Miracle-dz/UniFAR-FTUs huggingface dataset:
Angiotensinogen T235 and ACE Insertion/Deletion Polymorphisms Associated With Albuminuria in Chinese Type 2 Diabetic Patients

OBJECTIVE Genetic polymorphisms of the renin-angiotensin system (RAS) have been implicated in the pathogenesis of diabetic proteinuria. Ethnic differences in the frequencies of these genotypes have also been reported. To date, most of these studies have been performed in white and Japanese populations. In this study, we examined the associations between albuminuria and RAS genetic polymorphisms in Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS In a case-control study, the ACE insertion/deletion (I/D) gene, the angiotensinogen (AGT) gene (M235T), and the angiotensin II (AII) type 1 receptor gene (AT1 A1166C) were examined in 110 Chinese type 2 diabetic patients. Increased urinary albumin excretion (UAE) was defined as ≥ 30 mg/day on at least two occasions during a 6-week study period. RESULTS Compared with whites, there were high frequencies of the AGT TT genotype in Chinese control subjects (120/183 = 70%) and type 2 diabetic patients (74/110 = 67%). The frequencies of the MM genotype were 5 and 3%, respectively, and those of the ACE DD genotype were 13 and 10%, respectively. Although 9% of subjects carried the C allele, the AT1 CC genotype was not found in either group. Chinese type 2 diabetic patients with increased albuminuria (n = 56) had higher systolic blood pressure (160 ± 26 mmHg vs 145 ± 27 mmHg, P < 0.001) than the normoalbuminuric patients (n = 54). Both the AGT TT genotype (78.6% [44/56] vs. 55.6% [30/54], odds ratio [OR]: 3.0 [1.3–6.8]) and the T allele (88% [99/112] vs. 77% [83/108], OR: 2.5 [1.3–5.4]) were associated with an increased risk of albuminuria. Patients with the AGT TT genotype (n = 74) had higher 24-h UAE than those with the MT or MM genotypes (n = 36) (median: 37.8 mg/day vs. 17.8 mg/day, P < 0.01). This association remained significant in patients with normotension (56 mg/day [n = 19] for patients with the TT genotype vs. 22 mg/day [n = 14] for those with the MT/MM genotype, P = 0.03). The D allele carriers (DD or DI, n = 61) had higher serum ACE activities (75.5 ± 29 U/l vs. 60.5 ± 36.3 U/l, P < 0.01) than the noncarriers (II genotype). The median 24-h UAE also tended to be higher in the D allele carriers (38.9 mg/day vs. 21.4 mg/day, P = 0.07). The lowest UAE was observed in patients with the MM/MT/II genotype (16.3 mg/day [n = 18]) and the highest, in patients with the TT/DD/DI genotype (52.3 mg/day [n = 43]). No association was found between the TT genotype or D allele and hypertension. CONCLUSIONS The high frequencies of the TT genotype and T allele in Chinese populations may contribute to the high prevalence of albuminuria in patients with type 2 diabetes. The possibility of synergism between the AGT TT genotype and the ACE D allele should also be explored.
Functional analysis of putative restriction-modification system genes in the Helicobacter pylori J99 genome.

Helicobacter pylori is a gram-negative bacterium, which colonizes the gastric mucosa of humans and is implicated in a wide range of gastroduodenal diseases. The genomic sequences of two H.pylori strains, 26695 and J99, have been published recently. About two dozen potential restriction-modification (R-M) systems have been annotated in both genomes, which is far above the average number of R-M systems in other sequenced genomes. Here we describe a functional analysis of the 16 putative Type II R-M systems in the H. pylori J99 genome. To express potentially toxic endonuclease genes, a unique vector was constructed, which features repression and antisense transcription as dual control elements. To determine the methylation activities of putative DNA methyltransferases, we developed polyclonal antibodies able to detect DNA containing N6-methyladenine or N4-methylcytosine. We found that <30% of the potential Type II R-M systems in H.pylori J99 strain were fully functional, displaying both endonuclease and methyltransferase activities. Helicobacter pylori may maintain a variety of functional R-M systems, which are believed to be a primitive bacterial 'immune' system, by alternatively turning on/off a subset of numerous R-M systems.
PGR5 ensures photosynthetic control to safeguard photosystem I under fluctuating light conditions

In a plant’s natural environment, the intensity of light can change rapidly due to sunflecks, cloudiness and intermittent shading. Fluctuations between high and low illumination phases expose the photosynthetic machinery to rapidly changing signals that can be overlapping or contradictory, and accordingly plants have developed astute acclimation strategies to maintain optimal photosynthetic performance in these conditions. Continuous exposure to high light induces an array of protective mechanisms at anatomical, chemical and molecular levels, but when high light phases are short, such as under fluctuating light conditions, the protective strategies that afford protection to constant high light are not employed by plants. One mechanism that is engaged under both constant and fluctuating high light is the photosynthetic control of the Cyt b6f complex, which prevents hyper-reduction of the electron transfer chain in order to protect PSI from photodamage. The PGR5 protein was recently shown to play an indispensable role in this protective mechanism. This review revisits the findings of earlier studies into photosynthetic control and places PGR5 within the broader context of photoprotection and light acclimation strategies.
Evaluation of pulmonary tuberculosis case detection improvement with the deployment of XpertMTB/Rif in the tuberculosis control program of cross River State, Nigeria

Objective/Background: Global indices show that Nigeria has the highest tuberculosis (TB)-related mortality rate. Overdependence on Ziehl–Neelsen (ZN) smear microscopy for diagnosis and human immunodeficiency virus (HIV)/AIDS has limited control efforts. The new polymerase chain reaction-based XpertMTB/Rif (Cepheid Inc., CA, USA), which detects Mycobacterium tuberculosis and rifampicin resistance, was introduced in Cross River State in 2014. We evaluated the increment in pulmonary TB case detection following introduction of XpertMTB/Rif into the Cross River State TB control program. Materials and Methods: Data from three XpertMTB/Rif centers in Cross River were prospectively collected from June 2014 to December 2015. One spot specimen and one early morning sputum specimen were collected from each patient and tested using microscopy while one specimen was used for XpertMTB/Rif. Results: A total of 2326 patients comprising 47.4. 0% (1103) males and 52.6% (1223) females were evaluated. Their mean age was 38.8 years (range 4–89 years); 42.6% (991) were HIV positive and 50.9% (1183) HIV negative, and for 6.5% (158) HIV status was unknown. XpertMTB/Rif detected M. tuberculosis in 22.9% (534) of patients, while 16.8% (391) were ZN smear positive. Smear microscopy missed 24.5% (131/534) of cases (P < 0.0001). When patients where categorized according to HIV status, XpertMTB/Rif detected 23.7% (280/1183) and ZN smear microscopy detected 18.5% (219/1183) of HIV-negative patients. XpertMTB/Rif detected 21.5% (213/991) and ZN smear 14.1% (140/991) of HIV-positive patients. TB case detection was significantly higher in HIV-negative patients than in HIV-positive patients when either XpertMTB/Rif and/or ZN was used (P = 0.018 and 0.012, respectively). Conclusion: The use of XpertMTB/Rif has significantly increased TB case detection and data in Cross River State. Scale-up of additional strategies such as culture is still required to improve TB detection in HIV patients.
Exploring formal programmes supporting pre-competitive research collaboration in science & technology in European Research Area

At the Lisbon Summit in 2000, the European Union (EU) Heads of States confirmed that knowledge and innovation are vital to Europe's growth and agreed to make the EU the most competitive knowledge-driven economy. The EU's ability to facilitate innovation by strengthening its research capacities is central to achieving this goal. Some of the practical initiatives under this innovation policy determined at the Lisbon Summit integrate research capacities already existing in individual states through pan-European participation in collaborative projects in science and technology. The EU is financing a number of formal pre-competitive networking programmes aiming at a better deployment of existing national research capacities via their inclusion in joint research initiatives. Although there is a general consensus that increasing levels of collaboration amongst researchers produce better results, the issue of research networking and of related research outcomes continues to generate debate with a wide variety of views on what roles such programmes play and their general implications for research and scientific performance. This paper explores whether such formal networking programmes contribute to facilitating innovation in the European Research Area (ERA) by enabling Science & Technology (S&T) participants to achieve anticipated research outcomes from their involvement in such programmes.
Phosphorylation of Serine‐880 in GluR2 by Protein Kinase C Prevents Its C Terminus from Binding with Glutamate Receptor‐Interacting Protein

Abstract : Phosphorylation of the glutamate receptor is an important mechanism of synaptic plasticity. Here, we show that the C terminus of GluR2 of the α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptor is phosphorylated by protein kinase C and that serine‐880 is the major phosphorylation site. This phosphorylation also occurs in human embryonic kidney (HEK) cells by addition of 12‐O‐tetradecanoylphorbol 13‐acetate. Our immunoprecipitation experiment revealed that the phosphorylation of serine‐880 in GluR2 drastically reduced the affinity for glutamate receptor‐interacting protein (GRIP), a synaptic PDZ domain‐containing protein, in vitro and in HEK cells. This result suggests that modulation of serine‐880 phosphorylation in GluR2 controls the clustering of AMPA receptors at excitatory synapses and consequently contributes to synaptic plasticity.
Klinefelter’s Syndrome and Prader-Willi Syndrome: A Rare Combination

In this paper a review is presented of the rare combination of Klinefelter’s syndrome and Prader-Willi syndrome (PWS) and a second case of this combination with a uniparental disomy (UPD) etiology of PWS is described. Patients outlined in all other 8 reports and the present case have a PWS phenotype. Virtually no information is available on the behavioral and psychopathological phenotype in this combination. The latter may be explained by the observation that psychiatric syndromes are especially prevalent in PWS patients with a UPD. It is concluded that instability in mood and behavior in this and other syndromes should be preferentially treated with mood stabilizing agents.
Oxygen-Dependent Transcriptional Regulator Hap1p Limits Glucose Uptake by Repressing the Expression of the Major Glucose Transporter Gene RAG1 in Kluyveromyces lactis

ABSTRACT The HAP1 (CYP1) gene product of Saccharomyces cerevisiae is known to regulate the transcription of many genes in response to oxygen availability. This response varies according to yeast species, probably reflecting the specific nature of their oxidative metabolism. It is suspected that a difference in the interaction of Hap1p with its target genes may explain some of the species-related variation in oxygen responses. As opposed to the fermentative S. cerevisiae, Kluyveromyces lactis is an aerobic yeast species which shows different oxygen responses. We examined the role of the HAP1-equivalent gene (KlHAP1) in K. lactis. KlHap1p showed a number of sequence features and some gene targets (such as KlCYC1) in common with its S. cerevisiae counterpart, and KlHAP1 was capable of complementing the hap1 mutation. However, the KlHAP1 disruptant showed temperature-sensitive growth on glucose, especially at low glucose concentrations. At normal temperature, 28°C, the mutant grew well, the colony size being even greater than that of the wild type. The most striking observation was that KlHap1p repressed the expression of the major glucose transporter gene RAG1 and reduced the glucose uptake rate. This suggested an involvement of KlHap1p in the regulation of glycolytic flux through the glucose transport system. The ΔKlhap1 mutant showed an increased ability to produce ethanol during aerobic growth, indicating a possible transformation of its physiological property to Crabtree positivity or partial Crabtree positivity. Dual roles of KlHap1p in activating respiration and repressing fermentation may be seen as a basis of the Crabtree-negative physiology of K. lactis.
Perceived quality and availability of fruit and vegetables are associated with perceptions of fruit and vegetable affordability among socio-economically disadvantaged women

Abstract Objective Perceptions that fruit and vegetables are expensive have been found to be associated with lower consumption of fruit and vegetables among disadvantaged women; however, the determinants of these perceptions are relatively unknown. The purpose of the current paper is to examine whether perceived availability and quality of fruit and vegetables, and social support for healthy eating, are associated with perceptions of fruit and vegetable affordability among women residing in disadvantaged neighbourhoods. Design Cross-sectional self-report survey. Setting The study was conducted in Melbourne, Australia. Subjects An Australian sample of 4131 women, aged 18–45 years, residing in neighbourhoods ranked in the lowest Victorian tertile of relative disadvantage by the Australian Bureau of Statistics, an index that considers aspects of disadvantage such as residents’ income, education, motor vehicle access and employment. Results Results showed that irrespective of education, income and other key covariates, women who perceived poor availability and quality of fruit and vegetables in their local neighbourhood were more likely to perceive fruit and vegetables as expensive. Conclusions Our results suggest that perceptions of fruit and vegetable affordability are not driven exclusively by lack of financial or knowledge-related resources, but also by women's psychological response and interpretation of their local nutrition environment.
Codon Usage Selection Can Bias Estimation of the Fraction of Adaptive Amino Acid Fixations.

A growing number of molecular evolutionary studies are estimating the proportion of adaptive amino acid substitutions (α) from comparisons of ratios of polymorphic and fixed DNA mutations. Here, we examine how violations of two of the model assumptions, neutral evolution of synonymous mutations and stationary base composition, affect α estimation. We simulated the evolution of coding sequences assuming weak selection on synonymous codon usage bias and neutral protein evolution, α = 0. We show that weak selection on synonymous mutations can give polymorphism/divergence ratios that yield α-hat (estimated α) considerably larger than its true value. Nonstationary evolution (changes in population size, selection, or mutation) can exacerbate such biases or, in some scenarios, give biases in the opposite direction, α-hat < α. These results demonstrate that two factors that appear to be prevalent among taxa, weak selection on synonymous mutations and non-steady-state nucleotide composition, should be considered when estimating α. Estimates of the proportion of adaptive amino acid fixations from large-scale analyses of Drosophila melanogaster polymorphism and divergence data are positively correlated with codon usage bias. Such patterns are consistent with α-hat inflation from weak selection on synonymous mutations and/or mutational changes within the examined gene trees.
FGF23 contributes to insulin sensitivity in obese adolescents – preliminary results

Fibroblast growth factor‐23 (FGF23) is a hormonal regulator of circulating phosphate and vitamin D levels. Recent investigations revealed that besides a key role in the pathogenesis of calcium–phosphorus disorders, in some patients FGF23 may be an indicator of cardiovascular complications. As a ‘hormone‐like’ factor, it may also be involved in some metabolic processes, especially in the metabolism of glucose and fat. Its potential contribution to metabolic syndrome (MS) development has not been confirmed yet.
Criteria for Selection of IgG Isotype and Glycoform of Antibody Therapeutics

LEVEL: INTERMEDIATE T he efficacy of recombinant antibodies (rMAbs) results from their specificity for target antigens and the biological activities (effector functions) activated by the immune complexes formed. Numerous parameters influence the effector function profile (including antibody class, IgG subclass, and glycoform), and their definition offers opportunities for optimizing a recombinant MAb for a given disease indication. Five classes of human antibodies (immunoglobulins) are defined: IgM, IgG, IgA, IgD, and IgE; four subclasses of IgG and two of IgA are designated IgG1, IgG2, IgG3, or IgG4 and IgA1 or IgA2 according to their relative concentrations in serum. Each antibody class and subclass expresses a unique profile of effector functions (1). All currently licensed rMAbs are of the IgG class, predominantly of the IgG1 subclass, and produced in Chinese hamster ovary (CHO), mouse NS0, or Sp2/0 plasma cell lines. The choice of IgG subclass is increasingly appreciated as a critical decision when developing a recombinant MAb therapeutic (2). In oncology it would seem beneficial to maximize the potential to induce antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) to eliminate targeted cancer cells. However, in chronic diseases, neutralization of a soluble target (a cytokine, for example) may be the central objective, and excessive effector activity could be detrimental. One example is when a target is also expressed as a membrane protein on certain cells, such as targeting of TNFα by infliximab (Remicade, www. centocor.com) in patients with rheumatoid arthritis. Consequently, IgG1 may not be the automatic choice, and the other IgG subclasses are now being evaluated, both in native and engineered forms. Some companies have selected IgG4 as the preferred alternative subclass, and two IgG4 rMAbs are already licensed. However, recent studies suggest that IgG4 may not be the best alternative because it has been shown to activate inflammatory reactions through cellular IgG-Fc receptors (3–5). It should be noted that the “superagonistic” anti-CD28 antibody TGN 1412, which appears to have induced a “cytokine storm” in healthy volunteers, is a humanized IgG4 recombinant antibody (6, 7). In addition IgG4 is secreted as a mixture of covalent and noncovalently assembled molecules; the latter dissociate to “half molecules” in nonreducing SDS gel electrophoresis (5, 8). The proportions of each molecular species vary between cell lines and clones, posing a problem for product consistency. A preferred alternative may be the IgG2 subclass because it is very stable, exhibits a minimum of IgG-Fc effector activities, and has a long serum half-life. Aglycosylated IgG may also be explored because it also exhibits minimal effector activity and retains the long catabolic half-life of glycosylated forms.
Challenging and changing stress-producing thinking

“Your patient had a severe adverse reaction to the medication you prescribed. ” Receiving this information, you as the patient's physician are flooded with negative thoughts and feelings and a desire to escape. Through selection, training, and reinforcement, you have been conditioned to think, “I must be thoroughly competent,” “I cannot make mistakes,” and “I need to be totally responsible and in control. ” This stress-producing belief system can be identified, challenged, and modified to increase well being without sacrificing integrity and work quality. I describe some cognitive-behavioural techniques that can help physicians break this cycle of negative thinking. Figure 1 shows a physician's initial negative interpretation of the clinical …
Muscle–tendon unit scaling methods of Hill-type musculoskeletal models: An overview

This article gives an overview of the state of the art in scaling methods of generic Hill-type muscle model parameters in view of different applications and implementation of experimental data. This article establishes the requirements used to alter a generic model toward subject-specific musculoskeletal models. This article aims to improve model transparency by a structured description of scaling methods and the associated limitations in musculoskeletal models and highlight the importance of selecting a scaling method supporting the purpose of the model.
Results of Radical Prostatectomy and Adjuvant Therapy in the Management of Locally Advanced, Clinical Stage TC, Prostate Cancer

Fifty-seven patients with locally advanced, clinical stage TC, adenocarcinoma of the prostate underwent treatment consisting of surgery, external beam radiation therapy and, in selected patients, early hormonal ablation and/or systemic chemotherapy. Surgical morbidity from radical retropubic prostatectomy and limited pelvic lymph node dissection was acceptable with an early complication rate of 11%. Follow-up ranged from 3.5 to 19.9 years (median 5.4 years). Actuarial 5 and 7.5 years survival rates for all patients was 91.2% and 77.6%, respectively. Of the 57 study patients 19 (33%) were alive with no evidence of disease, including a prostate specific antigen (PSA) less than 0.4 ng/ml at all times during follow-up. The estimated 5 year probability of clinical recurrence was 18.6%. and the 5 year probability of clinical and PSA recurrence (>0.4 ng/ml) was 54.5%. Local recurrence occurred in only 3 patients. This included 2 (4%) patients who received adjuvant radiotherapy. Our results suggest that patients with locally advanced prostate cancer can be successfully treated with low morbidity using a combination of radical prostatectomy and planned adjuvant radiotherapy.
The wrist arthropathy of "pseudogout" occurring with and without chondrocalcinosis.

A distinctive arthropathy of the wrist, characterized by joint space narrowing, sclerosis and subchondral cyst formation, predilecting the radiocarpal joint cavity, was present in 18 patients. Of these individuals, 14 had symptoms compatible with the “pseudogout” syndrome, 7 had calcium pyrophosphate dihydrate crystals demonstrable in joint aspirations, 9 had radiologic evidence of “local” Chondrocalcinosis in the wrist, and 7 had “distant” Chondrocalcinosis in other articulations. Because in some individuals with “pseudogout” a degenerative arthritis appears to precede Chondrocalcinosis, it is important that the radiologist recognize the arthropathy and not let absence of visible calcification in local or distant sites dissuade him from the diagnosis.