Miracle-dz/UniFAR-FTUs huggingface dataset:
Aggregated and Monomeric α-Synuclein Bind to the S6′ Proteasomal Protein and Inhibit Proteasomal Function*

The accumulation of aggregated α-synuclein is thought to contribute to the pathophysiology of Parkinson's disease, but the mechanism of toxicity is poorly understood. Recent studies suggest that aggregated proteins cause toxicity by inhibiting the ubiquitin-dependent proteasomal system. In the present study, we explore how α-synuclein interacts with the proteasome. The proteasome exists as a 26 S and a 20 S species. The 26 S proteasome is composed of the 19 S cap and the 20 S core. Aggregated α-synuclein strongly inhibited the function of the 26 S proteasome. The IC50 of aggregated α-synuclein for ubiquitin-independent 26 S proteasomal activity was 1 nm. Aggregated α-synuclein also inhibited 26 S ubiquitin-dependent proteasomal activity at a dose of 500 nm. In contrast, the IC50 of aggregated α-synuclein for 20 S proteasomal activity was > 1 μm. This suggests that aggregated α-synuclein selectively interacts with the 19 S cap. Monomeric α-synuclein also inhibited proteasomal activity but with lower affinity and less potency. Recombinant monomeric α-synuclein inhibited the activity of the 20 S proteasomal core with an IC50 > 10 μm, exhibited no inhibition of 26 S ubiquitin-dependent proteasomal activity at doses up to 5 μm, and exhibited only partial inhibition (50%) of the 26 S ubiquitin-independent proteasomal activity at doses up to 10 mm. Binding studies demonstrate that both aggregated and monomeric α-synuclein selectively bind to the proteasomal protein S6′, a subunit of the 19 S cap. These studies suggest that proteasomal inhibition by aggregated α-synuclein could be mediated by interaction with S6′.
Effector memory T cells, early metastasis, and survival in colorectal cancer.

BACKGROUND The role of tumor-infiltrating immune cells in the early metastatic invasion of colorectal cancer is unknown. METHODS We studied pathological signs of early metastatic invasion (venous emboli and lymphatic and perineural invasion) in 959 specimens of resected colorectal cancer. The local immune response within the tumor was studied by flow cytometry (39 tumors), low-density-array real-time polymerase-chain-reaction assay (75 tumors), and tissue microarrays (415 tumors). RESULTS Univariate analysis showed significant differences in disease-free and overall survival according to the presence or absence of histologic signs of early metastatic invasion (P<0.001). Multivariate Cox analysis showed that an early conventional pathological tumor-node-metastasis stage (P<0.001) and the absence of early metastatic invasion (P=0.04) were independently associated with increased survival. As compared with tumors with signs of early metastatic invasion, tumors without such signs had increased infiltrates of immune cells and increased levels of messenger RNA (mRNA) for products of type 1 helper effector T cells (CD8, T-BET [T-box transcription factor 21], interferon regulatory factor 1, interferon-gamma, granulysin, and granzyme B) but not increased levels of inflammatory mediators or immunosuppressive molecules. The two types of tumors had significant differences in the levels of expression of 65 combinations of T-cell markers, and hierarchical clustering showed that markers of T-cell migration, activation, and differentiation were increased in tumors without signs of early metastatic invasion. The latter type of tumors also had increased numbers of CD8+ T cells, ranging from early memory (CD45RO+CCR7-CD28+CD27+) to effector memory (CD45RO+CCR7-CD28-CD27-) T cells. The presence of high levels of infiltrating memory CD45RO+ cells, evaluated immunohistochemically, correlated with the absence of signs of early metastatic invasion, a less advanced pathological stage, and increased survival. CONCLUSIONS Signs of an immune response within colorectal cancers are associated with the absence of pathological evidence of early metastatic invasion and with prolonged survival.
Social Infrastructure as Catalyst for Nation Building Nigeria

The development of any nation’s infrastructure is the catalyst and most singular factor for nation building. Social Infrastructure development is the basis of any society be primitive or modern and it is the foundation of good governance. Infrastructure is the medium, the tools and techniques of a project or programme or strategy that is use in building a viable nation and functional state. Even before the independent, social infrastructure is the unique feature that could be attributed towards nation’s development. These infrastructures made us realized the amalgamation of 1914 as a way of bringing Nigerians together even though it was purely for the British economic gain. The civilian government as contributed in no small ways toward provision of social infrastructural development in Nigeria. The military era in Nigeria was for the most part of the economic boom succeeded in widening the gap in infrastructure demand and provision. Most infrastructures are now decayed and need repair or replacement. Demand for infrastructural development is higher and resources used in provision of infrastructure are limited. As well the challenges are numerous and include finance, technology for development and maintenance. Ethnic-interest agitation and lobbying are common things in democratic governance. A major reason that has been responsible for her socio-economic stagnation is bad leadership and corruption which had mar development since 1960 and deter the purpose of nation building. Therefore, there is an urgent need for rapid improvement in the Nigeria infrastructure to avert impending dangers towards nation building. This paper therefore, examines the social infrastructure as a panacea to build a viable and united Nigeria.
Wound contraction and scar synthesis during development of the amphibian Rana catesbeiana

Certain characteristics of skin wound healing in the North American bullfrog, Rana catesbeiana, were studied grossly and histologically at various stages of development. The contraction kinetics of excisional skin wounds were monitored for 50 days in animals from four larval developmental stages (tadpoles) and from adults (frogs). The percentage of original wound area which remained after contraction had stopped in the four larval groups decreasing steadily from 59.2%± 6.8% for the least developed larvae to 9.9%± 2.3% for the most developed ones. Wounds in adults contracted at a much lower rate than for larvae and the percentage of original wound area remaining after 50 days was less than 10%. The morphologic features characterizing the intact dermis and epidermis outside the wound bed in the larvae were also observed in qualitatively similar detail inside the wound bed. In the adults, the subepidermal connective tissue inside the wound bed was distinctly different from the physiologic dermis outside and was classified as amphibian scar. We conclude that, during larval development, wound contraction increasingly displaced skin regeneration as a mechanism for wound closure. Adults closed skin wounds by a combination of contraction and synthesis of scar tissue. It is hypothesized that the mechanism for synthesis of scar in this amphibian is established during metamorphosis from larva to adult.
Energy compensation after sprint- and high-intensity interval training

Background Many individuals lose less weight than expected in response to exercise interventions when considering the increased energy expenditure of exercise (ExEE). This is due to energy compensation in response to ExEE, which may include increases in energy intake (EI) and decreases in non-exercise physical activity (NEPA). We examined the degree of energy compensation in healthy young men and women in response to interval training. Methods Data were examined from a prior study in which 24 participants (mean age, BMI, & VO2max = 28 yrs, 27.7 kg•m-2, and 32 mL∙kg-1∙min-1) completed either 4 weeks of sprint-interval training or high-intensity interval training. Energy compensation was calculated from changes in body composition (air displacement plethysmography) and exercise energy expenditure was calculated from mean heart rate based on the heart rate-VO2 relationship. Differences between high (≥ 100%) and low (< 100%) levels of energy compensation were assessed. Linear regressions were utilized to determine associations between energy compensation and ΔVO2max, ΔEI, ΔNEPA, and Δresting metabolic rate. Results Very large individual differences in energy compensation were noted. In comparison to individuals with low levels of compensation, individuals with high levels of energy compensation gained fat mass, lost fat-free mass, and had lower change scores for VO2max and NEPA. Linear regression results indicated that lower levels of energy compensation were associated with increases in ΔVO2max (p < 0.001) and ΔNEPA (p < 0.001). Conclusions Considerable variation exists in response to short-term, low dose interval training. In agreement with prior work, increases in ΔVO2max and ΔNEPA were associated with lower energy compensation. Future studies should focus on identifying if a dose-response relationship for energy compensation exists in response to interval training, and what underlying mechanisms and participant traits contribute to the large variation between individuals.
Sex difference in nitric oxide synthase-dependent dilatation of cerebral arterioles during long-term alcohol consumption.

BACKGROUND Although long-term alcohol consumption impairs both endothelial nitric oxide synthase (NOS) (eNOS)-dependent and neuronal NOS (nNOS)-dependent reactivity of cerebral arterioles in male rats, the influence of sex on alcohol consumption-induced impairment of NOS-dependent cerebral vasodilation has not been examined. Therefore, the authors' first goal was to determine whether long-term alcohol consumption alters eNOS-dependent and nNOS-dependent reactivity of pial arterioles in female rats. Their second goal was to examine potential mechanisms for impaired responses of pial arterioles during long-term alcohol consumption. METHODS Male and female rats were fed liquid diets with or without alcohol for 2-3 months. The authors measured the in vivo diameter of pial arterioles in response to eNOS-dependent agonists (acetylcholine and ADP), nNOS-dependent agonists (kainate and NMDA), and NOS-independent agonists (nitroglycerin and diethylaminodiazen (NONOate)) in the absence and presence of tetrahydrobiopterin (BH4). RESULTS Topical application of acetylcholine (1.0 and 10 microM), ADP (10 and 100 microM), kainate (100 and 300 microM), and NMDA (100 and 300 microM) produced dose-related dilatation of pial arterioles. However, the magnitude of vasodilation in response to acetylcholine and ADP was significantly less in alcohol-fed male and female rats, and the magnitude of vasodilation in response to kainate and NMDA was significantly less in alcohol-fed male rats. Nitroglycerin and NONOate produced similar vasodilation in non-alcohol-fed and alcohol-fed male and female rats. Application of BH4 did not alter vasodilation in non-alcohol-fed rats but improved impaired eNOS-dependent vasodilation in alcohol-fed male and female rats. CONCLUSIONS Our findings suggest that long-term alcohol consumption impairs eNOS-dependent but not nNOS-dependent dilatation of cerebral arterioles in female rats and that impaired eNOS-dependent vasodilation may be related to a deficiency or alteration in the utilization of BH4.
The complete mitochondrial genome of the grooved carpet shell, Ruditapes decussatus (Bivalvia, Veneridae)

Despite the large number of animal complete mitochondrial genomes currently available in public databases, knowledge about mitochondrial genomics in invertebrates is uneven. This paper reports, for the first time, the complete mitochondrial genome of the grooved carpet shell, Ruditapes decussatus, also known as the European clam. Ruditapes decussatus is morphologically and ecologically similar to the Manila clam Ruditapes philippinarum, which has been recently introduced for aquaculture in the very same habitats of Ruditapes decussatus, and that is replacing the native species. Currently the production of the European clam is almost insignificant, nonetheless it is considered a high value product, and therefore it is an economically important species, especially in Portugal, Spain and Italy. In this work we: (i) assembled Ruditapes decussatus mitochondrial genome from RNA-Seq data, and validated it by Sanger sequencing; (ii) analyzed and characterized the Ruditapes decussatus mitochondrial genome, comparing its features with those of other venerid bivalves; (iii) assessed mitochondrial sequence polymorphism (SP) and copy number variation (CNV) of tandem repeats across 26 samples. Despite using high-throughput approaches we did not find evidence for the presence of two sex-linked mitochondrial genomes, typical of the doubly uniparental inheritance of mitochondria, a phenomenon known in ∼100 bivalve species. According to our analyses, Ruditapes decussatus is more genetically similar to species of the Genus Paphia than to the congeneric Ruditapes philippinarum, a finding that bolsters the already-proposed need of a taxonomic revision. We also found a quite low genetic variability across the examined samples, with few SPs and little variability of the sequences flanking the control region (Largest Unassigned Regions (LURs). Strikingly, although we found low nucleotide variability along the entire mitochondrial genome, we observed high levels of length polymorphism in the LUR due to CNV of tandem repeats, and even a LUR length heteroplasmy in two samples. It is not clear if the lack of genetic variability in the mitochondrial genome of Ruditapes decussatus is a cause or an effect of the ongoing replacement of Ruditapes decussatus with the invasive Ruditapes philippinarum, and more analyses, especially on nuclear sequences, are required to assess this point.
Characterization of the Drosophila Lipid Droplet Subproteome*S

Lipid storage droplets are universal organelles essential for the cellular and organismal lipometabolism including energy homeostasis. Despite their apparently simple design they are proposed to participate in a growing number of cellular processes, raising the question to what extent the functional multifariousness is reflected by a complex organellar proteome composition. Here we present 248 proteins identified in a subproteome analysis using lipid storage droplets of Drosophila melanogaster fat body tissue. In addition to previously known lipid droplet-associated PAT (Perilipin, ADRP, and TIP47) domain proteins and homologues of several mammalian lipid droplet proteins, this study identified a number of proteins of diverse biological function, including intracellular trafficking supportive of the dynamic and multifaceted character of these organelles. We performed intracellular localization studies on selected newly identified subproteome members both in tissue culture cells and in fat body cells directly. The results suggest that the lipid droplets of fat body cells are of combinatorial protein composition. We propose that subsets of lipid droplets within single cells are characterized by a protein “zip code,” which reflects functional differences or specific metabolic states.
Role of Plasmepsin V in Export of Diverse Protein Families from the Plasmodium falciparum Exportome

Plasmodium falciparum exports several hundred effector proteins that remodel the host erythrocyte and enable parasites to acquire nutrients, sequester in the circulation and evade immune responses. The majority of exported proteins contain the Plasmodium export element (PEXEL; RxLxE/Q/D) in their N‐terminus, which is proteolytically cleaved in the parasite endoplasmic reticulum by Plasmepsin V, and is necessary for export. Several exported proteins lack a PEXEL or contain noncanonical motifs. Here, we assessed whether Plasmepsin V could process the N‐termini of diverse protein families in P. falciparum. We show that Plasmepsin V cleaves N‐terminal sequences from RIFIN, STEVOR and RESA multigene families, the latter of which contain a relaxed PEXEL (RxLxxE). However, Plasmepsin V does not cleave the N‐terminal sequence of the major exported virulence factor erythrocyte membrane protein 1 (PfEMP1) or the PEXEL‐negative exported proteins SBP‐1 or REX‐2. We probed the substrate specificity of Plasmepsin V and determined that lysine at the PEXEL P3 position, which is present in PfEMP1 and other putatively exported proteins, blocks Plasmepsin V activity. Furthermore, isoleucine at position P1 also blocked Plasmepsin V activity. The specificity of Plasmepsin V is therefore exquisitely confined and we have used this novel information to redefine the predicted P. falciparum PEXEL exportome.
Adrenomedullin gene transfer induces neointimal apoptosis and inhibits neointimal hyperplasia in injured rat artery

Arterial wall injury leads to inflammatory reaction and release of growth factors that may mediate intimal regrowth. It is hypothesized that the neointimal cells may originate from adventitial myofibroblasts, medial smooth muscle cells, or differentiated bone marrow derived cells. Adrenomedullin (AM), an auto/paracrine cardiovascular peptide that is secreted from fibroblasts, endothelial cells, and vascular smooth muscle cells, may have a regulatory role in the intimal regeneration. In order to investigate the role of AM in neointimal growth, stimulation of stem cell migration, and apoptosis, we overexpressed AM with recombinant adenovirus in a rat arterial injury model. The intimae were significantly thinner in the arteries treated with AM adenovirus compared to the control group. Intima/media ratios were 0.48 ± 0.18 and 1.01 ± 0.20 (P < 0.05) in the AM group and the control group, respectively. In addition, a significantly higher apoptotic index of neointimal cells was seen in the AM gene transfer group compared to the control (2.78 ± 0.5 vs. 0.57 ± 0.20, P < 0.01). The neointimal cells stained positive for α‐smooth muscle actin and negative for desmin suggesting possible myofibroblast origin. Very few c‐Kit+ or MDR1+ cells were detected 2 weeks after the injury. We conclude that AM overexpression inhibits neointimal growth. The inhibition is associated with enhanced apoptosis of the neointimal cells which may be of myofibroblast origin. Copyright © 2006 John Wiley & Sons, Ltd.
Signal interactions between nitric oxide and reactive oxygen intermediates in the plant hypersensitive disease resistance response

Nitric oxide (NO) and reactive oxygen intermediates (ROIs) play key roles in the activation of disease resistance mechanisms both in animals and plants. In animals NO cooperates with ROIs to kill tumor cells and for macrophage killing of bacteria. Such cytotoxic events occur because unregulated NO levels drive a diffusion-limited reaction with O2− to generate peroxynitrite (ONOO−), a mediator of cellular injury in many biological systems. Here we show that in soybean cells unregulated NO production at the onset of a pathogen-induced hypersensitive response (HR) is not sufficient to activate hypersensitive cell death. The HR is triggered only by balanced production of NO and ROIs. Moreover, hypersensitive cell death is activated after interaction of NO not with O2− but with H2O2 generated from O2− by superoxide dismutase. Increasing the level of O2− reduces NO-mediated toxicity, and ONOO− is not a mediator of hypersensitive cell death. During the HR, superoxide dismutase accelerates O2− dismutation to H2O2 to minimize the loss of NO by reaction with O2− and to trigger hypersensitive cell death through NO/H2O2 cooperation. However, O2− rather than H2O2 is the primary ROI signal for pathogen induction of glutathione S-transferase, and the rates of production and dismutation of O2− generated during the oxidative burst play a crucial role in the modulation and integration of NO/H2O2 signaling in the HR. Thus although plants and animals use a similar repertoire of signals in disease resistance, ROIs and NO are deployed in strikingly different ways to trigger host cell death.
Experimental evaluation of query processing on encrypted Telemedicine data

While Telemedicine technology greatly increases the quality of medical care with less health care costs, it also raises critical challenges for data security and privacy in the course of data entry, data review, patient education, video conference, and electronic monitoring. To meet these various needs, a number of different of security strategies can be utilized. In this study, we aim to secure user-related Telemedicine data by storing and distributing them in an encrypted form, so that on the one hand the requirement on secure medical data management is satisfied, while on the other hand efficient processing, particularly the efficient querying of encrypted medical data can still be guaranteed. Given the increasing use of eXtensible Markup Language (XML) in describing and interchanging data between systems and users, querying over encrypted XML Telemedicine data becomes more and more important. In [3], we develop an effective hash-based approach to enable efficient querying over encrypted XML data. The basic idea is to augment encrypted XML data with encodings which characterize the topology and content of tree-structured XML data, and then filter out candidate XML data for decryption and query execution by examining XPath queries against these encodings. A generic framework is provided which consists of three phases, namely, “query preparation”, “query pre-processing” and “query execution”, for the proposed search strategy. This paper presents a comprehensive experimental evaluation of querying over encrypted XML-formated Telemedicine data.
Free Shiga toxin 1-encoding bacteriophages are less prevalent than Shiga toxin 2 phages in extraintestinal environments.

Stx bacteriophages are involved in the pathogenicity of Stx-producing Escherichia coli. Induction of the Stx phage lytic cycle increases Stx expression and releases Stx phages that reach extracellular environments. Stx phage family comprises different phages that harbour any stx subtype. Stx2 is closely related with severe disease and therefore previous studies focused on free Stx2 phages in extraintestinal environments. To provide similar information regarding Stx1 phages, we evaluate free Stx1 phages in 357 samples of human and animal wastewater, faeces, river water, soil, sludge and food. Our method, based on quantification of stx1 in the DNA from the viral fraction, was validated using electron microscopy counting of phages and infectivity. The overall prevalence of Stx1 phages was very low: 7.6% of positive samples and values below 3 × 10(3) GC (gene copies) ml(-1) . These results contrast starkly with the abundance of Stx2 phages in the samples (68.4%). This environmental scarcity of free Stx1 phages is attributed to their lower rates of induction and the fact that Stx1 does not require phage induction to be expressed because it possesses an independent promoter. The implications of the low prevalence of free Stx1 phages for the emergence of new pathogenic strains in the environment are discussed.
Validation of C-Band Permittivity of Fresh Water using Periodic Jets

This letter presents the results of a free space experiment that validated the Meissner and Wentz model of fresh water permittivity at 13°C in C-Band. The experiment consisted of creating a periodic water jet array inside a focused beam measurement system. The focused beam system measures the radio frequency (RF) response to a finite array of free flowing water jets. The results of the experiment are compared to a one-dimensional Rigorous Coupled-Wave Analysis (RCWA) prediction for infinitely periodic cylinders of water. The consistency between the measured and predicted values appears to validate the permittivity of fresh water at 13°C in C-Band as predicted by the Meissner and Wentz model. This method for measuring and predicting the one-dimensional RCWA solver could be used to characterize properties of other liquids.