Miracle-dz/UniFAR-FTUs huggingface dataset:
Thermodynamic stability of ribonuclease A in alkylurea solutions and preferential solvation changes accompanying its thermal denaturation: A calorimetric and spectroscopic study

The effect of methylurea, N,N'‐dimethylurea, ethylurea, and butylurea as well as guanidine hydrochloride (GuHCl), urea and pH on the thermal stability, structural properties, and preferential solvation changes accompanying the thermal unfolding of ribonuclease A (RNase A) has been investigated by differential scanning calorimetry (DSC), UV, and circular dichroism (CD) spectroscopy. The results show that the thermal stability of RNase A decreases with increasing concentration of denaturants and the size of the hydrophobic group substituted on the urea molecule. From CD measurements in the near‐ and far‐UV range, it has been observed that the tertiary structure of RNase A melts at about 3 °C lower temperature than its secondary structure, which means that the hierarchy in structural building blocks exists for RNase A even at conditions at which according to DSC and UV measurements the RNase A unfolding can be interpreted in terms of a two‐state approximation. The far‐UV CD spectra also show that the final denatured states of RNase A at high temperatures in the presence of different denaturants including 4.5 M GuHCl are similar to each other but different from the one obtained in 4.5 M GuHCl at 25 °C. The concentration dependence of the preferential solvation change Δγ23, expressed as the number of cosolvent molecules entering or leaving the solvation shell of the protein upon denaturation and calculated from DSC data, shows the same relative denaturation efficiency of alkylureas as other methods.
Activation of MEK/ERK and PI3K/Akt pathways by fibronectin requires integrin αv‐mediated ADAM activity in hepatocellular carcinoma: A novel functional target for gefitinib

We have shown that the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib (‘Iressa’, ZD1839) inhibits the development of intrahepatic metastases of hepatocellular carcinoma CBO140C12, and EGFR transactivation by tumor necrosis factor‐α is a possible target of gefitinib. In the present study, we focused on the fibronectin (FN)‐dependent signaling pathway to further elucidate the antimetastatic activity of gefitinib in CBO140C12 cells. We initially observed that FN induced activation of extracellular signal‐regulated kinase (ERK), p38 and Akt, as well as cell proliferation and CBO140C12 cell invasion. These responses were mediated by EGFR tyrosine kinase, because gefitinib inhibited these effects of FN. FN‐induced ERK, p38 and Akt activation was partly blocked by the Arg‐Gly‐Asp (RGD)‐pseudo‐peptide FC‐336, anti‐αv integrin antibody RMV‐7, the broad‐spectrum matrix metalloprotease inhibitor GM6001 and the broad spectrum a disintegrin and metalloprotease (ADAM) inhibitor TAPI‐1. But these inhibitors had no effect on EGF‐induced signaling pathways, suggesting that integrins and ADAM may be upstream components of EGFR in these responses. These results suggest that FN‐induced activation of ERK, p38, Akt, cell proliferation and invasion was mediated, at least in part, via integrins, ADAM and EGFR, and that this FN‐induced signaling pathway might be involved in the antimetastatic activity of gefitinib. (Cancer Sci 2006; 97: 155 –162)
RpoS is required for natural transformation of Vibrio cholerae through regulation of chitinases.

Vibrio species naturally reside in the aquatic environment and a major metabolite in this habitat is the chitinous exoskeletons of crustacean zooplankton. In addition to serving as a nutrient, chitin-derived oligosaccharides also induce natural genetic competence in many Vibrio spp. , a physiological state in which bacteria take up DNA from the extracellular environment and can integrate it into their chromosome by homologous recombination. Another inducing cue required for competence are quorum-sensing autoinducers. The alternative sigma factor RpoS is critical for natural transformation in Vibrio cholerae, and it was previously presumed to exert this effect through regulation of quorum sensing. Here, we show that RpoS does not affect quorum sensing-dependent regulation of competence. Instead, we show that an rpoS mutant has reduced chitinase activity, which is required to liberate the soluble chitin oligosaccharides that serve as an inducing cue for competence. Consistent with this, we demonstrate that RpoS is required for growth of V. cholerae on insoluble chitin. RpoS also regulates the mucosal escape response in pathogenic strains of V. cholerae. Thus, in addition to promoting egress from its human host, RpoS may also prime this pathogen for successful reentry into the aquatic environment.
Relationship of the delta-opioid receptor gene to heroin abuse in a large Chinese case/control sample.

Pharmacological and electrophysiological evidence has shown that opioid receptors are involved in the mechanism of heroin dependence. Thus, opioid receptors are appropriate candidate genes for case-control association studies of heroin dependence. Previously, two single nucleotide polymorphisms (SNPs), OPRD1 921T > C and 80G > T, of the human delta opioid receptor gene were used in population-based studies of heroin dependence. One study in a German population found that OPRD1 921T > C was associated with heroin dependence. This finding, however, was not replicated in a different German sample. To test the hypothesis that OPRD1 or a closely linked gene is associated with heroin dependence, we used 5' nuclease assays to genotype both OPRD1 SNPs in 450 Chinese heroin dependent patients and 304 unaffected controls from the same population. In addition, five SNPs distributed in four other genes: ADH2, ALDH2, OPRM1, and DRD1, were used as genomic control loci to test the case and control populations for stratification bias. Genotype and allele frequencies at OPRD1 921T > C were not significantly different, and the OPRD1 80G was absent from both Chinese opioid dependence patients and controls. Based on the genotype and allele frequencies of the genomic control loci, there was no evidence for stratification bias capable of masking an association of OPRD1 to heroin dependence in this large and homogenous Chinese sample. Therefore, these data do not support an association between the OPRD1 gene and heroin dependence in the Chinese population.
The Comparative Method of language acquisition research: a Mayan case study*

ABSTRACT This article demonstrates how the Comparative Method can be applied to cross-linguistic research on language acquisition. The Comparative Method provides a systematic procedure for organizing and interpreting acquisition data from different languages. The Comparative Method controls for cross-linguistic differences at all levels of the grammar and is especially useful in drawing attention to variation in contexts of use across languages. This article uses the Comparative Method to analyze the acquisition of verb suffixes in two Mayan languages: K'iche' and Yucatec. Mayan status suffixes simultaneously mark distinctions in verb transitivity, verb class, mood, and clause position. Two-year-old children acquiring K'iche' and Yucatec Maya accurately produce the status suffixes on verbs, in marked distinction to the verbal prefixes for aspect and agreement. We find evidence that the contexts of use for the suffixes differentially promote the children's production of cognate status suffixes in K'iche' and Yucatec.
Therapeutic Effect of Irradiation of Magnetic Infrared Laser on Osteoarthritis Rat Model

Osteoarthritis (OA) is a degenerative joint disease caused by articular cartilage loss. Many complementary and alternative medicines for OA have been reported so far, but the effectiveness is controversial. Previously, we have shown anti‐inflammatory effects of low level laser therapy with static magnetic field, magnetic infrared laser (MIL), in various animal models. Therefore, the beneficial effects were examined in OA rat model. Rats were divided by six groups; no treatment controls of sham and OA model, three MIL treatment groups of OA model at 6.65, 2.66 and 1.33 J cm−2, and Diclofenac group of OA model with 2 mg kg−1 diclofenac sodium. The OA control exhibited typical symptoms of OA, but 4‐week MIL treatment improved the functional movement of knee joint with reduced edematous changes. In addition, cartilage GAGs were detected more in all MIL treatment groups than OA control. It suggests that 4‐week MIL irradiation has dose‐dependent anti‐inflammatory and chondroprotective effects on OA. Histopathological analyses revealed that MIL treatment inhibits the cartilage degradation and enhances chondrocyte proliferation. The fact that MIL has an additional potential for the cartilage formation and no adverse effects can be regarded as great advantages for OA treatment. These suggest that MIL can be useful for OA treatment.
Novel flavohemoglobins of mycobacteria

Flavohemoglobins (flavoHbs) constitute a distinct class of chimeric hemoglobins in which a globin domain is coupled with a ferredoxin reductase such as FAD‐ and NADH‐binding modules. Structural features and active site of heme and reductase domains are highly conserved in various flavoHbs. A new class of flavoHbs, displaying crucial differences in functionally conserved regions of heme and reductase domains, have been identified in mycobacteria. Mining of microbial genome data indicated that the occurrence of such flavoHbs might be restricted to a small group of microbes unlike conventional flavoHbs that are widespread among prokaryotes and lower eukaryotes. One of the representative flavoHbs of this class, encoded by Rv0385 gene (MtbFHb) of Mycobacterium tuberculosis, has been cloned, expressed, and characterized. The ferric and deoxy spectra of MtbFHb displayed a hexacoordinate state indicating that its distal site may be occupied by an intrinsic amino acid or an external ligand and it may not be involved in nitric oxide detoxification. Phylogenetic analysis revealed that mycobacterial flavoHbs constitute a separate cluster distinct from conventional flavoHbs and may have novel function(s). © 2011 IUBMB IUBMB Life, 63(5): 337–345, 2011
Enhancing Creativity Through "Mindless" Work: A Framework of Workday Design

We propose that organizations use a new framework of workday design to enhance the creativity of today's chronically overworked professionals. Although insights from creativity research have been integrated into models of work design to increase the stimulants of creativity (e.g., intrinsic motivation), this has not led to work design models that have effectively reduced the obstacles to creativity (e.g., workload pressures). As a consequence, creative output among professionals in high-workload contexts remains disappointing. In response, we offer a framework of work design that focuses on the design of entire workdays rather than the typical focus on designing either specific tasks or very broad job descriptions (e.g., as the job characteristics model in Hackman et al. 1975). Furthermore, we introduce the concept of “mindless” work (i.e., work that is low in both cognitive difficulty and performance pressures) as an integral part of this framework. We suggest that to enhance creativity among chronically overworked professionals, workdays should be designed to alternate between bouts of cognitively challenging and high-pressure work (as suggested in the original model by Hackman et al. 1975), and bouts of mindless work (as defined in this paper). We discuss the implications of our framework for theories of work design and creativity.
The periodontal health of homosexual men with HIV infection: a controlled study.

OBJECTIVE Identify types, prevalence and severity of periodontal changes associated with HIV infection. DESIGN Cross-sectional controlled blinded study. SETTING Open access genito-urinary medicine clinic. PARTICIPANTS Convenience sample of 794 homosexual men aged 18-65. OUTCOME MEASURES Prevalence, extent and severity of probing attachment loss (PAL), pocketing, gingival ulceration, gingivitis, bleeding on probing (BOP), gingival red bands and diffuse and punctate erythema of the attached gingiva (selected a priori). RESULTS Prevalences in men with (n = 312) and without HIV (n = 260) were: PAL (> or = 1 site > or = 4mm), 59.6% and 28.5% respectively (P < 0.001, chi 2); pocketing (> or = 1 site > or = 4mm) 51.0% and 31.9% (P < 0.001); BOP, 96.5% and 92.3% (P = 0.038); gingival ulceration, 3.2% and 1.0% (P = 0.031), red banding, 12.2% and 10.0% (P = 0.410); diffuse erythema, 12.5% and 3.1% (P < 0.001) and punctate erythema, 9.6% and 1.1% (P < 0.001). Decreased CD4 lymphocyte counts predicted the presence, extent and severity of PAL (P = 0.023, 0.027 and 0.060) but not pocketing. Oral candidiasis predicted the extent and severity of gingivitis and the presence of diffuse and punctate erythema. (P = 0.037, 0.011, 0.002 and < 0.001). CONCLUSIONS Destruction of periodontal attachment is associated with progression of HIV disease whereas pocketing is associated with HIV infection but not disease progression. Gingival ulceration is associated with HIV but gingivitis and erythema of the attached gingiva are most strongly associated with oral candidiasis. Gingival red bands were not associated with HIV infection.
Assessing the Impact of Changing Economic Environment on Productivity Growth: The Case of the Spanish Dairy Processing Industry

ABSTRACT This article analyzes the productivity growth of the Spanish dairy processing industry from 1996 till 2011, which concerns the period of increased EU regulation regarding food safety as well as economic crisis. Data envelopment analysis is used to compute the Malmquist index and its components. The results suggest that productivity on average declined during the period under investigation. The decomposition of the Malmquist index finds that technical regress contributed to productivity decline despite improvements in technical and scale efficiencies. Our results also suggest that food safety regulations did not have a negative impact on productivity growth. Technical change and scale efficiency change made significant negative contributions to productivity growth in the period under crisis, whereas firms significantly improved their technical efficiency in that period.
Gene-expression profiling elucidates molecular signaling networks that can be therapeutically targeted in vestibular schwannoma.

OBJECT Vestibular schwannomas (VS) are common benign tumors of the vestibular nerve that cause significant morbidity. The current treatment strategies for VS include surgery or radiation, with each treatment option having associated complications and side effects. The transcriptional landscape of schwannoma remains largely unknown. METHODS In this study the authors performed gene-expression profiling of 49 schwannomas and 7 normal control vestibular nerves to identify tumor-specific gene-expression patterns. They also interrogated whether schwannomas comprise several molecular subtypes using several transcription-based clustering strategies. The authors also performed in vitro experiments testing therapeutic inhibitors of over-activated pathways in a schwannoma cell line, namely the PI3K/AKT/mTOR pathway. RESULTS The authors identified over 4000 differentially expressed genes between controls and schwannomas with network analysis, uncovering proliferation and anti-apoptotic pathways previously not implicated in VS. Furthermore, using several distinct clustering technologies, they could not reproducibly identify distinct VS subtypes or significant differences between sporadic and germline NF2-associated schwannomas, suggesting that they are highly similar entities. The authors identified overexpression of PI3K/AKT/mTOR signaling networks in their gene-expression study and evaluated this pathway for therapeutic targeting. Testing the compounds BEZ235 and PKI-587, both novel dual inhibitors of PI3K and mTOR, attenuated tumor growth in a preclinical cell line model of schwannoma (HEI-293). In vitro findings demonstrated that pharmacological inhibition of the PI3K/AKT/mTOR pathway with next-generation compounds led to decreased cell viability and increased cell death. CONCLUSIONS These findings implicate aberrant activation of the PI3K/AKT/mTOR pathway as a molecular mechanism of pathogenesis in VS and suggest inhibition of this pathway as a potential treatment strategy.
Adherence to the WCRF/AICR Guidelines for Cancer Prevention Is Associated with Lower Mortality among Older Female Cancer Survivors

Background: The 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines encourage cancer survivors to follow its cancer prevention recommendations. We evaluated whether adherence to the WCRF/AICR guidelines for cancer prevention was associated with lower mortality among older female cancer survivors. Methods: From 2004 to 2009, 2,017 participants in the Iowa Women's Health Study who had a confirmed cancer diagnosis (1986–2002) and completed the 2004 follow-up questionnaire were followed. Adherence scores for the WCRF/AICR guidelines for body weight, physical activity, and diet were computed assigning one, 0.5 or 0 points to each of eight recommendations depending on the degree of adherence. All-cause (n = 461), cancer-specific (n = 184), and cardiovascular disease (CVD)-specific mortality (n = 145) were compared by the total adherence score and by adherence scores for each of the three components of the recommendations. Results: Women with the highest (6–8) versus lowest (0–4) adherence score had lower all-cause mortality [HR = 0.67; 95% confidence of interval (CI), 0.50–0.94]. Meeting the physical activity recommendation was associated with lower all-cause (Ptrend < 0.0001), cancer-specific (Ptrend = 0.04), and CVD-specific mortality (Ptrend = 0.03). Adherence to dietary recommendations was associated with lower all-cause mortality (Ptrend < 0.05), whereas adherence to the body weight recommendation was associated with higher all-cause mortality (Ptrend = 0.009). Conclusions: Adherence to the WCRF/AICR guidelines was associated with lower all-cause mortality among older female cancer survivors. Adherence to the physical activity recommendation had the strongest association with lower all-cause and disease-specific mortality. Impact: Older cancer survivors may decrease their risk of death by leading a healthy lifestyle after a cancer diagnosis. Cancer Epidemiol Biomarkers Prev; 22(5); 792–802. ©2013 AACR.
Metformin as targeted treatment in fragile X syndrome

Individuals with fragile X syndrome (FXS) have both behavioral and medical comorbidities and the latter include obesity in approximately 30% and the Prader‐Willi Phenotype (PWP) characterized by severe hyperphagia and morbid obesity in less than 10%. Metformin is a drug used in individuals with type 2 diabetes, obesity or impaired glucose tolerance and it has a strong safety profile in children and adults. Recently published studies in the Drosophila model and the knock out mouse model of FXS treated with metformin demonstrate the rescue of multiple phenotypes of FXS.
An Evaluation of Evidence on Depressive Classification and Some Alternative Suggestions from Physiology*

The wealth of material on depressive classification provides both researcher and clinician with a sorting task of monumental proportions. Moreover the criticisms which have been fired at studies of depressive classification using symptoms as a data base, also require systematic sorting and elucidation. An attempt has been made to review the major studies of depressive classification in a systematic way, together with the principal criticisms which have been made of them. The survey is not exhaustive but aims at providing a relatively ordered overview of the area. The most critical issue, that of subjectivity of data collection is taken up, and it is suggested that biological measures may form a more objective data base for studies of depressive classification than ratings of symptoms and behaviour.
RivR and the small RNA RivX: the missing links between the CovR regulatory cascade and the Mga regulon

The CovR/S two‐component system regulates the transcription of many genes that are crucial for the virulence of Streptococcus pyogenes (group A Streptococcus, GAS). Previously, we demonstrated that one gene repressed directly by CovR is rivR, which encodes a member of the RofA‐like family of transcriptional regulators. In this study, we deleted rivR and its downstream gene rivX in a ΔcovR background. Microarray analysis revealed that the products of the rivRX locus exert positive control over the transcription of members of the Mga regulon. Using mutational analysis, we established that rivX encodes a small regulatory RNA. We found that RivR enhances transcriptional activation by Mga in vivo and in vitro. An M1 ΔcovRΔrivRX strain is attenuated for virulence in a murine model of invasive soft tissue infection and this attenuation is complemented by rivRX expressed from a plasmid, demonstrating the importance of the rivRX locus in pathogenesis. This study provides the first link between the CovR and Mga regulatory networks. By integrating the signals received through these two global regulators, GAS is able to select from its repertoire different combinations of specific virulence factors to express in response to a broad spectrum of environmental conditions.
Effect of Abscisic Acid on Accumulation of Five Active Components in Root of Glycyrrhiza uralensis

Licorice is one of the most generally used herbal medicines in the world; however, wild licorice resources have decreased drastically. Cultivated Glycyrrhiza uralensis Fischer are the main source of licorice at present, but the content of main active components in cultivated G. uralensis are lower than in wild G. uralensis. Therefore, the production of high-quality cultivated G. uralensis is an urgent issue for the research and production fields. In this study, the content of five active components and seven endogenous phytohormones in cultivated G. uralensis (two-year-old) were determined by high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA), respectively. Furthermore, different concentrations (25–200 mg/L) of exogenous abscisic acid (ABA) were sprayed on the leaves of G. uralensis in the fast growing period. Results showed that ABA, zeatin riboside (ZR), and dihydrozeatin riboside (DHZR) had strong correlation with active components. In addition, the content of five active components increased remarkably after ABA treatment. Our results indicate that ABA is significantly related to the accumulation of active components in G. uralensis, and the application of exogenous ABA at the proper concentration is able to promote the accumulation of main components in G. uralensis.
The universal banking feedback effet: U.S. and Canada evidence

Bank non-traditional business lines have significant feedback effects on both economic activity and the stock market. These effects appear in the non-interest income series after 1997 strucutral break. Based on U.S. and Canadian data, we find that the banking cycle tends to lead the business cycle in both countries over the whole sample period (frist quarter of 1984 to last quarter of 2013), and particularly in the last decades. Despite these results, the impact of monetary policy on net interest income remains surprisingly stable after the emergence of universal banking.