Miracle-dz/UniFAR-FTUs huggingface dataset:
Renal fibrosis.

Renal fibrosis causes significant morbidity and mortality as the primary acquired lesion leading to the need for dialysis or kidney transplantation. Fibrosis can occur in either the filtering or reabsorptive component of the nephron, the functional unit of the kidney. Experimental models have identified a number of factors that contribute to renal scarring, particularly derangements of physiology involved in the autoregulation of glomerular filtration. This in turn leads to replacement of normal structures with accumulated extracellular matrix (ECM). A spectrum of changes in the physiology of individual cells leads to the production of numerous peptide and non-peptide fibrogens that stimulate alterations in the balance between ECM synthesis and degradation to favor scarring. Other proteins and small molecules may have anti-fibrotic effects. Manipulation of these opposing systems holds the promise of effective treatments for chronic progressive kidney disease.
Regulatory Network Identification by Genetical Genomics: Signaling Downstream of the Arabidopsis Receptor-Like Kinase ERECTA1[W][OA]

Gene expression differences between individuals within a species can be largely explained by differences in genetic background. The effect of genetic variants (alleles) of genes on expression can be studied in a multifactorial way by the application of genetical genomics or expression quantitative trait locus mapping. In this paper, we present a strategy to construct regulatory networks by the application of genetical genomics in combination with transcript profiling of mutants that are disrupted in single genes. We describe the network identification downstream of the receptor-like kinase ERECTA in Arabidopsis (Arabidopsis thaliana). Extending genetical genomics on the Landsberg erecta/Cape Verde Islands (Ler/Cvi) recombinant inbred population with expression profiling of monogenic mutants enabled the identification of regulatory networks in the so far elusive ERECTA signal transduction cascade. We provide evidence that ERECTA is the causal gene for the major hotspot for transcript regulation in the Arabidopsis Ler/Cvi recombinant inbred population. We further propose additional genetic variation between Ler and Cvi in loci of the signaling pathway downstream of ERECTA and suggest candidate genes underlying these loci. Integration of publicly available microarray expression data of other monogenic mutants allowed us to link ERECTA to a downstream mitogen-activated protein kinase signaling cascade. Our study shows that microarray data of monogenic mutants can be effectively used in combination with genetical genomics data to enhance the identification of genetic regulatory networks.
Cardiovascular risk factors and prevention of cardiovascular disease in patients with chronic renal disease

Importance of the field: Patients with chronic kidney disease (CKD) have an increased prevalence and incidence of cardiovascular events. In predialysis stages as well as in end-stage renal disease (ESRD), mortality in patients with chronic renal failure is most frequently due to cardiovascular disease. Areas covered in the review: This review examines the prevalence and incidence of cardiovascular disease in the different stages of CKD, summarizes risk factors of cardiovascular disease (CVD) in patients with reduced renal function and examines treatment strategies in nontraditional risk factors and lifestyle modifications of importance in patients with CKD. What the reader will gain: The reader will be brought up to date with the relative contribution of traditional and nontraditional risk factors of cardiovascular disease in CKD patients. Take home message: Lifestyle modifications, including weight control, cessation of smoking and dietary salt restriction, are measures that should have a major impact in the cardiovascular morbidity and mortality in patients with CKD. Additional benefit may be gained by treating nontraditional cardiovascular risk factors that are characteristic of chronic renal failure.
Fe(III) Reduction and U(VI) Immobilization by Paenibacillus sp. Strain 300A, Isolated from Hanford 300A Subsurface Sediments

ABSTRACT A facultative iron-reducing [Fe(III)-reducing] Paenibacillus sp. strain was isolated from Hanford 300A subsurface sediment biofilms that was capable of reducing soluble Fe(III) complexes [Fe(III)-nitrilotriacetic acid and Fe(III)-citrate] but unable to reduce poorly crystalline ferrihydrite (Fh). However, Paenibacillus sp. 300A was capable of reducing Fh in the presence of low concentrations (2 μM) of either of the electron transfer mediators (ETMs) flavin mononucleotide (FMN) or anthraquinone-2,6-disulfonate (AQDS). Maximum initial Fh reduction rates were observed at catalytic concentrations (<10 μM) of either FMN or AQDS. Higher FMN concentrations inhibited Fh reduction, while increased AQDS concentrations did not. We also found that Paenibacillus sp. 300A could reduce Fh in the presence of natural ETMs from Hanford 300A subsurface sediments. In the absence of ETMs, Paenibacillus sp. 300A was capable of immobilizing U(VI) through both reduction and adsorption. The relative contributions of adsorption and microbial reduction to U(VI) removal from the aqueous phase were ∼7:3 in PIPES [piperazine-N,N′-bis(2-ethanesulfonic acid)] and ∼1:4 in bicarbonate buffer. Our study demonstrated that Paenibacillus sp. 300A catalyzes Fe(III) reduction and U(VI) immobilization and that these reactions benefit from externally added or naturally existing ETMs in 300A subsurface sediments.
Quantitative specificity‐based display library screening identifies determinants of antibody‐epitope binding specificity

Despite the critical importance of molecular specificity in bimolecular systems, in vitro display technologies have been applied extensively for affinity maturation of peptides and antibodies without explicitly measuring the specificity of the desired interaction. We devised a general strategy to measure, screen, and evolve specificity of protein ligand interactions analogous to widely used affinity maturation strategies. The specificity of binding to target and nontarget antibodies labeled with spectrally distinct fluorophores was measured simultaneously in protein mixtures via multiparameter flow cytometry, thereby enabling screening for high target antibody specificity. Isolated antibody specific ligands exhibited varying specificity, revealing critical amino acid determinants for target recognition and nontarget avoidance in complex mixtures. Molecular specificity in the mixture was further enhanced by quantitative directed evolution, yielding a family of epitopes exhibiting improved specificities equivalent, or superior to, the native peptide antigen to which the antibody was raised. Specificity screening simultaneously favored affinity, yielding ligands with three‐fold improved affinity relative to the parent epitope. Quantitative specificity screening will be useful to screen, evolve, and characterize the specificity of protein and peptide interactions for molecular recognition applications.
The pace of potential output growth in the South African economy

In a flexible inflation-targeting framework the output and inflation gaps are key measures of inflationary pressures and play an important role in determining the optimal policy interest rate. The estimation of potential output is, however, a challenge since it cannot be directly observed. This note explains the methodologies currently used by the South African Reserve Bank to estimate potential output growth and discusses changes to the estimate since the onset of the global financial and economic crisis.
Evidence Supporting a Paracrine Effect of IGF-1/VEGF on Human Mesenchymal Stromal Cell Commitment

Healing of skeletal defects is strictly dependent on osteogenesis and efficient vascularization of engineered scaffolds. Insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) are both involved in these processes. The in vitro administration of IGF-1 in association with VEGF is able to modulate the osteoblastic or endothelial commitment of mesenchymal stromal cells (MSCs) of different origins (e.g. periosteum and skin). In the present study, in order to deepen a possible paracrine effect of IGF-1 and VEGF on periosteum-derived progenitor cells (PDPCs) and skin-derived MSCs (S-MSCs), a Transwell coculture approach was used. We explored the genes involved in endothelial and osteoblastic differentiation, those modulating mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3′-kinase (PI3K)-AKT signaling pathways as well as genes implicated in stemness (i.e. Sox2, Oct4, and Nanog). Periosteal cells, which are typically committed toward osteoblastogenesis, are driven in the direction of endothelial gene expression when influenced by S-MSCs. The latter, once influenced by PDPCs, lose their endothelial commitment and increase the expression of osteoblast-associated genes. PI3K/AKT and MAPK signaling pathways seem to be markedly involved in this behavior. Our results evidence that paracrine signals between MSCs may differently modulate their commitment in a bone microenvironment, opening stimulating viewpoints for skeletal tissue engineering strategies coupling angiogenesis and osteogenesis processes.
Up-regulated expression of WNT5a increases inflammation and oxidative stress via PI3K/AKT/NF-κB signaling in the granulosa cells of PCOS patients.

CONTEXT Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder accompanied by chronic low-grade inflammation, but the molecular mechanism remains unclear. OBJECTIVE We investigated the action of WNT5a in the development of chronic inflammation in PCOS and the related molecular signaling pathways. DESIGN AND SETTING This was a prospective study conducted at the Division of Reproduction Center, Peking University Third Hospital. PATIENTS A total of 35 PCOS patients and 87 control women who reported to the clinic for the in vitro procedure and the cause of marital infertility was male azoospermia were included. MAIN OUTCOME MEASURES Mural granulosa cells (GCs) of 35 PCOS patients and 37 controls were collected during oocyte retrieval and gene expression was analyzed. The human KGN cells and mural GCs from 50 control subjects (six to eight samples were pooled together for each experiment) were cultured in vitro. The regulation of inflammation and oxidative stress was confirmed by quantitative PCR, flow-cytometric assay, and dual-luciferase reporter assay after inflammatory stimuli or WNT5a overexpression. Relevant signaling pathways were identified using specific inhibitors. RESULTS Our data demonstrate significantly elevated WNT5a expression in the mural GCs of PCOS patients compared with the controls. Lipopolysaccharide stimulation increased WNT5a expression in KGN cells and mural GCs, and BAY-117082 and pyrrolidinedithiocarbamic acid [nuclear factor-κB (NF-κB) inhibitor] treatments suppressed WNT5a mRNA below the control level. WNT5a overexpression also enhanced the expression of inflammation-related genes and increased intracellular reactive oxygen species, whereas both BAY-117082 and LY-294002 (phosphatidylinositol 3-kinase inhibitor) significantly inhibited WNT5a-induced inflammation and oxidative stress. CONCLUSIONS WNT5a acts as a proinflammatory factor in human ovarian GCs. The up-regulated expression of WNT5a in PCOS increases inflammation and oxidative stress predominantly via the phosphatidylinositol 3-kinase/AKT/NF-κB signaling pathway. The proinflammatory cytokines induced might further enhance WNT5a expression via NF-κB-dependent regulation, indicating a novel regulatory system for chronic inflammation in PCOS.
Quantitative Phosphoproteomics Reveals Wee1 Kinase as a Therapeutic Target in a Model of Proneural Glioblastoma

Glioblastoma (GBM) is the most common malignant primary brain cancer. With a median survival of about a year, new approaches to treating this disease are necessary. To identify signaling molecules regulating GBM progression in a genetically engineered murine model of proneural GBM, we quantified phosphotyrosine-mediated signaling using mass spectrometry. Oncogenic signals, including phosphorylated ERK MAPK, PI3K, and PDGFR, were found to be increased in the murine tumors relative to brain. Phosphorylation of CDK1 pY15, associated with the G2 arrest checkpoint, was identified as the most differentially phosphorylated site, with a 14-fold increase in phosphorylation in the tumors. To assess the role of this checkpoint as a potential therapeutic target, syngeneic primary cell lines derived from these tumors were treated with MK-1775, an inhibitor of Wee1, the kinase responsible for CDK1 Y15 phosphorylation. MK-1775 treatment led to mitotic catastrophe, as defined by increased DNA damage and cell death by apoptosis. To assess the extensibility of targeting Wee1/CDK1 in GBM, patient-derived xenograft (PDX) cell lines were also treated with MK-1775. Although the response was more heterogeneous, on-target Wee1 inhibition led to decreased CDK1 Y15 phosphorylation and increased DNA damage and apoptosis in each line. These results were also validated in vivo, where single-agent MK-1775 demonstrated an antitumor effect on a flank PDX tumor model, increasing mouse survival by 1.74-fold. This study highlights the ability of unbiased quantitative phosphoproteomics to reveal therapeutic targets in tumor models, and the potential for Wee1 inhibition as a treatment approach in preclinical models of GBM. Mol Cancer Ther; 15(6); 1332–43. ©2016 AACR.
Do microsporidia function as “biological weapon” for Harmonia axyridis under natural conditions?

Invasive alien species, such as the multicoloured Asian ladybird Harmonia axyridis, are often regarded as major drivers of biodiversity loss. Therefore understanding which characteristics or mechanisms contribute to their invasive success is important. Here the role of symbiotic microsporidia in the hemolymph of H. axyridis was investigated in the context of intraguild predation between wild‐caught H. axyridis and the native ladybird species Coccinella septempunctata. The microsporidia were recently discussed to contribute to the unpalatability of Harmonia for other coccinellids during intraguild predation and to function as “biological weapons”. In the present study, visual detection of microsporidia in hemolymph samples revealed that 73.5 % of H. axyridis were infected. Intraguild predation experiments between larvae of the two species showed a significant competitive advantage for H. axyridis, even against larger larvae of C. septempunctata. Adult C. septempunctata always killed and fed on H. axyridis larvae. However only 11.4 % (4 of 47) of C. septempunctata that fed on infected H. axyridis died within 4 months. In contrast to previous studies this suggests that microsporidia or harmonine, the chemical defense compound of H. axyridis, do not lead to death of C. septempunctata preying on larvae of H. axyridis. Instead our results support the idea that competitive advantage during intraguild predation greatly facilitates the success of H. axyridis and that this may help this highly invasive species to outcompete native species. The impact of microsporidia on Harmonia itself as well as on interspecific interactions require further studies.
Introduction The Politics of Participation in Latin America: New Actors and Institutions

A the start of 2019, the struggle for citizenship across Latin America includes a remarkable tally of fragile victories. Social policies and protections have unexpectedly expanded to benefit more individuals than ever before. Governments have granted official recognition and new citizenship rights to previously neglected ethnoracial, gender, sexuality, and employment-based groups. What explains such inclusionary shifts in public policy, and can these tenuous legal advances translate into durable practice? Contemporary scholarship has sought to understand these changes by focusing on the effects of Latin America’s dual transition toward democracy and free market economics in the 1980s and 1990s. Many works have shown how the backlash against neoliberalism led to new class-based and indigenous movements (Arce and Bellinger 2007; Rossi 2015; Silva 2009; Simmons 2016a, b; Yashar 2005), and in some cases to the rise of new party systems (Anria 2018; Cyr 2017; Roberts 2014). Some have even called the early 2000s a “new incorporation” period, pointing to new relationships of mutual support between popular sector movements and political parties (Silva 2017; Silva and Rossi 2018; Wolff 2018). According to these scholars, the expansion in social citizenship stems directly from changes in party systems in Latin America in response to neoliberal reforms. Seeing the recent expansion of social citizenship as dependent on these shifts in the party system, and in particular on the rise of left-wing populists, some scholars recently have questioned the durability of these advances in social citizenship. Following this logic, the end of the commodity boom (Campello 2015), the slip of leftwing populist governments into illiberal democracy or competitive authoritarianism (Anria 2016; Conaghan 2016; Cameron 2018; Levitsky and Way 2010), and the return of right-wing parties to power (Luna and Rovira Kaltwasser 2014) threaten to unravel the political foundations of these policy changes. By focusing primarily on partisan politics and a narrow set of civil society activists, however, conventional political science approaches capture only part of the story behind the recent expansion of social policy and citizenship rights. In many cases, new social rights and policies expanded before the commodity boom and
Production and Purification of Mycolyl Transferase B of Mycobacterium tuberculosis

Background Antigen 85 complex of Mycobacterium tuberculosis includes three immunogenic proteins which are TB vaccine candidates of great importance. As they are very hard to be achieved in natural form, recombinant production of them fuels immunological experiments. Production of such apolar mycobacterial proteins located in the cell wall faces substantial challenges mainly regarding their solubility. This study reports the production of soluble recombinant Ag85B with an efficient yield. Materials and Methods Ag85B gene was cloned in pJET1.2 and subsequently in pET32a (+). Both recombinant plasmids were sequenced. Expression of the recombinant protein was induced with 1mM IPTG. Recombinant Ag85B was purified through dissolving inclusions in 8M urea buffer, absorbing to Ni-NTA resins, washing by buffers with decreasing urea concentrations and finally eluted in imidazole. Western blot analysis was performed using anti-6His tag antibody, rabbit anti- M. tuberculosis polyclonal antibody and serum of hospitalized TB patients. Results Ag85B gene was successfully cloned in both plasmid vectors. The recombinant Ag85B was expressed in E. coli host and purified with significant yield. Conclusion Western blot results along with those of sequencing ensured accurate production of recombinant Ag85B and retaining of its antigenic structure.
Joint video encoding in DVB/ATSC multi-program transmission: MPEG-2 vs. H.264/AVC bitrate control

The main constrains in DVB/ATSC systems are limited bandwidths of available broadcasting channels. Obviously, providers want to broadcast as many video programs as possible with the best possible quality of service. However, the picture quality of encoded video is inversely proportional to the compression factor. In addition, the bandwidth required to broadcast an individual video program with high quality depends on the nature of the contents and it varies in time. A more uniform picture quality and a more efficient utilization of channel capacity are achieved using joint video encoding in multiprogram transmission. The objective of joint rate control is to dynamically distribute the channel capacity among programs according to their respective complexities. More existing approaches are based on MPEG-2 standard. This paper presents a framework which allows the comparison MPEG-2 vs. H.264 standard in joint coding of multiple programs. Operational encoder control and optimized bitrate allocation in standard simulation models are explained in-depth. It is shown experimentally that joint bitrate control can keep almost the user-required picture quality among multiple programs in comparison to an independent encoding.
Context-aware Video Recommendation by Mining Users' View Preferences Based on Access Points

With the astronomical growth of online video population, the video recommendation system is crucial for users to locate videos fitting their interests. The collaborative filtering (CF) realizing personalized recommendation by analyzing users' historical view records is currently the most prevalent algorithm adopted by existing systems. Nevertheless, video recommendation performance can be improved for most cases, particularly the one with cold-start problem, if additional information is involved. In this article, we propose an AP-based Context-Aware (APCA) recommendation scheme on top of the traditional factor-based CF algorithm by utilizing the information of access points which has not been explored yet by existing works. The underlying principle is that users' view preferences are expected to be different with different contexts, e.g., hotel, home, public areas, which can be inferred by mining the information of access points via which users launch video requests. With the data collected from Tencent Video, a leading online video provider in China, we present a measurement study to show user view preferences in different contexts before our APCA algorithm is introduced. Experiments are executed driven by the trace data collected from Tencent Video to validate the effectiveness of our scheme in improving recommendation performance.
Predicting mRNA targets for HSV-1 miRNAs

Herpes simplex virus type 1 (HSV-1) has been reported to implicate in many human diseases. The virulence of HSV-1 and the invoked immunologic responses can be understood by studying the miRNA targets. As a regulatory gene, miRNAs were reported to involve in translational repression and mRNA cleavage. The binding of miRNA to mRNA has a consequence in the gene expression, and thus may influence the protein abundance. In this study, an in silico approach has been adopted to predict HSV-1 miRNA targets. Both seed region and miRNA 3' base pairing have been taken into consideration for the complementarity analysis. Using our methods, 7 pairing sites have been identified for 6 HSV-1 miRNAs. Our work may shed light to the drug design and therapeutic strategies against HSV-1 infection.