarm particles in the exploration of the solution space towards the cluster of relevant images; 2) to dynamically modify the feature space by appropriately weighting the descriptive features according to the users' perception of relevance. Extensive simulations showed that the proposed technique outperforms traditional deterministic RF approaches of the same class, thanks to its stochastic nature, which allows a better exploration of complex, nonlinear, and highly-dimensional solution spaces.
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