Miracle-dz/UniFAR-FTUs huggingface dataset:
Side chain dynamics in unfolded protein states: an NMR based 2H spin relaxation study of delta131delta.

NMR relaxation data on disordered proteins can provide insight into both structural and dynamic properties of these molecules. Because of chemical shift degeneracy in correlation spectra, detailed site-specific analyses of side chain dynamics have not been possible. Here, we present new experiments for the measurement of side chain dynamics in methyl-containing residues in unfolded protein states. The pulse schemes are similar to recently proposed methods for measuring deuterium spin relaxation rates in (13)CH(2)D methyl groups in folded proteins. (1) However, because resolution in (1)H-(13)C correlation maps of unfolded proteins is limiting, relaxation data are recorded as a series of (1)H-(15)N spectra. The methodology is illustrated with an application to the study of side chain dynamics in delta131delta, a large disordered fragment of staphylococcal nuclease containing residues 1-3 and 13-140 of the wide-type protein. A good correlation between the order parameters of the symmetry axes of the methyl groups and the backbone (1)H-(15)N bond vectors of the same residue is observed. Simulations establish that such a correlation is only possible if the unfolded state is comprised of an ensemble of structures which are not equiprobable. A motional model, which combines wobbling-in-a-cone and Gaussian axial fluctuations, is proposed to estimate chi(1) torsion angle fluctuations, sigma(chi)()1, of Val and Thr residues on the basis of the backbone and side chain order parameters. Values of sigma(chi)()1 are approximately 10 degrees larger than what has previously been observed in folded proteins. Of interest, the value of sigma(chi)()1 for Val 104 is considerably smaller than for other Val or Thr residues, suggesting that it may be part of a hydrophobic cluster. Notably large (15)N transverse relaxation rates are observed in this region. To our knowledge, this is the first time that side chain dynamics in an unfolded state have been studied in detail by NMR.
Genetic sensitivity to thiamine deficiency and development of alcoholic organic brain disease.

HE RELATIVE CONTRIBUTIONS of ethanol neuT rotoxicity and thiamine deficiency in development of alcoholic organic brain disease remain controversial. It is well established that thiamine deficiency can cause a life-threatening neuropsychiatric syndrome called Wernicke’s encephalopathy in the alcoholic ~ a t i e n t . ~ In animal models, it has been demonstrated that thiamine deficiency is accompanied by diverse changes in intermediary metabolism, including decreased lipid incorporation into myelin, marked alterations in the biosynthesis and turnover of several putative neurotransmitters, and focal regions of metabolic acidosis in the brain, all of which may modify the neurotoxic effects of e t h a n ~ l . ~ . ~ Treatment with thiamine rapidly reverses most of the acute manifestations of thiamine deficiency, or Wernicke’s encephalopathy, but may leave significant clinical sequelae (deficits in learning and memory, problem-solving behavior, and perceptual/ motor functions, and personality changes) called KorsakOBS psychosis (KP) with characteristic neuropathologic finding^. '. ^ In autopsy studies, those alcoholics with neuropathologically confirmed Wernicke-Korsakoff (W-K) syndrome consistently demonstrated more severe brain morphometric abnormalities (i.e., reductions in brain and cerebellar weights and volume of white matter) than alcoholics without such brain histopathologic evidence of significant previous thiamine defi~iency. ~ The fact that there may be a genetic predisposition to development of brain damage associated with chronic alcoholism is suggested by the following: ( 1 ) only a subset of chronic alcoholics (approximately 13%) show the autopsy findings of W-K syndrome’ and (2) the concordance rate for alcoholic organic brain disease is greater for monozygotic than dizygotic twins. ’ Although the genetic mechanism(s) underlying alcoholic organic brain disease remain to be determined, it has been hypothesized’ that a heritable
An anatomical assessment of branch abscission and branch-base hydraulic architecture in the endangered Wollemia nobilis.

BACKGROUND AND AIMS The branch-base xylem structure of the endangered Wollemia nobilis was anatomically investigated. Wollemia nobilis is probably the only extant tree species that produces only first-order branches and where all branches are cleanly abscised. An investigation was carried out to see if these unusual features might influence branch-base xylem structure and water supply to the foliage. METHODS The xylem was sectioned at various distances along the branch bases of 6-year-old saplings. Huber values and relative theoretical hydraulic conductivities were calculated for various regions of the branch base. KEY RESULTS The most proximal branch base featured a pronounced xylem constriction. The constriction had only 14-31 % (average 21 %) of the cross-sectional area and 20-42 % (average 28 %) of the theoretical hydraulic conductivity of the more distal branch xylem. Wollemia nobilis had extremely low Huber values for a conifer. CONCLUSIONS The branch-base xylem constriction would appear to facilitate branch abscission, while the associated Huber values show that W. nobilis supplies a relatively large leaf area through a relatively small diameter 'pipe'. It is tempting to suggest that the pronounced decline of W. nobilis in the Tertiary is related to its unusual branch-base structure but physiological studies of whole plant conductance are still needed.
Reduction of resting K+ current by metabotropic glutamate and muscarinic receptors in rat CA3 cells: mediation by G‐proteins.

1. Effects of 1S,3R‐1‐aminocyclopentane‐1,3‐dicarboxylate (1S,3R‐ACPD) acting at metabotropic glutamate receptors (mGluRs), and methacholine (MCh), acting at cholinergic muscarinic receptors, were investigated in CA3 neurones in hippocampal slice cultures using the patch‐clamp technique. 2. Both 1S,3R‐ACPD (10 microM) and MCh (0.5 microM) activated an inward current associated with a decrease in membrane conductance. The current was observed when the slow calcium‐dependent after‐hyperpolarizing current (IAHP) and the voltage‐dependent current (IM) were not activated, reversed close to the reversal potential for K+ (EK) (Erev = ‐92.8 +/‐ 10.7 and ‐89.2 +/‐ 8.6 mV for 1S,3R‐ACPD and MCh, respectively), varied linearly with membrane potential, and thus corresponds to a leak K+ current. 3. The decrease in K+ conductance elicited with 1S,3R‐ACPD (50 microM) was substantially reduced (> 70%) with bath application of (RS)‐alpha‐methyl‐4‐carboxyphenylglycine (MCPG, 1 mM), a selective mGluR antagonist and was not mimicked by the enantiomer 1R,3S‐ACPD (100 microM). 4. The effects of 1S,3R‐ACPD and MCh were mediated by activation of G‐proteins since no inward current could be elicited in GDP beta S‐loaded cells (500 microM). When cells were dialysed with GTP (100 microM) or GTP gamma S (250 microM), however, the amplitude of the current was significantly enhanced. 5. These findings provide evidence that G‐proteins couple the activation of mGluRs and muscarinic receptors to a decrease in leak K+ conductance.
The role of TGF‐β1 during skeletal muscle regeneration

The injury of adult skeletal muscle initiates series of well‐coordinated events that lead to the efficient repair of the damaged tissue. Any disturbances during muscle myolysis or reconstruction may result in the unsuccessful regeneration, characterised by strong inflammatory response and formation of connective tissue, that is, fibrosis. The switch between proper regeneration of skeletal muscle and development of fibrosis is controlled by various factors. Amongst them are those belonging to the transforming growth factor β family. One of the TGF‐β family members is TGF‐β1, a multifunctional cytokine involved in the regulation of muscle repair via satellite cells activation, connective tissue formation, as well as regulation of the immune response intensity. Here, we present the role of TGF‐β1 in myogenic differentiation and muscle repair. The understanding of the mechanisms controlling these processes can contribute to the better understanding of skeletal muscle atrophy and diseases which consequence is fibrosis disrupting muscle function.
A Distributed Virtual Environment for Collaborative Engineering

This article details research to develop a distributed collaborative engineering environment (DCEE) system that will allow members of a geographically dispersed multidisciplinary team to collaborate during product development. This article addresses the problems of integrating the information that is generated during product development (product data) with a distributed virtual environment, and the problems of supporting multidisciplinary teams in the development process. The DCEE is an enhanced distributed virtual environment with a rich set of engineering applications and information as it provides an architecture and engineering tools that allow the direct sharing of standard product data among the users with immediate propagation of any changes. Each user has a local environment that can be configured with the tools and data that each specialist requires in the product development lifecycle. An implementation of the architecture has been built to demonstrate this approach, and its performance has also been evaluated.
Comparison of DES vs DES + chlorambucil in women with first recurrence of breast cancer

Thirty‐four women with first recurrence of breast cancer were randomized into two groups, and received either Diethystilbesterol (DES) 5 mg orally (PO) t.i. d. alone, or in combination with Chlorambucil (CB) 0.1–0.2 mg/kg/day PO. All patients randomized were greater than 5 years postmenopausal at the time of the study and had no prior chemical or hormonal therapy. Estrogen receptors were not available. There was no significant difference between Groups A and B with respect to frequency of objective response or mean duration of that response, with the values for Group A being 46.2% and 4.8 months, respectively, and for Group B, 46.7% and 4.8 months (P > 0.05). The most common toxicities noted for both groups were nausea and vomiting, edema, weakness, and thrombophlebitis. The risk of major toxicity necessitating withdrawal from the study was greater in Group B due to the added danger of thrombocytopenia/pancytopenia. The addition of CB to DES does not appear to offer any significant advantage over DES alone in women with first recurrence of breast cancer.
Electric-dipole spin resonance in wurtzite ZnO

The electron spin resonance (ESR) measurements of the electric-dipole spin resonance (EDSR) of donor-bound electrons in ZnO wurtzite crystals are reported. This phenomenon was measured in longitudinal Voigt geometry (E1 || B0 ⊥ ) at low magnetic field and at low microwave frequency. The ESR transitions observed consist of two comparable signals: magnetic dipole spin resonance (MDSR) and electric dipole spin resonance (EDSR).
Neutrino and antineutrino quasielastic interactions with nuclei

We investigate the interaction of neutrinos and antineutrinos with nuclei. We explore, in particular, the role played by multinucleon excitations, which can contaminate the quasielastic cross section. For neutrinos the multinucleon term produces a sizable increase in the quasielastic cross section. Part of the effect arises from tensor correlations. For antineutrinos this influence is smaller, owing to the axial-vector interference, which increases the relative importance of the terms that are not affected by these multinucleon excitations.
Multi-scale Block Weber Local Descriptor for Face Recognition

In this paper, we provide a novel local descriptor Multi-scale Block Weber Local Descriptor (MBWLD) for face recognition. It is a LBP-based descriptor which combines MBLBP with WLD for integrating both their advantages. Firstly, Multi-scale block filters is used on the face image to calculate the average gray-values of sub-regions. Secondly, differential excitation and orientation of WLD is extracted using the average neighbors and center. MBWLD extracts both the micro and macro patterns from face image, and becomes more descriptive and robust to face representation. The feasibility and availability are validated by comparing with the standard LBP, MBLBP and WLD on FERET database in expression, illumination and age changes. The experimental result shows that, MBWLD is appropriate for face recognition, and the recognition performance is much well improved especially in illumination and age changes.
A comparison of self‐reported function assessed before and after depression treatment among depressed geriatric inpatients

The purpose of this study was to determine whether self‐perception of function among depressed, geriatric psychiatry inpatients improved as their depression resolved. Sixty‐four older adults diagnosed with major depression were asked to evaluate their function upon admission to an inpatient psychiatry unit, and then again 3 months post‐discharge. Subjects' caregivers also rated the patients' function at admission and 3 months after being discharged. Self‐perceptions of function improved over time, while caregivers' perceptions remained stable, suggesting that patients' perceptions of function is in part influenced by their depression. Further, correlations between patient and caregiver perceptions of function were higher at 3 months post discharge (when patients were not depressed) than they were at admission. The implication is that self‐perceptions of function are more accurate when not depressed. Copyright © 2000 John Wiley & Sons, Ltd.
[Association of the PADI4 gene polymorphism and HLA-DRB1 shared epitope alleles with rheumatoid arthritis].

OBJECTIVE To investigate the association of single nucleotide polymorphisms (SNPs) of the peptidylarginine deiminase IV (PADI4) and HLA-DRB1 shared epitope (SE) alleles with rheumatoid arthritis(RA) in a Chinese population. METHODS Four exonic SNPs of the PADI4 gene (PADI 4_89*A/G, PADI 4_90*C/T, PADI 4_92*C/G and PADI 4_104*C/T) were genotyped in 67 unrelated patients with RA and 81 healthy controls, using cDNA sequencing and T vector cloning. HLA-DRB 1*01, *04 and *10 subtypes were determined by polymerase chain reaction with sequence specific primers (PCR-SSP). RESULTS The distributions of the 4 SNPs were different in the two groups, and increased RA susceptibility was significantly associated with the minor alleles of PADI 4_89*G (P was 0.023), PADI 4_90*T (P was 0.004), PADI 4_104*T (P was 0.003), and the haplotypes carrying the 4 minor alleles (P was 0.008). HLA-DRB1 SE alleles are composed of HLA-DRB 1*0101, *0102, *0401, *0404, *0405, *0408, *0409, *0410 and *1001. Individuals carrying the SE alleles were associated with increased RA susceptibility (P was 0.002). Individuals carrying both the SE alleles and minor alleles of the 4 SNPs were more susceptible to RA than individuals carrying neither the minor SNP alleles nor the SE alleles. CONCLUSION The PADI4 SNPs and haplotypes are associated with RA susceptibility in Chinese. HLA-DRB1 shared epitope is also an important risky factor for RA. There may exist certain synergistic effect between the PADI4 minor alleles and the HLA-DRB1 shared epitope.
STUDIES OF MURAMIDASE IN HAEMATOLOGICAL DISORDERS: SERUM AND MARROW MURAMIDASE IN LEUKAEMIA

Summary Estimations of serum and marrow plasma muramidase were made in 39 adults with leukaemia. In the 33 patients studied prior to therapy, the absolute levels of marrow muramidase paralleled those of serum muramidase and reflected the type of leukaemia present. The normal marrow to serum muramidase ratio lies between 1.5 : 1 and 3 : 1 and in only 2 of the untreated patients was the marrow to serum muramidase ratio grossly elevated, being 10 : 1 and 12 : 1. This may be due to excessive intramedullary death of muramidase‐containing cells. Serial studies of this enzyme were carried out in 17 patients and in the majority both the marrow and the serum muramidase levels fluctuated in parallel with the changes in haematological status and returned to consistently normal levels only when patients entered complete remission. In 4 of the 7 patients who entered complete remission there was a transient rise in marrow to serum muramidase ratios following the beginning of chemotherapy. This study confirms the value of serum muramidase in the diagnosis and assessment of leukaemia. Marrow muramidase levels may occasionally provide extra information on the mechanisms of changes in intramedullary granulopoiesis.
The Significance of Tetramerization in Promoter Recruitment by Stat5

ABSTRACT Stat5a and Stat5b are rapidly activated by a wide range of cytokines and growth factors, including interleukin-2 (IL-2). We have previously shown that these signal transducers and activators of transcription (STAT proteins) are key regulatory proteins that bind to two tandem gamma interferon-activated site (GAS) motifs within an IL-2 response element (positive regulatory region III [PRRIII]) in the human IL-2Rα promoter. In this study, we demonstrate cooperative binding of Stat5 to PRRIII and explore the molecular basis underlying this cooperativity. We demonstrate that formation of a tetrameric Stat5 complex is essential for the IL-2-inducible activation of PRRIII. Stable tetramer formation of Stat5 is mediated through protein-protein interactions involving a tryptophan residue conserved in all STATs and a lysine residue in the Stat5 N-terminal domain (N domain). The functional importance of tetramer formation is shown by the decreased levels of transcriptional activation associated with mutations in these residues. Moreover, the requirement for STAT protein-protein interactions for gene activation from a promoter with tandemly linked GAS motifs can be relieved by strengthening the avidity of protein-DNA interactions for the individual binding sites. Taken together, these studies demonstrate that a dimeric but tetramerization-deficient Stat5 protein can activate only a subset of target sites. For functional activity on a wider range of potential recognition sites, N-domain-mediated oligomerization is essential.
Dynamic expression of HSP90B1 mRNA in the hypothalamus of two Chinese chicken breeds under heat stress and association analysis with a SNP in Huainan chickens

Wan Y. , Ma C. , Wei P., Fang Q. , Guo X. , Zhou B. , Jiang R. (2017): Dynamic expression of HSP90B1 mRNA in the hypothalamus of two Chinese chicken breeds under heat stress and association analysis with a SNP in Huainan chickens. Czech J. Anim. Sci., 62, 82–87. The effects of heat stress on HSP90B1 messenger RNA (mRNA) expression in the hypothalamus of chicken were investigated and HSP90B1 variations were detected. Females of two Chinese chicken breeds (Huainan and Wenchang) were used for the experiments. At 64 days of age, the ambient temperature (24 ± 1°C) was increased to 35 ± 1°C for 24 h (heat stress), then decreased to 24 ± 1°C for 24 h (recovery). Hypothalamus samples were collected at 0, 12, and 24 h during heat stress, as well as 12 and 24 h during recovery. The HSP90B1 mRNA expression increased significantly during heat stress and significantly decreased during recovery being higher in Huainan chickens. Fifteen primer pairs were designed to amplify the exons of HSP90B1 by a polymerase chain reaction, and single nucleotide polymorphisms (SNPs) were detected by Sanger sequencing. In Huainan chickens, we identified a SNP (NC_006088.3:g.6798G>A) in exon 14 of HSP90B1 which did not cause amino acid variation but caused a codon for glutamic acid change from GAG to GAA. The frequencies for genotypes AA, GA, and GG were 0.49, 0.27, and 0.24, respectively. Individuals with the GG genotype survived heat stress at 42°C for a longer time (248.2 ± 39.3 min) than individuals with GA and AA genotypes, which survived for 227.2 ± 44.5 min and 179.3 ± 36.5 min, respectively. The results suggested that the increased heat tolerance was associated with the higher expression of HSP90B1, and genotype GG could be used as a potential marker for heat resistance in chickens.
Cyclic GMP-dependent Protein Kinase Regulates CCAAT Enhancer-binding Protein β Functions through Inhibition of Glycogen Synthase Kinase-3*

The CCAAT enhancer-binding protein (C/EBPβ) plays an important role in the regulation of gene expression during cell proliferation, differentiation, and apoptosis. We previously showed that C/EBPβ participates in cGMP-regulated transcription of c-fos in osteoblasts (Chen, Y., Zhuang, S., Cassenaer, S., Casteel, D. E., Gudi, T., Boss, G. R., and Pilz, R. B. (2003) Mol. Cell. Biol. 23, 4066–4082). In the present work, we show that cGMP/cGMP-dependent protein kinase (PKG) induced dephosphorylation and activation of C/EBPβ by inhibiting glycogen synthase kinase-3β (GSK-3β). Phosphorylation of GSK-3β on Ser9 negatively regulates the enzyme activity, and we found that PKG phosphorylated this site both in vitro and in vivo; the in vivo phosphorylation occurred rapidly and preceded C/EBPβ dephosphorylation. Previous studies with GSK-3 inhibitors suggest that GSK-3β is a C/EBPβ kinase in resting cells. We determined that GSK-3β phosphorylated C/EBPβ in vitro on Thr189, Ser185, Ser181, and Ser177; C/EBPβ was phosphorylated on these same sites in intact, unstimulated osteoblasts, and phosphorylation was decreased in cGMP-treated cells. Mutation of the GSK-3 phosphorylation sites in C/EBPβ prevented C/EBPβ phosphorylation in resting cells, enhanced C/EBPβ DNA binding, and led to increased target gene transactivation, mimicking the stimulatory effects of cGMP on C/EBPβ. cGMP regulation of C/EBPβ was disrupted by a mutant GSK-3β(Ala9) resistant to cGMP/PKG phosphorylation and inhibition. We conclude that cGMP increases the DNA binding potential of C/EBPβ by preventing the negative effects of GSK-3 phosphorylation.
Isolation of the gene encoding the Saccharomyces cerevisiae centromere-binding protein CP1

CP1 is a sequence-specific DNA-binding protein of the yeast Saccharomyces cerevisiae which recognizes the highly conserved DNA element I (CDEI) of yeast centromeres. We cloned and sequenced the gene encoding CP1. The gene codes for a protein of molecular weight 39,400. When expressed in Escherichia coli, the CP1 gene directed the synthesis of a CDEI-binding protein having the same gel mobility as purified yeast CP1. We have given the CP1 gene the genetic designation CEP1 (centromere protein 1). CEP1 was mapped and found to reside on chromosome X, 2.0 centimorgans from SUP4. Strains were constructed in which most of CEP1 was deleted. Such strains lacked detectable CP1 activity and were viable; however, CEP1 gene disruption resulted in a 35% increase in cell doubling time and a ninefold increase in the rate of mitotic chromosome loss. An unexpected consequence of CP1 gene disruption was methionine auxotrophy genetically linked to cep1. This result and the recent finding that CDEI sites in the MET25 promoter are required to activate transcription (D. Thomas, H. Cherest, and Y. Surdin-Kerjan, J. Mol. Biol. 9:3292-3298, 1989) suggest that CP1 is both a kinetochore protein and a transcription factor.
Electrogenesis of embryonic chick skeletal muscle cells differentiated in vitro

Electrogenesis of embryonic chick skeletal muscle cells differentiated in monolayer cultures was investigated. Muscle fibers in vitro generate spike potentials similar to those of fibers in vivo. However, other responses, plateaux resembling those in heart muscle, are also elicited. These results suggest that a functional differentiation exists in cultured muscle fibers.