Miracle-dz/UniFAR-FTUs huggingface dataset:
Gender-Dependent Effect of ACE I/D and AGT M235T Polymorphisms on the Progression of Urinary Albumin Excretion in Taiwanese with Type 2 Diabetes

Background: We investigated the gender differences in the effect of ACE I/D and AGT M235T polymorphisms on the prognosis of diabetic nephropathy (DN). Methods: A total of 525 type 2 diabetics were enrolled to participate in this prospective observational study. ACE and AGT gene polymorphisms were analyzed by polymerase chain reaction. The progression of DN was defined as a shift to a higher stage of DN or a doubling of the baseline serum creatinine level by the end of the study. Results: The baseline biophysical parameters show no gender differences in progression and non-progression of DN. The women who were ACE D allele carriers were found to be at an increased risk of DN progression compared to those with II genotypes (p = 0.024, OR 2.176). No such difference was seen in male patients (p = 0.619, OR 0.833). After adjusting for confounding factors (age, SBP, DBP, BMI, HbA1c, total cholesterol, TG, HDL-C, LDL-C, ACEI, and ARB) in our multiple regression analysis, these women were still found to be at increased risk of progressing to more severe DN (p = 0.008, OR 3.082) but not the men (p = 0.183, OR 0.586). Neither the AGT TT genotype nor the T allele were associated with the progression of DN in either sex after adjusting for confounding factors. Conclusion: Our follow-up study suggests that female diabetic carriers of the ACE D allele might be at an increased risk of DN progression.
National kidney foundation K/DOQI clinical practice guidelines for nutrition in chronic renal failure.

The National Kidney Foundation Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Nutrition in Chronic Renal Failure was recently published in the American Journal of Kidney Diseases. This publication provides 27 clinical practice guidelines for adults and 10 clinical practice guidelines for children. The adult guidelines focus primarily on patients undergoing maintenance dialysis therapy, although there are several clinical practice guidelines on nutritional issues for patients with advanced chronic renal failure (CRF) not undergoing dialysis therapy. The pediatric guidelines focus entirely on children undergoing maintenance dialysis treatment. The present article discusses a number of the more prominent clinical practice guidelines for the adults. Among these is the recommendation that the protein-energy nutritional status in these patients should be assessed by a panel of measures rather than by any single measure. Also, non-dialyzed patients with advanced CRF (ie, glomerular filtration rate <25 mL/min) and those undergoing maintenance hemodialysis or chronic peritoneal dialysis should be prescribed a dietary energy intake of 35 kcal/kg/day for patients who are <60 years of age and 30 kcal/kg for patients >/=60 years of age. Maintenance hemodialysis patients should be prescribed 1.2 g protein/kg/d; chronic peritoneal dialysis patients should be prescribed 1.2 to 1.3 g protein/kg/d. For non-dialyzed patients with CRF (glomerular filtration rate <25 mL/min), 0.60 g protein/kg/d should be prescribed. For patients who will not accept such a diet or are unable to maintain an adequate energy intake on that diet, a protein intake of up to 0.75 g protein/kg/d may be prescribed. At least 50% of the protein intake for all of these patients should be of high biologic value. A guideline concerning indications for inaugurating maintenance dialysis treatment or renal transplantation on the basis of deteriorating nutritional status is also given.
Effects of basic fibroblast growth factor and leukaemia inhibitory factor on proliferation and short‐term culture of human spermatogonial stem cells

In this study, isolated spermatogonial stem cells (SSCs) and Sertoli cells using enzymatic digestion from patients with maturation arrest of spermatogenesis were grown in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% foetal calf serum in three different groups: (1) SSCs cultured without Sertoli cells (2) SSCs co‐cultured with Sertoli cells (as control group), (3) SSCs co‐cultured with Sertoli cells and adding different concentrations of basic fibroblast growth factor (0.1, 1, 10 ng ml−1) and human leukaemia inhibitory factor (1000, 1200, 1500 unit ml−1) as experimental groups. The assessment of colonies every 10 days during 5‐week cultures showed that in the first group, the average number and diameter of the colonies were significantly lower than in the other groups (P < 0.05). The largest number of colonies was observed in control condition (32.29 ± 9.15) in day 30. The largest diameter of colonies was formed in combination dosages of 1 ng ml−1 basic fibroblast growth factor (bFGF) + 1500 unit ml−1 leukaemia inhibitory factor (LIF) (302.93 ± 37.68) and 10 ng ml−1 bFGF and 1200 unit ml−1 LIF (262.87 ± 35.54) in day 30 respectively. Isolated SSCs were positive for spermatogonial cell markers such as Oct4, Stra8, Piwil2 and Vasa but negative for Nanog. Transplantation technique indicated that hSSCs have good efficiency for colonisation of mouse seminiferous tubules after proliferation in culture system.
Efficacy of oral powder compared with chewable tablets for lanthanum carbonate administration in hemodialysis patients

Lanthanum carbonate (LC) has been administered in a chewable tablet form for patients with hyperphosphatemia undergoing dialysis. However, some patients have difficulty chewing the tablets. LC oral powder has recently been released in Japan. The purpose of this study was to clarify the efficacy of LC oral powder form compared with that of chewable tablet form. The efficacy and safety of LC oral powder was retrospectively assessed in hemodialysis patients who switched from chewable tablet form to oral powder form without dose modification. Thirty‐six patients (mean age, 66.8 ± 10.5 years; male, 64%; 39% with diabetes; mean duration of dialysis treatment, 99.2 ± 95.6 months) were enrolled in this study between June and July of 2012. Changes in clinical data and adverse events after the switch to oral powder form were investigated. The average dose of LC was 1180 ± 520 mg/day. Serum phosphorus levels were significantly decreased after the switch from chewable tablet form to oral powder form (5.3 ± 1.7 mg/dL at baseline vs. 4.9 ± 1.2 mg/dL at after 1 month after, P = 0.038). In contrast, no significant differences were observed in serum calcium and parathyroid hormone levels. Furthermore, no significant differences were evident in weight gain after the switch to oral powder form (2.5 ± 1.2 kg at baseline vs. 2.4 ± 1.1 kg at 1 month after the switch, P = 0.29). No serious adverse events were recorded. Our results suggest that LC is more effective in oral powder form than chewable tablet form for hemodialysis patients.
Disorders of Tumoral Calcification of the Spine: Illustrative Case Study and Review of the Literature

Tumoral calcium pyrophosphate dihydrate crystal deposition disease and tumoral calcinosis (TC) are rare non-neoplastic conditions which may cause symptoms of spinal cord compression when they manifest in the perispinal tissues. There is little information available to compare these conditions with each other. We report a case of a patient with such a calcified mass impinging on the spinal cord. A 39-year-old woman on hemodialysis presents with progressive quadriparesis and monoplegia and is found to have a large calcified mass impinging on the spinal cord at the level of C3-4. The mass is excised by an anterior approach with corpectomy and fusion. Pathology was tumoral calcium pyrophosphate dihydrate crystal deposition disease versus TC. Both conditions are very rare in the perispinal tissues with 21 reported cases of tumoral calcium pyrophosphate dihydrate deposition disease and 39 cases of TC. Both cause compressive symptoms depending on the site of occurrence. Tumoral calcium pyrophosphate deposition disease is characterized by smaller, round, masses typically in ligamentous structures which may erode into adjacent bone. Tumoral calcinosis displays larger, lobulated, irregular lesions which do not erode into bone. Either lesion may contain calcium pyrophosphate dihydrate or hydroxyapatite. Treatment is surgical decompression, though lesions may recur.
Water and Ion Permeation of Aquaporin-1 in Planar Lipid Bilayers

The aquaporin-1 (AQP1) water channel protein is known to facilitate the rapid movement of water across cell membranes, but a proposed secondary role as an ion channel is still unsettled. Here we describe a method to simultaneously measure water permeability and ion conductance of purified human AQP1 after reconstitution into planar lipid bilayers. Water permeability was determined by measuring Na+ concentrations adjacent to the membrane. Comparisons with the known single channel water permeability of AQP1 indicate that the planar lipid bilayers contain from 106 to 107 water channels. Addition of cGMP induced ion conductance in planar bilayers containing AQP1, whereas cAMP was without effect. The number of water channels exceeded the number of active ion channels by approximately 1 million-fold, yet p-chloromethylbenzenesulfonate inhibited the water permeability but not ion conductance. Identical ion channel parameters were achieved with AQP1 purified from human red blood cells or AQP1 heterologously expressed in Saccharomyces cerevisae and affinity purified with either N- or C-terminal poly-histidine tags. Rp-8-Br-cGMP inhibited all of the observed conductance levels of the cation selective channel (2, 6, and 10 pS in 100 mmNa+ or K+). Deletion of the putative cGMP binding motif at the C terminus by introduction of a stop codon at position 237 yielded a truncated AQP1 protein that was still permeated by water but not by ions. Our studies demonstrate a method for simultaneously measuring water permeability and ion conductance of AQP1 reconstituted into planar lipid bilayers. The ion conductance occurs (i) through a pathway distinct from the aqueous pathway, (ii) when stimulated directly by cGMP, and (iii) in only an exceedingly small fraction of AQP1 molecules.
Trauma and inflammation modulate lymphocyte localization in vivo: Quantitation of tissue entry and retention using Indium‐111‐labeled lymphocytes

Objective: Determine the in vivo localization pattern of indium‐111‐labeled lymphocytes after a standardized extremity injury or standardized laparotomy and after sterile inflammation of the central nervous system. Design: Prospective animal study with concurrent controls. Setting: Animal research laboratory. Subjects: Male Lewis rats weighing 150‐175 g. Interventions: Indium‐111‐labeled splenic lymphocytes were injected into animals after a standardized hind limb trauma or laparotomy and after induction of sterile central nervous system inflammation. Measurements and Main Results: Lymphoid and non‐lymphoid organs were removed at fixed intervals after lymphocyte injection and the proportion of injected lymphocytes/gram of tissue was determined using a quantitative radionuclide calculation. Results from treated animals were compared with results from untreated control animals. Muscle injury caused early localization of lymphocytes to injured hind limbs, liver, and spleen compared with controls, whereas laparotomy decreased lymphocyte localization in the thymus and colon. Encephalitis increased localization to the central nervous system with no effect on other tissues. Conclusions: These results identify a sensitive method to track in vivo leukocyte localization and specifically demonstrate that lymphocyte localization is altered in both traumatic and nontraumatic models of inflammation.
Estimation of neonatal outcome and perinatal therapy use.

OBJECTIVES To learn whether US obstetricians and pediatricians accurately estimate rates of survival and freedom from handicap in preterm infants and to learn whether their knowledge and attitudes influence their choice of interventions that may enhance survival. METHODS A cross-sectional survey of obstetricians and pediatricians practicing in the United States was performed using a pretested questionnaire designed to identify their knowledge regarding survival and handicap-free rates of infants born at 23 to 36 weeks of gestation. At each week of gestation, they were asked whether they would provide specific therapeutic interventions to either the expectant mother or infant. Survival and handicap-free rates were compared with published national rates. Obstetricians and pediatricians were divided into an optimists group and a pessimists group, based on their estimates of survival. The rates at which each group used therapeutic interventions were compared. RESULTS Both obstetricians and pediatricians underestimated survival rates from 24 through 35 weeks of gestation and freedom from serious handicap from 23 through 36 weeks of gestation. On the average, optimists accurately predicted neonatal survival. Obstetricians who underestimated neonatal survival would less often administer antenatal corticosteroids, perform a cesarean section for fetal distress, and transfer a mother to a tertiary center. Pediatricians who underestimated neonatal survival would less often use mechanical ventilation, cardiopulmonary resuscitation, inotropes, intravenous fluids, thermal support, and oxygen supplementation. CONCLUSION Physicians underestimate survival and freedom from handicap in preterm infants. Underestimation of outcome is associated with restriction in the use of appropriate interventions.
Advances in Influenza Virus Vaccine Research a

Influenza epidemics occur annually in the United States and are characterized by high frequencies of illness among children and young adults, high hospitalization rates among infants and older persons, and high death rates among the elderly. Vaccines that can prevent infection must stimulate anti-hemagglutinin antibody in serum and secretions; those that stimulate anti-neuraminidase antibody or T cell cytotoxic responses can reduce the severity of infection and illness or hasten recovery. Advances in vaccine research are permitting evaluation of pure subunit vaccines, new adjuvants, topical immunization, and the use of immunomodulators for enhancing immune responses. In young adults, doses of HA of up to 405 micrograms were well tolerated and provided enhanced antibody responses. Although use of a muramyl-dipeptide derivative as an adjuvant resulted in unacceptable reactogenicity, other adjuvants may be acceptable. Development of topical immunization and immunomodulators are under way. The cold-adapted live attenuated influenza virus vaccines for nasal administration are nearing availability. They are safe, immunogenic, and protective with greatest effectiveness among young children, in whom inactivated vaccines are less useful. Use among children should moderate the high frequencies of illness and hospitalization in this group and reduce spread of influenza in the community. CRV also provide an alternative to inactivated vaccines among young adults, in whom they can be equally protective.
Isolation and Biochemical Characterization of a Ca2+-independent α-Latrotoxin-binding Protein*

α-Latrotoxin, a black widow spider neurotoxin, can bind to high affinity receptors on the presynaptic plasma membrane and stimulate massive neurotransmitter release in the absence of Ca2+. Neurexins, previously isolated as α-latrotoxin receptors, require Ca2+ for their interaction with the toxin and, thus, may not participate in the Ca2+-independent α-latrotoxin activity. We now report the isolation of a novel protein that binds α-latrotoxin with high affinity in the presence of various divalent cations (Ca2+, Mg2+, Ba2+, and Sr2+) as well as in EDTA. This protein, termed here latrophilin, has been purified from detergent-solubilized bovine brain membranes by affinity chromatography on immobilized α-latrotoxin and concentrated on a wheat germ agglutinin affinity column. The single polypeptide chain of latrophilin is N-glycosylated and has an apparent molecular weight of 120,000. Sucrose gradient centrifugations demonstrated that latrophilin and α-latrotoxin form a stable equimolar complex. In the presence of the toxin, anti-α-latrotoxin antibodies precipitated iodinated latrophilin, whose binding to immobilized toxin was characterized by a dissociation constant of 0.5-0.7 n. This presumably membrane-bound protein is localized to and differentially distributed among neuronal tissues, with about four times more latrophilin expressed in the cerebral cortex than in the cerebellum; subcellular fractionation showed that the protein is highly enriched in synaptosomal plasma membranes. Our data suggest that latrophilin may represent the Ca2+-independent receptor and/or molecular target for α-latrotoxin.
Metal ion coordination in the E. coli Nudix hydrolase dihydroneopterin triphosphate pyrophosphatase: New clues into catalytic mechanism

Dihydroneopterin triphosphate pyrophosphatase (DHNTPase), a member of the Mg2+ dependent Nudix hydrolase superfamily, is the recently-discovered enzyme that functions in the second step of the pterin branch of the folate biosynthetic pathway in E. coli. DHNTPase is of interest because inhibition of enzymes in bacterial folate biosynthetic pathways is a strategy for antibiotic development. We determined crystal structures of DHNTPase with and without activating, Mg2+-mimicking metals Co2+ and Ni2+. Four metal ions, identified by anomalous scattering, and stoichiometrically confirmed in solution by isothermal titration calorimetry, are held in place by Glu56 and Glu60 within the Nudix sequence motif, Glu117, waters, and a sulfate ion, of which the latter is further stabilized by a salt bridge with Lys7. In silico docking of the DHNTP substrate reveals a binding mode in which the pterin ring moiety is nestled in a largely hydrophobic pocket, the β-phosphate activated for nucleophilic attack overlays with the crystallographic sulfate and is in line with an activated water molecule, and remaining phosphate groups are stabilized by all four identified metal ions. The structures and binding data provide new details regarding DHNTPase metal requirements, mechanism, and suggest a strategy for efficient inhibition.
Attenuation of DNA-dependent protein kinase activity and its catalytic subunit by the herpes simplex virus type 1 transactivator ICP0

The DNA-dependent protein kinase (DNA-PK) is involved in several fundamental nuclear processes, including DNA double-strand break repair, V(D)J recombination, and transcription by RNA polymerases I and II. In this study, we show that infection of mammalian cells with herpes simplex virus type 1 attenuates DNA-PK activity by specifically depleting the p350/DNA-PKcs catalytic subunit. The half-life of the p350/DNA-PKcs protein decreases from greater than 24 h to less than 4 h following infection. The depletion of DNA-PK activity and p350/DNA-PKcs abundance is dependent on expression of the viral immediate-early protein ICP0. As ICP0 acts as a promoter-independent transactivator of gene expression, these data suggest that ICP0 may function by directly or indirectly targeting the p350/DNA-PKcs subunit of DNA-PK, thereby altering the inhibitory effects of DNA-PK on RNA polymerase II transcription.
Saccades to Explicit and Virtual Features in the Poggendorff Figure Show Perceptual Biases

Human participants made saccadic eye movements to various features in a modified vertical Poggendorff figure, to measure errors in the location of key geometrical features. In one task, subjects (n = 8) made saccades to the vertex of the oblique T-intersection between a diagonal pointer and a vertical line. Results showed both a small tendency to shift the saccade toward the interior of the angle, and a larger bias in the direction of a shorter saccade path to the landing line. In a different kind of task (visual extrapolation), the same subjects fixated the tip of a 45° pointer and made a saccade to the implicit point of intersection between pointer and a distant vertical line. Results showed large errors in the saccade landing positions and the saccade polar angle, in the direction predicted from the perceptual Poggendorff bias. Further experiments manipulated the position of the fixation point relative to the implicit target, such that the Poggendorff bias would be in the opposite direction from a bias toward taking the shortest path to the landing line. The bias was still significant. We conclude that the Poggendorff bias in eye movements is in part due to the mislocation of visible target features but also to biases in planning a saccade to a virtual target across a gap. The latter kind of error comprises both a tendency to take the shortest path to the landing line, and a perceptual error that overestimates the vector component orthogonal to the gap.
Accepted Manuscript Title : Review : Salt stress sensing and early signalling events in plant roots : current knowledge and hypothesis

Soil salinity is a major environmental constraint to crop production. While the molecular identity and functional expression of Na+ transport systems mediating Na+ exclusion from the cytosol has been studied in detail, far less is known about the mechanisms by which plants sense high Na+ levels in the soil and the rapid signalling events that optimise plant performance under saline conditions. This review aims to fill this gap. We first discuss the nature of putative salt stress sensors, candidates which include Na+ transport systems, mechanosensory proteins, proteins with regulatory Na+ binding sites, sensing mediated by cyclic nucleotide-gated channels, purine receptors, annexin and voltage gating. We suggest that several transport proteins may be clustered together to form a microdomain in a lipid raft, allowing rapid changes in the activity of an individual protein to be translated into stress-induced Ca2+ and H2O2 signatures. The pathways of stress signalling to downstream targets are discussed, and the kinetics and specificity of salt stress signalling between glycophytes and halophytes is compared. We argue that these sensing mechanisms operate in parallel, providing plants with a robust system for decoding information about the specific nature and severity of the imposed salt stress.
Nano-Optical Control of Hot-Spot Field Superenhancement on a Corrugated Silver Surface

Coherent control of ultrafast nano-optical excitations of a corrugated silver surface is demonstrated by means of predetermined few-parameter scans and adaptive polarization laser pulse shaping. “Hot spots” in the multiphoton photoemission signals are enhanced and manipulated with a high contrast. Switching between separated and closely spaced hot spots is shown. The latter allows controlling the shape of hot spots and yields improved nanofocusing and “purification” of the photoemission signals. Complex pulse shapes were obtained in adaptive optimizations whose features were reproducible in repeated runs. Predetermined few-parameter control scans provide insight into the interpretation of optimal pulse shapes. The results indicate the existence of long coherence lifetimes on a corrugated silver surface. This combination of collective strong nanoplasmonic near-field enhancement and long-lived coherence may be used to achieve an even stronger field enhancement (“superenhancement”) making these hot spots ideal candidates for future nanophotonic, spectroscopic, sensor and quantum information applications. In addition the observation of such long coherence lifetimes is relevant to the understanding of surface-enhanced spectroscopies such as single-molecule Raman spectroscopy.