Miracle-dz/UniFAR-FTUs huggingface dataset:
HSF1 mediated TNF‐α production during proteotoxic stress response pioneers proinflammatory signal in human cells

The proteotoxic stress response that safeguards the cellular proteome from various stressors was shown to activate NF‐κB signaling pathways (NκBS) with an underlying mechanism that is poorly understood. We show here that the TNFα gene, a pleiotropic NκBS inducer, is a direct target of heat shock factor 1 (HSF1). Human HSF1 drives this process by assembling a multiprotein activation complex at a heat shock element (HSE) located at the 3′‐UTR of the TNF‐α gene (HSE5). HSF1 associated with the HSE5 at the TNF‐α 3′‐UTR communicates with the promoter through chromatin looping by recruiting lymphoid enhancer–binding factor 1 at an adjacent Wnt‐responsive element through its transactivation domain. TNF‐α thus produced guides the activation of NκBS by acting through TNF‐α receptor 1 (TNFR1). Notably, cells with TNFR1−/− background or masked HSE5 through Clustered Regularly Interspaced Short Palindromic Repeats/dead CRISPR‐associated protein 9 were defective in NκBS and exhibited marked alteration in cellular biology, which includes loss of ability of cancer cells to migrate, to clear the protein aggregates, and associated toxicity upon heat shock. For the first time, our results suggest that TNF‐α thus produced pioneers the proinflammatory signal during proteotoxic stress response with an important implication for inflammation and cancer. —Ali, A. , Biswas, A. , Pal, M. HSF1 mediated TNF‐α production during proteotoxic stress response pioneers proinflammatory signal in human cells. FASEB J. 33, 2621–2635 (2019). www.fasebj. org
Intranuclear Degradation of Polyglutamine Aggregates by the Ubiquitin-Proteasome System*

Huntington disease and its related autosomal-dominant polyglutamine (pQ) neurodegenerative diseases are characterized by intraneuronal accumulation of protein aggregates. Studies on protein aggregates have revealed the importance of the ubiquitin-proteasome system as the front line of protein quality control (PQC) machinery against aberrant proteins. Recently, we have shown that the autophagy-lysosomal system is also involved in cytoplasmic aggregate degradation, but the nucleus lacked this activity. Consequently, the nucleus relies entirely on the ubiquitin-proteasome system for PQC. According to previous studies, nuclear aggregates possess a higher cellular toxicity than do their cytoplasmic counterparts, however degradation kinetics of nuclear aggregates have been poorly understood. Here we show that nuclear ubiquitin ligases San1p and UHRF-2 each enhance nuclear pQ aggregate degradation and rescued pQ-induced cytotoxicity in cultured cells and primary neurons. Moreover, UHRF-2 is associated with nuclear inclusion bodies in vitro and in vivo. Our data suggest that UHRF-2 is an essential molecule for nuclear pQ degradation as a component of nuclear PQC machinery in mammalian cells.
Tumorigenesis and Neoplastic Progression Alterations in Nucleolar Structure and Gene Expression Programs in Prostatic Neoplasia Are Driven by the MYC Oncogene

From the Departments of Pathology,* Urology, Oncology, Hematology, and Cell Biology, the McKusick-Nathans Institute of Genetic Medicine, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, and The Brady Urological Research Institute, The Johns Hopkins University, School of Medicine, Baltimore, Maryland; the Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and the Siteman Cancer Center and the Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
PHARMCOPIEAL STANDARDS FOR THE FRUITS OF CASSIA FISTULA AND CASSIA PODOCARPA

The pods of Cassia fistula L. and C. podocarpa Guill. et Perr. known for their laxative properties were examined macro- and microscopially. The pods can be distinguished in powder form by the presence of uniseriate trichomes in the C. podocarpa, which are absent in C. fistula. Chemical evaluation showed that both pods contain freee and combined (O- and C- glycosides) anthraquinones, while biological evaluation of the infusions of the pods of the two Cassia species showed that there is a significant differences in the amounts of wet faeces produced, with C. fistula showing a higher activity than C. podocarpa at the same dose levels when compared with Senna (Cassia acutifolia Delile) under the same experimental conditions. The Biological senna Equivalent and Percentage Senna Activity for C. fistula and C. podocarpa are 1.13, 113% and 0.70, 70% respectively at 500mg/kg. Both Cassia species pods can as substitutes for the official senna. Key Words: Cassia fistula, C. podocarpa, Leguminosae-Caesalpinoidiae, anthraquinones laxative Nig. J. Nat Prod. And Med. Vol.4 2000: 23-26
A Case of Exercise-Induced Hematuria Presenting as Gross Hematuria Lasting One Week

Exercise-induced hematuria is a phenomenon occurring in subjects who participate in strenuous exercise. Rapid resolution is an important feature of exercise-induced hematuria. We report here a case of exercise-induced hematuria presenting as gross hematuria lasting 1 week in a 19-year-old male patient. Gross hematuria developed after strenuous exercise about 3 years ago. Three months ago, recurrent gross hematuria was lasting 1 week, regardless of exercise intensity. Compression of the left renal vein between the aorta and superior mesenteric artery, without prominent venous collaterals, was detected by computed tomography. However, no abnormalities were detected by renal venography, arteriography or kidney biopsy. Exercise-induced hematuria occurs with a high incidence, but is self-limiting. In contrast, recurrent and gross hematuria can be associated with bladder carcinoma or vascular abnormality. This should be kept in mind, and urological evaluations such as cystoscopy and angiography are necessary in gross and recurrent hematuria. (Korean J Med 2012;82:95-99)
Cytokine production by leukocytes in patients with periodontitis

In the present study, we investigated the relation between clinical parameters and levels of interleukin (IL) -4 and -5, and tumour necrosis factor-α (TNF-α) in the leukocyte incubation medium (LIM) obtained from 26 patients with chronic periodontitis (P) and 26 control group subjects (C). The levels of cytokines IL-4 and IL -5 produced by the LIM stimulated with non-opsonised E. coli were determined using the Enzyme-Linked Immunosorbent Assay (ELISA) method and the levels of TNF-α were evaluated by applying Enzyme Amplified Sensitivity Immunoassay (EASIA). TNF-α levels in stimulated LIM were strongly positively correlated with clinical parameters such as the pocket probing depths (PPD), the clinical attachment level (CAL), the bleeding on probing (BOP) and oral hygiene index (OHI), whereas the IL-4 and IL-5 levels in the analogous medium were strongly negatively correlated with the clinical parameters. IL-4 and IL-5 levels in stimulated LIM of P group patients were significantly lower, whereas TNF-α levels were significantly higher than that in analogous medium of C group subjects. These differences were associated with the severity of periodontal disease.
Roles of Protein-disulfide Isomerase-mediated Disulfide Bond Formation of Yeast Mnl1p in Endoplasmic Reticulum-associated Degradation

The endoplasmic reticulum (ER) has a strict protein quality control system. Misfolded proteins generated in the ER are degraded by the ER-associated degradation (ERAD). Yeast Mnl1p consists of an N-terminal mannosidase homology domain and a less conserved C-terminal domain and facilitates the ERAD of glycoproteins. We found that Mnl1p is an ER luminal protein with a cleavable signal sequence and stably interacts with a protein-disulfide isomerase (PDI). Analyses of a series of Mnl1p mutants revealed that interactions between the C-terminal domain of Mnl1p and PDI, which include an intermolecular disulfide bond, are essential for subsequent introduction of a disulfide bond into the mannosidase homology domain of Mnl1p by PDI. This disulfide bond is essential for the ERAD activity of Mnl1p and in turn stabilizes the prolonged association of PDI with Mnl1p. Close interdependence between Mnl1p and PDI suggests that these two proteins form a functional unit in the ERAD pathway.
Regulation of the RSP5 Ubiquitin Ligase by an Intrinsic Ubiquitin-binding Site*

Rsp5 is a homologous to E6AP C terminus (HECT) ubiquitin ligase (E3) that controls many different cellular processes in budding yeast. Although Rsp5 targets a number of different substrates for ubiquitination, the mechanisms that regulate Rsp5 activity remain poorly understood. Here we demonstrate that Rsp5 carries a noncovalent ubiquitin-binding site in its catalytic HECT domain. The N-terminal lobe of the HECT domain mediates binding to ubiquitin, and point mutations that disrupt interactions with ubiquitin alter the ability of the Rsp5 HECT domain to assemble polyubiquitin chains in vitro. Point mutations that disrupt ubiquitin binding also result in temperature-sensitive growth defects in yeast, indicating that the Rsp5 ubiquitin-binding site is important for Rsp5 function in vivo. The Nedd4 HECT domain N-lobe also contains ubiquitin-binding activity, suggesting that interactions between the N-lobe and ubiquitin are conserved within the Nedd4 family of ubiquitin ligases. We propose that a subset of HECT E3s are regulated by a conserved ubiquitin-binding site that functions to restrict the length of polyubiquitin chains synthesized by the HECT domain.
Transcriptional Switches: Chemical Approaches to Gene Regulation*

Given the role of transcriptional misregulation in the pathogenesis of human disease, there is enormous interest in the development of molecules that exogenously control transcription in a defined manner. The past decade has seen many exciting advancements in the identification of molecules that mimic or inhibit the interactions between natural transcriptional activators and their binding partners. In this minireview, we focus on four activator·target protein complexes, highlighting recent advances as well as challenges in the field.
Different Production of Interleukin-1a, Interleukin-1ß and Interleukin-8 from Cholesteatomatous and Normal Epithelium

Cholesteatomatous bone destruction is caused by an increase in collagenase activity and activation of the osteoclasts. Cytokines, such as interleukins (IL), are important in intercellular communication in the mechanism of bone destruction. Middle ear cholesteatomas and external auditory canal skins (EACS) can be surgically obtained and cultured. The quantities of IL-1
Estrogen Signaling via Estrogen Receptor β*

Estrogens act by binding to and activating two estrogen receptors (ERs), ERα and ERβ. Transcriptional regulation by ERs is controlled by a complex array of factors such as ER-ligand binding, the DNA sequence bound by ERs, ER-interacting cofactors, and chromatin context. This minireview will provide an overview of the most recent advances in the identification of ERβ-regulated target gene networks and ERβ DNA-binding sites. We also highlight the recent work establishing new roles of ERβ signaling, including protective functions in the epithelial-mesenchymal transition and in atherosclerosis, as well as regulation of cell proliferation in the colon.
Mass Spectrometry Strategies in Metabolomics*

MS has evolved as a critical component in metabolomics, which seeks to answer biological questions through large-scale qualitative and quantitative analyses of the metabolome. MS-based metabolomics techniques offer an excellent combination of sensitivity and selectivity, and they have become an indispensable platform in biology and metabolomics. In this minireview, various MS technologies used in metabolomics are briefly discussed, and future needs are suggested.
Catalytic transfer hydrogenation by a trivalent phosphorus compound: phosphorus-ligand cooperation pathway or P(III) /P(V) redox pathway?

Main-group-element catalysts are a desirable alternative to transition-metal catalysts because of natural abundance and cost. However, the examples are very limited. Catalytic cycles involving a redox process and E-ligand cooperation (E=main-group element), which are often found in catalytic cycles of transition-metal catalysts, have not been reported. Herein theoretical investigations of a catalytic hydrogenation of azobenzene with ammonia-borane using a trivalent phosphorus compound, which was experimentally proposed to occur through P(III) /P(V) redox processes via an unusual pentavalent dihydridophosphorane, were performed. DFT and ONIOM(CCSD(T):MP2) calculations disclosed that this catalytic reaction occurs through a P-O cooperation mechanism, which resembles the metal-ligand cooperation mechanism of transition-metal catalysts.
THE EFFECT OF n-3 LC-PUFA SUPPLEMENTATION ON TENNIS SKILL ACQUISITION IN 10-12 YEAR OLD GIRLS

The purpose of this study was to investigate the effects of 16 weeks of n-3 LC-PUFA (omega 3 longchain polyunsaturated fatty acid) supplementation on tennis skill acquisition in 10-12 year old girls. This research was a single-blind placebo-controlled trial. 29 girls (10-12 years of age) who had never played tennis before took part in the study. Ball Throws to the Target (BTT) and Tennis Ability Test (TAT) were performed three times. Before participants were allocated to the groups and received n-3 LC-PUFA or olive oil, they underwent preparatory training for three weeks. Anthropometric measurements, nutrition analysis, and 1st BTT and TAT tests were performed and they continued the preparatory training until the 3rd week. Then they were randomly allocated to two groups to receive either n-3 LC-PUFA (omega group; 670 mg · day-1; n=16) or olive oil (placebo group; 670 mg · day-1; n=13) during 16 weeks of tennis training which involved 3 hours per week for 19 weeks. The results show that significant improvements in TAT were found in both groups but the omega group had significantly higher scores than the placebo group at the 3rd measurements. Although there were no differences between groups at all measurements of BTT, the omega group showed significant improvement between the 1st and 3rd measurements. This study suggests that daily 670 mg n-3 LC-PUFA supplementation for 16 weeks might improve tennis ability test scores of 10-12 year old girls.
Hair Loss Dysmorphic Disorder – a Frequently Encountered and Often Neglected Disorder

A Note from the Editors DERMATOLOGY + PSYCHOSOMATICS is a journal dedicated to a high scientific standard. Therefore, a review process is a prerequisite for publication of manuscripts. Nevertheless, the editors of the journal feel the need to offer a platform for comments which can be printed without the demand for corrections and adaptation to rather formalistic criteria. To provide the opportunity for the presentation of ‘methodologically unstandardized’ spontaneous observations in clinical practice / of clinical experience or comments concerning previously published articles we maintain the section ‘Letters to the Editors’ to hereby encourage the interaction among psychodermatology researchers and clinical practitioners. We would be pleased to promote a discussion within the context of psychodermatological issues in a broad sense and to contribute to interdisciplinary discussions. Furthermore, the section ‘Letters to the Editors’ can be used to give feedback on articles published in the latest issues of the journal. We are grateful for comments with respect to methodological aspects of the treatises as well as to the results or conclusions drawn by the authors. We hope that the new section will be taken up by interest and will contribute to a lively and interesting discussion. Background: Preoccupation with hair loss and fear of getting bald is a frequent finding among patients referred to dermatological clinics. Objective: Identification of depression and anxieties that may be the underlying psychopathology of a patient with this preoccupation. Patients and Methods: 50 patients with the preoccupation of pathological hair loss who were referred to our clinic within a period of 2 months. The Beck, Taylor and Maudsley inventories were performed on all patients to determine the presence and level of depression, anxiety, obsessive-compulsive disorder (OCD) and obsessive-compulsive personality disorder (OCPD). Results: 45 out of 50 patients, i.e. 90%, were found to have affective disorder such as depression, anxiety, OCD, OCPD or a combination of these. Different levels of depression could be identified in 33 cases, OCD in 32, OCPD in 19, and anxiety in 29 patients. Most patients suffered from more than one psychological disorder: 21 patients suffered from 3, and 14 patients from 2 disorders. 10 patients suffered from only one co-existing disorder: 4 from mild depression, 4 from OCD, and 2 from OCPD. The remaining 5 patients showed no psychological problem according to the inventories used. Conclusion: Many patients with normal looking hair but the preoccupation of losing too much hair and the fear of getting bald may actually suffer from hair loss dysmorphic disorder. These people may have one or more psychopathologies, which should be identified and treated properly.
Tumorigenesis and Neoplastic Progression Ets-1 Activates Overexpression of JunB and CD 30 in Hodgkin ’ s Lymphoma and Anaplastic Large-Cell Lymphoma

From the Department of Hematology,* School of Medicine, Kitasato University, Kanagawa, Japan; the Department of Pathology, School of Medicine, Toho University, Tokyo, Japan; the Department of Dermatology and Skin Surgery and the Roger Williams Medical Center, Boston University School of Medicine, Providence, Rhode Island; and the Laboratory of Tumor Cell Biology, the Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan
The low temperature response pathways for cold acclimation and vernalization are independent.

Vernalization is the promotion of flowering in response to the prolonged cold of winter. To survive sub-zero winter temperatures, plants must first acclimate to low, non-freezing temperatures (cold acclimation). Induction of VERNALIZATION INSENSITIVE 3 (VIN3), the first gene in the vernalization pathway, is initiated within the same time frame as the induction of genes in the cold acclimation pathway raising the question of whether there are common elements in the signal transduction pathways that activate these two responses to cold. We show that none of the signalling components required for cold acclimation, including the 'master regulator'INDUCTION OF CBF EXPRESSION1 (ICE1) or HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 (HOS1), which has been described as a link between cold acclimation and vernalization, play a role in VIN3 induction. We also show that the hormone abscisic acid (ABA) does not modulate VIN3 induction, consistent with earlier reports that ABA signalling plays no role in the vernalization response. The cold acclimation pathway is activated at 12 °C, at which temperature there is no induction of VIN3 expression. Taken together, our data demonstrate that the responses to low temperatures leading to cold acclimation and vernalization are controlled by distinct signalling pathways.
Signaling, Regulation, and Specificity of the Type II p21-activated Kinases*

The p21-activated kinases (PAKs) are a family of six serine/threonine kinases that act as key effectors of RHO family GTPases in mammalian cells. PAKs are subdivided into two groups: type I PAKs (PAK1, PAK2, and PAK3) and type II PAKs (PAK4, PAK5, and PAK6). Although these groups are involved in common signaling pathways, recent work indicates that the two groups have distinct modes of regulation and have both unique and common substrates. Here, we review recent insights into the molecular level details that govern regulation of type II PAK signaling. We also consider mechanisms by which signal transduction is regulated at the level of substrate specificity. Finally, we discuss the implications of these studies for clinical targeting of these kinases.
Coordination of Protein Phosphorylation and Dephosphorylation in Synaptic Plasticity*

A central theme in nervous system function is equilibrium: synaptic strengths wax and wane, neuronal firing rates adjust up and down, and neural circuits balance excitation with inhibition. This push/pull regulatory theme carries through to the molecular level at excitatory synapses, where protein function is controlled through phosphorylation and dephosphorylation by kinases and phosphatases. However, these opposing enzymatic activities are only part of the equation as scaffolding interactions and assembly of multi-protein complexes are further required for efficient, localized synaptic signaling. This review will focus on coordination of postsynaptic serine/threonine kinase and phosphatase signaling by scaffold proteins during synaptic plasticity.
Complex genetics controls natural variation among seed quality phenotypes in a recombinant inbred population of an interspecific cross between Solanum lycopersicum × Solanum pimpinellifolium.

Seed quality in tomato is associated with many complex physiological and genetic traits. While plant processes are frequently controlled by the action of small- to large-effect genes that follow classic Mendelian inheritance, our study suggests that seed quality is primarily quantitative and genetically complex. Using a recombinant inbred line population of Solanum lycopersicum × Solanum pimpinellifolium, we identified quantitative trait loci (QTLs) influencing seed quality phenotypes under non-stress, as well as salt, osmotic, cold, high-temperature and oxidative stress conditions. In total, 42 seed quality traits were analysed and 120 QTLs were identified for germination traits under different conditions. Significant phenotypic correlations were observed between germination traits under optimal conditions, as well as under different stress conditions. In conclusion, one or more QTLs were identified for each trait with some of these QTLs co-locating. Co-location of QTLs for different traits can be an indication that a locus has pleiotropic effects on multiple traits due to a common mechanistic basis. However, several QTLs also dissected seed quality in its separate components, suggesting different physiological mechanisms and signalling pathways for different seed quality attributes.
Increased Production of Tumor Necrosis Factor (cid:97) , and Not of Interferon (cid:103) , Preceding Disease Activity in Patients With Multiple Sclerosis

Objective: To study whether tumor necrosis factor (TNF) (cid:97) or interferon (IFN) (cid:103) production by stimulated white blood cells precedes or accompanies clinical and magnetic resonance imaging signs of disease activity in patients with multiple sclerosis. Design: Prospective study with a follow-up of 9 months. Setting: Patients visiting an outpatient university clinic. Patients: The 30 Amsterdam-based patients (28 com-pleting all evaluations) participating in a multicenter, ran-domized, placebo-controlled, double-blind trial of a chi-meric anti-CD4 antibody in the treatment of active relapsing-remitting and secondary progressive multiple sclerosis. Patients in both treatment arms were included, because for these patients anti-CD4 treatment in this study did not affect TNF- (cid:97) and IFN- (cid:103) production and did not reduce signs of disease activity on magnetic resonance imaging. Main Outcome Measure: Distribution of classes of TNF- (cid:97) and IFN- (cid:103) production (expressed as z scores) in patients with or without clinical or magnetic resonance imaging signs of disease activity. Results: One month preceding exacerbations of multiple sclerosis, there was a shift toward higher z scores of TNF- (cid:97) production ( P (cid:44) . 05), but not of IFN- (cid:103) production. There was no statistically significant relationship between IFN- (cid:103) and TNF- (cid:97) production and magnetic resonance imaging markers of multiple sclerosis activity. Conclusion: The production of TNF- (cid:97)