Miracle-dz/UniFAR-FTUs huggingface dataset:
Parkin-catalyzed Ubiquitin-Ester Transfer Is Triggered by PINK1-dependent Phosphorylation*

Background: Parkin is a ubiquitin ligase activated by a decrease in the mitochondrial membrane potential (ΔΨm). However, details regarding its mechanism remain limited. Results: PINK1-dependent phosphorylation of Parkin at Ser-65 following dissipation of ΔΨm triggers ubiquitin-ester transfer by the RING2 domain of Parkin to Cys-431. Conclusion: Parkin catalyzes trans- (ubiquitin-thioester)ification upon PINK1-dependent phosphorylation. Significance: The molecular process of Parkin-catalyzed ubiquitylation has been determined. PINK1 and PARKIN are causal genes for autosomal recessive familial Parkinsonism. PINK1 is a mitochondrial Ser/Thr kinase, whereas Parkin functions as an E3 ubiquitin ligase. Under steady-state conditions, Parkin localizes to the cytoplasm where its E3 activity is repressed. A decrease in mitochondrial membrane potential triggers Parkin E3 activity and recruits it to depolarized mitochondria for ubiquitylation of mitochondrial substrates. The molecular basis for how the E3 activity of Parkin is re-established by mitochondrial damage has yet to be determined. Here we provide in vitro biochemical evidence for ubiquitin-thioester formation on Cys-431 of recombinant Parkin. We also report that Parkin forms a ubiquitin-ester following a decrease in mitochondrial membrane potential in cells, and that this event is essential for substrate ubiquitylation. Importantly, the Parkin RING2 domain acts as a transthiolation or acyl-transferring domain rather than an E2-recruiting domain. Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. A phosphorylation-deficient mutation completely inhibited formation of the Parkin ubiquitin-ester intermediate, whereas phosphorylation mimics, such as Ser to Glu substitution, enabled partial formation of the intermediate irrespective of Ser-65 phosphorylation. We propose that PINK1-dependent phosphorylation of Parkin leads to the ubiquitin-ester transfer reaction of the RING2 domain, and that this is an essential step in Parkin activation.
Multi-layer sparse coding model-based ship detection for optical remote-sensing images

ABSTRACT Ship detection plays an important role in remote-sensing image processing. In this article, we propose a multi-layer sparse coding model-based ship detection (MSCMSD) method, integrating bottom-up and top-down mechanisms, for ship detection with high-resolution remote-sensing images. The multi-layer sparse coding model was designed to reveal the way how information is processed by human visual system. It is adopted in MSCMSD to detect candidate regions containing ships before any further processing. To detect ships from candidate regions, an omnidirectional solution is also proposed for deformable parts model-based ship detection. As demonstrated in the experiments, MSCMSD can detect ships from optical remote-sensing images with a higher accuracy than other state-of-the-art algorithms.
Short-Term Calorie Restriction in Male Mice Feminizes Gene Expression and Alters Key Regulators of Conserved Aging Regulatory Pathways

Background Calorie restriction (CR) is the only intervention known to extend lifespan in a wide range of organisms, including mammals. However, the mechanisms by which it regulates mammalian aging remain largely unknown, and the involvement of the TOR and sirtuin pathways (which regulate aging in simpler organisms) remain controversial. Additionally, females of most mammals appear to live longer than males within species; and, although it remains unclear whether this holds true for mice, the relationship between sex-biased and CR-induced gene expression remains largely unexplored. Methodology/Principal Findings We generated microarray gene expression data from livers of male mice fed high calorie or CR diets, and we find that CR significantly changes the expression of over 3,000 genes, many between 10- and 50-fold. We compare our data to the GenAge database of known aging-related genes and to prior microarray expression data of genes expressed differently between male and female mice. CR generally feminizes gene expression and many of the most significantly changed individual genes are involved in aging, hormone signaling, and p53-associated regulation of the cell cycle and apoptosis. Among the genes showing the largest and most statistically significant CR-induced expression differences are Ddit4, a key regulator of the TOR pathway, and Nnmt, a regulator of lifespan linked to the sirtuin pathway. Using western analysis we confirmed post-translational inhibition of the TOR pathway. Conclusions Our data show that CR induces widespread gene expression changes and acts through highly evolutionarily conserved pathways, from microorganisms to mammals, and that its life-extension effects might arise partly from a shift toward a gene expression profile more typical of females.
Sodium Butyrate Stimulates Expression of Fibroblast Growth Factor 21 in Liver by Inhibition of Histone Deacetylase 3

Fibroblast growth factor 21 (FGF21) stimulates fatty acid oxidation and ketone body production in animals. In this study, we investigated the role of FGF21 in the metabolic activity of sodium butyrate, a dietary histone deacetylase (HDAC) inhibitor. FGF21 expression was examined in serum and liver after injection of sodium butyrate into dietary obese C57BL/6J mice. The role of FGF21 was determined using antibody neutralization or knockout mice. FGF21 transcription was investigated in liver and HepG2 hepatocytes. Trichostatin A (TSA) was used in the control as an HDAC inhibitor. Butyrate was compared with bezafibrate and fenofibrate in the induction of FGF21 expression. Butyrate induced FGF21 in the serum, enhanced fatty acid oxidation in mice, and stimulated ketone body production in liver. The butyrate activity was significantly reduced by the FGF21 antibody or gene knockout. Butyrate induced FGF21 gene expression in liver and hepatocytes by inhibiting HDAC3, which suppresses peroxisome proliferator–activated receptor-α function. Butyrate enhanced bezafibrate activity in the induction of FGF21. TSA exhibited a similar set of activities to butyrate. FGF21 mediates the butyrate activity to increase fatty acid use and ketogenesis. Butyrate induces FGF21 transcription by inhibition of HDAC3.
Human thymic epithelial cells express an endogenous lectin, galectin-1, which binds to core 2 O-glycans on thymocytes and T lymphoblastoid cells

Thymic epithelial cells play a crucial role in the selection of developing thymocytes. Thymocyte-epithelial cell interactions involve a number of adhesion molecules, including members of the integrin and immunoglobulin superfamilies. We found that human thymic epithelial cells synthesize an endogenous lectin, galectin-1, which binds to oligosaccharide ligands on the surface of thymocytes and T lymphoblastoid cells. Binding of T lymphoblastoid cells to thymic epithelial cells was inhibited by antibody to galectin-1 on the epithelial cells, and by two antibodies, T305 and 2B11, that recognize carbohydrate epitopes on the T cell surface glycoproteins CD43 and CD45, respectively. T lymphoblastoid cells and thymocytes bound recombinant galectin-1, as demonstrated by flow cytometric analysis, and lectin binding was completely inhibited in the presence of lactose. The degree of galectin-1 binding to thymocytes correlated with the maturation stage of the cells, as immature thymocytes bound more galectin-1 than did mature thymocytes. Preferential binding of galectin- 1 to immature thymocytes may result from regulated expression of preferred oligosaccharide ligands on those cells, since we found that the epitope recognized by the T305 antibody, the core 2 O-glycan structure on CD43, was expressed on cortical, but not medullary cells. The level of expression of the UDP-GlcNAc:Gal beta 1,3GalNAc-R beta 1, 6GlcNAc transferase (core 2 beta 1, 6 GlcNAc transferase, or C2GnT), which creates the core 2 O-glycan structure, correlated with the glycosylation change between cortical and medullary cells. Expression of mRNA encoding the C2GnT was high in subcapsular and cortical thymocytes and low in medullary thymocytes, as demonstrated by in situ hybridization. These results suggest that galectin-1 participates in thymocyte-thymic epithelial cell interactions, and that this interaction may be regulated by expression of relevant oligosaccharide ligands on the thymocyte cell surface.
Oxidative stress responses in the aquatic macrophyte, Ceratophyllum demersum L., as biomarkers of metal exposure

iii ACKNOWLEDGEMENTS . vi DEDICATION . vii TABLE OF CONTENTS . xi LIST OF FIGURES . xviii LIST OF TABLES . xxii GLOSSARY . xxiv LIST OF TERMS AND CONCEPTS . xxvii Chapter 1 . 1 GENERAL INTRODUCTION . 1 1.1. Pollution in aquatic ecosystems . 1 1.2. Metal pollution in aquatic ecosystems and aquatic plants . 2 1.1.3. Plants as biomonitors of metal pollution . 4 1.3. 1. Macrophytes as biomonitors in freshwater ecosystems . 5 1.4. Phytoremediation . 6 1.5. Biomarkers . 7 1.6. Metal-induced oxidative stress in plants . 8 1.7. Oxidative stress biomarkers . 10
Aeromonas salmonicida‐secreted protein AopP is a potent inducer of apoptosis in a mammalian and a Drosophila model

Some pathogens are able to establish themselves within the host because they have evolved mechanisms to disrupt host innate immunity. For example, a number of pathogens secrete preformed effector proteins via type III secretion apparatuses that influence innate immune or apoptotic signalling pathways. One group of effector proteins that usurp innate immune signalling is the YopJ‐like family of bacterial effector proteins, which includes AopP from Aeromonas salmonicida. Aeromonas species are known to cause gastrointestinal disease in humans, and are associated mainly with subcutaneous wound infections and septicaemia in other metazoans, particularly fish. AopP has been reported to have inhibitory activity against the NF‐κB pathway in cultured cells, although the pathological outcomes of AopP activity have not been examined. Here, we show that AopP has potent pro‐apoptotic activity when expressed in cultured mammalian macrophage or epithelial cells, or when ectopically expressed in Drosophila melanogaster haemocytes or imaginal disk epithelial cells. Furthermore, apoptosis was significantly elevated upon concurrent AopP expression and TNF‐α cellular stimulation. Together, our results demonstrate how the specificity of a YopJ‐like protein towards signalling pathways directly governs cellular pathological outcome in disease.
A Single-Boundary Implicit and FFT-Accelerated Time-Domain Finite Element-Boundary Integral Solver

A novel time-domain finite-element boundary integral (FE-BI) solver for analyzing broadband scattering and radiation from free-standing electromagnetically large and perfect electrically conducting platforms supporting inhomogeneous and geometrically intricate structures is presented. The solver has three distinctive features that render it especially attractive for broadband analysis of installed antennas. i) The FE and BI solver components are hybridized using a single-surface interface. ii) The hybrid equations are solved by an implicit time-marching scheme accelerated by an (outer) Jacobi iterative solver that leverages (inner) direct FE and iterative BI solvers. iii) The BI solver component is accelerated by a distributed memory parallel implementation of the time-domain adaptive integral method based on the message-passing interface. The accuracy, late-time stability, and performance of the proposed time-domain FE-BI solver are demonstrated via its application to various scattering and radiation problems; moreover, the solver is used to characterize conformally mounted antennas on several platforms including an aircraft
Chromatin immunoprecipitation-sequencing predicts p300 binding sites in the MCF7 human breast cancer cell line

After the publication of the article, the authors noted that the name of the first author had been spelt incorrectly. The name of the first author should be correctly written as XIUMEI WANG and not as XIEMEI WANG. This had occurred due to a typing error on behalf of the authors upon submission. [the original article was published in the International Journal of Molecular Medicine 35: 973-978, 2015; DOI: 10.3892/ijmm.2015. 2081].
Short- and Long-Term Spatial Delayed Response Performance Across the Lifespan

Delayed response paradigms have been used to examine the neural basis of short and long-term memory in humans. However, limited information exists on how delayed response performance changes across the lifespan. Using a well-validated spatial delayed response (SDR) task, we examined performance at short and long delays in over 300 control participants, 7 to 80 years old. We found a significant nonlinear relation between age and short delay performance (children and older adults worse than young adults) and a significant effect of delay length across the entire lifespan (long worse than short; largest in the youngest children, diminishing nonlinearly with age). This study compares short and long-term spatial memory and suggests that the relation between these systems may alter across the lifespan.
Breast Cancer Genes PSMC3IP and EPSTI1 Play a Role in Apoptosis Regulation

A key element to delineate the biology of individual tumors is the regulation of apoptosis. In this work, we functionally characterize two breast cancer associated genes, the proteasome 26S subunit ATPase 3 interacting protein (PSMC3IP) and the epithelial-stromal interaction 1 (EPSTI1), to explore their potential apoptotic role in breast cancer. We first explore the existence of direct physical interactions with annotated BC-apoptotic genes. Based on the generated interaction network, we examine several apoptotic markers to determine the effect of PSMC3IP and EPSTI1 gene expression modulation in two different human breast cancer cell lines to suggest potential molecular mechanisms to unveil their role in the disease. Our results show that PSMC3IP and EPSTI1 are able to modulate the extrinsic apoptotic pathway in estrogen receptor positive and triple negative breast cancer cell lines, highlighting them as potential therapeutic targets.
The abundance of 36S in IRC+10216 and its production in the Galaxy

The $J=2{-}1$ and $3{-}2$ rotational lines of the rare isotopomer C 36 S and the $J=5{-}4$ and $6{-}5$ transitions of Si 36 S were detected in the carbon star IRC+10216 (CW Leo). These are the first detections of 36 S-bearing molecules in a star and the first spectroscopic detection of Si 36 S. From a comparison of 34 S- and 36 S-bearing isotopomers, the 34 S/ 36 S isotopic ratio is 107($\pm 15$). This value is comparable to values in the interstellar medium of the inner Galactic disk (115) but is smaller than the solar value of 288 (Ding et al. [CITE]). The increase of the 36 S abundance relative to 34 S only qualitatively follows model predictions of a low mass AGB star. Quantitative agreement of the observed 34 S/ 36 S ratio with the stellar models can be reached if the age of IRC+10216 and Galactic chemical evolution are taken into account. Other less likely possibilities are the presence of considerable inhomogeneities in the interstellar medium and either IRC+10216 or the Sun started with a peculiar 36 S abundance. Other production mechanisms potentially capable of enhancing the Galactic interstellar medium are discussed. From the observed line density toward IRC+10216 and toward Galactic star forming regions, we estimate the confusion limit toward those sources.
Double relativistic electron-accelerating mirror

A numerical simulation of the interaction of a laser pulse with ultrathin targets has revealed a possibility of generating thin dense relativistic electron layers. The maximum kinetic energy of the electron mirror can be gained using an optimal combination of the target thickness and the laser pulse intensity and duration. It is proposed to use an additional (second) laser target, located at an optimal distance from the first target to cut off the laser pulse from the electron layer when the latter gains a maximum kinetic energy. This relativistic electron mirror can be used for efficient generation of ‘hard’ coherent radiation via counter reflection of an additional (probe) laser pulse from the mirror.
Joint Linear Filter Design in Multi-User Non-Regenerative MIMO-Relay Systems

This paper addresses the filter-design issues for multi-user non-regenerative MIMO-relay systems. Based on the perfect channel state information (CSI), optimal joint linear filter schemes at the base station and the relay are derived, aiming to minimize the mean squared error (MSE). We first propose the joint optimal filter scheme in the downlink scenario along with a more practical suboptimal scheme, and then a closed-form optimal solution in the uplink scenario is exploited. Numerical results show that the proposed joint schemes can reduce the bit error rate (BER) significantly, especially for the high SNR case.
Water planning using an expert GIS

The development of an expert geographic information system (expert GIS) for long-term regional water resources planning is discussed. The system is comprised of an expert system to capture the expertise and technical considerations of water planning experts, and a geographic information system to store and analyze spatially distributed data for a region under study. The feasibility of this type of planning approach is being investigated using a case study of the capacity expansion of an existing water supply system with several water supply sources and demand centers. Water demand forecasts and supply data are used along with appropriate analysis routines, in the expert GIS which is being designed to follow the logic of current planning methods. Results are presented of applying the expert GIS to a simple example analyzing the existing water supply system for the San Antonio-Nueces and Nueces-Rio Grande Coastal basins. Given annual yields for water supply reservoirs, demand forecasts and institutional requirements, the expert GIS system calculates potential water supply deficits over a fifty year planning horizon and suggests cost effective alternatives for additional water supply development.
Genomic Approach to Identification of Mycobacterium bovis Diagnostic Antigens in Cattle

ABSTRACT Differential delayed-type hypersensitivity skin testing with tuberculin purified protein derivatives from Mycobacterium bovis and M. avium is the standard for diagnosing bovine tuberculosis. However, improved tests based on defined, specific antigens are urgently needed. In the present study, a combination of bioinformatics, molecular biology, and bovine models of infection were used to screen mycobacterial proteins for their potential as diagnostic reagents which could be used in a whole-blood assay for diagnosis of tuberculosis. Initial screening of 28 proteins selected in silico and expressed as recombinants in Escherichia coli indicated that CFP-10, ESAT-6, TB27.4, TB16.2, TB15.8, and TB10.4 induced strong gamma interferon responses in experimentally infected cattle. A more thorough investigation over time in two groups of animals infected with a high (106 CFU) and a low (104 CFU) dose of M. bovis revealed that, for both groups, the strength of the in vitro response to individual antigens varied greatly over time. However, combining the results for ESAT-6, CFP-10, and TB27.4, possibly supplemented with TB10.4, gave sensitivities at different infection stages close to those obtained with M. bovis purified protein derivative. Importantly, while responsiveness to ESAT-6 and CFP-10 correlated strongly for individual samples, the same was not the case for ESAT-6 and TB27.4 responsiveness. The results suggest that combinations of specific antigens such as these have great potential in development of optimized diagnostic systems for bovine tuberculosis.
Polymorphisms Associated with Age at Onset in Patients with Moderate-to-Severe Plaque Psoriasis

Psoriasis is a chronic skin disease in which genetics play a major role. Although many genome-wide association studies have been performed in psoriasis, knowledge of the age at onset remains limited. Therefore, we analyzed 173 single-nucleotide polymorphisms in genes associated with psoriasis and other autoimmune diseases in patients with moderate-to-severe plaque psoriasis type I (early-onset, <40 years) or type II (late-onset, ≥40 years) and healthy controls. Moreover, we performed a comparison between patients with type I psoriasis and patients with type II psoriasis. Our comparison of a stratified population with type I psoriasis (n = 155) and healthy controls (N = 197) is the first to reveal a relationship between the CLMN, FBXL19, CCL4L, C17orf51, TYK2, IL13, SLC22A4, CDKAL1, and HLA-B/MICA genes. When we compared type I psoriasis with type II psoriasis (N = 36), we found a significant association between age at onset and the genes PSORS6, TNF-α, FCGR2A, TNFR1, CD226, HLA-C, TNFAIP3, and CCHCR1. Moreover, we replicated the association between rs12191877 (HLA-C) and type I psoriasis and between type I and type II psoriasis. Our findings highlight the role of genetics in age of onset of psoriasis.
The Tubulin Code

Microtubules create diverse arrays with specific cellular functions such as the mitotic spindle, cilia, and bundles inside neurons. How microtubules are regulated to enable specific functions is not well understood. Recent work has shown that posttranslational modifications of the tubulin building blocks mark subpopulations of microtubules and regulate downstream microtubule-based functions. In this way, the tubulin modifications generate a “code” that can be read by microtubule-associated proteins in a manner analogous to how the histone code directs diverse chromatin functions. Here we review recent progress in understanding how the tubulin code is generated, maintained, and read by microtubule effectors.