The diagnosis of Parkinson’s disease (PD) remains primarily a clinical issue, based mainly on phenotypic patterns. The identification of biomarkers capable of permitting the preclinical detection of PD is critically needed. α-Synuclein is a key protein in PD, with missense and multiplication mutations in the gene encoding α-synuclein (SNCA) having been reported in familial cases of PD, and accumulation of the protein identified in Lewy bodies (LBs) and Lewy neurites (LNs) in affected brain regions. With the objective of validating the use of α-synuclein as a clinical or progressive biomarker in an accessible tissue, we used an enzyme-linked immunosorbent assay (ELISA) to measure α-synuclein levels in the peripheral blood plasma of idiopathic PD and LRRK2 mutation carrier patients and compared our findings with healthy control subjects. Compared to healthy controls, we found a significant decrease in plasma total α-synuclein levels in idiopathic PD (iPD) patients (n = 134, p = 0.010). However, the reduction was less significant in patients who were LRRK2 mutation carriers (n = 32, p = 0.133). This lack of significance could be due to the small number of individuals employed in this group. No predictive value of total α-synuclein in the diagnosis of PD was found in a receiver operating characteristic (ROC) curve analysis. Although this is a pilot study requiring corroboration on a larger cohort of patients, our results highlight the possible use of plasma α-synuclein as a biomarker for PD. 相似文献
Hydrological conditions prevailing before, during and after the Messinian salinity crisis in Sicily have been approached using dinoflagellate cyst records. The synthetic sequence considered is based on five classical sections from the Caltanissetta Basin. Our interpretations are based on the recognition of autochthonous, allochthonous and reworked population among the dinocyst assemblages. For the first time, sea-surface temperatures and seasonal salinity contrasts were tentatively reconstructed using a “Mutual Climatic Range Method”. Sicilian late Tortonian deposits correspond to marine environment with significant terrestrial inputs favourable to eutrophic dinocyst species. Immediately after the beginning of the Messinian Stage, euryhaline assemblages took place, followed by meso-hyperhaline taxa, within a general trend to shallowing. At the end of the Tripoli diatomitic Formation, environment appears confined, with regular oceanic inflows. Such marine inflows remain persistent during the deposition of the salt Member, witnessing the probable persistence of nearby normal marine sea-surface water conditions in the Mediterranean Sea but with possible reduced hydrological circulation and/or low nutrient component. Such inflows are slightly decreasing up to the top of the Sicilian Upper Evaporites. At the same time, river inputs appear weak during the salt deposition, as the consequence of a rather dry climatic context. As shown by reworking activity, terrestrial inputs increase progressively from the base of the Upper Evaporites. During the Lago Mare period, while climate remains rather dry (absence of freshwater algae inputs, very low amount in trees requiring humid conditions), local deposition environment is confined with mesohaline to hypohaline sea-surface waters, in a context with relatively high seasonal sea-surface salinity contrast (up to 6‰). The very high reworking observed in the Arenazzolo silts, in addition to slightly increasing water depth, led us to consider the presence of a discontinuity between the Lago Mare and the Arenazzolo Fms. We consider the Arenazzolo Formation as a transgressive facies following a deep downcutting period. The Arenazzolo Formation presents a two-step development. The first one, correlative with the presence of a G. etrusca (a species with Paratethyan affinities), corresponds to a relative high-stand sea-level with oceanic influxes, low seasonal sea-surface salinity contrast and probable more humid context, as revealed by the important freshwater algal inputs. During the second step, salinity becomes much more variable, with a clear increase of seasonal sea-surface salinity contrast, a possible slight mean sea-surface temperature increase (only few degrees) and a clear weakening of the river inputs. Taking the proposed Zanclean position of the Arenazzolo Fm. into consideration, we state that mean sea-surface temperature did not change significantly from the base of the Messinian to the earliest Zanclean. At 5.33 Ma, the suddenly achieved flooding restored a fair, deep oceanic environment characterized, at the beginning, by a clear mean sea-surface temperature cooling (up to 6-7 °C) and a nutrient depletion, associated with the basins starvation. Sea-surface salinities were normal, with very low seasonal contrast. Hydrodynamics then nutrient supply became then quite normal from c.a. 5.08 Ma. The status of the Sicilian Caltanissetta Basin as a marginal basin although fastly deepening and the stratigraphical location of the Messinian discontinuity at the base of the Arenazzolo is the scenario that best matches our dinocyst record. 相似文献
In the desert locust, Schistocerca gregaria (Forskål) (Orthoptera: Acrididae), the threshold density inducing the gregarization phenomenon has never been determined under natural conditions. The influence of environmental factors on this phenomenon has been studied mostly in controlled environments. Based on data collected during several years by the survey teams of the National Center for Locust Control in Mauritania, we analyzed the influence of locust density, vegetation cover, and vegetation status on the probability of observing gregarious locusts. We assumed that a probability to observe gregarious locusts of 0.5 corresponded to the density threshold of gregarization. The results showed in detail the change in the threshold of gregarization according to the cover and status of the vegetation. Low cover and dry vegetation led to a low density threshold of gregarization probably due to high probability of individuals to touch each other. Dense and green vegetation favored a high threshold of gregarization probably due to a dispersion of the individuals and a low probability of individual encounters. These findings should help the management of locusts and decision making during control operations. 相似文献
Label‐free quantitative imaging is highly desirable for studying live cells by extracting pathophysiological information without perturbing cell functions. Here, we demonstrate a novel label‐free multimodal optical imaging system with the capability of providing comprehensive morphological and molecular attributes of live cells. Our morpho‐molecular microscopy (3M) system draws on the combined strength of quantitative phase microscopy (QPM) and Raman microscopy to probe the morphological features and molecular fingerprinting characteristics of each cell under observation. While the commonr‐path geometry of our QPM system allows for highly sensitive phase measurement, the Raman microscopy is equipped with dual excitation wavelengths and utilizes the same detection and dispersion system, making it a distinctive multi‐wavelength system with a small footprint. We demonstrate the applicability of the 3M system by investigating nucleated and nonnucleated cells. This integrated label‐free platform has a promising potential in preclinical research, as well as in clinical diagnosis in the near future. 相似文献
Intermittently submergence and drainage status of paddy fields can cause alterations in morphological and chemical characteristics of soils. We conducted a sequential fractionation study to provide an insight into solubility of Sulfur (S) and Molybdenum (Mo) in flooded alluvial paddy soils. The samples (0–15 and 15–30 cm) were taken from marine and riverine alluvial soils in Kedah and Kelantan areas, respectively, and were sequentially extracted with NaHCO3, NaOH, HCl, and HClO4–HNO3. Total S in upper and lower layers of Kedah and Kelantan ranged between 273 and 1121 mg kg?1, and 177 to 1509 mg kg?1, respectively. In upper layers and subsoil of Kedah, average total Mo were 0.34 and 0.27 mg kg?1, respectively. Average total Mo in Kelantan were 0.25 mg kg?1 (surface layer) and 0.28 mg kg?1 (subsoil). Cation exchange capacity (CEC) was positively correlated with plant available amounts of Mo in upper layers of Kedah area. Also, total and medium-term plant-available S was correlated with total carbon (C) at lower layers of Kelantan soil series. But in surface layers of Kelantan soil series, CEC was strongly correlated with total and medium-term plant-available S. Our results indicates that the influence of flooding conditions on soil S and Mo contents in paddy fields may cause long-term changes in S and Mo chemical reactivities. 相似文献
Tumour cryotherapy has been described as both immunostimulatory and immunoinhibitory in previous studies. However, previous studies have not accurately reproduced the precise conditions of current clinical cryotherapy. The objective of this study is to assess the immunological effects of cryotreated whole tumour cells on dendritic cells (DC) maturation and function using an in vitro model. Prostate cancer cells were cooled using Endocare cryo-system to mimic temperatures achieved during clinical cryotherapy. Human DC were prepared from cluster of differentiation (CD) 14 monocytes and matured with lipopolysaccharide (LPS). Cryotreated cancer cells were added to DC on day 3. On day 7, DC were harvested and phenotyped. Cytokine gene expression was assessed using real time quantitative polymerase chain reaction (RT-PCR). Functional activity of DC was assessed in allogenic mixed lymphocyte reaction (MLR) and the molecular changes using gene microarray technology. There was statistically significant upregulation of costimulatory molecules and maturation markers (CD86, CD83, CD80 and CL II) in DC loaded with cryotreated whole tumour cells compared to both control DC and DC matured with LPS (P < 0.001). There was a significant increase in stimulatory cytokines gene expression (IL-2, IL-12, IL-15, IL-18 and IFN-γ). However, IL-10 and TGF-β expression reduced significantly. The effect of different freezing temperature was equal. cDNA microarray analysis showed upregulation of interleukin 1 (IL-1) and cycline dependent kinase inhibitor 1A (CDKN1A (p21) and downregulation of Caspase 8 and BCL2. Overall, our findings suggest that the effect of cryotherapy is generally stimulatory to DC which may enhance anti-tumour effects. Therefore, the combination of cryotherapy and DC vaccine may represent a novel method to increase the efficacy of cryotherapy especially at the peripheral zones of the prostate where cells are exposed to sub-lethal temperature. 相似文献
Paenibacillus alvei NP75, a Gram-positive bacterium, produces two different antimicrobial peptides, paenibacillin N and P, which has potent antimicrobial activity against many clinical pathogens. The synthesis pattern of these antimicrobial peptides by P. alvei NP75 was studied extensively. The results were outstanding in a way that the paenibacillin N was synthesized irrespective of the growth of bacteria (non-ribosomal mediated), whereas paenibacillin P production was carried out by ribosomal mediated. In addition to the antimicrobial peptides, P. alvei NP75 also produces an immunogenic extracellular protease to defend itself from its own antimicrobial peptide, paenibacillin P. Furthermore, this immunogenic protease production was impaired by the addition of protease inhibitor, phenylmethylsulfonyl fluoride (PMSF). The sodium dodecyl sulfate (SDS) treated strain (mutant) failed to produce paenibacillin P, whereas the production of neither paenibacillin N nor the protease was affected by the plasmid curing. The plasmid curing studies that divulge the genes responsible for the synthesis of paenibacillin N and protease were found to be genome encoded, and paenibacillin P was plasmid encoded. We are reporting, first of its kind, the co-production of two different antimicrobial peptides from P. alvei NP75 through non-ribosomal and ribosomal pathways that could be used as effective antibiotics.