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Climate change presents a serious threat to global biodiversity. Loss of pollinators in particular has major implications, with extirpation of these species potentially leading to severe losses in agriculture and, thus, economic losses. In this study, we forecast the effects of climate change on the distribution of hoverflies in Southeast Europe using species distribution modelling and climate change scenarios for two time-periods. For 2041–2060, 19 analysed species were predicted to increase their areas of occupancy, with the other 25 losing some of their ranges. For 2061–2080, 55% of species were predicted to increase their area of occupancy, while 45% were predicted to experience range decline. In general, range size changes for most species were below 20%, indicating a relatively high resilience of hoverflies to climate change when only environmental variables are considered. Additionally, range-restricted species are not predicted to lose more area proportionally to widespread species. Based on our results, two distributional trends can be established: the predicted gain of species in alpine regions, and future loss of species from lowland areas. Considering that the loss of pollinators from present lowland agricultural areas is predicted and that habitat degradation presents a threat to possible range expansion of hoverflies in the future, developing conservation management strategy for the preservation of these species is crucial. This study represents an important step towards the assessment of the effects of climate changes on hoverflies and can be a valuable asset in creating future conservation plan, thus helping in mitigating potential consequences.  相似文献   
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Cancer genome sequencing has shown that driver genes can often be distinguished not only by the elevated mutation frequency but also by specific nucleotide positions that accumulate changes at a high rate. However, properties associated with a residue's potential to drive tumorigenesis when mutated have not yet been systematically investigated. Here, using a novel methodological approach, we identify and characterize a compendium of 180 hotspot residues within 160 human proteins which occur with a significant frequency and are likely to have functionally relevant impact. We find that such mutations (i) are more prominent in proteins that can exist in the on and off state, (ii) reflect the identity of a tumor of origin, and (iii) often localize within interfaces which mediate interactions with other proteins or ligands. Following, we further examine structural data for human protein complexes and identify a number of additional protein interfaces that accumulate cancer mutations at a high rate. Jointly, these analyses suggest that disruption and dysregulation of protein interactions can be instrumental in switching functions of cancer proteins and activating downstream changes.  相似文献   
114.

Background

Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease.

Methods

Plasma samples of 1128 CLBP patients and 760 healthy controls were collected in clinical centers in Italy, Belgium and Croatia and used for N-glycosylation profiling by hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) after N-glycans release, fluorescent labeling and clean-up. Observed N-glycosylation profiles have been compared with a cohort of 126 patients with acute inflammation that underwent abdominal surgery.

Results

We have found a statistically significant increase in the relative amount of high-branched (tri-antennary and tetra-antennary) N-glycan structures on CLBP patients' plasma glycoproteins compared to healthy controls. Furthermore, relative amounts of disialylated and trisialylated glycan structures were increased, while high-mannose and glycans containing bisecting N-acetylglucosamine decreased in CLBP.

Conclusions

Observed changes in CLBP on the plasma N-glycome level are consistent with N-glycosylation changes usually seen in chronic inflammation.

General significance

To our knowledge, this is a first large clinical study on CLBP patients and plasma N-glycome providing a new glycomics perspective on potential disease pathology.  相似文献   
115.
Kv1.3 is a voltage gated potassium channel that has been implicated in pathophysiology of multiple sclerosis (MS). In the present study we investigated temporal and cellular expression pattern of this channel in the lumbar part of spinal cords of animals with experimental autoimmune encephalomyelitis (EAE), animal model of MS. EAE was actively induced in female Dark Agouti rats. Expression of Kv1.3 was analyzed at different time points of disease progression, at the onset, peak and end of EAE. We here show that Kv1.3 increased by several folds at the peak of EAE at both gene and protein level. Double immunofluorescence analyses demonstrated localization of Kv1.3 on activated microglia, macrophages, and reactive astrocytes around inflammatory lesions. In vitro experiments showed that pharmacological block of Kv1.3 in activated astrocytes suppresses the expression of proinflammatory mediators, suggesting a role of this channel in inflammation. Our results support the hypothesis that Kv1.3 may be a therapeutic target of interest for MS and add astrocytes to the list of cells whose activation would be suppressed by inhibiting Kv1.3 in inflammatory conditions.  相似文献   
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Tetanus toxoid (TTd) is a highly immunogenic, detoxified form of tetanus toxin, a causative agent of tetanus disease, produced by Clostridium tetani. Since tetanus disease cannot be eradicated but is easily prevented by vaccination, the need for the tetanus vaccine is permanent. The aim of this work was to investigate the possibility of optimizing TTd purification, i.e., ammonium sulfate precipitation process. The influence of the percentage of ammonium sulfate, starting amount of TTd, buffer type, pH, temperature, and starting purity of TTd on the purification process were investigated using optimal design for response surface models. Responses measured for evaluation of the ammonium sulfate precipitation process were TTd amount (Lf/mL) and total protein content. These two parameters were used to calculate purity (Lf/mgPN) and the yield of the process. Results indicate that citrate buffer, lower temperature, and lower starting amount of TTd result in higher purities of precipitates. Gel electrophoresis combined with matrix-assisted laser desorption ionization–mass spectrometric analysis of precipitates revealed that there are no inter-protein cross-links and that all contaminating proteins have pIs similar to TTd, so this is most probably the reason for the limited success of purification by precipitation.  相似文献   
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The Cenomanian–Turonian boundary (CTB) in the ?i?arija Mountain region (northern Istria, Croatia) is characterized by calcisphere limestone successions with a firmground and glauconite horizon, bioturbated intervals, tempestites, and slumped structures as well as microbially laminated and organic-rich interbeds deposited in the northwestern part of the intra-Tethyan Adriatic Carbonate Platform (AdCP). Compilation of the results from three studied sections (Vodice–Jelovica, Martinjak and Planik) of litho-, bio-, and microfacies analyses, X-ray diffraction, SEM, EDS, and stable isotope analyses allowed reconstruction of marine paleoenvironmental conditions during this time period. Shallow-marine carbonate deposits of the Milna Formation underlie a drowned-platform succession of the Sveti (Sv.) Duh Formation. The contact between these two formations is sharp and commonly marked by slumped deposits. The Sv. Duh Formation consists of about 100 m of calcisphere wackestone enriched in organic matter. The results of preliminary δ13C and δ18O stable isotope analyses indicate the influence of the global Oceanic Anoxic Event (OAE2) on the deposition of this carbonate succession. Anoxic and hypoxic conditions in the water column lead to major changes in the shallow-marine carbonate system of the AdCP. Numerous benthic foraminifera declined during that time, but planktonic foraminifera and calcareous dinoflagellates diversified and expanded greatly. The results of this research provide new insights into the character of the CTB interval in this part of the Tethyan realm. Local and regional synsedimentary tectonics combined with global upper Cretaceous sea-level dynamics allows the correlation of the investigated deeper-marine lithostratigraphic units with OAE2.  相似文献   
120.
Chronic obstructive pulmonary disease (COPD) is a complex disease influenced by genetic and environmental factors. Cystic fibrosis transmembrane conductance regulator (CFTR) protein is an important component of the lung tissue homeostasis, involved in the regulation of the rate of mucociliary clearance. As it is known that certain CFTR variants have consequences on the function of CFTR protein, the aim of this study was to examine the possible role of F508del, M470V, Tn locus, and R75Q variants in COPD development and modulation. Total number of 86 COPD patients and 102 control subjects were included in the study. Possible association between COPD susceptibility, severity, and onset of the disease and allele or genotype of four analyzed CFTR variants was examined. No associations were detected between COPD development, onset of the disease and tested CFTR alleles and genotypes. However, VV470 genotype was associated with mild/moderate COPD stages in comparison to severe/very severe ones (OR = 0.29, 95%CI = 0.11-0.80, p = 0.016). Our study showed that patients with VV470 genotype had a 3.4-fold decreased risk for the appearance of severe/very severe COPD symptoms, and the obtained results indicate that this genotype may have a protective role. These results also suggest the importance of studying CFTR gene as a modifier of this disease.  相似文献   
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