Miracle-dz/UniFAR-FTUs huggingface dataset:
Lower Hippocampal Volume Predicts Decrements in Lane Control Among Drivers With Amnestic Mild Cognitive Impairment

Objectives: There are few methods to discern driving risks in patients with early dementia and mild cognitive impairment (MCI). We aimed to determine whether structural magnetic resonance imaging (MRI) of the hippocampus—a biomarker of probable Alzheimer pathology and a measure of disease severity in those affected—is linked to objective ratings of on-road driving performance in older adults with and without amnestic MCI. Methods: In all, 49 consensus-diagnosed participants from an Alzheimer’s Disease Research Center (15 diagnosed with amnestic MCI and 34 demographically similar controls) underwent structural MRI and on-road driving assessments. Results: Mild atrophy of the left hippocampus was associated with less-than-optimal ratings in lane control but not with other discrete driving skills. Decrements in left hippocampal volume conferred higher risk for less-than-optimal lane control ratings in the patients with MCI (B = −1.63, standard error [SE] = .74, Wald = 4.85, P = .028), but not in controls (B = 0.13, SE = .415, Wald = 0.10, P = .752). The odds ratio and 95% confidence interval for below-optimal lane control in the MCI group was 4.41 (1.18-16.36), which was attenuated to 3.46 (0.88-13.60) after accounting for the contribution of left hippocampal volume. Conclusion: These findings suggest that there may be a link between hippocampal atrophy and difficulties with lane control in persons with amnestic MCI. Further study appears warranted to better discern patterns of brain atrophy in MCI and Alzheimer disease and whether these could be early markers of clinically meaningful driving risk.
Generation and Use of Cultured Human Primary Myotubes

Cell culture is a widely used technique in biomedical research. It permits the analysis of cell specific functions which can relate to changes in certain disease states at the single cell level. A number of cell culture models have been established. These include immortalised cell lines which replicate indefinitely in culture and retain the ability to differentiate and primary cell lines which can be isolated directly from the host tissue and grown in culture. However, primary cell lines have limited replicative potential and become senescent in culture. In the case of muscle cells, cell lines can provide a valuable means of investigating physiology in the absence of confounding factors (such as circulating hormones, adipokines and other bioactive molecules) which arise when dealing with the body as a whole.
A Novel Lensless Miniature Contact Imaging System for Monitoring Calcium Changes in Live Neurons

Here, we report on the design, fabrication, and verification of a novel CMOS-imager-based contact imaging system. We acquired fluorescent images from live neurons by monitoring calcium changes with Fura-2 dye. Our current device consists of a removable absorption filter interfaced with a CMOS imaging sensor and an external DG-4 lamp for excitation. Fura-2 loaded Lymnaea stagnalis neurons were stimulated with dual excitation wavelengths of 340 and 380 nm; our image sensor detected 510-nm emission. We show that our system is capable of detecting intracellular calcium changes in Fura-2 loaded neurons. Further, this sensor also enabled viewing of multiple neurons over a large surface area simultaneously, an option that is not readily available in conventional light microscopy.
Biology and physiology of the lower Trypanosomatidae

IETRODUCTION . 140 GENERAL BIOLOGY AND SYSTEMATICS . 141 Systematics . 141 Examination of Genera . 143 Distribution . 143 Ecology . 144 Life histories . 144 Pathogenicity and Possible Zoonosis . 148 CELL BIOLOGY AND PHYSIOLOGY OF THE LOWER TRYPANOSOMATIDS 151 Cell Surface and Plasma Membrane. 151 Cytoplasmic Organelles . 154 Kinetoplast-Mitochondrion Complex . 156 Nucleus and Cell Division . 160 Flagellar Structure and Activity . 161 Endosymbiotes . 163 LITERATURE CITED . 164
Thyroid Dysfunction Following Supraclavicular Irradiation in The Management of Carcinoma of the Breast.

Radiation induced thyroid dysfunction is usually underestimated in patients with breast cancer who had supraclavicular irradiation (RT). In the present study, a total of 28 patients with breast cancer received supraclavicular RT were evaluated focusing on radiation dose-volume factors in relation to thyroid function. Thyroid function tests, including serum thyroid stimulating hormone, free thyroxine, free triiodothyronine, were analyzed prior to RT and 3, 6, 9, 12, 18 and 24 months after RT. Based on each patient’s dose volume histogram (DVH), total volume of the thyroid, mean radiation dose the thyroid and percentages of thyroid volume which received radiation doses 10-50 Gy (V10-V50) were considered for statistical analysis. The median follow-up time was 25 months (range, 12.3-36 months). Of 28 patients 6 (21%) were diagnosed with hypothyroidism (HT). The median time to the development of HT was 9 months (range: 3-18 months). Mean thyroid dose was 31 Gy (19-48 Gy) and mean thyroid volume was 32 cc (12-64 cc). We found that V20 (OR= 10, 95% CI= 1.15-86.88, p= 0.05), V30 (OR= 10, 95% CI= 1.15-86.88, p= 0.05) and V40 (OR= 21, 95% CI= 1.61-273.34, p= 0.02) and mean thyroid dose ≥36 Gy (OR= 10, 95% CI= 1.15-86.88) (p= 0.05), had a significant impact on development of HT. Moreover, significant elevation was observed in mean TSH level between baseline (1.85±1.47 mIU/L) and at 6 months (3.80±7.42 mIU/L), (p= 0.003). Supraclavicular RT in patients with breast cancer appear to amplify the risk of HT. We believe further investigations in larger cohort are required to confirm our results.
Autoimmunity to endometrium and ovary in endometriosis.

Antibody titres to whole ovary, theca cells, granulosa cells and endometrium were determined by passive haemagglutination and immunofluorescence assays in sera and in cervical and vaginal secretions from 13 patients with endometriosis. Antibody titres to endometrium (mean log2 +/- s.e.m., 7.08 +/- 0.80; P less than 0.0001), ovary (3.58 +/- 0.87; P = 0.0092), theca cells (4.42 +/- 0.73; P less than 0.0001) and granulosa cells (3.33 +/- 0.63; P = 0.0024) were significantly higher in the patients' sera than in sera from 15 normal non-pregnant females. Antibody titres to granulosa cells were elevated (7.97 +/- 1.46; P = 0.0424) in their cervical secretions. Antibody titres to all tissues tested were similar in vaginal secretions of patients and controls. Immunofluorescent antibody assay of biopsied endometrial tissue and sera from the patients revealed the antibodies to be primarily IgG and IgA. The results suggest that autoantibodies to endometrium and ovary are present in patients with endometriosis.
Simultaneous Optical Pulse Multiplication and Shaping Based on the Amplitude-Assisted Phase-Only Filter Utilizing a Fiber Bragg Grating

A novel all-optical simultaneous pulse multiplication and shaping approach is proposed, which is based on the simultaneous utilization of two amplitude-assisted phase-only spectral filters realizable by using a short fiber Bragg grating. This proposed method enables to create a high-repetition-rate rectangular pulse train with both an ideal rectangular envelop and a high energy efficiency. As a particular example, a repetition rate of 90 GHz rectangular pulse train is numerically demonstrated from an initial 10 GHz Gaussian pulse train.
Superficial and deep juxtaglomerular apparatus renin activity of the rat kidney. Effect of surgical preparation and NaCl intake.

The intrarenal gradient of renin activity was determined in rats by using superficial (S) and deep (D) cortical juxtaglomerular apparatuses (JGA's), identified and microdissected after silicone-rubber compound injection. Angiotensin generated from single JGA's using partially purified sheep renin substrate was quantified by rat bioassay. When, in rats on a normal NaCl diet, silicone-rubber was injected into a carotid artery, alone or with abdominal aorta catheterization, S:D renin activity ratios were 1.18+/-0.08 (SEM) and 1.21+/-0.12, respectively. The S:D renin activity ratios obtained when silicone-rubber was injected into the abdominal aorta (2.52+/-0.09) or a chronic carotid artery catheter (3.44+/-0.40) were significantly higher (P < 0.001). The lower S:D renin activity ratios after carotid artery manipulation were due to significantly higher D-JGA renin activities. This increased D-JGA renin activity and the lack of a renin gradient appear to be related to acute carotid artery manipulation. Alterations in JGA renin activity were examined relative to NaCl intake. 2 wk after high-NaCl diet the absolute net renin activity decreased (P < 0.001) more in S (5.84+/-0.11 ng AI.JGA(-1). h(-1)) than D (1.73+/-0.06 ng AI.JGA(-1). h(-1)) JGA's, and the intrarenal renin gradient was lost (S:D-JGA renin activity, 1.00+/-0.07), as compared to the regular NaCl diet. 2 wk of a low-NaCl diet resulted in a greater (P < 0.01) increase in S (14.28+/-1.47 ng AI.JGA(-1). h(-1)) than D (9.62+/-1.19 ng AI.JGA(-1). h(-1)) JGA renin activity and a renin gradient (S:D-JGA renin activity) of 1.75+/-0.12. These results demonstrate that NaCl intake clearly influences total JGA renin content and may also affect the relative intrarenal distribution of renin activity.
Cokriging estimation of the conductivity field under variably saturated flow conditions

A linear estimator, cokriging, was applied to estimate hydraulic conductivity, using pressure head, solute concentration, and solute arrival time measurements in a hypothetical, heterogeneous vadose zone under steady state infiltrations at different degrees of saturation. Covariances and cross‐covariances required by the estimator were determined by a first‐order approximation in which sensitivity matrices were calculated using an adjoint state method. The effectiveness of the pressure, concentration, and arrival time measurements for the estimator were then evaluated using two statistical criteria, L1 and L2 norms, i.e., the average absolute error and the mean square error of the estimated conductivity field. Results of our analysis showed that pressure head measurements at steady state flow provided the best estimation of hydraulic conductivity among the three types of measurements. In addition, head measurements of flow near saturation were found more useful for estimating conductivity than those at low saturations. The arrival time measurements do not have any significant advantage over concentration. Factors such as variability, linearity, and ergodicity were discussed to explain advantage and limitation of each type of data set. Finally, to take advantage of different types of data set (e.g., head and concentration), a computationally efficient estimation approach was developed to combine them sequentially to estimate the hydraulic conductivity field. The conductivity field estimated by using this sequential approach proves to be better than all the previous estimates, using one type of data set alone.
Protein structure determination using metagenome sequence data

Filling in the protein fold picture Fewer than a third of the 14,849 known protein families have at least one member with an experimentally determined structure. This leaves more than 5000 protein families with no structural information. Protein modeling using residue-residue contacts inferred from evolutionary data has been successful in modeling unknown structures, but it requires large numbers of aligned sequences. Ovchinnikov et al. augmented such sequence alignments with metagenome sequence data (see the Perspective by Söding). They determined the number of sequences required to allow modeling, developed criteria for model quality, and, where possible, improved modeling by matching predicted contacts to known structures. Their method predicted quality structural models for 614 protein families, of which about 140 represent newly discovered protein folds. Science, this issue p. 294; see also p. 248 Combining metagenome data with protein structure prediction generates models for 614 families with unknown structures. Despite decades of work by structural biologists, there are still ~5200 protein families with unknown structure outside the range of comparative modeling. We show that Rosetta structure prediction guided by residue-residue contacts inferred from evolutionary information can accurately model proteins that belong to large families and that metagenome sequence data more than triple the number of protein families with sufficient sequences for accurate modeling. We then integrate metagenome data, contact-based structure matching, and Rosetta structure calculations to generate models for 614 protein families with currently unknown structures; 206 are membrane proteins and 137 have folds not represented in the Protein Data Bank. This approach provides the representative models for large protein families originally envisioned as the goal of the Protein Structure Initiative at a fraction of the cost.
The moral disengagement in sport scale–short

Abstract A scale has recently been developed to measure moral disengagement in sport (Boardley & Kavussanu, 2007). It consists of 32 items that measure the eight mechanisms of moral disengagement proposed by Bandura (1991). In the present study, we aimed to: (a) examine whether a subset of these items could form a short version of the scale; (b) provide evidence for the construct validity of the short version; and (c) test its measurement invariance across sex and sport type. A total of 992 football, rugby, hockey, basketball, and netball players from three different samples completed the long version of the scale. Data analyses indicated that the short version of the scale consisted of eight items and had high internal consistency. Construct validity of the scale was evidenced via correlations with sport moral disengagement and prosocial and antisocial behaviour. Multisample confirmatory factor analyses established measurement invariance across sex and partial measurement invariance across four team sports. In conclusion, the short version of the scale is a reliable and valid measure of moral disengagement in sport.
Probiotic modulation of dendritic cells co-cultured with intestinal epithelial cells.

AIM To investigate cytokine production and cell surface phenotypes of dendritic cells (DC) in the presence of epithelial cells stimulated by probiotics. METHODS Mouse DC were cultured alone or together with mouse epithelial cell monolayers in normal or inverted systems and were stimulated with heat-killed probiotic bacteria, Bifidobacterium lactis AD011 (BL), Bifidobacterium bifidum BGN4 (BB), Lactobacillus casei IBS041 (LC), and Lactobacillus acidophilus AD031 (LA), for 12 h. Cytokine levels in the culture supernatants were determined by enzyme-linked immunosorbent assay and phenotypic analysis of DC was investigated by flow cytometry. RESULTS BB and LC in single-cultured DC increased the expression of I-Ad, CD86 and CD40 (I-Ad, 18.51 vs 30.88, 46.11; CD86, 62.74 vs 92.7, 104.12; CD40, 0.67 vs 6.39, 3.37, P < 0.05). All of the experimental probiotics increased the production of inflammatory cytokines, interleukin (IL)-6 and tumor necrosis factor (TNF)-α. However, in the normal co-culture systems, LC and LA decreased the expression of I-A(d) (39.46 vs 30.32, 33.26, P < 0.05), and none of the experimental probiotics increased the levels of IL-6 or TNF-α. In the inverted co-culture systems, LC decreased the expression of CD40 (1.36 vs -2.27, P < 0.05), and all of the experimental probiotics decreased the levels of IL-6. In addition, BL increased the production of IL-10 (103.8 vs 166.0, P < 0.05) and LC and LA increased transforming growth factor-β secretion (235.9 vs 618.9, 607.6, P < 0.05). CONCLUSION These results suggest that specific probiotic strains exert differential immune modulation mediated by the interaction of dendritic cells and epithelial cells in the homeostasis of gastrointestinal tract.
Therapies for treatment of osteoporosis in US women: cost-effectiveness and budget impact considerations.

OBJECTIVE To evaluate the cost-effectiveness of osteoporosis treatments for women at high fracture risk and estimate the population-level impact of providing bisphosphonate therapy to all eligible high-risk US women. STUDY DESIGN Fractures, healthcare costs, and quality-adjusted life-years (QALYs) were estimated over 10 years using a Markov model. METHODS No therapy, risedronate, alendronate, ibandronate, and teriperatide (PTH) were compared among 4 risk groups. Sensitivity analyses examined the robustness of model results for 65-year-old women with low bone density and previous vertebral fracture. RESULTS Women treated with a bisphosphonate experienced fewer fractures and more QALYs compared with no therapy or PTH. Total costs were lowest for the untreated cohort, followed by risedronate, alendronate, ibandronate, and PTH in all risk groups except women aged 75 years with previous fracture. The incremental cost-effectiveness of risedronate compared with no therapy ranged from cost saving for the base case to $66,722 per QALY for women aged 65 years with no previous fracture. Ibandronate and PTH were dominated in all risk groups. (A dominated treatment has a higher cost and poorer outcome.) Treating all eligible women with a bisphosphonate would cost an estimated additional $5563 million (21% total increase) and would result in 390,049 fewer fractures (35% decrease). In the highest risk group, the additional cost of therapy was offset by other healthcare cost savings. CONCLUSIONS Osteoporosis treatment of high-risk women is cost-effective, with bisphosphonates providing the most benefit at lowest cost. For highest risk women, costs are offset by savings from fracture prevention.
Failure to ferment dietary resistant starch in specific mouse models of obesity results in no body fat loss.

UNLABELLED Resistant starch (RS) is a fermentable fiber that decreases dietary energy density and results in fermentation in the lower gut. The current studies examined the effect of RS on body fat loss in mice. In a 12 week study (study 1), the effect of two different types of RS on body fat was compared with two control diets (0% RS) in C57Bl/6J mice: regular control diet or the control diet that had energy density equal to that of the RS diet (EC). All testing diets had 7% (w/w) dietary fat. In a 16 week study (study 2), the effect of RS on body fat was compared with EC in C57BL/6J mice and two obese mouse models (NONcNZO10/LtJ or Non/ShiLtJ). All mice were fed control (0% RS) or 30% RS diet for 6 weeks with 7% dietary fat. On the seventh week, the dietary fat was increased to 11% for half of the mice and remained the same for the rest. Body weight, body fat, energy intake, energy expenditure, and oral glucose tolerance were measured during the study. At the end of the studies, the pH of cecal contents was measured as an indicator of RS fermentation. Compared with EC, dietary RS decreased body fat and improved glucose tolerance in C57BL/6J mice but not in obese mice. For other metabolic characteristics measured, the alterations by RS diet were similar for all three types of mice. The difference in dietary fat did not interfere with these results. The pH of cecal contents in RS fed mice was decreased for C57BL/6J mice but not for obese mice, implying the impaired RS fermentation in obese mice. CONCLUSIONS (1) decreased body fat by RS is not simply due to dietary energy dilution in C57Bl/6J mice, and (2) along with their inability to ferment RS, RS fed obese mice did not lose body fat. Thus, colonic fermentation of RS might play an important role in the effect of RS on fat loss.
Dual regulation of upstream binding factor 1 levels by IRS‐1 and ERKs in IGF‐1‐receptor signaling

The Upstream Binding Factor 1 (UBF1) is a nucleolar protein that participates in the regulation of RNA polymerase I activity and ribosomal RNA (rRNA) synthesis. In 32D myeloid cells expressing the type 1 insulin‐like growth factor receptor (IGF‐IR), the UBF1 protein (but not its mRNA) is down regulated when the cells are shifted from Interleukin‐3 (IL‐3) to IGF‐1. Ectopic expression of insulin receptor substrate‐1 (IRS‐1) in these cells inhibits the down‐regulation of UBF1. We now show that the stability of UBF1 in 32D‐derived cells requires also a signal from the extracellular regulated kinases (ERKs). When ERKs signaling is defective, as in cells over‐expressing the insulin receptor (InR) or selected mutants of the IGF‐1R, UBF1 is down‐regulated, even in the presence of IRS‐1. The down‐regulation is corrected by the expression of an activated Ha‐ras, which stimulates ERKs activity. Mutations at threonines 117 and 201 of UBF1, known to be phosphorylated by ERKs, cause its down‐regulation. However, when IRS‐2, instead of IRS‐1, is ectopically expressed in 32D InR cells, ERKs phosphorylation is increased and UBF is stabilized. Taken together, these results indicate that in 32D‐derived myeloid cells expressing either the IGF‐IR or the InR, UBF1 levels are regulated by signaling from both IRS proteins and ERKs. J. Cell. Physiol. 212:780–786, 2007. © 2007 Wiley‐Liss, Inc.
E. coli methionine sulfoxide reductase with a truncated N terminus or C terminus, or both, retains the ability to reduce methionine sulfoxide

The monomeric peptide methionine sulfoxide reductase (MsrA) catalyzes the irreversible thioredoxin‐dependent reduction of methionine sulfoxide. The crystal structure of MsrAs from Escherichia coli and Bos taurus can be described as a central core of about 140 amino acids that contains the active site. The core is wrapped by two long N‐ and C‐terminal extended chains. The catalytic mechanism of the E. coli enzyme has been recently postulated to take place through formation of a sulfenic acid intermediate, followed by reduction of the intermediate via intrathiol‐disulfide exchanges and thioredoxin oxidation. In the present work, truncated MsrAs at the N‐ or C‐terminal end or at both were produced as folded entities. All forms are able to reduce methionine sulfoxide in the presence of dithiothreitol. However, only the N‐terminal truncated form, which possesses the two cysteines located at the C‐terminus, reduces the sulfenic acid intermediate in a thioredoxin‐dependent manner. The wild type displays a ping‐pong mechanism with either thioredoxin or dithiothreitol as reductant. Kinetic saturation is only observed with thioredoxin with a low KM value of 10 μM. Thus, thioredoxin is likely the reductant in vivo. Truncations do not significantly modify the kinetic properties, except for the double truncated form, which displays a 17‐fold decrease in kcat/KMetSO. Alternative mechanisms for sulfenic acid reduction are also presented based on analysis of available MsrA sequences.
Temperature-induced experimental myocardial hypertrophy in chick embryos. An electron-microscopic and chemical study.

Several reports have described both the chemical and morphologic findings in the various types of human glycogen-storage disease.9 Because the materials for these studies on liver, heart, and skeletal muscle were obtained from human biopsies or necropsies, limitations were present with respect to an extensive basic experimental approach to this group of diseases. We have observed that chick embryonic development was considerably modified by different temperatures of incubation. The chick heart was greatly altered in size and weight under such conditions. These observations were made in the course of experiments on the morphology of Walker 256 carcinosarcoma placed on the chorioallantoic membrane of chick eggs incubated at various temperatures.10 The presence of increased glycogen and the persistence and increased numbers of annulate lamellae were found in the enlarged hearts obtained from chicks incubated at a lower than normal temperature. Thus, the cardiac hypertrophy produced provides a possible experimental model for the study of the glycogenoses and, indeed, of myocardial hypertrophy and failure during an early period of life. The present report is a chemical and electron-microscopic study of myocardial hypertrophy in the chick embryo induced by an abnormal incubation temperature during the latter half of gestation.