Phylogenetic utility of the glycerol-3-phosphate acyltransferase gene: evolution and implications in Paeonia (Paeoniaceae).
The nuclear-encoded chloroplast-expressed glycerol-3-phosphate acyltransferase (GPAT) gene has been found to be single-copy in a number of angiosperm families. In this study we investigated the phylogenetic utility of the GPAT gene at the interspecific level using the genus Paeonia (Paeoniaceae) as an example. An approximately 2.3- to 2.6-kb fragment of the GPAT gene, containing a large intron of more than 2 kb, was amplified, cloned, and sequenced from 19 accessions representing 13 Paeonia species. The GPAT gene phylogeny inferred by parsimony analysis supported interspecific relationships that were previously unresolved, suggesting that large introns of low-copy nuclear genes are particularly informative in the resolution of close relationships at low taxonomic levels. Whereas the GPAT phylogeny is largely congruent with the previous phylogenetic hypothesis of Paeonia, it shows a significant discordance involving the paraphyly of section Paeonia. Given evidence of an ancient duplication and the subsequent silencing of one GPAT locus in P. anomala, this discordance is most likely the result of paralogy. Two distinct genomic clones containing partial GPAT genes were isolated from P. anomala. The GPAT sequence from one clone corresponded to the functional copy of the gene, and the second genomic clone was determined to contain a GPAT pseudogene. The insertion of a retrotransposon in an intron of this pseudogene may have been responsible for the silencing of this GPAT locus in P. anomala. This study suggests that, although it is unlikely that universal nuclear gene markers free from paralogy are usually available, low-copy nuclear genes can be very useful in plant phylogenetic reconstruction, especially at low taxonomic levels, as long as the evolutionary dynamics of the genes are carefully examined.


Pharmacologic treatment of manic and depressive illness.
In following the course of any patient who is being treated with psychiatric medication, the treating physician must at all times focus on the course of the primary symptom complex for which the treatment was undertaken; the therapeutic changes induced by the medication, following an appropriate latency; toxic side-effects and other effects of the medication, and their influence upon the patient's resistance to drug therapy and psychotherapy; the effect of the movement on the manic-depressive spectrum induced by the drug on the patient's affect, attitude, and behavior; and the psychodynamic responses to all these inputs.


In vivo properties of an anti-GnRH Spiegelmer: an example of an oligonucleotide-based therapeutic substance class.
Spiegelmers are high-affinity l-enantiomeric oligonucleotide ligands that display high resistance to enzymatic degradation compared with d-oligonucleotides. The target binding properties of Spiegelmers can be designed by an in vitro-selection process starting from a random pool of oligonucleotides. Applying this method, a Spiegelmer with high affinity (K(D) = 20 nM) for the peptide hormone, gonadotropin-releasing hormone (GnRH) was isolated. The Spiegelmer acts as an antagonist to GnRH in Chinese hamster ovary cells stably expressing the human GnRH receptor, and its activity is unchanged by linking to 40-kDa polyethylene glycol. In a castrated rat model the Spiegelmer further demonstrated strong GnRH antagonist activity, which is more pronounced and persists longer with the polyethylene glycol-linked derivative. Furthermore, in rabbits the anti-GnRH Spiegelmer was shown to have a very low, possibly negligible immunogenic potential. These studies suggest that Spiegelmers could be of substantial interest in the development of new pharmaceutical approaches against GnRH and other targets.


Oxytocin links mothering received, mothering bestowed and adult stress responses.
We review recent discoveries that implicate oxytocin in the intergenerational transmission of similar levels of maternal behavior and acute stress responses in female rats. First, ICV-infused oxytocin antagonist decreased the display by nursing dams of pup-licking (PL) and arched-back nursing (ABN), but not other components of maternal behavior, and increased maternal self-grooming suggesting that oxytocin may shift the balance of oral grooming by dams away from themselves and toward pups. Second, oxytocin receptor concentrations in areas of the adult brain where oxytocin stimulates maternal behavior or diminishes anxiety and adrenal axis responses to acute stress were positively related to PL-ABN received during infancy. Third, oxytocin and oxytocin antagonist treatments of pups on postnatal days 2-10, respectively increased and decreased PL by the treated rats when adult and themselves nursing dams. This indicates that oxytocin activity in female pups, which may be regulated by PL-ABN received from their mothers, influences their adult levels of PL. These three lines of evidence suggest that oxytocin selectively enhances PL-ABN by rat dams, which then increases oxytocin activity in female pups and, thereby, facilitates their expression of central oxytocin receptors (and perhaps other aspects of central oxytocin systems) and, consequently, their adult PL-ABN frequencies and acute stress responses.


Locally advanced esophageal adenocarcinoma: response to neoadjuvant chemotherapy and survival predicted by ([18F])FDG-PET/CT.
([18F])fluorodeoxyglycose-Positron Emission Tomography/Computer Tomography (([18F])FDG-PET/CT) is commonly used in staging of locally advanced esophageal cancer. Its predictive value for response to neoadjuvant therapy and survival after multimodality therapy is controversial. Sixty-six consecutive patients with locally advanced adenocarcinoma of the esophagus or esophagogastric junction underwent surgery after neoadjuvant chemotherapy. Staging was done prospectively with ([18F])FDG-PET/CT, before and after completion of neoadjuvant therapy. Pre- and post-therapy maximal standardized uptake values for the primary tumor (SUV1 and SUV2) were determined, and their relative change (SUV∆%) calculated. Percentage change in SUV1 was compared with histopathologic response (HPR, complete or subtotal histologic remission), disease-free- (DFS) and overall survival (OS). Resection with negative margins was achieved in 60 patients. HPR rate was 14 of 66 (21.2%). Median follow-up was 16 months (range 4-72). For all patients, OS probability at three years was 59% and DFS 50%. In receiver operating characteristics (ROC) analysis, HPR was optimally predicted by a > 67% change in baseline maximal SUV (sensitivity 79% and specificity 75%). In univariate survival analysis (Cox regression proportional hazards), HPR associated with improved DFS (HR 0.208, p = 0.033) but not OS (HR 0.030, p = 0.101), SUV % > 67% associated with improved OS (HR 0.249, p = 0.027) and DFS (HR 0.383, p = 0.040). In a multivariate model (adjusted by age, sex, and ASA score), neither HPR nor SUV∆% > 67% was predictive of improved OS and DFS. However, SUV∆% as a continuous variable was an independent predictor of OS (HR 0.966, p < 0.0001) or DFS (HR 0.973, p < 0.0001). Our results support previous results showing that ([18F])FDG-PET/CT can distinguish a group of patients with worse prognosis after neoadjuvant chemotherapy in adenocarcinoma of the esophagus or esophagogastric junction. This information could offer a new independent preoperative marker of prognosis.


Microalbuminuria, cardiovascular, and renal risk in primary hypertension.
Microalbuminuria is defined as abnormal urinary excretion of albumin between 30 and 300 mg/d. It can be measured accurately by several widely available and sensitive methods. This abnormality can be found in 8 to 15% of nondiabetic patients with primary hypertension, although its prevalence varies greatly in the literature, likely due to differences in the methods used to detect it and to the criteria applied in the selection of patients. The pathogenetic mechanisms leading to the development of microalbuminuria are still not completely known. BP load and increased systemic vascular permeability, possibly due to early endothelial damage, seem to play a major role. Increased urinary albumin excretion has been associated with several unfavorable metabolic and nonmetabolic risk factors and subclinical hypertensive organ damage. In fact, a higher prevalence of concentric left ventricular hypertrophy and subclinical impairment of left ventricular performance, as well as the presence of carotid atherosclerosis, have been reported in patients with microalbuminuria. These associations might per se justify a greater incidence of cardiovascular events. Long-term longitudinal studies have recently confirmed the unfavorable prognostic significance of microalbuminuria in hypertensive patients. It has also been hypothesized that microalbuminuria might be a forerunner of overt renal damage in primary hypertension. Clinical studies, however, have shown conflicting results, and this hypothesis has to be considered tempting but speculative at present. In conclusion, microalbuminuria is a specific, integrated marker of cardiovascular risk and target organ damage in primary hypertension and one that is suitable for identifying patients at higher global risk. A wider use of this test in the diagnostic work-up of hypertensive patients is recommended.


Assessment of the effects of socioeconomic factors on child mortality in the Amman upgrading areas, 1985.
"Data from the 1985 Amman Follow-Up Health and Population Survey are used to examine the association between child mortality and socioeconomic and environmental conditions which are directly influenced by...[government sponsored development activities]. Ordinary least squares regression is used in the analysis and the estimates show that the proportionate effects of mother's education, housing quality, water and electricity supply, availability of soap for handwashing and sewage connection are highly significant."


Indole Mannich bases and their antimycobacterial effect.
3-[(4-arylpiperazin-1-yl)methyl]lindoles (2a-h) and 3-[(4-hydroxy-4-phenylpiperazin-1-yl)methyl]indole (3) were prepared and characterized by 1H NMR and mass spectrometry. All eight compounds (2a-c, e-h and 3) tested inhibited in vitro the growth of Mycobacterium tuberculosis H37Rv in the range of 98-7% at a concentration of > or = 6.25 microg/ml. From the preliminary microbiological data it is possible to observe that a simple increasing of lipophilicity of the compounds tested to above logPcalc> or =3.8 significantly increases the potencies of their antitubercular action.


Hematopoietic growth factors in the treatment of the myelodysplastic syndromes.
Clinical trials with hematopoietic growth factors (granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin-3, and erythropoietin) have been performed in patients with myelodysplastic syndromes. Absolute neutrophil counts can be readily raised to within the normal range by treatment with granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor. Moderate increases in platelet counts have been reported for approximately 20% of patients during treatment with interleukin-3. Treatment with high-dose erythropoietin leads to an increase in hematocrit or decrease in transfusion needs in 15% to 20% of patients, but an improved response rate of approximately 40% has been reported for the combined treatment of erythropoietin with either granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor. Although meta-analyses of published phase I/II trials allow a rough estimation of response rates and an improved selection of patients who are most likely to respond, phase III trials have not yet been published.


HFE gene mutation and iron overload in Egyptian pediatric acute lymphoblastic leukemia survivors: a single-center study.
Hereditary hemochromatosis gene (HFE) mutations have a role in iron overload in pediatric acute lymphoblastic leukemia (ALL) survivors. We aimed to evaluate the genotype frequency and allelic distribution of the two HFE gene mutations (C282Y and H63D) in a sample of Egyptian pediatric ALL survivors and to detect the impact of these two mutations on their iron profile. This study was performed on 35 ALL survivors during their follow-up visits to the Hematology and Oncology Unit, Pediatric Department, Menoufia University Hospitals. Thirty-five healthy children of matched age and sex were chosen as controls. After completing treatment course, ALL survivors were screened for the prevalence of these two mutations by polymerase chain reaction-restriction fragment length polymorphism. Serum ferritin levels were measured by an enzyme-linked immunosorbent assay technique (ELISA). C282Y mutation cannot be detected in any of the 35 survivors or the 35 controls. The H63D heterozygous state (CG) was detected in 28.6% of the survivors group and in 20% of controls, while the H63D homozygous (GG) state was detected in 17.1% of survivors. No compound heterozygosity (C282Y/H63D) was detected at both groups with high G allele frequency (31.4%) in survivors more than controls (10%). There were significant higher levels of iron parameters in homozygote survivors than heterozygotes and the controls. H63D mutation aggravates the iron overload status in pediatric ALL survivors.


Human CD8 beta, but not mouse CD8 beta, can be expressed in the absence of CD8 alpha as a beta beta homodimer.
The T cell coreceptor CD8 exists on mature T cells as disulfide-linked homodimers of CD8 alpha polypeptide chains and heterodimers of CD8 alpha- and CD8 beta-chains. The function of the CD8 alpha-chain for binding to MHC class I and associating with the tyrosine kinase p56lck was demonstrated with CD8 alpha alpha homodimers. CD8 alpha beta functions as a better coreceptor, but the actual function of CD8 beta is less clear. Addressing this issue has been hampered by the apparent inability of CD8 beta to be expressed without CD8 alpha. This study demonstrates that human, but not mouse, CD8 beta can be expressed on the cell surface without CD8 alpha in both transfected COS-7 cells and murine lymphocytes. By creating chimeric proteins, we show that the murine Ig domain of CD8 beta is responsible for the lack of expression of murine CD8 beta beta dimers. In contrast to CD8 alpha alpha, CD8 beta beta is unable to bind MHC class I in a cell-cell adhesion assay. Detection of this form of CD8 should facilitate studies on the function of the CD8 beta-chain and indicates that caution should be used when interpreting studies on CD8 function using chimeric protein with the murine CD8 beta beta Ig domain. In addition, we demonstrate that the Ig domains of CD8 alpha are also involved in controlling the ability of CD8 to be expressed. Mutation of B- and F-strand cysteine residues in CD8 alpha reduced the ability of the protein to fold properly and, therefore, to be expressed.


Emotions and physical health in the second half of life: interindividual differences in age-related trajectories and dynamic associations according to socioeconomic status.
The importance of socioeconomic status (SES) for psychological functioning over the life span is increasingly acknowledged in psychological research. The Reserve Capacity Model by Gallo and Matthews (2003) suggests that SES is not only linked to physical health but also to the experience of positive and negative emotions. Moreover, due to differential amounts of psychosocial resources, cross-domain associations between emotions and health might differ according to SES. The present study examined age-related developments in positive affect (PA), negative affect (NA), and physical health, as well as dynamic associations between health and emotions in the second half of life. We looked at differences in these trajectories and their interrelationships according to education as one aspect of SES. We used data of up to three waves spanning 12 years from the nationally representative German Ageing Survey (N = 3,847, AgeT1 = 40-85 years). Applying multiple-group dual change score models, we found differential age-related change in PA and physical health, but not in NA, in two groups differing in level of education. NA did only predict change in physical health in low-educated individuals, whereas physical health was equally strongly related to change in PA in both education groups. These results indicate that SES not only affects changes in physical health and emotional functioning but also their interrelationships.


Morphology of intraepithelial corpuscular nerve endings in the nasal respiratory mucosa of the dog.
Corpuscular nerve endings in the nasal respiratory mucosa of the dog were investigated by immunohistochemical staining specific for protein gene product 9.5 by light and electron microscopy. In the nasal respiratory mucosa, complex corpuscular endings, which displayed bulbous, laminar and varicose expansions, were distributed on the dorsal elevated part of the nasal septum and on the dorsal nasal concha. The endings were 300-500 microm long and 100-250 microm wide. Some axons gave rise to a single ending while others branched into 2 endings. Cryostat sections revealed that the corpuscular endings were located within the nasal respiratory epithelium. On electron microscopy, immunoreactive nerve terminals that contained organelles, including mitochondria and neurofilaments, were observed within the epithelial layer near the lumen of the nasal cavity. Some terminals contacted the goblet cell. Such terminal regions were covered by the cytoplasmic process of ciliated cells and were never exposed to the lumen of the nasal cavity. These nerve endings are probably activated by pressure changes.


The potential role of selected bioactive compounds from spelt and common wheat in glycemic control.
Diet is an important lifestyle factor which influences people's health and the prevention of chronic diseases such as type 2 diabetes. Cereal-based foods constitute the main component of the everyday diet worldwide. Old cereal species like spelt (Triticum spelta L.) are becoming more and more popular, especially in Europe. This review focuses on the role of bioactive compounds from spelt and their possible biological mechanisms of action in glycemic control. Spelt grain contains a high amount of dietary fiber, which can modulate postprandial glycemia. Other phytochemicals, such as phytic acid and alkylresorcinols, also contribute to controlling blood glucose levels, insulin sensitivity and hiperinsulinemia. Antioxidant compounds present in spelt grain may act as protection from negative outcomes of chronic hyperglycemia. In this paper the composition and beneficial properties of spelt are also compared with those of widely consumed cereals like common wheat (Triticum aestivum L.). The health benefits of whole grain as opposed to refined products are also discussed.


Active surveillance of low-risk papillary thyroid cancer: A meta-analysis.
This study evaluates the safety and efficacy of active surveillance for low-risk papillary thyroid carcinoma. MEDLINE, EMBASE, and PubMed were searched from inception for relevant studies of active surveillance for low-risk papillary thyroid carcinoma, defined as T1a or T1b, N0, M0 disease. Main outcomes of interest were growth of primary tumor, metastatic spread, thyroid cancer-related mortality, and disease recurrence after delayed thyroid surgery. Nine publications with 4,156 patients were included. Primary analysis of the 9 studies revealed pooled proportion of tumor growth during active surveillance to be 4.4% (95% confidence interval 3.2-5.8%). The pooled rate of metastatic spread to cervical nodes was 1.0% (95% confidence interval 0.7-1.4%), and pooled mortality due to thyroid cancer was 0.03% (95% confidence interval 0.0005-0.2%). Eight studies assessed incidence of delayed thyroid surgery with pooled proportion of 9.9% (95% confidence interval 6.4-14.0%). The main indication for surgery was patient preference, not disease progression, at 51.9% (95% confidence interval 44.9-58.9%). The pooled proportion of recurrence after delayed thyroid surgery was 1.1% (95% confidence interval 0.1-3.8%). Active surveillance appears to be a safe alternative to surgery for the management of low-risk papillary thyroid carcinoma, without increased risk of recurrence or death. This strategy allows for avoidance of exposure to surgical risk and need for subsequent thyroid replacement therapy.


Laparoscopic management of neonatal paraesophageal hernia with intrathoracic gastric volvulus.
Intrathoracic gastric volvulus associated with neonatal paraesophageal hernia is very rare in the newborn period. We report a case of a 3-week-old term infant who presented to the hospital with a history of non-bilious vomiting. Workup for hypertrophic pyloric stenosis eventually revealed the presence of a congenital hiatal hernia and intrathoracic gastric volvulus requiring urgent surgical management. The infant underwent successful laparoscopic repair. We discuss the diagnosis and management of this extremely rare surgical cause of neonatal nonbilious emesis.


Simple approach for charge renormalization in highly charged macroions.
We revisit the notion of renormalized charge, which is a concept of central importance in the field of highly charged colloidal or polyelectrolyte solutions. Working at the level of a linear Debye-Hückel-like theory only, we propose a versatile method to predict the saturated amount of charge renormalization, which is, however, a nonlinear effect arising at strong electrostatic coupling. The results are successfully tested against nonlinear Poisson-Boltzmann theory for polyions of various shapes (planar, cylindrical, and spherical), both in the infinite dilution limit or in confined geometry, with or without added electrolyte. Our approach, accurate for monovalent microions in solvents such as water, is finally confronted against experimental results on charged colloids and B-DNA solutions.


Data Mining-Based Analysis of Modern Chinese Medicine for the Treatment of Stable Angina Pectoris in Coronary Heart Disease.
The aim of this study is to explore the clinical effects of Chinese medicine in the treatment of stable angina pectoris in coronary heart disease. Chinese medicine has multitarget, multilevel, and multilink effects in the treatment of coronary angina, which can significantly improve patients' symptoms. Its mechanism of action involves multiple levels such as regulating lipid metabolism, improving platelet function, antioxidant, and protecting endothelial function. The design was based on data mining to analyse the dosing pattern of modern Chinese medicine for the treatment of stable angina pectoris in coronary heart disease. The number of episodes of angina pectoris, the duration of the episodes, and the changes in the electrocardiogram before and after taking the medicine were observed and compared between the two groups. The number and duration of angina attacks ((2.23 ± 0.77) per week and (1.31 ± 0.34) min/time, respectively) in the study group were found to be significantly better than those in the control group ((3.86 ± 1.03) per week and (2.46 ± 1.21) min/time, respectively).


Distribution of Photosynthetic Enzymes between Mesophyll, Specialized Parenchyma and Bundle Sheath Cells of Arundinella hirta.
Arundinella hirta L. is a C(4) plant having an unusual C(4) leaf anatomy. Besides mesophyll and bundle sheath cells, A. hirta leaves have specialized parenchyma cells which look morphologically like bundle sheath cells but which lack vascular connections and are located between veins, running parallel to them. Activities of phosphoenolpyruvate and ribulose-1,5-bisphosphate carboxylases and phosphoenolpyruvate carboxykinase, NADP-and NAD-malic enzymes were determined for whole leaf extracts and isolated mesophyll protoplasts, specialized parenchyma cells, and bundle sheath cells. The data indicate that A. hirta is a NADP-malic enzyme type C(4) species. In addition, specialized parenchyma cells and bundle sheath cells are enzymatically alike. Compartmentation of enzymes followed the C(4) pattern with phosphoenolpyruvate carboxylase being restricted to mesophyll cells while ribulose-1,5-bisphosphate carboxylase and decarboxylating enzymes were restricted to bundle sheath and specialized parenchyma cells.


Developmental expression of pIgR gene in sheep mammary gland and hormonal regulation.
Secretory IgA found in external secretions are constituted by polymeric IgA (pIgA) bound to the extra-cellular part of the polymeric immunoglobulin receptor (pIgR). The receptor mediates transcytosis of pIgA across epithelial cells. The aim of the present study was to analyse the evolution of pIgR expression in the sheep mammary gland during the development of the mammary gland and to analyse its hormonal regulation. Gene expression of the pIgR was analysed in sheep mammary gland during pregnancy and lactation. By Northern Blot analysis, we observed that low levels of pIgR mRNA are expressed until day 70 of pregnancy. Accumulation of pIgR mRNA started during the third part of pregnancy and intensified 3 d after parturition to reach highest levels during established lactation (day 70). In situ hybridization analysis was used to confirm the increase in pIgR gene expression per mammary epithelial cell. In order to examine the hormonal regulation of the pIgR expression, virgin ewes were hormonally treated. Treatment with oestradiol and progesterone increased pIgR mRNA levels slightly. Subsequent addition of gluocotricoids induced a significant accumulation of pIgR mRNA in the mammary gland of the treated animals. Immunohistochemical analysis was performed to verify that the increase of pIgR mRNA level was associated with enhancement of the pIgR protein in mammary cells. No increase of pIgR mRNA levels were observed if PRL secretion was blocked by bromocryptine injections throughout the hormonal procedure. In conclusion, the present experiments suggest that the enhancement of pIgR levels during lactation result from combined effects of both prolactin and glucocorticoids.


Topography of orientation centre connections in the primary visual cortex of the cat.
The functional topography of lateral connections to orientation-centre zones was studied by optical imaging of intrinsic signals in combination with tracer injections (fluorescent beads and biocytin) and electrophysiological recordings. Three-dimensional reconstruction of anterogradely labelled axon terminals and retrogradely labelled somata revealed a uniform distribution across all orientations in a non-patchy manner. The overall lateral extent of the labelling was 3-4 mm in layer 3, that is about half of the extent observed for orientation domain connections in the same layer. These bulk injection data are in contrast with the reportedly sharp orientation tuning of neurons of centre zones and suggest that orientation specificity here does not require highly specific connections. Nonetheless, another plausible scenario is that orientation centre connections are orientation specific but their specificity present at the single cell level cannot be revealed by bulk labelling due to their large spatial overlap.


Vaccination with a fowl adenovirus chimeric fiber protein (crecFib-4/11) simultaneously protects chickens against hepatitis-hydropericardium syndrome (HHS) and inclusion body hepatitis (IBH).
In the past decades, fowl adenovirus (FAdV)-related diseases became an increasing concern for the poultry industry worldwide. Various immunization strategies against FAdVs have been experimentally investigated, with a particular focus on subunit vaccines against hepatitis-hydropericardium syndrome (HHS), caused by FAdV serotype 4, and inclusion body hepatitis (IBH), caused by serotypes 2, 8a, 8b and 11. In this study, we extended our innovative concept of recombinant chimeric fiber proteins to design a novel chimera combining epitopes from two distinct serotypes, FAdV-4 and -11, and we investigated its efficacy to simultaneously protect chickens against HHS and IBH. Specific pathogen-free chickens were vaccinated with the novel recombinant chimeric fiber and subsequently challenged with either a HHS- or IBH-causing strain. Vaccinated/challenged birds exhibited a reduction of clinical signs, limited hepatomegaly and lower levels of AST compared to the respective challenge controls. Furthermore, the vaccine prevented atrophy of HHS-affected lymphoid organs, such as thymus and bursa of Fabricius, and viral load in the target organs was significantly reduced. Clinical protection was associated with high levels of pre-challenge antibodies measured on ELISA plates coated with the vaccination antigen. Interestingly, the development of neutralizing antibodies was limited against FAdV-11 and absent against FAdV-4, indicating that protection granted by such an antigen may be linked to different immunization pathways. In conclusion, we proved that the concept of chimeric fiber vaccines can be extended across viral species boundaries and represents the first single-component FAdV subunit vaccine providing comprehensive protection against different FAdV-associated diseases.


Assimilation and Transport of Nitrogen in Nonnodulated (NO(3)-grown) Lupinus albus L.
The response of nonnodulated white lupin (Lupinus albus L. cv. Ultra) plants to a range of NO(3) levels in the rooting medium was studied by in vitro assays of extracts of plant parts for NO(3) reductase (EC 18.104.22.168) activity, measurements of NO(3)-N in plant organs, and solute analyses of root bleeding (xylem) sap and phloem sap from stems and petioles. Plants were grown for 65 days with 5 millimolar NO(3) followed by 10 days with 1, 5, 15, or 30 millimolar NO(3). NO(3) reductase was substrate-induced in all tissues. Roots contained 76, 68, 62 and 31% of the total NO(3) reductase activity of plants fed with 1, 5, 15, and 30 millimolar NO(3), respectively. Stem, petioles, and leaflets contained virtually all of the NO(3) reductase activity of a shoot, the activity in extracts of fruits amounting to less than 0.3% of the total enzyme recovered from the plant. Xylem sap from NO(3)-grown nonnodulated plants contained the same organic solutes as from nodulated plants grown in the absence of combined N. Asparagine accounted for 50 to 70% and glutamine 10 to 20% of the xylem-borne N. The level of NO(3) in xylem sap amounted to 4, 13, 12, and 17% of the total xylem N at 1, 5, 15, and 30 millimolar NO(3), respectively. Xylem to phloem transfer of N appeared to be quantitatively important in supplying fruits and vegetative apices with reduced N, especially at low levels of applied NO(3). NO(3) failed to transfer in any quantity from xylem to phloem, representing less than 0.3% of the phloem-borne N at all levels of applied NO(3). Shoot organs were ineffective in storing NO(3). Even when NO(3) was supplied in great excess (30 millimolar level) it accounted for only 8% of the total N of stem and petioles, and only 2 and 1% of the N of leaflets and fruits, respectively.


DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation.
Parkinson's disease (PD) pathology is characterized by the degeneration of midbrain dopamine neurons (DNs) ultimately leading to a progressive movement disorder in patients. The etiology of DN loss in sporadic PD is unknown, although it is hypothesized that aberrant protein aggregation and cellular oxidative stress may promote DN degeneration. Homozygous mutations in DJ-1 were recently described in two families with autosomal recessive inherited PD (Bonifati et al. 2003). In a companion article (Martinat et al. 2004), we show that mutations in DJ-1 alter the cellular response to oxidative stress and proteasomal inhibition. Here we show that DJ-1 functions as a redox-sensitive molecular chaperone that is activated in an oxidative cytoplasmic environment. We further demonstrate that DJ-1 chaperone activity in vivo extends to alpha-synuclein, a protein implicated in PD pathogenesis.


Undulations enhance the effect of helical structure on DNA interactions.
During the past decade, theory and experiments have provided clear evidence that specific helical patterns of charged groups and adsorbed (condensed) counterions on the DNA surface are responsible for many important features of DNA-DNA interactions in hydrated aggregates. The effects of helical structure on DNA-DNA interactions result from a preferential juxtaposition of the negatively charged sugar phosphate backbone with counterions bound within the grooves of the opposing molecule. Analysis of X-ray diffraction experiments confirmed the mutual alignment of parallel molecules in hydrated aggregates required for such juxtaposition. However, it remained unclear how this alignment and molecular interactions might be affected by intrinsic and thermal fluctuations, which cause structural deviations away from an ideal double helical conformation. We previously argued that the torsional flexibility of DNA allows the molecules to adapt their structure to accommodate a more electrostatically favorable alignment between molecules, partially compensating disruptive fluctuation effects. In the present work, we develop a more comprehensive theory, incorporating also stretching and bending fluctuations of DNA. We found the effects of stretching to be qualitatively and quantitatively similar to those of twisting fluctuations. However, this theory predicts more dramatic and surprising effects of bending. Undulations of DNA in hydrated aggregates strongly amplify rather than weaken the helical structure effects. They enhance the structural adaptation, leading to better alignment of neighboring molecules and pushing the geometry of the DNA backbone closer to that of an ideal helix. These predictions are supported by a quantitative comparison of the calculated and measured osmotic pressures in DNA.


Brain Cholesterol Metabolism and Its Defects: Linkage to Neurodegenerative Diseases and Synaptic Dysfunction.
Cholesterol is an important constituent of cell membranes and plays a crucial role in the compartmentalization of the plasma membrane and signaling. Brain cholesterol accounts for a large proportion of the body's total cholesterol, existing in two pools: the plasma membranes of neurons and glial cells and the myelin membranes . Cholesterol has been recently shown to be important for synaptic transmission, and a link between cholesterol metabolism defects and neurodegenerative disorders is now recognized. Many neurodegenerative diseases are characterized by impaired cholesterol turnover in the brain. However, at which stage the cholesterol biosynthetic pathway is perturbed and how this contributes to pathogenesis remains unknown. Cognitive deficits and neurodegeneration may be associated with impaired synaptic transduction. Defects in cholesterol biosynthesis can trigger dysfunction of synaptic transmission. In this review, an overview of cholesterol turnover under physiological and pathological conditions is presented (Huntington's, Niemann-Pick type C diseases, Smith-Lemli-Opitz syndrome). We will discuss possible mechanisms by which cholesterol content in the plasma membrane influences synaptic processes. Changes in cholesterol metabolism in Alzheimer's disease, Parkinson's disease, and autistic disorders are beyond the scope of this review and will be summarized in our next paper.


Eosinophilic gastroenteritis: review of a rare and treatable disease of the gastrointestinal tract.
Eosinophilic gastroenteritis is a rare disease of the gastrointestinal tract characterized by crampy abdominal pain, nausea, vomiting, diarrhea, gastrointestinal bleeding, and weight loss associated with peripheral eosinophilia leading to eosinophilic infiltrates in stomach and intestine, usually in a patient with a prior history of atopy. In this article, we describe our encounter with a 59-year-old female presenting with severe abdominal pain, nausea, vomiting, and weight loss with an extensive evaluation including an upper endoscopy with biopsies resulting in a diagnosis of eosinophilic gastroenteritis. The patient was eventually treated with oral prednisone for three weeks with complete resolution of her symptoms.


"Immune" Nairobi women also have "killer" T-cells.
Further evidence that so-called "killer T-cells" could be the key to an HIV-vaccine has come from "immune" sex-workers in Nairobi, Kenya. Earlier this year, British researcher Sarah Rowland-Jones discovered a group of sex-workers in Gambia, West Africa, who seemed to be immune to HIV-infection. Study of six of the women's blood revealed that five had the T-cells, which seek out and destroy infected cells. T-cells are produced as part of the immune-system's response to infection. A second group of 30 "immune" sex-workers had been noted by social scientists in Nairobi. In April 1995, Rowland-Jones studied six of these women and again found that five had the T-cells. However, because the six Kenyan women were all of the same genetic group, the results are far from conclusive. One explanation for the women's resistance in Gambia is that they were first infected with HIV-2--a weaker strain of HIV prevalent in West Africa and India. In Nairobi, the women may have first been exposed to a defective HIV-1 virus, or their immunity may be the result of a rare genetic make-up. Rowland-Jones will return to Gambia at the end of this year to study a larger cross-section of sex-workers.


Synthesis, Characterization and Biological Application of Pyrazolo[1,5-a]pyrimidine Based Organometallic Re(I) Complexes.
The neutral rhenium(I) complexes (I-VI) of type [ReCl(CO)3Ln-] where L1 = 7-phenyl-5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine, L2 = 7-(4-bromophenyl)-5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimi- dine, L3 = 7-(4-chlorophenyl)-5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine, L4 = 7-(2-chlorophenyl) -5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine, L5 = 7-(4-methoxyphenyl)-5-(pyridin-2-yl)pyrazolo [1,5-a]pyrimidine, L6 = 5-(pyridin-2-yl)-7-(p-tolyl)pyrazolo[1,5-a]pyrimidine were synthesized and characterized by 13C-APT, 1H-NMR, IR, electronic spectra, magnetic moment and conductance measurement. The anti-proliferative activity on HCT116 cells by MTT assay suggests potent cytotoxic nature of complexes, even some complexes have better activity than standard drug cisplatin, oxaliplatin, and carboplatin. The complexes found to have better antimicrobial activity compare to pyrazolo pyrimidine ligands. The theoretical study of compounds-DNA interactions was examined by molecular docking as a supportive tool to the experimental data, which suggests the groove mode of binding. The values of docking energy for compounds-DNA interaction were found in the range of -230.31 to -288.34 kJ/mol. The intrinsic binding constant values of complexes (1.1-3.5×105 M-1) were found higher than the ligands (0.32-1.8×105 M-1).


Socio-demographic profile and help-seeking behaviour of buprenorphine abusers in Singapore.
The US Food and Drug Administration (FDA) approved buprenorphine or Subutex for the treatment of opiate dependence in October 2002. Buprenorphine is a partial agonist of the mu-opioid receptor; although initial animal research suggested a low abuse potential for buprenorphine, it was subsequently shown to have an abuse potential similar to that of morphine or hydromorphone. The objectives of this study were to establish the sociodemographic profile and help-seeking behaviour of buprenorphine abusers attending the deaddiction treatment clinics of the Community Addictions Management Programme. One hundred and twenty subjects, all buprenorphine abusers fulfilling the diagnostic criteria for opiate dependence, who consented to the study, completed an interviewer-administered questionnaire. The mean age of those participating in the study was 39.2 [standard deviation (SD) 8.0] years. The majority of the participants were male (90%), 52.5% were currently employed and 98% had at least primary education. A family history of drug abuse was reported by 27% of the subjects. Illicit drug abuse occurred at an early age with mean age of onset of illicit drug abuse being 16.9 (SD 4.8) years with gateway drugs like marijuana and glue. It is vital for our medical profession to be aware of the trend in the local population to move from the abuse of illicit substances, to the abuse of prescriptive medications. It makes it necessary to increase the understanding of addictions both amongst our practising medical fraternity, and amongst those training to enter the profession. At the hospital level, it necessitates a higher level of vigilance among our emergency room physicians and those treating infectious diseases.


[Role of pyroptosis pathway related molecules in acute lung injury induced by gas explosion in rats].
Objective: To explore the role and significance of pyroptosis in gas explosion-induced acute lung injury (ALI) in rats. Methods: In February 2018, 126 SPF male SD rats were selected and randomly divided into blank control group (18 rats) and experimental group (40 m, 80 m, 120 m, 160 m, 200 m and 240 m, 18 per group) . The experimental group carried out gas explosion in the roadway to build the ALI model, the control group did not carry out gas explosion, and other conditions were consistent with the experimental group. Respiratory function indexes such as respiratory frequency (f) , tidal volume (TV) , minute ventilation (MV) and airway stenosis index (Penh) were measured 24 hours after the explosion. 5 rats in each group were sacrificed after anesthesia, Hematoxylin-Eosin (HE) staining was used to observe the pathological morphology of lung tissue. Immunohistochemistry was used to detect the content of Caspase-1. Western blotting was used to detect the content of cell pyroptosis including nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) , Caspase-1, interleukin-1β (IL-1β) and interleukin-18 (IL-18) in lung tissue related protein expression. Results: The f and MV of rats in the experimental group were higher than those in the control group (P<0.05) . Except for the 40 m and 80 m groups, the TV of rats in the other experimental groups were higher than those in the control group (P<0.05) . Except for the 40 m group, the Penh of rats in the experimental groups were lower than those in the control group (P<0.05) . HE staining showed that the lung tissue of the experimental groups at different distance points showed obvious edema of the pulmonary interstitium and alveoli, a large number of red blood cells and inflammatory cells exuded in the alveolar space, thickening of the pulmonary interstitium, and increased lung injury score (P<0.05) . The results of immunohistochemistry showed that the positive expression of Caspase-1 in each experimental group was higher than that in the control group (P<0.05) . Western blotting results showed that the expression of pyroptosis-related proteins in each experimental group was higher than that in the control group (P<0.05) . Conclusion: Pyroptosis is involved in the pathophysiological process of gas explosion-induced ALI in rats.


Intimate partner violence. The gynaecologist's perspective.
From a questionnaire-based surveillance study among pregnant women constituting a regional probability sample of East-Flanders, we estimated that IPV occurred overall with one in ten women (10.1%, 95% CI 7.7-13.0%) and with about one in 30 women (3.4%, 95% CI 2.1-5.4%) during pregnancy and/or in the year preceding pregnancy. We also revealed that women experiencing IPV rarely disclose abuse spontaneously to the widely available health care services and providers, but in general approve routine questioning by their GP or gynaecologist. The crux of IPV is that most victims will not present with overt signs of abuse, but rather with a wide variety of vague and non-specific symptoms, if any. Hence there seems to exist a window of opportunities to detect women suffering from IPV through screening in the health care sector. From a questionnaire based Knowledge-Practice and Attitude Survey among OB/GYN in Flanders, it appeared that OB/GYN feel uncomfortable with a routine screening policy. They underestimate the prevalence and perceive a lack of self-efficacy in dealing with the problem and properly referring patients, they lack time and perceive it as inappropriate to question patients about IPV. On the other hand they acknowledge that there is a need for training on violence. It therefore appears that most barriers should be remediable through proper OB/GYN training and education, together with enabling strategies such as screening tools and formal referral pathways. In concordance with the National Action Plan to combat IPV, health care workers, including gynaecologists, need to develop guidelines, in order to deal with this important public health problem.


rBPI(21) promotes lipopolysaccharide aggregation and exerts its antimicrobial effects by (hemi)fusion of PG-containing membranes.
Antimicrobial peptides (AMPs) are important potential alternatives to conventional therapies against bacterial infections. rBPI(21) is a 21 kDa peptide based on the N-terminal region of the neutrophil bactericidal/permeability-increasing protein (BPI). This AMP possesses highly selective bactericidal effects on Gram-negative bacteria and have affinity for lipopolysaccharide (LPS) which is believed to be at the origin of its neutralizing effect of the LPS segregated into the bloodstream. We aim at understanding the molecular bases of rBPI(21) bactericidal and LPS neutralization actions, using biomembrane model systems. Using dynamic light scattering spectroscopy we demonstrate that rBPI(21) promotes aggregation of negatively charged large unilamellar vesicles (LUV), even in the absence of LPS, and LPS aggregates, while for zwitterionic phosphatidylcholine (POPC) LUV the size remains unchanged. The peptide also promotes the fusion (or hemifusion) of membranes containing phosphatidylglycerol (POPG). The aggregation and fusion of negatively charged LUV are peptide concentration-dependent until massive aggregation is reached, followed by sample flocculation/precipitation. Concomitantly, there is a progressive change in the zeta-potential of the LUV systems and LPS aggregates. LUV systems composed of phosphatidylglycerol (POPG) and lipid mixtures with POPG have higher zeta-potential variations than in the absence of POPG. The interaction of rBPI(21) with lipid vesicles is followed by leakage, with higher effect in POPG-containing membranes. LPS aggregation can be related with a decreased toxicity, possibly by facilitating its clearance by macrophage phagocytosis and/or blocking of LPS specific receptor recognition. Our data indicate that rBPI(21) mechanism of action at the molecular level involves the interaction with the LPS of the outer membrane of Gram-negative bacteria, followed by internalization and leakage induction through the (hemi)fusion of the bacterial outer and inner membranes, both enriched in phosphatidylglycerol.


Avoidance and accommodation of surface height changes by healthy, community-dwelling, young, and elderly men.
The purpose of this study was to compare avoidance and accommodation strategies during gait between healthy, community-dwelling, young and elderly males. Ten young (28.4 +/- 5.4 years) and ten elderly (69.5 +/- 6.1 years) males were tested while walking on the level, avoiding a 11.75-cm-high obstacle, and accommodating a change in floor height of 11.75 cm. Three dimensional, kinematic, and kinetic analyses were performed bilaterally. Both age groups used the same general sagittal plane strategies in order to avoid and accommodate the obstructions, but the elderly group had significantly reduced lead toe clearances. These riskier toe clearances by the elderly group were found to be due to limited, frontal plane pelvic motion, shorter stride lengths, and subtle differences in the interplay of lower limb energetic patterns within the sagittal plane. These results are discussed with respect to diminishing physical capacity in the elderly populations.


Potential energy surface, bound states, and rotational inelastic cross sections of the He-CH4 system: a theoretical investigation.
We determined two potential energy surfaces (PES) for the He-CH(4) system by means of MP4 and Valence Bond (VB) calculations. The MP4 potential is similar to the one commonly adopted for this system [U. Buck, K. H. Kohl, A. Kolhase, M. Faubel, and U. Staemmler, Mol. Phys. 55, 1255 (1985)], while the VB PES is slightly more attractive. To evaluate the reliability of these potentials, we investigated the scattering properties by performing close coupling calculations, and concluded that: (i) the available experimental data do not permit the ranking among the PES considered; (ii) some theoretical predictions differ considerably from the experimental data, and these discrepancies cannot entirely be ascribed to the inaccuracy of the ab initio calculations; (iii) the scattering properties at low energy might discriminate between the MP4 and VB potentials.


Giant Unilamellar Vesicle Microarrays for Cell Function Study.
Giant unilamellar vesicles (GUVs) are widely used as artificial cell models which contribute to elucidate fundamental questions on origin of life and cell functions. Herein, the GUV microarrays were developed using a point-to-plane electrode system combined with microcontact stripping technique. The biomolecules (DNA, etc.) were selectively encapsulated only inside patterned GUVs. The GUV arrays were used to investigate species mass transport across cell membranes. The release of carboxyfluorescein from GUVs showed a melittin concentration dependent manner. The diffusion coefficient were 0.37 × 10-11, 0.36 × 10-11, 0.54 × 10-11, 1.10 × 10-11, 1.74 × 10-11, 2.31 × 10-11, and 3.62 × 10-11 m2/s for 0, 0.5, 1.0, 2.0, 3.0, 4.0, and 5.0 μM melittin, respectively. The GUV arrays were also a good platform for cell metabolism investigation. Horseradish peroxidase (HRP) loaded GUV microarrays were used to mimic internal metabolism by exposing them to the substrates of H2O2 and o-PD to yield fluorescent 2,3-diaminophenazine (2,3-DAP).The proposed GUV arrays have great potential in cell function studies.


Active back school: prophylactic management for low back pain. A randomized, controlled, 1-year follow-up study.
A randomized, controlled, single-center trial with a stratified group design. To investigate the secondary prophylactic effect of the Active Back School program on minimizing recurrences of low back pain episodes. The results of back school interventions are controversial. Previous work often used short intervention periods and low doses of practical training. However, studies with the highest methodologic scores have shown the best results, especially when conducted in occupational settings and coupled with a comprehensive rehabilitation program. By block randomization, 19 men and 24 women were allocated to Active Back School, with 18 men and 20 women as control subjects. The Slumps test and number of low back pain episodes during the previous 36 months were used as stratification factors. There were no significant differences between the groups with regard to demographic factors and initially observed variables. Active Back School consisted of 20 lessons over a 13-week period. Each lesson was divided into a 20-minute theoretical part and a 40-minute exercise part. All participants were examined on enrollment, then 5 and 12 months after initiation of the program. Outcome measures were recurrence of low back pain episodes and number of days of sick leave. The recurrence of new low back pain episodes was significantly lower (P < 0.05) and the time from inclusion to the first new episode significantly longer (P < 0.01) in the Active Back School group than in the control group. In the Active Back School group, seven participants took sick leave because of low back pain episodes during the first 12 months of follow-up compared with 11 among the control subjects. The number of sick leave days was significantly lower (P < 0.05) in the Active Back School group than in the control group. Active Back School reduced the recurrence and severity of new low back pain episodes according to results of follow-up examinations performed 5 and 12 months after enrollment.


Can an anomalous lumbo-sacral or lumbo-iliac articulation cause low back pain? A retrospective study of 12 cases.
Although anomalous lumbo-sacral articulations are present in 5 to 7% of the population at large, their clinical relevance remains a matter of debate. Articulation between the L5 transverse process and the sacrum or ilium has been implicated as a cause of low back pain. To define symptoms and effects of steroid injections in patients with an articulation between a L5 transverse process and the sacrum or ilium. Patients with low back pain and an expanded L5 transverse process articulating with the sacrum or ilium were studied retrospectively. Patients with an expanded transverse process that did not articulate with the sacrum or ilium were excluded. Demographic data, symptoms, physical findings and results of investigations were recorded. Efficacy of steroid injections into the anomalous articulation performed under fluoroscopic monitoring was evaluated in the short, medium and long term. Twelve patients (seven men and five women) with a mean age of 41.1 years (17-90 years) and a mean time since symptom onset of 1.9 years (0.2-4 years) were studied. All 12 patients reported pain on the side of the anomalous articulation (left, n = 10), either in the low back (n = 6) or in the buttock (n = 6). Eight patients had pain radiation to all (n = 1) or part (n = 7) of the lower limb on the same side. One patient had mild motor loss (4/5) and another had paresthesia in the foot. Radiographs were obtained in all 12 patients, computed tomography in six, magnetic resonance imaging in two, myelography in two, a bone scan in two and an electromyogram in one. Three of the 11 patients treated by steroid injection experienced pain during the procedure. Ten patients were improved in the short term and nine reported a 50% decrease in their pain after one month. Of the eight patients who were reevaluated after six to 24 months, seven were improved or free of symptoms and one was unchanged. An anomalous transitional articulation should be considered as a possible factor in the genesis of low back pain in patients who do not have the degenerative lesions classically responsible for this symptom. Local steroid injections should be tried before surgery is considered.


Scattered seeding of CAR T cells in solid tumors augments anticancer efficacy.
Chimeric antigen receptor T cell (CAR T) therapy was a milestone in the treatment of relapsed and refractory B cell malignancies. However, beneficial effects of CAR T cells have not been obtained in solid tumors yet. Herein, we implement a porous microneedle patch that accommodates CAR T cells and allows in situ penetration-mediated seeding of CAR T cells when implanted in the tumor bed or in the post-surgical resection cavity. CAR T cells loaded in the pores of the microneedle tips were readily escorted to the tumor in an evenly scattered manner without losing their activity. Such microneedle-mediated local delivery enhanced infiltration and immunostimulation of CAR T cells as compared to direct intratumoral injection. This tailorable patch offers a transformative platform for scattered seeding of living cells for treating a variety of tumors.


Predicting the anti-hypertensive effect of nitrendipine from plasma concentration profiles using artificial neural networks.
Nitrendipine is an effective and safe calcium-channel blocker for the treatment of mild to moderate hypertension. The aim of this study is to show that an artificial neural network (ANN) model of the relationship between nitrendipine plasma levels and pharmacodynamic effects can be built and used for pressure-drop prediction after oral administration of the drug in spite of the poor correlation between plasma concentrations and the effect. To achieve the goal, the following steps were taken: evaluation of the quality of the database for training the ANN, definition of the optimal input set for the ANN, and prediction of the diastolic pressure drop using the ANN. The possible consequences of successful ANN modelling are an optimisation of the drug administration regimen, to achieve the best possible effect, as well as optimal drug formulation for drugs with complicated pharmacokinetic/pharmacodynamic relationships.


[Using 137Cs and 210Pb(ex) to trace the impact of soil erosion on soil organic carbon at a slope farmland in the black soil region].
Soil cores were collected from a 28.5 hm2 slope farmland in the black soil region of Northeast China. Based on the sampled data of 137Cs, 210Pb(ex) and SOC, the potentials of applying 137Cs and 210Pb(ex) for assessing SOC redistribution were evaluated, aimed to approach the impact of soil erosion on soil organic carbon (SOC) in black soil region. At both planar and vertical directions, the 137Cs, 210Pb(ex) and SOC in the farmland had similar distribution patterns. Although there were large planar variations in the 137Cs and 210Pb(ex) areal activities and the SOC stock as affected by soil erosion and deposition, the 137Cs, 210Pb(ex) and SOC had similar changing trends over the landscape. Two depth distribution profiles were also used to study the relations of 137Cs and 210Pb(ex) with SOC. At eroded site, the radioactivities of 137Cs and 210Pb(ex) and the SOC mass fraction did not show large variations in 0-25 cm soil layer, but decreased sharply below 25 cm. For the deposition sample, the radioactivities of 137Cs and 210Pb(ex) in 0-100 cm soil increased firstly and then decreased. The SOC mass fraction also had similar depth distribution pattern in this soil layer. The 137Cs and 210Pb(ex) presented positive linear correlations with the SOC, indicating that 137Cs, 210Pb(ex) and SOC moved with the same physical mechanism in the farmland, and fallout 137Cs and 210Pb(ex) could be used to study spatio-temporal distribution characteristics of SOC in the black soil region under the condition of soil erosion.


Pedicled anterior lateral thigh flap in managing a bilateral groin contracture.
A fifteen-year-old female patient presented with a severe bilateral groin contracture for the last 8 years. She had sustained burns at the age of seven years. Three attempts to release the contracture with split thickness skin grafts had been done without success. A pedicled anterior lateral thigh flap was raised and advanced into the defect after the contracture had been released. Postoperatively the patient healed well without any complications and was able to achieve hip abduction of about 130 degrees.


High-Pressure-High Temperature (HP-HT) Stability of Polytetrafluoroethylene: Raman Spectroscopic Study Up to 10 GPa and 600 ℃.
The increasing demand for use of polymers at extreme conditions makes important the exploration of their behavior in a wide pressure and temperature range, which remains unknown for polytetrafluoroethylene (PTFE), one of the most common materials. An in situ Raman spectroscopic study of PTFE shows that it is stable within the range of 2-6 GPa at 500 ℃ and up to 12 GPa at 400 ℃. At T > 500 ℃ and P > 3.5 GPa, the graphitization of PTFE is observed, but judging from the preservation of liquid run products, PTFE can be used as a material for sample container up to 600 ℃ at this pressure. The obtained data allow the suggestion that the triple point between liquid, solid, and decomposed (carbonized) PTFE is located between 3 and 4 GPa at about 550 ℃, by analogy with the behavior of polycyclic aromatic hydrocarbons.


Effects of Glycolate Pathway Intermediates on Glycine Decarboxylation and Serine Synthesis in Pea (Pisum sativum L.).
Glycine decarboxylation and serine synthesis were studied in pea (Pisum sativum L.) leaf discs, in metabolically active intact chloroplasts, and in mitochondria isolated both partially by differential centrifugation (i.e. ;crude') and by further purification on a Percoll gradient. Glycolate, glyoxylate, and formate reduced glycine decarboxylase activity ((14)CO(2) and NH(3) release) in the crude green-colored mitochondrial fractions, and in the leaf discs without markedly altering serine synthesis from [1-(14)C]glycine. Glycolate acted because it was converted to glyoxylate which behaves as a noncompetitive inhibitor (K(i) = 5.1 +/- 0.5 millimolar) on the mitochondrial glycine decarboxylation reaction in both crude and Percoll-purified mitochondria. In contrast, formate facilitates glycine to serine conversion by a route which does not involve glycine breakdown in the crude mitochondrial fraction and leaf discs. Formate does not alter the conversion of two molecules of glycine to one CO(2), one NH(3), and one serine molecule in the Percoll-purified mitochondria. In chloroplasts which were unable to break glycine down to CO(2) and NH(3), serine was labeled equally from [(14)C]formate and [1-(14)C]glycine. The maximum rate of serine synthesis observed in chloroplasts is similar to that in isolated metabolically active mitochondria. Formate does not appear to be able to substitute for the one-carbon unit produced during mitochondrial glycine breakdown but can facilitate serine synthesis from glycine in a chloroplast reaction which is probably a secondary one in vivo.


Fucosylation of membrane proteins in soybean cultured cells : effects of tunicamycin and swainsonine.
Cultures of soybean cells incorporate [5,6-(3)H]-l-fucose into various cellular components including lipids and proteins. The membrane glyco-proteins were digested with pronase to produce glycopeptides, and the glycopeptides were isolated on columns of Biogel P-4. The major fucoselabeled glycopeptide sized as a Hexose(15-17)-N-acetylglucosamine(2) (GlcNAc(2)) on columns of Biogel P-4. Fucose incorporation was also examined in the presence of the processing inhibitor swainsonine, and the glycosylation inhibitor tunicamycin. In the presence of swainsonine, the incorporation of fucose was not reduced but the glycopeptides were smaller in size and migrated like Hexose(12-13)-GlcNAc(2) structures. On the other hand, tunicamycin inhibited the incorporation of fucose into the glycopeptides by 70 to 80%, indicating that the l-fucose was present in N-linked oligosaccharides.The membrane glycoproteins were doubly-labeled by incubating soybean cells in [(3)H]fucose and [(14)C]mannose. By repeated separation on Biogel P-4, six glycopeptides were purified that ranged in size from Hexose(8)GlcNAc(2) to Hexose(15-17)-GlcNAc(2). The three larger glycopeptides (I, II, III) were highly labeled with [(3)H]fucose and also contained [(14)C] mannose. Evidence that both isotopes were in the same glycopeptide was obtained by the finding that the mannose-labeled glycopeptides were shifted to smaller-sized structures when the [(3)H]fucose was removed by mild acid hydrolysis. Glycopeptide IV also contained [(3)H]fucose and [(14)C] mannose but only part of the [(3)H]fucose was released by mild hydrolysis. Glycopeptides V and VI contained only small amounts of tritium, but were labeled with [(14)C]mannose. None of the six glycopeptides was susceptible to the action of endo-beta-N-acetylglucosaminidase H, and none of these glycopeptides was bound to columns of concanavalin A-sepharose. The smaller glycopeptides (IV, V, VI) were partially susceptible to alpha-mannosidase digestion, but this enzyme did not release any radioactive mannose from the larger-sized glycopeptides. These data indicate that the fucosylated glycopeptides are N-linked structures containing fucose, mannose, GlcNAc, and probably other sugars, and that the mannose units are blocked by other sugars. Thus, these results indicate that plant membrane glycoproteins contain a significant amount of modified oligosaccharide side chains.


Sestamibi scintigraphy for the application of minimally invasive surgery of hyperfunctioning parathyroid lesions.
Complete surgical resection of hyperfunctioning parathyroid tissue is essential for the curative treatment of hyperparathyroidism. It is very important to identify the accurate location of the affected parathyroid glands by imaging tests to successfully achieve this surgical treatment. Tc-99m labeled sestamibi is a radiopharmaceutical with high affinity for endocrinologically active parathyroid tissue, and scintigraphic evaluation using this radioactive agent is very useful in confirming the location of the affected parathyroid glands. The recent remarkable development of hand-held gamma-ray detectors makes it easy to perform radio-guided surgery, which is a combination of a preoperative intravenous injection of sestamibi and intraoperative navigation by the gamma-rays radiating from the pathological sites. This strategy can be easily applied to the resection of the ectopically located gland and is also useful to confirm the absence of endocrinologically active tissue after the operation. Additional chest SPECT imaging might be effective in the risk assessment of cardiac incidence in the perioperative period, as sestamibi was originally developed for the evaluation of myocardial perfusion. In conclusion, Tc-99m sestamibi will be more popularly applied to the treatment of hyperparathyroidism as minimally invasive surgery increases in favor.


Phenotypic responses to climate change are significantly dampened in big-brained birds.
Anthropogenic climate change is rapidly altering local environments and threatening biodiversity throughout the world. Although many wildlife responses to this phenomenon appear largely idiosyncratic, a wealth of basic research on this topic is enabling the identification of general patterns across taxa. Here, we expand those efforts by investigating how avian responses to climate change are affected by the ability to cope with ecological variation through behavioural flexibility (as measured by relative brain size). After accounting for the effects of phylogenetic uncertainty and interspecific variation in adaptive potential, we confirm that although climate warming is generally correlated with major body size reductions in North American migrants, these responses are significantly weaker in species with larger relative brain sizes. Our findings suggest that cognition can play an important role in organismal responses to global change by actively buffering individuals from the environmental effects of warming temperatures.


Breast-sparing reconstruction with latissimus dorsi miniflaps.
Volume loss following breast-conserving surgery (BCS) is the key reason for major local deformity and a bad cosmetic outcome. Latissimus dorsi miniflaps can be used to reconstruct central and upper quadrant resection defects, replacing the volume excised with autogenous tissue. Partial mastectomy, axillary dissection, flap harvest and reconstruction of the resection defect is performed as a one-stage procedure through a single lateral incision. This oncoplastic approach allows extensive local excision during BCS without cosmetic penalties in a group of patients normally treated by mastectomy.


Update on surgical site infections: The new CDC guidelines.
Surgical site infections (SSIs) occur near or at the incision site and/or deeper underlying tissue spaces and organs within 30 days of a surgical procedure (or up to 90 days for implanted prosthetics). SSIs are the most common healthcare-associated infections experienced by patients who undergo surgery, increase overall cost and length of hospital stay, and are largely preventable. This article reviews the recently updated CDC guidelines for preventing SSIs.


Identifying culturally acceptable cognitive tests for use in remote northern Australia.
A lack of culturally appropriate tests hampers accurate assessment of cognition in remote Australian Aboriginal communities. In Arnhem Land, this study employed a community consultation process to evaluate commonly used Western tests of executive function, memory, attention, and visuospatial function. An initial consultation process and a follow-up pilot study resulted in the rejection of some common tests, the development of new tests, and culturally adapted versions of others. In the subsequent 30-person main trial, adult Aboriginal volunteers were examined on nine tests, plus the Kimberly Indigenous Cognitive Assessment screen, and a brief literacy test. Executive function, memory, and attention tests were found to group separately after an exploratory principal components analysis. Correlations between new tests and similar Kimberly screen items were not significant, but ceiling effects may be relevant. Six of 13 test scores were found to correlate with the literacy measure. A selection of cognitive tests were identified that Aboriginal people found culturally acceptable and engaging. In particular, Self-Ordered Pointing, Trail-Making, a verbal-switching task, and a new test "Which car?" show promise for further development. This work may contribute to the need for culturally appropriate cognitive testing in Aboriginal communities.


Membrane permeabilization is mediated by distinct epitopes in mouse and human orthologs of the necroptosis effector, MLKL.
Necroptosis is a lytic programmed cell death pathway with origins in innate immunity that is frequently dysregulated in inflammatory diseases. The terminal effector of the pathway, MLKL, is licensed to kill following phosphorylation of its pseudokinase domain by the upstream regulator, RIPK3 kinase. Phosphorylation provokes the unleashing of MLKL's N-terminal four-helix bundle (4HB or HeLo) domain, which binds and permeabilizes the plasma membrane to cause cell death. The precise mechanism by which the 4HB domain permeabilizes membranes, and how the mechanism differs between species, remains unclear. Here, we identify the membrane binding epitope of mouse MLKL using NMR spectroscopy. Using liposome permeabilization and cell death assays, we validate K69 in the α3 helix, W108 in the α4 helix, and R137/Q138 in the first brace helix as crucial residues for necroptotic signaling. This epitope differs from the phospholipid binding site reported for human MLKL, which comprises basic residues primarily located in the α1 and α2 helices. In further contrast to human and plant MLKL orthologs, in which the α3-α4 loop forms a helix, this loop is unstructured in mouse MLKL in solution. Together, these findings illustrate the versatility of the 4HB domain fold, whose lytic function can be mediated by distinct epitopes in different orthologs.


Controlling the false discoveries in LASSO.
The LASSO method estimates coefficients by minimizing the residual sum of squares plus a penalty term. The regularization parameter λ in LASSO controls the trade-off between data fitting and sparsity. We derive relationship between λ and the false discovery proportion (FDP) of LASSO estimator and show how to select λ so as to achieve a desired FDP. Our estimation is based on the asymptotic distribution of LASSO estimator in the limit of both sample size and dimension going to infinity with fixed ratio. We use a factor analysis model to describe the dependence structure of the design matrix. An efficient majorization-minimization based algorithm is developed to estimate the FDP at fixed value of λ. The analytic results are compared with those of numerical simulations on finite-size systems and are confirmed to be correct. An application to the high-throughput genomic riboavin data set also demonstrates the usefulness of our method.


Content based information retrieval in forensic image databases.
This paper gives an overview of the various available image databases and ways of searching these databases on image contents. The developments in research groups of searching in image databases is evaluated and compared with the forensic databases that exist. Forensic image databases of fingerprints, faces, shoeprints, handwriting, cartridge cases, drugs tablets, and tool marks are described. The developments in these fields appear to be valuable for forensic databases, especially that of the framework in MPEG-7, where the searching in image databases is standardized. In the future, the combination of the databases (also DNA-databases) and possibilities to combine these can result in stronger forensic evidence.


Effects of radiation on protein oxidation and lipid peroxidation in the brain tissue.
Radiation produces reactive oxygen species that modify macromolecules such as protein and lipid by oxidation and act in many pathological processes, causing serious damage to the brain. This study sought to evaluate the effects of radiation and the protective effect of N-acetylcysteine (NAC) on the brain tissue of guinea pigs based on the levels of lipid peroxidation and protein oxidation. Thirty-two guinea pigs were divided into groups of eight animals each: control group (group I); radiation group (group II); NAC group (group III), and NAC administered before radiation exposure group; (group IV). Guinea pigs in groups II and IV were exposed to Co(60) radiotherapy using the Source-Axis-Distance = 80 technique. The levels of protein carbonyl content and malondialdehyde (MDA), which is a marker for lipid peroxidation, were investigated by the Evans-Levine and Uchiyama-Mihara methods, respectively. The protein carbonyl and MDA levels of group II were significantly greater than those of group I (P < .01). The protein carbonyl and MDA levels of group IV were lower than those of group II. The difference between the MDA levels of group IV and group II was significant (P < .01); however, the difference in protein carbonyl levels between the two groups was not significant. The results indicated that radiation increased protein oxidation and lipid peroxidation in the brain, and NAC administration before radiation exposure may aid in the treatment by decreasing protein and lipid oxidation.


Blauth II thumb hypoplasia: a management algorithm for the unstable metacarpophalangeal joint.
Blauth Type II thumb hypoplasia is defined by first web space narrowing, deficiency of thenar musculature, and instability of the metacarpophalangeal joint (MCPJ). This instability can be uni-axial (type IIA) or multi-axial (type IIB). The aim of this study was to assess the results of treating type II thumb hypoplasia using an algorithm based on the type of instability present. Cases of uni-axial MCPJ laxity (type IIA) underwent stabilization as part of a flexor digitorum superficialis opposition transfer. Type IIB cases with multi-axial instability were treated with an MCPJ chondrodesis and an abductor digit minimi transfer for opposition. First web space release was achieved using a z-plasty approach in all patients. An analysis was carried out of all cases of type II thumb hypoplasia treated by the senior author within the setting of a tertiary referral children's hospital over a 9 year period. Using our management algorithm, equivalent functional results were seen in each subgroup in terms of first web space release, MCPJ stabilization, and opposition.


[Distribution of the 14C-hydrated analog of phenazepam in the organs and tissues of mice].
The absorption kinetics of hydrated phenazepam analog into the liver, spleen, brain, kidney, blood, lungs, heart, skeletal and fat tissues is studied at 0.25-24 hour intervals after its intraperitoneal (i/p) administration to mice. Drug concentration in the above mentioned organs was maximal 0.5-1 hour later. The decrease of the drug and its metabolite level in the organs under study is a biexponential process, consisting of "quick" (1-6 hours) and "slow" phases. The rate of absorption of hydrated phenazepam analog into the organs and tissues and its elimination is lower than that of phenanzepam.


Long-term dosing of arzoxifene lowers cholesterol, reduces bone turnover, and preserves bone quality in ovariectomized rats.
Long-term effects of a new selective estrogen receptor modulator (SERM) arzoxifene were examined in ovariectomized (OVX) rats. Arzoxifene was administered postoperatively (po) at 0.1 mg/kg per day or 0.5 mg/kg per day to 4-month-old rats, starting 1 week after OVX for 12 months. At study termination, body weights for arzoxifene groups were 16-17% lower than OVX control, which was caused by mainly reduced gain of fat mass. Longitudinal analysis of the proximal tibial metaphysis (PTM) by computed tomography (CT) at 0, 2, 4, 6,9, and 12 months showed that OVX induced a 22% reduction in bone mineral density (BMD) at 2 months, which narrowed to a 12% difference between sham-operated (sham) and OVX rats by 12 months. Both doses of arzoxifene prevented the OVX-induced decline in BMD. Histomorphometry of the PTM showed that arzoxifene prevented bone loss by reducing osteoclast number in OVX rats. Arzoxifene maintained bone formation indices at sham levels and preserved trabecular number above OVX controls. Micro-CT analysis of lumbar vertebrae showed similar preservation of BMD compared with OVX, which were not different from sham. Compression testing of the vertebra and three-point bending testing of femoral shaft showed that strength and toughness were higher for arzoxifene-treated animals compared with OVX animals. Arzoxifene reduced serum cholesterol by 44-59% compared with OVX. Uteri wet weight from arzoxifene animals was 38-40% of sham compared with OVX rats, which were 29% of sham. Histology of the uterine endometrium showed that cell heights from both doses of arzoxifene were not significantly different from OVX controls. In summary, treatment of OVX rats with arzoxifene for nearly one-half of a lifetime maintained beneficial effects on cholesterol and the skeleton. These data suggest that arzoxifene may be a useful therapeutic agent for osteoporosis in postmenopausal women.


Prekallikrein deficiency in a 15-year-old boy with Ménière's disease: a case report.
Congenital prekallikrein deficiency is a rare disorder in which there is an in vitro clotting defect despite absence of bleeding or thrombotic tendency. In this report, a 15-year-old boy with an unexpected markedly prolonged activated partial thrombin time, a normal prothrombin time, and without personal nor familial history of bleeding or thrombosis is presented. Laboratory investigation revealed a severe prekallikrein deficiency. This case highlights the importance of following a diagnostic algorithm to establish the correct diagnosis. Moreover, by selecting appropriate laboratory tests, unnecessary and repeatedly testing can be avoided.


Real-time detection of isothermal amplification reactions with thermostable catalytic hairpin assembly.
Catalytic hairpin assembly (CHA) is an enzyme-free amplification method that has previously proven useful in amplifying and transducing signals at the terminus of nucleic acid amplification reactions. Here, for the first time, we engineered CHA to be thermostable from 37 to 60 °C and in consequence have generalized its application to the real-time detection of isothermal amplification reactions. CHA circuits were designed and optimized for both high- and low-temperature rolling circle amplification (RCA) and strand displacement amplification (SDA). The resulting circuits not only increased the specificity of detection but also improved the sensitivity by as much as 25- to 10000-fold over comparable real-time detection methods. These methods have been condensed into a set of general rules for the design of thermostable CHA circuits with high signals and low noise.


[Progress in the study of stem Leydig cells].
Leydig cells are the primary source of testosterone. As is true for all specialized cells, Leydig cells originally arise from primitive undifferentiated stem cells, stem Leydig cells (SLCs). The huge potential of SLCs is to be used therapeutically to restore testosterone levels in males with androgen deficiency due to diverse causes. The initial paradigm for cell therapy would call for harvesting the SLCs of an androgen deficient male, amplifying these cells in vitro, inducing differentiation in vitro, and then implanting the mature Leydig cells back into the same individual.


Effect of extracellular matrix proteins on platelet-activating factor-induced eosinophil chemotaxis.
Eosinophils accumulate in tissues during various allergic inflammatory processes. Selective eosinophil recruitment is the result of orchestrated events involving cell adhesion molecules and chemoattractants. However, the exact mechanism of the regulation of integrin avidity during interstitial migration is poorly understood. The purpose of this study was to investigate whether extracellular matrix proteins might activate human eosinophil chemotaxis and, if so, to clarify the mechanism in terms of integrin avidity. Eosinophils were purified from the peripheral blood of healthy donors. Eosinophil migration was measured using Boyden chambers with filter membranes coated with fibronectin (Fn), vitronectin (Vn), laminin (Ln), hyaluronic acid, collagen type IV, or bovine serum albumin (BSA) overnight. Platelet-activating factor (PAF) was introduced into the lower chamber of each well. Eosinophils were placed in the upper chamber after incubation with IL-5 for 15 min. The number of eosinophils that transmigrated into the lower chamber was calculated by measuring the eosinophil peroxidase activity. Fn, Ln and BSA enhanced PAF-induced chemotaxis of eosinophils. Inhibition experiments using blocking monoclonal antibodies showed that in the early phase of chemotaxis, Fn and Ln facilitated eosinophil chemotaxis that was mediated by alpha4 and alpha6 integrins, respectively. In the late phase of chemotaxis, BSA, but not other matrix proteins, facilitated both chemokinesis and chemotaxis that was mediated by beta2 integrin. Our data strongly suggest that during chemotaxis, matrix proteins might activate eosinophils via binding with integrins to facilitate PAF-induced chemotaxis, and that such a mechanism might participate in allergic inflammatory processes.


Free energy of mixing of acetone and methanol: a computer simulation investigation.
The change of the Helmholtz free energy, internal energy, and entropy accompanying the mixing of acetone and methanol is calculated in the entire composition range by the method of thermodynamic integration using three different potential model combinations of the two compounds. In the first system, both molecules are described by the OPLS, and in the second system, both molecules are described by the original TraPPE force field, whereas in the third system a modified version of the TraPPE potential is used for acetone in combination with the original TraPPE model of methanol. The results reveal that, in contrast with the acetone-water system, all of these three model combinations are able to reproduce the full miscibility of acetone and methanol, although the thermodynamic driving force of this mixing is very small. It is also seen, in accordance with the finding of former structural analyses, that the mixing of the two components is driven by the entropy term corresponding to the ideal mixing, which is large enough to overcompensate the effect of the energy increase and entropy loss due to the interaction of the unlike components in the mixtures. Among the three model combinations, the use of the original TraPPE model of methanol and modified TraPPE model of acetone turns out to be clearly the best in this respect, as it is able to reproduce the experimental free energy, internal energy, and entropy of mixing values within 0.15 kJ/mol, 0.2 kJ/mol, and 1 J/(mol K), respectively, in the entire composition range. The success of this model combination originates from the fact that the use of the modified TraPPE model of acetone instead of the original one in these mixtures improves the reproduction of the entropy of mixing, while it retains the ability of the original model of excellently reproducing the internal energy of mixing.


Differential Gene Expression Changes in Human Primary Dental Pulp Cells Treated with Biodentine and TheraCal LC Compared to MTA.
This study aimed to analyze the effects of pulp capping materials on gene expression changes in primary tooth-derived dental pulp cells using next-generation sequencing. Dental pulp cells were extracted and treated with mineral trioxide aggregate (MTA), Biodentine (BD), or TheraCal LC (TC). Cell viability assays were performed. Total RNA was extracted and analyzed through mRNA sequencing. Bioinformatic analysis of differential gene expression in dental pulp cells exposed to BD or TC versus MTA was performed. MTA, BD, and TC exposure had no significant effect on pulp cell viability (p > 0.05). Gene sets associated with inflammatory response (p = 2.94 × 10-5) and tumor necrosis factor alpha (TNF-α) signaling via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway (p = 2.94 × 10-5) were enriched in all materials. In BD-treated cells, Wnt/β-catenin signaling (p = 3.15 × 10-4) gene sets were enriched, whereas enrichment of interferon gamma (IFN-γ) response (p = 3 × 10-3) was observed in TC-treated cells. In gene plot analysis, marked increases in receptor activator of nuclear factor kappa-Β ligand (RANKL) expression were seen in TC-treated cells over time. Despite the similar cell viabilities exhibited among MTA-, BD-, and TC-treated cells, patterns of gene networks differed, suggesting that diverse functional gene differences may be associated with treatment using these materials.


The effects of sitting Tai Chi on physical and psychosocial health outcomes among individuals with impaired physical mobility.
Impaired physical mobility, most often seen in people with neurological disorders (i.e., stroke and spinal cord injury survivors), musculoskeletal diseases or frailty, is a limitation in independent and purposeful physical movement of the body or one or more extremities. The physical restrictions result in negative consequences on an individual's physical and psychosocial functions. This proposal describes a systematic review protocol to determine the effectiveness and approaches of sitting Tai Chi intervention for individuals with impaired physical mobility. Our review would inform stakeholders' decisions in integrating this complementary therapy into current rehabilitation services. Randomized controlled trials or quasi-experimental studies that compared an intervention group receiving sitting Tai Chi with a control group among adult participants with impaired physical mobility resulting from any health condition(s) will be included. Outcomes of interest will include physical and psychosocial health outcomes. The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PubMed, CINAHL, Scopus, Web of Science, AMED, PsycINFO, SPORDiscus, PEDro, WanFang Data and China National Knowledge Infrastructure will be searched from their inception to January 2020. Additional searches will be performed to identify studies that are being refereed, to be published, unpublished or ongoing. Two reviewers will select the trials and extract data independently. The risk of bias of the included studies will be assessed using the Cochrane risk-of-bias tools. The Grading of Recommendations, Assessment, Development and Evaluation will be used to assess evidence quality for each review outcome. Data synthesis will be performed using Review Manager 5.3. When a meta-analysis is possible, we will assess the heterogeneity across the studies by computing the I statistics. A high-quality synthesis of current evidence of sitting Tai Chi for impaired physical mobility will be stated from several aspect using subjective reports and objective measures of performance. This protocol will present the evidence of whether sitting Tai Chi is an effective intervention for impaired physical mobility. CRD 42019142681.


Sequence Knowledge on When and What Supports Dual-Tasking.
The constraints in overlapping response selection have been established in dual-tasking studies with random sequence of stimuli and responses as well as random stimulus onset asynchrony (SOA). While this approach makes it possible to control for advance activation of upcoming stimuli or responses, it leaves open whether such preparatory processing can indeed influence dual-task performance. We investigated whether and how the sequence of stimuli and responses and the sequence of SOAs can be learned and used under dual-tasking. In each trial, participants (N = 28 in Experiment 1 and N = 30 in Experiment 2) were first presented with a random two-choice task followed by a four-choice Serial Reaction Time Task (SRTT), presented in a sequence of length four (position sequence). The SOA (timing) sequence also had length four. In test phases, one or both of the sequences were randomized. Results showed that both position and timing sequences were learned and supported dual-task performance, suggesting that predictive processing with respect to timing and identity of stimuli and responses can help to circumvent the response selection bottleneck constraints. Furthermore, in contrast to previous work on acquisition of interval sequences in single tasking, we found that the sequence of what (i.e. stimulus) and the sequence of when (i.e. interval between two tasks) contributed independently to performance.


PAN3 encodes a subunit of the Pab1p-dependent poly(A) nuclease in Saccharomyces cerevisiae.
The Pab1p-dependent poly(A) nuclease (PAN) from Saccharomyces cerevisiae copurifies with polypeptides of approximately 127 and 76 kDa. Previously, it was demonstrated that the 127-kDa Pan2 protein is required for PAN activity (R. Boeck, S. Tarun, M. Reiger, J. Deardorff, S. Müller-Auer, and A.B. Sachs, J. Biol. Chem. 271:432-438, 1996). Here we demonstrate that the 76-kDa protein, encoded by the nonessential PAN3 gene, is also required for enzymatic activity. Deletion of PAN3 resulted in the loss of PAN activity in yeast extracts, and immunodepletion of Pan3p from purified PAN fractions abolished enzymatic activity. We show by coimmunoprecipitation and directed two-hybrid studies that the Pan2 and Pan3 proteins physically interact. In addition, we demonstrate that a deletion of PAN2, PAN3, or both resulted in similar increases in mRNA poly(A) tail lengths in vivo. These data strongly suggest that both Pan2p and Pan3p are required subunits of the PAN enzyme and that PAN functions in vivo to shorten mRNA poly(A) tails.


Hypertension in pregnancy.
Formal assessment of the risk of pre-eclampsia should be made early in pregnancy and antenatal care planned accordingly. Recommendations will emerge by the end of this year in a consensus statement (PRECOG guidelines) prepared by clinicians and the lay organisation Action on Pre-eclampsia (APEC) www.apec.org.uk. Some hospitals complement clinical risk assessment with Doppler screening of uterine artery waveforms in mid-pregnancy. Severe pre-eclampsia often takes an explosive course, evolving over a period of hours. Recognition may, therefore, not be amenable to intermittent blood pressure recording and urine testing, but requires women reporting relevant symptoms and GPs being sensitive to the possible significance of complaints such as vomiting and epigastric pain. Severe hypertension demands urgent antihypertensive treatment in hospital. Magnesium sulphate now has an accepted role in the prevention of eclampsia. Possible prevention of pre-eclampsia by antioxidant therapy is the subject of a clinical trial. Low-dose aspirin has a modest but beneficial effect in high-risk women. Delivery remains the definitive treatment for pre-eclampsia, but there may be initial deterioration after birth, especially in the HELLP syndrome.


Characterization of nigericin-stimulated ATPase from sealed microsomal vesicles of tobacco callus.
To understand the function and membrane origin of ionophore-stimulated ATPases, the activity of nigericin-stimulated ATPase was characterized from a low-density microsomal fraction containing sealed vesicles of autonomous tobacco (Nicotiana tabacum Linnaeous cv. Wisconsin no. 38) callus. The properties of KCl-stimulated, Mg-requiring ATPases (KCl-Mg,ATPase) were similar in the absence or presence of nigericin. Nigericin (or gramicidin) stimulation of a KCl-Mg,ATPase activity was optimum at pH 6.5 to 7.0. The enzyme was inhibited completely by N,N'-dicyclohexylcarbodiimide (10 mum), tributyltin (5 mum), and partially by vanadate (200 mum), but it was insensitive to fusicoccin and mitochondrial ATPase inhibitors, such as azide (1 mm) and oligomycin (5 mug/ml). The ATPase was more sensitive to anions than cations. Cations stimulated ATPase activity with a selectivity sequence of NH(4) (+) > K(+), Rb(+), Cs(+), Na(+), Li(+) > Tris(+). Anions stimulated Mg, ATPase activity with a decreasing sequence of Cl(-) = acetate > SO(4) (2-) > benzene sulfonate > NO(3) (-). The anion stimulation was caused partly by dissipation of the electrical potential (interior positive) by permeant anions and partly by a specific ionic effect. Plant membranes had at least two classes of nigericin-stimulated ATPases: one sensitive and one insensitive to vanadate. Many of the properties of the nigericin-sensitive, salt-stimulated Mg,ATPase were similar to a vanadate-sensitive plasma membrane ATPase of plant tissues, yet other properties (anion stimulation and vanadate insensitivity) resembled those of a tonoplast ATPase. These results support the idea that nigericin-stimulated ATPases are mainly electrogenic H(+) pumps originated in part from the plasma membrane and in part from other nonmitochondrial membranes, such as the tonoplast.


Does smoking influence the surgical outcome of a myringoplasty?
To investigate the relationship between a patient's smoking habits and surgical outcome of his/her myringoplasty. The medical records of patients who had undergone myringoplasty were retrospectively reviewed for age, gender, smoking habits, perforation size, perforation location, surgical technique, graft material, and surgical outcome. Surgical success was defined as the perforation having remained closed 12 months postoperatively. The study group included 65 patients (41 females and 24 males, age range 18-79, average 35.9 years). Eight females were smokers (19.5%) compared to 10 male smokers (41.7%, p = 0.054). The overall surgical success rate was 63/65 (96.9%) with the 2 failures occurring in nonsmoker females. The graft taken was temporalis fascia in 20/21 (95.2%) and tragal perichondrium in 43/44 (97.7%) cases (p = 0.587). There was no significant gender-based (39/41 vs. 24/24, p = 0.272) or smoker status-based (45/47 for nonsmokers vs. 18/18 for smokers, p = 0.374) success rate. There was no significant difference in fascia versus perichondrium grafting success for smokers (p = 0.421) versus nonsmokers (p = 0.583). Primary myringoplasty performed by an experienced otologist had a surgical success rate of 96.9% for closure of tympanic membrane defects, regardless of the choice of graft material, perforation size or location, and patient's age, gender and smoking habits.


The renal transcriptome of db/db mice identifies putative urinary biomarker proteins in patients with type 2 diabetes: a pilot study.
We sought to identify novel urinary biomarkers of kidney function in type 2 diabetes. We screened the renal transcriptome of db/db and db/m mice for differentially expressed mRNA transcripts that encode secreted proteins with human orthologs. Whether elevated urine levels of the orthologous proteins correlated with diminished glomerular filtration rate was tested in a cross-sectional study of n = 56 patients with type 2 diabetes. We identified 36 putative biomarker genes in db/db kidneys: 31 upregulated and 5 downregulated. Urinary protein levels of six selected candidates (endothelin-1, lipocalin-2, transforming growth factor-β, growth and differentiation factor-15, interleukin-6, and macrophage chemoattractant protein-1) were elevated in type 2 diabetic patients with subnormal glomerular filtration rate (i.e., <90 ml·min(-1)·1.73 m(-2)), independent of microalbuminuria, age, sex, race, and use of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists. In contrast, urinary levels of fibroblast growth factor were not increased. A composite variable of urine albumin and any of the six candidate markers was associated with subnormal estimated glomerular filtration rate more closely than albumin alone. In addition, urinary endothelin-1, growth and differentiation factor-15, and interleukin-6 were associated with a marker of proximal tubule damage, N-acetyl-β-d-glucosaminidase activity. These results suggest that gene expression profiling in diabetic mouse kidney can complement existing proteomic-based approaches for renal biomarker discovery in humans.