Immunological comparison between prostate-specific antigen and gamma-seminoprotein.
Prostate-specific antigen (PA) and gamma-seminoprotein (gamma-Sm) were compared by immunocytochemical, immunodiffusion and immunoblotting methods using rabbit anti-PA antibody and rabbit anti-gamma-Sm antibody. Enzyme immunoassays (EIAs) were developed for measurements of PA and gamma-Sm to determine a correlation between serum PA and gamma-Sm levels in patients with prostate cancer. The patterns of localization and distribution of PA and gamma-Sm were identical in prostate tissue sections, including benign and cancerous human prostates. The immunodiffusion study showed that the antigens with which anti-PA antibody and anti-gamma-Sm antibody reacted in seminal plasma and prostate tissue homogenates were identical to each other. In the immunoblotting study, anti-PA antibody and anti-gamma-Sm antibody recognized a single antigen corresponding to a molecular weight of approximately 33,000 both in seminal plasma and prostate tissue homogenates. The EIAs developed in this study were sensitive, specific, and reproducible, and the correlation between serum PA and gamma-Sm values determined by these EIAs was highly significant (r = 0.99, P less than 0.001). These results indicated that PA and gamma-Sm were immunologically identical and that serum PA and gamma-Sm determined by immunoassays using anti-PA antibody and anti-gamma-Sm antibody should be evaluated as identical tumor markers for serodiagnosis of prostate cancer.


Canopy management in rainfed vineyards (cv. Tempranillo) for optimising water use and enhancing wine quality.
Rainfed viticulture, mainly in semi-arid environments, is limited by environmental variability, particularly precipitation and its seasonal distribution, and soil water availability, thus ultimately determining the final quality of grape and wine. Studies on the feasibility of practices such as canopy management to adapt plant growth and yield to soil water availability open up possibilities to preserve wine quality and reinforce the characteristics of the terroir. Principal components analysis was used to identify the relationships between a large set of variables, including soil, plant, canopy management, and wine characteristics. Canopy management was found to have a predominant influence on plant response to soil water by modifying plant water status, changing the amino acid profile in berries and, concomitantly, altering the sensorial attributes of the wine obtained. Grapevine canopy management strategies, such as reiterate shoot trimming to restrict growth during early phases, are effective in adapting plant response to soil water availability. Such strategies affect berry and wine quality, mainly the amino acid profile and sensorial attributes of the wine, without changing yield or grape harvest quality control parameters. Also, in such conditions, nitrogen does not make a significant contribution to grapevine growth or yield or to grape quality.


Ultrasound in schistosomiasis mansoni.
We reviewed ultrasound features in patients with schistosomiasis mansoni. The alterations that we observed in acute and hepatosplenic schistosomiasis are described. The advantages and disadvantages of using ultrasound patterns in the evaluation of liver fibrosis are discussed. Other diseases that are important in the differential diagnosis of schistosomal liver fibrosis are presented. Ultrasound is an effective and flexible diagnostic tool in the evaluation of a variety of diseases. It presents no harmful effects to patients, allowing non-invasive studies in hospitalized patients and in other facilities.


Sexually dimorphic nonreproductive behaviors as indicators of endocrine disruption.
Measures of cognitive and other behaviors not specifically related to reproduction are often sex-linked. Males and females perform differently on many tasks and often interact with members of their species in dissimilar ways. If such differences are diminished, reversed, or widened by prenatal chemical exposures, a reasonable inference is that exposure interfered with sexual differentiation of the brain, largely, but not exclusively, through interference with the actions of gonadal hormones. Explicit recognition of sex differences in performance is not a prominent feature of toxicity testing, however, except for reproduction studies, and is not a recognized criterion in developmental neurotoxicity testing. In contrast to the low visibility accorded sex differences in testing protocols for the assessment of developmental neurotoxicity, the literature is filled with examples showing that the developing male and female respond differently to many chemical agents, with subsequent expression in behavior. Quite often, even when such differences are reported, further analyses are not carried out nor are subsequent studies conducted for clarification. Moreover, many investigators include only male subjects. Both polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) studies provide several examples of striking differences between the behavioral responses of male and female offspring to developmental exposure. They offer examples, as well, of how to approach the study and analysis of such differences. Given the societal importance of risk assessments applied to potential developmental neurotoxicants, studies should be deemed questionable if they fail to include outcome measures based on sexual dimorphisms in nonreproductive behaviors.


Jak inhibitor ; possibility and mechanism as a new disease modifying anti-rheumatic drug.
Treatment of rheumatoid arthritis (RA) has developed dramatically by the appearance of biologics. However the development of a new anti-rheumatic drug is necessary because of its issue on route of administration and expense. Recently, inhibitors targeting tyrosine kinase known as Janus kinase (Jak) has shown prominent effect on RA. Jak family is comprised by Jak1, Jak2, Jak3 and Tyk2 which is necessary for signal transduction for inflammatory cytokines. INCB18424 targeting Jak1/2 and CP690,550 targeting Jak3 has been developed and is now on phase II clinical study for RA. Results from those clinical studies have proven that these inhibitors can be effective as biologics with few side effects. However, it has been reported that inhibitors are less specific than it has been expect and that non-specificity can be important for its effect. Therefore, we think that the mechanism of inhibitors cannot be explained by its inhibition of a single kinase. Herein, we describe IL-10 overproduction by Jak3 and Stat6 deficient dendritic cell. We speculate that this is one possible mechanism of action for CP690,550 although as for its non-specificity we need further investigation to predict not only its effect but also its side effect in a long term administration.


alpha-L-fucosidase polymorphism in human semen, blood, and vaginal fluid.
The diallelic enzyme alpha-L-fucosidase has been found to be highly active in semen. Eight distinct enzyme bands were observed in each homozygote and the heterozygote consisted of a combination of bands. The isoelectric points ranged between pI 4.34 and 6.65. Activity was found to be much lower in vaginal fluid, not more than three cathodal bands were visible in any sample examined. In leucocytes, 5 bands were detected in homozygotes whilst in serum only two faint anodal bands could be detected. Activity was low in vaginal fluid and could not be detected in urine or saliva. Population studies were carried out on semen samples from Oxford and Basingstoke and on lymphocyte samples from Oxford. The data were in agreement with Hardy-Weinburg equilibrium. The common allele (Fu 1) had a frequency of 0.704 in Oxford semen samples.


Isolation of acetylcholine receptor-like protein from fetal calf thymus.
Cobrotoxin-binding protein from fetal calf thymus was isolated by affinity chromatography after solubilization with Triton X-100 or sodium cholate. Its specificity as a nicotinic acetylcholine receptor (AChR) was determined by assessing the binding to radiolabeled alpha-bungarotoxin (BuTx) and to serum containing antibody against AChR obtained from a patient with myasthenia gravis (MG). AChR-like protein was detected in the amount of 0.41 -2.04 X 10(-9) mol alpha-BuTx binding sites per g protein. Polyacrylamide gel electrophoresis in sodium dedecylsulfate (SDS) revealed polypeptide bands with molecular weights of 40,000, 46,000, 55,000, 70,000, 35,000, and 26,000 daltons. As this protein may play an important role in immunopathological changes in MG, related studies are underway.


Trait Impulsivity and Newlyweds' Marital Trajectories.
Despite the relationship of impulsivity with interpersonal dysfunction, including romantic relationship dysfunction, surprisingly little research has examined the degree to which impulsivity predicts how marriages unfold over time. The current study used data from 172 newlywed couples to examine spouses' impulsivity in relation to their 4-year trajectories of marital satisfaction, marital problems, relationship commitment, and verbal aggression, as well as their 10-year divorce rates. Hierarchical linear modeling indicated that husbands' and wives' impulsivity predicted their own intercepts of marital satisfaction and marital problems, reflecting lower levels of satisfaction and higher levels of problems. Wives' impulsivity also predicted their relationship commitment and their verbal aggression intercepts. No cross-spouse effects or effects on slopes were found, and impulsivity did not predict 10-year divorce rates. These findings indicate that the relationship distress associated with impulsivity begins early in marriage, and they suggest a need for further research on the processes by which impulsivity undermines marital quality.


Comparative Genomic Analysis of Pathogenic Factors of Pectobacterium Species Isolated in South Korea Using Whole-Genome Sequencing.
In this study, we conducted whole-genome sequencing with six species of Pectobacterium composed of seven strains, JR1.1, BP201601.1, JK2.1, HNP201719, MYP201603, PZ1, and HC, for the analysis of pathogenic factors associated with the genome of Pectobacterium. The genome sizes ranged from 4,724,337 bp to 5,208,618 bp, with the GC content ranging from 50.4% to 52.3%. The average nucleotide identity was 98% among the two Pectobacterium species and ranged from 88% to 96% among the remaining six species. A similar distribution was observed in the carbohydrate-active enzymes (CAZymes) class and extracellular plant cell wall degrading enzymes (PCWDEs). HC showed the highest number of enzymes in CAZymes and the lowest number in the extracellular PCWDEs. Six strains showed four subsets, and HC demonstrated three subsets, except hasDEF, in type I secretion system, while the type II secretion system of the seven strains was conserved. Components of human pathogens, such as Salmonella pathogenicity island 1 type type III secretion system (T3SS) and effectors, were identified in PZ1; T3SSa was not identified in HC. Two putative effectors, including hrpK, were identified in seven strains along with dspEF. We also identified 13 structural genes, six regulator genes, and five accessory genes in the type VI secretion system (T6SS) gene cluster of six Pectobacterium species, along with the loss of T6SS in PZ1. HC had two subsets, and JK2.1 had three subsets of T6SS. With the GxSxG motif, the phospholipase A gene did locate among tssID and duf4123 genes in the T6SSa cluster of all strains. Important domains were identified in the vgrG/paar islands, including duf4123, duf2235, vrr-nuc, and duf3396.


Urinary obstruction in azotemic patients: detection by sonography.
Renal sonography is frequently requested in patients with an elevated or rising creatinine, often with the instruction to "rule out obstruction." A prospective study of patients undergoing renal sonography for newly discovered azotemia (creatinine greater than 1.8 mg/dl) or worsening renal failure was undertaken to evaluate the clinical utility of the sonographic examination. Patients with known obstructive uropathy, renal calculi, renal mass, or hematuria were excluded. In 189 patients, 17 (9%) had hydronephrosis: 11 unilateral (one with a solitary kidney) and six bilateral. Obstructive causes were subsequently established in the solitary kidney and in four patients with bilateral dilatation. These five patients (2.6%) with clinically significant hydronephrosis were shown subsequently to have a clinical history that strongly suggested the presence of urinary tract obstruction. Our data suggest that, in patients without a clinical history that suggests obstruction (such as calculi, bladder outlet obstruction, or pelvic mass), the likelihood of finding bilateral hydronephrosis by sonography is small.


Natural history and treatment of chronic delta hepatitis.
Chronic delta hepatitis (CDH) represents a severe form of chronic viral hepatitis, induced by the hepatitis delta virus (HDV) in conjunction with the hepatitis B virus (HBV). Delta hepatitis may lead to disease in humans through co-infection. The former leads to acute hepatitis which clinically can range from mild hepatitis to fulminant hepatitis and death. Severe or fulminant hepatitis is more often observed with HBV-HDV co-infection compared to HBV mono-infection. Chronic infection after acute hepatitis B + D co-infection is infrequent and similar to the rate in mono-infected patients. CDH develops in 70-90% of patients with superinfection. CDH runs a more progressive course than chronic hepatitis B and may lead to cirrhosis within 2 years in 10-15% of patients. However, as with any immune-mediated disease, different patterns of progression, ranging from mild to severe progressive disease, are observed. Active replication of both HBV and HDV may be associated with a more progressive disease pattern. Further, different HDV and HBV genotypes may contribute to various disease outcomes. CDH may be frequently associated with hepatocellular carcinoma development although recent studies provided conflicting results. The only established therapy for CDH is treatment with interferons for a duration of at least 1 year. On treatment, 6 month HDV RNA assessment may give clues as to whether to stop treatment at 1 year or continue beyond 1 year. New approaches to treatment of CDH are an urgent need of which the use of prenylation inhibitors appears the most promising.


The wisdom of polarized crowds.
As political polarization in the United States continues to rise1-3, the question of whether polarized individuals can fruitfully cooperate becomes pressing. Although diverse perspectives typically lead to superior team performance on complex tasks4,5, strong political perspectives have been associated with conflict, misinformation and a reluctance to engage with people and ideas beyond one's echo chamber6-8. Here, we explore the effect of ideological composition on team performance by analysing millions of edits to Wikipedia's political, social issues and science articles. We measure editors' online ideological preferences by how much they contribute to conservative versus liberal articles. Editor surveys suggest that online contributions associate with offline political party affiliation and ideological self-identity. Our analysis reveals that polarized teams consisting of a balanced set of ideologically diverse editors produce articles of a higher quality than homogeneous teams. The effect is most clearly seen in Wikipedia's political articles, but also in social issues and even science articles. Analysis of article 'talk pages' reveals that ideologically polarized teams engage in longer, more constructive, competitive and substantively focused but linguistically diverse debates than teams of ideological moderates. More intense use of Wikipedia policies by ideologically diverse teams suggests institutional design principles to help unleash the power of polarization.


Tricuspid endocarditis in an adult patient with Ebstein's anomaly who has a residual pacemaker lead.
Ebstein's anomaly is defined as an apical displacement of the attachment of the septal tricuspid valve leaflet from the right atrioventricular annulus that exceeded 1.2 cm in length. Patients with Ebstein's anomaly are known to have a high potential for developing arrhythmia, in the vast majority, of the tachycardia type. Infective endocarditis is characterized by ulcerovegetational lesions that result from the graft of a microorganism, usually bacterial, on the valvuler endocardium (native valve endocarditis) or on a prosthesis (prosthetic valve endocarditis). Ebstein's anomaly with tricuspid regurgitation is also thought to be a predisposing condition for infective endocarditis. In this case, we report a patient who presented with atrial flutter and infective endocarditis due to residual pacemaker lead and Ebstein's anomaly.


Intraoperative Hypotension and Acute Kidney Injury after Noncardiac Surgery in Infants and Children: A Retrospective Cohort Analysis.
Age- and sex-specific reference nomograms for intraoperative blood pressure have been published, but they do not identify harm thresholds. The authors therefore assessed the relationship between various absolute and relative characterizations of hypotension and acute kidney injury in children having noncardiac surgery. The authors conducted a retrospective cohort study using electronic data from two tertiary care centers. They included inpatients 18 yr or younger who had noncardiac surgery with general anesthesia. Postoperative renal injury was defined using the Kidney Disease Improving Global Outcomes definitions, based on serum creatinine concentrations. The authors evaluated potential renal harm thresholds for absolute lowest intraoperative mean arterial pressure (MAP) or largest MAP reduction from baseline maintained for a cumulative period of 5 min. Separate analyses were performed in children aged 2 yr or younger, 2 to 6 yr, 6 to 12 yr, and 12 to 18 yr. Among 64,412 children who had noncardiac surgery, 4,506 had creatinine assessed preoperatively and postoperatively. The incidence of acute kidney injury in this population was 11% (499 of 4,506): 17% in children under 6 yr old, 11% in children 6 to 12 yr old, and 6% in adolescents, which is similar to the incidence reported in adults. There was no association between lowest cumulative MAP sustained for 5 min and postoperative kidney injury. Similarly, there was no association between largest cumulative percentage MAP reduction and postoperative kidney injury. The adjusted estimated odds for kidney injury was 0.99 (95% CI, 0.94 to 1.05) for each 5-mmHg decrease in lowest MAP and 1.00 (95% CI, 0.97 to 1.03) for each 5% decrease in largest MAP reduction from baseline. In distinct contrast to adults, the authors did not find any association between intraoperative hypotension and postoperative renal injury. Avoiding short periods of hypotension should not be the clinician's primary concern when trying to prevent intraoperative renal injury in pediatric patients.


Single-Cell Profiles of Age-Related Osteoarthritis Uncover Underlying Heterogeneity Associated With Disease Progression.
Objective: Osteoarthritis (OA) is the most common chronic degenerative joint disease, which represents the leading cause of age-related disability. Here, this study aimed to depict the intercellular heterogeneity of OA synovial tissues. Methods: Single-cell RNA sequencing (scRNA-seq) data were preprocessed and quality controlled by the Seurat package. Cell cluster was presented and cell types were annotated based on the mRNA expression of corresponding marker genes by the SingleR package. Cell-cell communication was assessed among different cell types. After integrating the GSE55235 and GSE55457 datasets, differentially expressed genes were identified between OA and normal synovial tissues. Then, differentially expressed marker genes were overlapped and their biological functions were analyzed. Results: Totally, five immune cell subpopulations were annotated in OA synovial tissues including macrophages, dendritic cells, T cells, monocytes and B cells. Pseudo-time analysis revealed the underlying evolution process in the inflammatory microenvironment of OA synovial tissue. There was close crosstalk between five cell types according to the ligand-receptor network. The genetic heterogeneity was investigated between OA and normal synovial tissues. Furthermore, functional annotation analysis showed the intercellular heterogeneity across immune cells in OA synovial tissues. Conclusion: This study offered insights into the heterogeneity of OA, which provided in-depth understanding of the transcriptomic diversities within synovial tissue. This transcriptional heterogeneity may improve our understanding on OA pathogenesis and provide potential molecular therapeutic targets for OA.


The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide.
1. The interactions between endothelium-derived nitric oxide (NO) and prostacyclin as inhibitors of platelet aggregation were examined. 2. Porcine aortic endothelial cells treated with indomethacin and stimulated with bradykinin (10-100 nM) released NO in quantities sufficient to account for the inhibition of platelet aggregation attributed to endothelium-derived relaxing factor (EDRF). 3. In the absence of indomethacin, stimulation of the cells with bradykinin (1-3 nM) released small amounts of prostacyclin and EDRF which synergistically inhibited platelet aggregation. 4. EDRF and authentic NO also caused disaggregation of platelets aggregated either with collagen or with U46619. 5. A reciprocal potentiation of both the anti- and the dis-aggregating activity was also observed between low concentrations of prostacyclin and authentic NO or EDRF released from endothelial cells. 6. It is likely that interactions between prostacyclin and NO released by the endothelium play a role in the homeostatic regulation of platelet-vessel wall interactions.


Seadragon VI: a 7-day dry saturation dive at 31 ATA. III. Alterations in basal and circadian endocrinology.
Four male divers were exposed to an environment of 1 ATA air for 7 d, followed by 7 d of 31 ATA He-O2, and following decompression to a postdive 1 ATA air environment for 3 d. Urine and blood were collected for hormonal measurements. Divided 24-h urine collections were obtained during 3 consecutive d at predive 1 ATA conditions, and at 31 ATA conditions. Two consecutive day collections were obtained at early decompression (31-25 ATA), at late decompression (14-8 ATA), and at postdive 1 ATA. Two blood samples were obtained, at predive 1 ATA, at 31 ATA, and at postdive 1 ATA. Plasma antidiuretic hormone (ADH) concentration decreased about 45% (P less than 0.005), while plasma aldosterone concentration and urinary aldosterone excretion were doubled (P less than 0.005) after the subjects were at 31 ATA. Plasma cortisol concentration and plasma parathyroid hormone concentration were not significantly affected by hyperbaria. Urinary excretion of aldosterone was not significantly different between day (0700-1900) and night (1900-0700) at any time, and both day and night excretion rates were increased at 31 ATA through late decompression (P less than 0.005). Urinary ADH excretion was greater during daytime at predive 1 ATA (P less than 0.005), but not thereafter. Both daytime and nighttime ADH excretion rates were decreased from 31 ATA through late decompression (P less than 0.005). It is concluded that hyperbaria eliminates the circadian release pattern of ADH and that the overall reduction of ADH may contribute to the increased free water clearance observed at hyperbaria. Also, increased parathyroid hormone was not associated with the phosphaturia observed at hyperbaria, but increased aldosterone coexisted with the increased kaliuresis observed.


TIGIT marks exhausted T cells and serves as a target for immune restoration in patients with chronic HBV infection.
Chronic HBV infection is a serious worldwide health problem that mainly causes liver cirrhosis and hepatocellular carcinoma (HCC). Few studies have explored how T cell exhaustion helps HBV avoid immune system attack and how to reverse that exhaustion. Recently, T cell immunoglobulin and immune receptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) have been identified as coinhibitory receptors, similar to PD-1. This study explores the expression of TIGIT and the T cell function changes in patients with chronic HBV infection. In this study, we found that the expression of TIGIT on T cells increased significantly in patients with chronic HBV infection. High expression of TIGIT on T cells is associated with functional exhaustion. Importantly, this study demonstrates that blocking TIGIT can reverse T cell exhaustion and restore function in patients with chronic HBV infection. HBV induces T cell exhaustion by up-regulating the expression of TIGIT. Blocking the TIGIT/PVR signaling pathway can reverse T cell exhaustion, so this discovery provides an immunotherapy target to battle chronic HBV infection.


Psychophysiological Effects of Lactobacillus plantarum PS128 in Patients with Major Depressive Disorder: A Preliminary 8-Week Open Trial.
Recent studies have suggested that gut-brain axis may be one of the mechanisms of major depression disorder (MDD). The current study aimed to investigate the effects of Lactobacillus plantarum PS128 (PS128) on psychophysiology in patients with MDD. We recruited 11 patients with MDD and gave them PS128 for 8 weeks. We compared depression symptoms, serum markers of inflammation and gut permeability, and gut microbiota before and after 8-week intervention and also explored the correlations among symptoms, biomarkers, and gut microbiota. After 8-week PS128 intervention, scores of Hamilton Depression Rating Scale-17 and Depression and Somatic symptoms Scale significantly decreased. Serum levels of high sensitivity c-reactive protein, interluekin-6, and tumor necrosis factor-α, zonulin and intestinal fatty acid binding protein, and the composition of gut microbiota did not significantly change after 8-week PS128 intervention. However, we found changes of some genera were correlated with changes of symptoms and biomarkers. In conclusion, this is an open trial with small sample size and has several limitations. The results need to be verified by randomized, double-blind, placebo-controlled trial with larger sample size.


Dietary fish oil protects against lung and liver inflammation and fibrosis in monocrotaline treated rats.
The purpose of the present study was to evaluate the effectiveness of fish oil in preventing tissue pathologies associated with monocrotaline (MCT) toxicity. Twenty-four weanling rats were randomly assigned to one of two groups: (1) 12 to a group fed a diet containing 15% (w/w) corn oil (control) and (2) 12 to a group fed a diet containing fish oil (13%) and corn oil (2%) as the source of fat. Rats were fed for 4 weeks prior to MCT treatment. Six rats in each group were subcutaneously injected with MCT and six injected with its vehicle (water) and all were continued on their respective diets. All rats were sacrificed 3 weeks after injection. In rats receiving MCT, we observed severe interstitial pneumonia, septal fibrosis, vasculitis with virtual obliteration of the lumen of the small arteries and arterioles, right ventricular hypertrophy (RVH), and hepatomegaly and hepatocyte vacuole formation. Dietary fish oil significantly reduced septal fibrosis and development of pneumonia. There was a slight, but statistically insignificant decrease in vasculitis and fish oil did not prevent RVH (pulmonary hypertension). In addition, fish oil effectively protected the MCT-treated rats from development of hepatocyte vacuoles (steatosis), hepatic inflammation and vasculitis, increased presence of fibroblasts and collagen deposition in the centrilobular and, to a lesser extent, in the periportal spaces. These results suggest that lung parenchymal inflammation can be attenuated without altering the course of development of pulmonary hypertension in the MCT model. These results also indicate that fish oil protects against inflammation and fibrosis in the lung and liver, and against hepatocyte vacuole formation in MCT-treated rats.


MUC1: antibodies and immunoassays.
High molecular weight mucins represent a unique challenge as tumor markers by virtue of their complex array of epitopes. The list is dominated by the high molecular weight mucins MUC1, CEA and CA125. While the currently accepted role for these tumor markers is in the prediction and detection of relapse, it is possible that their sensitivity and specificity can be improved. Although immunoassays detecting the tumor marker MUC1 are both sensitive and specific for predicting relapse in breast cancer, so far they are not in widespread use in the follow-up of this disease. Are there new combinations of conventional reagents that could improve assay sensitivity, or should we be looking for more radical changes in assay design incorporating combinatorial technology?


Automated low-redundancy large-scale DNA sequencing by primer walking.
Low-redundancy automated DNA sequencing by primer walking is described. T7 DNA polymerase is used together with computer-selected walking primers and fluorescein-dATP as internal label to sequence large plasmids or cosmids directly on a standard DNA sequencer with an error rate below 1% up to 500 bases (in the unedited raw data). The low error rate allows efficient sequencing with low (2-3 times) redundancy. Plasmid subclones covering 20 kb of a cosmid insert were sequenced with an overall redundancy of 2.7 in the course of the European community Saccharomyces cerevisiae genome sequencing project. Neighboring plasmid subclones were linked by direct cosmid sequencing. Sets of ten walking primers are synthesized on the EMBL multiple segmental DNA synthesizer at low costs and used for sequencing with greater than 95% efficiency. The accuracy of the directed approach is improved by simultaneous walking on both strands by designing two primers in opposite directions in the same starting region. One primer is used to confirm sequence data on the opposite strand, and the other primer to obtain new sequence data.


Context-Dependent Multiplexing by Individual VTA Dopamine Neurons.
Dopamine (DA) neurons of the VTA track cues and rewards to generate a reward prediction error signal during Pavlovian conditioning. Here we explored how these neurons respond to a self-paced, operant task in freely moving mice. The animal could trigger a reward-predicting cue by remaining in a specific location of an operant box for a brief time before moving to a spout for reward collection. VTA DA neurons were identified using DAT-Cre male mice that carried an optrode with minimal impact on the behavioral task. In vivo single-unit recordings revealed transient fast spiking responses to the cue and reward in correct trials, while for incorrect ones the activity paused, reflecting positive and negative error signals of a reward prediction. In parallel, a majority of VTA DA neurons simultaneously encoded multiple actions (e.g., movement velocity, acceleration, distance to goal, and licking) in sustained slow firing modulation. Applying a GLM, we show that such multiplexed encoding of rewarding and motor variables by individual DA neurons was only apparent while the mouse was engaged in the task. Downstream targets may exploit such goal-directed multiplexing of VTA DA neurons to adjust actions to optimize the task's outcome.SIGNIFICANCE STATEMENT VTA DA neurons code for multiple functions, including the reward prediction error but also motivation and locomotion. Here we show that about half of the recorded VTA DA neurons perform multiplexing: they exploit the phasic and tonic activity modes to encode, respectively, the cue/reward responses and motor parameters, most prominently when the mouse engages in a self-paced operand task. VTA non-DA neurons, by contrast, encode motor parameters regardless of task engagement.


Morphometric analysis of testis cord formation in Sox9-EGFP mice.
Sox9-EGFP knockin mice were generated to label Sertoli cells and visualize testis cord formation during development. Confocal microscopy and morphometric analysis of developing cords were performed. Serial histological sections were used for three-dimensional cord reconstruction. Initially, gonad length decreased from embryonic day (E) 11.5 to E13.5, but increased thereafter, while gonad width doubled every 12 hours from E11.5 through E14.5. At E12.5, the average number of cords was 12.5, whereas this decreased to 10.4 at E13.5 and E14.5. Cord number at a given time point varied between gonads and influenced dimensions. The initial cords that formed were complex and branches were common. Time-lapse imaging revealed an intricate behavior of the Sertoli-germ cell mass and cellular exchange between connected neighboring cords. These results suggest that cord formation is a highly dynamic process that subsequently becomes refined to establish the final number of seminiferous tubule precursors.


[Comparisons of volatile components in different parts of three species of Rhizoma Curcumae].
To provide the scientific basis for the reasonable development and use of the leaves of Rhizoma Curcumae. To extract the volatile oil from roots and leaves of three species Rhizoma Curcumae by steam distillation and isolate these products with the method of gas chromatography-mass spectrum. Taking Nist98 standard mass spectrometer database and contrast as control, the structure of the mass spectrogram was identified, and the relative contents of the components were determined with area normalization method. The anti-tumor active constituents such as curdione and germacrone in the leaves had the greater content than in its rhizome. The varieties of volatile components in different parts of three species of Rhizoma Curcumae are similar, but their contents are obviously various. We can make the leaves of Rhizoma Curcumae for recycling use.


The history of Trilucent implants, and a chemical analysis of the triglyceride filler in 51 consecutively removed Trilucent breast prostheses.
This study set out to detect specific classes of potentially genotoxic aldehydes resulting from soybean-oil peroxidation in oil samples from 51 Trilucent implants in 26 patients and two factory-retained prostheses. The chemical analysis was performed independently of AEI inc. All of the implants showed evidence of shell deterioration suggestive of lipid absorption, and of lipid bleed throughout the implant shell. The mean implant weight loss was found to be almost 2% per year. Although none of the implants had actually ruptured in-situ, we identified specific problems with anterior and posterior patch delaminations, making the implant prone to rupture. Our data suggest that the soybean oil in all the explanted Trilucent implants and the two factory-retained prostheses had undergone peroxidation, yielding aldehyde by-products in millimolar concentrations. These concentrations are over 1000 times that thought to be potentially genotoxic. The clinical implications of these findings remain unclear. Capsular tissue was submitted to AEI Inc for histological and chemical analysis, but the data have not been forthcoming, which is disappointing as this may provide further evidence for the risks of long-term complications in these patients.


Behavioral health: setting the rural health research agenda.
This article seeks to identify current research priorities in the area of rural behavioral health. The method for accomplishing this task begins by identifying several domains where policy has a potential to effect improvements in access or quality but has been hampered by lack of empirical knowledge. In each domain a synthesis of current research summarizes what is known and draws attention to knowledge gaps. Research questions in each domain are proposed. The policy domains are theoretically based, using a conceptual model of access to health care, with a focus on illness level (prevalence), enabling factors (the delivery system, organization and financing, the promise of telemedicine), and predisposing factors (special populations, beliefs, values, stigma).


How blind is double-blind? A study of fish oil versus placebo.
The distinctive aftertaste associated with fish oil preparations used in clinical trials of omega-3 fatty acids may weaken the double-blind. This double-blind pilot study was designed to examine whether normal subjects could correctly 'guess' if they were receiving capsules containing concentrated fish oil or capsules of pure olive oil. The informed consent was designed to give subjects ambiguous expectations about what oil they might be receiving to examine whether this would influence their guess. Despite a marked difference in taste experience, there was no significant difference in correct guesses between the two groups. The results suggest that altering subjects' expectations could further improve the validity of the double-blind.


A survival analysis of COVID-19 in the Mexican population.
At present, the Americas report the largest number of cases of COVID-19 worldwide. In this region, Mexico is the third country with most deaths (20,781 total deaths). A sum that may be explained by the high proportion of people over 50 and the high rate of chronic diseases. The aim of this analysis is to investigate the risk factors associated with COVID-19 deaths in Mexican population using survival analysis. Our analysis includes all confirmed COVID-19 cases contained in the dataset published by the Epidemiological Surveillance System for Viral Respiratory Diseases of the Mexican Ministry of Health. We applied survival analysis to investigate the impact of COVID-19 on the Mexican population. From this analysis, we plotted Kaplan-Meier curves, and constructed a Cox proportional hazard model. The analysis included the register of 16,752 confirmed cases of COVID-19 with mean age 46.55 ± 15.55 years; 58.02% (n = 9719) men, and 9.37% (n = 1569) deaths. Male sex, older age, chronic kidney disease, pneumonia, hospitalization, intensive care unit admission, intubation, and health care in public health services, were independent factors increasing the risk of death due to COVID-19 (p < 0.001). The risk of dying at any time during follow-up was clearly higher for men, individuals in older age groups, people with chronic kidney disease, and people hospitalized in public health services.


Recent trends in targeted anticancer prodrug and conjugate design.
Anticancer drugs are often nonselective antiproliferative agents (cytotoxins) that preferentially kill dividing cells by attacking their DNA at some level. The lack of selectivity results in significant toxicity to noncancerous proliferating cells. These toxicities along with drug resistance exhibited by the solid tumors are major therapy limiting factors that result into poor prognosis for patients. Prodrug and conjugate design involves the synthesis of inactive drug derivatives that are converted to an active form inside the body and preferably at the site of action. Classical prodrug and conjugate design have focused on the development of prodrugs that can overcome physicochemical (e.g., solubility, chemical instability) or biopharmaceutical problems (e.g., bioavailability, toxicity) associated with common anticancer drugs. The recent targeted prodrug and conjugate design, on the other hand, hinge on the selective delivery of anticancer agents to tumor tissues thereby avoiding their cytotoxic effects on noncancerous cells. Targeting strategies have attempted to take advantage of low extracellular pH, elevated enzymes in tumor tissues, the hypoxic environment inside the tumor core, and tumor-specific antigens expressed on tumor cell surfaces. The present review highlights recent trends in prodrug and conjugate rationale and design for cancer treatment. The various approaches that are currently being explored are critically analyzed and a comparative account of the advantages and disadvantages associated with each approach is presented.


Intracellular free calcium in isolated vestibular hair cells and potassium iontophoresis.
The resting free calcium level was measured in 128 isolated mammalian vestibular sensory cells using the calcium-sensitive dye fura-2. Iontophoresis was used to apply short, localised and limited pulses of K+ which evoked dynamic changes in intracellular free calcium concentration. While most of the type I hair cells tested showed brief reversible and specific calcium responses, some were unresponsive. The changes in intracellular free calcium were also measured by videomicroscopic analysis. Iontophoretic application of K+ ions is shown to be a suitable method for inducing fast, transient changes in intracellular free calcium in vestibular hair cells. This technique could be useful for applying several ions and charged molecules such as amino acids in in-vitro cellular methods.


Competition binding experiments for rapidly ranking lead molecules for their binding affinity to human serum albumin.
Many lead molecules that have high affinity for a therapeutic target in vitro exhibit a reduced efficacy in vivo. Drug binding to human serum albumin is a major contributor to this reduction in potency, and many drug discovery programs expand significant resources preparing compounds that have decreased albumin binding. As rational and structure-based approaches have already been demonstrated to design compounds that have reduced affinity for albumin, the ability to rapidly and accurately assess protein binding will be valuable in lead optimization. This review will summarize some of the NMR-based efforts towards developing universal, rapid, accurate, and site-specific assays for estimating protein binding.


Neuro-cognitive functioning in unaffected siblings of patients with bipolar disorder: Comparison with bipolar patients and healthy controls.
Neurocognitive tests can provide reliable endophenotypes for bipolar disorder (BD). The aim of this study was to compare the neurocognitive functioning of unaffected siblings of patients of bipolar affective disorder (BPAD) with that of patients with BD and a group of healthy controls. A total of 20 unaffected siblings of patients with BD-I, 20 patients of BD-I who were currently in remission and a group of 20 healthy control subjects were assessed for neurocognitive functions using Wisconsin Card Sorting Test, Brief Visuospatial Memory Test-Revised, Hopkins Verbal Learning Test-Revised and Wechsler Adult Intelligence Scale Digit Symbol Test. Compared to healthy controls, unaffected siblings of patients with BD performed poorly on tests of verbal learning, but no significant differences were seen between the two groups for executive functions, visual learning and psychomotor speed, concentration and graphomotor abilities. Compared to unaffected siblings, patients with BD performed poorly on the tests of executive functions, visual memory, verbal memory, psychomotor speed, concentration, and graphomotor abilities. Verbal memory can serve as an endophenotype of bipolar disorder.


Somatic DNA recombination in the brain.
Possible somatic DNA recombination in the brain has been investigated by attempting to capture direct or indirect evidence of it. Until recently, the biological significance of the DNA event, the genes is involved in the recombination, or even whether the event actually occurs in the brain has remained unclear. The DNA-rearranged locus-oriented approach and the recombination activity-oriented approach have mutually contributed to the elucidation of the biological features of extra-immune system somatic DNA recombination. There have been only 2 loci proposed for the candidate, one is a repetitive sequence and the other DNA recombination is nonrepetitive locus. This review states conventional concepts and discussions chronologically and finally to the newest aspects of DNA rearrangement in the brain.


Reflections on mental capacity assessments in general hospitals.
Research suggests that a significant proportion of inpatients in general medical wards may lack capacity to make treatment decisions, a situation that often goes unrecognised by clinicians. We would like to briefly discuss two cases from a non-psychiatric setting, where a mental disorder served to inhibit the individual's ability to weigh-up associated risks when deciding to refuse potentially life-sustaining healthcare interventions. In both cases the history of mental disorder was well established yet, for markedly different reasons, the respective presentation was such that the influence of the disorder on decision-making was not evident to the treating teams.


The evolution of modern agriculture and its future with biotechnology.
Since the dawn of agriculture, humans have been manipulating crops to enhance their quality and yield. Via conventional breeding, seed producers have developed the modern corn hybrids and wheat commonly grown today. Newer techniques, such as radiation breeding, enhanced the seed producers' ability to develop new traits in crops. Then in the 1980's-1990's, scientists began applying genetic engineering techniques to improve crop quality and yield. In contrast to earlier breeding methods, these techniques raised questions about their safety to consumers and the environment. This paper provides an overview of the kinds of genetically modified crops developed and marketed to date and the value they provide farmers and consumers. The safety assessment process required for these crops is contrasted with the lack of a formal process required for traditionally bred crops. While European consumers have expressed concern about foods and animal feeds containing ingredients from genetically modified crops, Americans have largely been unconcerned or unaware of the presence of genetically modified foods on the market. This difference in attitude is reflected in Europe's decision to label foods containing genetically modified ingredients while no such labeling is required in the U.S. In the future, genetic modification will produce a variety of new products with enhanced nutritional or quality attributes.


Limited regions of the alpha 2-domain alpha-helix control anti-A2 allorecognition: an analysis using a panel of A2 mutants.
The regions of the HLA-A2 molecule controlling anti-A2 alloreactivity were explored using naturally occurring allelic variants of HLA-A, and a panel of transfectants expressing the products of A2.1 genes that had been mutated at multiple positions encoding residues in the alpha 2 domain alpha-helix. As a means of detecting distant conformational effects, these altered A2.1 molecules were also examined serologically. Amino acid substitutions at the carboxy-terminal end of the alpha 2 domain alpha-helix led to diminished staining with the monoclonal antibody (mAb) MA2.1. The epitope for this antibody has previously been mapped to the alpha 1 domain alpha-helix (residues 62-65). This suggests that interdomain contacts may cause conformational alteration, and that mutants can have distant, as well as local effects. Of the 24 positions where substitutions were made, only six led to loss of the anti-A2 alloresponse by the three clones and three lines that were tested. In addition, the mutations that altered the MA2.1 epitope, located on the alpha 1 domain alpha-helix, did not inhibit allorecognition. This suggests that a limited number of regions on the A2.1 molecule are responsible for allodeterminant expression. The most influential substitutions were those at positions 152, 154, 162, and 166. It is notable that three of these are predicted to be T-cell receptor (Tcr)-contacting residues, and one (152) to contribute to peptide binding. These results suggest that the specificity of alloreactive T cells is determined by exposed polymorphisms, directly contacted by the Tcr, and by concealed polymorphisms which influence peptide binding.


4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1, 3-thiazol-2-amine hydrochloride (SSR125543A), a potent and selective corticotrophin-releasing factor(1) receptor antagonist. II. Characterization in rodent models of stress-related disorders.
The present study investigated the effects of the novel corticotrophin-releasing factor (CRF)(1) receptor antagonist 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine hydrochloride (SSR125543A) in a variety of rodent models of anxiety, including conflict procedures (punished drinking and four-plate), exploration models (elevated plus-maze and light/dark), a fear/anxiety defense test battery, and several procedures based on stress-induced changes in physiological (isolation-induced hyperthermia and tail pinch-induced cortical norepinephrine release) or behavioral (social defeat-induced anxiety, maternal separation-induced vocalization) parameters. Moreover, the effects of SSR125543A were investigated in acute (forced swimming) and chronic (chronic mild stress; CMS) models of depression. SSR125543A and the CRF(1) receptor antagonist antalarmin displayed limited efficacy in exploration-based anxiety models. In contrast, both compounds produced clear-cut anxiolytic-like activity in models involving inescapable stress, including the conflict procedures, the social defeat-induced anxiety paradigm and the defense test battery (3-30 mg/kg i.p. or p.o.). These effects paralleled those of the anxiolytic diazepam. In addition, SSR125543A and antalarmin antagonized stress-induced hyperthermia, distress vocalization, and cortical norepinephrine release. In the forced swimming test, 30 mg/kg p.o. SSR125543A and 3 to 30 mg/kg p.o. antalarmin produced clear antidepressant-like effects. These latter results were strengthened by the findings from the CMS, which showed that repeated administration of 10 mg/kg i.p. SSR125543A for 30 days improved the degradation of the physical state, the reduction of body weight gain, and anxiety produced by stress. Together, these data indicate that SSR125543A shows good activity in acute and chronic tests of unavoidable stress exposure, suggesting that it may have a potential in the treatment of depression and some forms of anxiety disorders.


Synergistic antitumor activity of sorafenib in combination with epidermal growth factor receptor inhibitors in colorectal and lung cancer cells.
Cancer cell survival, invasion, and metastasis depend on cancer cell proliferation and on tumor-induced angiogenesis. We evaluated the efficacy of the combination of sorafenib and erlotinib or cetuximab. Sorafenib, erlotinib, and cetuximab, alone or in combination, were tested in vitro in a panel of non-small cell lung cancer (NSCLC) and colorectal cancer cell lines and in vivo in H1299 tumor xenografts. Epidermal growth factor receptor (EGFR) ligand mRNAs were expressed in all NSCLC and colorectal cancer cell lines with variable levels ranging from 0.4- to 8.1-fold as compared with GEO colorectal cancer cells. Lung cancer cells had the highest levels of vascular endothelial growth factors (VEGF) A, B, and C, and of VEGF receptors as compared with colorectal cancer cells. Combined treatments of sorafenib with erlotinib or cetuximab produced combination index values between 0.02 and 0.5, suggesting a significant synergistic activity to inhibit soft agar colony formation in all cancer cell lines, which was accompanied by a marked blockade in mitogen-activated protein kinase and AKT signals. The in vitro migration of H1299 cells, which expressed high levels of both VEGF ligands and receptors, was inhibited by treatment with sorafenib, and this effect was significantly increased by the combination with anti-EGFR drugs. In nude mice bearing established human H1299 xenografts, treatment with the combination of sorafenib and erlotinib or cetuximab caused a significant tumor growth delay resulting in 70 to 90 days increase in mice median overall survival as compared with single-agent sorafenib treatment. Combination treatment with sorafenib and erlotinib or cetuximab has synergistic antitumor effects in human colorectal and lung cancer cells.


Endogenous levels of polyamines in the organs of cucumber plant (Cucumis sativus) and factors affecting leaf polyamine contents.
Polyamine compositions of various organs from hydroponically cultivated cucumber plants (Cucumis sativus L. cv. Sharp-1) and factors affecting the leaf polyamine content were examined. Diamine putrescine was found most abundantly in the root, while a relatively large amount of spermine was detected in the reproductive organs such as the immature fruit and the calyx (+stamen). Spermidine was present at the highest level in rapidly growing tissues such as newly expanded leaf and fruit at an early developing stage, implying the possible involvement of spermidine in the growth and development of these young tissues. Polyamine content of cucumber leaves changed during the day. Especially, the putrescine content of upper leaves showed a striking decrease from the morning to the night. Alterations of leaf Ca or Mg content did not significantly affect leaf polyamine composition. On the other hand, abnormal cucumber leaves showed altered polyamine composition. Yellowing of the leaf intervein resulted in a striking decrease in spermidine content without a significant change in putrescine and spermine content. By contrast, the leaves infected with the phytopathogen, powdery mildew, showed decreased putrescine and increased spermine content in response to the degree of fungi infection. The possible usefulness of polyamines as a diagnostic marker of plant development and physiological disorder is discussed.


[Our experience in diagnosis and surgical treatment of duodenal diverticula].
In view of the proteiform symptoms of duodenal diverticula, the Authors underline the diagnostic precision and surgical value of e.g.d. scopy. Indications for surgery in cases of symptomatic or complicated diverticula are also stressed, and the value of mechanical suturing is confirmed.


An Unusual Cytomegalovirus Ocular Manifestation in a Non-HIV Patient.
A 60-year-old Aboriginal man with underlying severe exfoliative dermatitis, treated with oral azathioprine and oral prednisolone, presented with left painful red eye for ten days. On initial presentation, left eye vision was poor at hand motion. There was corneal endotheliitis over the left eye with severe anterior chamber inflammation obscuring the fundus view. B-scan ultrasonography showed evidence of vitritis with a flat retina. An urgent aqueous tap for viral polymerase chain reaction (PCR) yielded positive cytomegalovirus (CMV) DNA results. As CMV infection commonly affects immunosuppressed individuals, his systemic immunosuppressants were withheld temporarily. He was successfully treated with combination intravenous ganciclovir, intravitreal ganciclovir 2mg/0.1ml, and topical ganciclovir 2%. His vision improved significantly from hand motion to 20/40. There was no reactivation of CMV infection post-treatment.


Ultrashort feedback control of luteinizing hormone-releasing hormone secretion in vitro.
The present experiments were performed to clarify whether LHRH might inhibit its own secretion via an ultrashort feedback mechanism acting directly on the hypothalamus. Using an in vitro system, mediobasal hypothalami (MBHs) of adult male rats were perifused in either the presence or absence of a LHRH agonistic analog [D-Ser(TBU)6,Des-Gly10] LHRH ethylamide shown not to cross-react in the LHRH RIA. In the first series of experiments, six MBHs per chamber were initially perifused with control medium and submitted to two K+ stimulations (110 mM) for 5 min every 30 min; the control medium was then replaced by medium containing the LHRH analog (5 microM), and three additional K+ pulses were applied. In the second series of experiments, a single MBH per chamber was exposed for the duration of the experiments to either control medium or medium containing the LHRH analog (5 microM). In both cases, pulses of K+ were applied to the tissue. The amounts of endogenous LHRH released both under basal conditions and after K+ stimulation were measured in the effluent (1 ml every 5 min) with a specific RIA. The results show that the LHRH analog inhibits basal secretion of endogenous LHRH from the MBH, and diminishes or abolishes the response to K+ stimulations. The specificity of the inhibitory effect exerted by the LHRH analog on LHRH secretion was shown by the inability of TRH to mimic the effect of the LHRH analog. The data are consistent with the hypothesis that LHRH, acting at a hypothalamic level, might participate in the control of its own release via an ultrashort feedback mechanism.


Comparative study of different polymeric coatings for the next-generation magnesium-based biodegradable stents.
Development of next-generation bioabsorbable stents based on magnesium alloys is gaining lots of attention. However, finding an appropriate coating in order to enhance its corrosion resistance along with preserving other requirements is still a challenge. In this study, three FDA-approved polymers, namely poly(lactic acid), polycaprolactone and poly(lactic-co-glycolic acid), have been investigated as potential coatings for magnesium-based stents to enhance their corrosion resistance, biocompatibility and haemocompatibility. Potentiodynamic and electrochemical impedance spectroscopy results demonstrated that PLA and PLGA coating performed better in improving corrosion resistance in comparison with uncoated and other coated samples. Although all coated and bare samples displayed desirable results of haemocompatibility assays, PLA-coated samples showed better outcome in terms of biocompatibility. The results revealed that PLA can be considered as a potential coating material to enhance the main characteristics of magnesium-based bioabsorbable stents.


[The finite element analysis of lumbar fusions].
To investigate the stability and the stress distributions of L(3-5) fused with three different approaches (interbody, posterolateral and circumferential fusions) and to investigate degeneration of the segment adjacent to the fused functional spinal unit. A detailed L(3-5) three-dimensional nonlinear finite element model of a normal man aged 32 was established and validated. Based on the model, the destabilized model, the interbody, posterolateral and circumferential fusions models of L45 were established. After the loadings were placed on all the models, we recorded the angular motions of the fused segment and the Von Mises stress of the adjacent intervertebral disc. The circumferential fusion was most stable than the others, and the interbody fusion was more stable than the posterolateral fusion. The maximal Von Mises stress of the adjacent L3.4 intervertebral finite all the models was ranked descendingly as flexion, lateral bending, torsion and extension. For the three kinds of fusions, the stress increment of the L34 intervertebral disc was ranked ascendingly as interbody fusion, posterolateral fusion and circumferential fusion. After destabilization of the L(4.5) segment, the stability of the circumferential fusion is better than that of the others, particularly under the fluxional or extensional loading. The stability of the interbody fusion is better than that of the posterolateral fusion, except for under the fluxional loading. The feasibility of adjacent segment degeneration can be ranked descendingly as: circumferential fusion, posterolateral fusion and interbody fusion.


Agriculture and rural out-migration in Central Asia, 1960-91.
"This article seeks to analyse agrarian structure and policy in the Soviet period and discuss their effect on migration from rural to urban areas. In the case of [Soviet] Central Asia, neither the various steps to bring down labour intensity in the farm sector, nor the falling standard of living in rural areas, could bring about migration from rural to urban areas. This was because in traditional societies economic mechanisms are not effective unless they are complemented by appropriate social and cultural policies. All policies were oriented towards the state's goal of vertical integration of regions with the central economy. In Central Asia in particular this policy resulted in serious distortions in the social and economic spheres."


Chinese hamster ovary cell performance enhanced by a rational divide-and-conquer strategy for chemically defined medium development.
Basal medium design is considered one of the most important steps in process development. To optimize chemically defined (CD) media efficiently and effectively for the biopharmaceutical industry, a two-step rational strategy was applied to optimize four antibody producing Chinese hamster ovary (CHO) cell lines. In the first step, 48 of 52 components of our in-house medium were divided into three groups according to their characteristics. In the next step, these groups were optimized by spent medium analysis, response surface methodology and mixture design. Because these steps in our strategy involved dividing medium components into groups and subsequently adjusting the concentration of the components, we termed this medium development strategy "divide and conquer". By applying the strategy, we were able to improve the titers of CHO-S, CHO-DG44 and two CHO-K1 cell lines 1.92, 1.86, 2.92 and 1.62-fold, respectively, in 8 weeks with fewer than 60 tests. This divide-and-conquer strategy was efficient, effective, scalable and universal in our current study and offered a new approach to CD media development.


Modelling and simulating decision processes of linked lives: An approach based on concurrent processes and stochastic race.
Individuals' decision processes play a central role in understanding modern migration phenomena and other demographic processes. Their integration into agent-based computational demography depends largely on suitable support by a modelling language. We are developing the Modelling Language for Linked Lives (ML3) to describe the diverse decision processes of linked lives succinctly in continuous time. The context of individuals is modelled by networks the individual is part of, such as family ties and other social networks. Central concepts, such as behaviour conditional on agent attributes, age-dependent behaviour, and stochastic waiting times, are tightly integrated in the language. Thereby, alternative decisions are modelled by concurrent processes that compete by stochastic race. Using a migration model, we demonstrate how this allows for compact description of complex decisions, here based on the Theory of Planned Behaviour. We describe the challenges for the simulation algorithm posed by stochastic race between multiple concurrent complex decisions.


A comparative study of routine laparoscopic versus open appendectomy.
We evaluated the outcomes of routine laparoscopy and laparoscopic appendectomy (LA) in patients with suspected appendicitis. This is a retrospective study of the outcomes of patients undergoing laparoscopic appendectomy compared with outcomes for patients undergoing open appendectomy (OA) during the time that LA came into use. Results of patients managed with routine laparoscopy and LA for suspected acute appendicitis were reviewed and analyzed. The preoperative and intraoperative findings were recorded. The clinical outcomes were compared with those of patients undergoing OA in the preceding 10 months. During the LA study period, 97 patients (47 men) with the median age of 34 years (range, 18 to 79) presented with clinical features of acute appendicitis. With the exclusion of 5 patients with open operations and 10 patients with other pathologies, 82 patients underwent laparoscopic appendectomy (Group A) for appendicitis. Thirty-one (37.8%) patients had complicated appendicitis (perforated or gangrenous appendicitis). Conversions were required in 6 patients (7.3%). During the OA period, 125 patients (57 men) with the median age of 42 (range, 19 to 79) years were operated on. With the exclusion of 6 patients with other pathologies, 119 underwent OA for acute appendicitis (Group B). Fifty-one (42.9%) had either perforated or gangrenous appendicitis. The median durations of surgery in Group A and Group B were 80 minutes (range, 40 to 195) and 60 minutes (range, 25 to 260), respectively (P < 0.005). Postoperative complication rates were comparable between the 2 groups (13.4% in Group A versus 15.8% in Group B). The median hospital stay for patients in Group A and Group B were 3.0 days (range, 1 to 47) and 4.0 days (range, 1 to 47), respectively (P = 0.037). We conclude that routine laparoscopy and LA for suspected acute appendicitis is safe and is associated with a significantly shorter hospital stay. Other intra-abdominal pathologies can also be diagnosed more accurately with the laparoscopic approach.


Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes.
Interleukin-6 (IL6) is critically involved in inflammation and metabolism. About 1% of people produce IL6 autoantibodies (aAb-IL6) that impair IL6 signaling in vivo. We tested the hypothesis that the prevalence of such aAb-IL6 is increased in type 2 diabetic patients and that aAb-IL6 plays a direct role in causing hyperglycemia. In humans, the prevalence of circulating high-affinity neutralizing aAb-IL6 was 2.5% in the type 2 diabetic patients and 1% in the controls (odds ratio 2.5, 95% confidence interval 1.2-4.9, P=0.01). To test for the role of aAb-IL6 in causing hyperglycemia, such aAb-IL6 were induced in mice by a validated vaccination procedure. Mice with plasma levels of aAb-IL6 similar to the 2.5% type 2 diabetic patients developed obesity and impaired glucose tolerance (area under the curve (AUC) glucose, 2056+/-62 vs 1793+/-62, P=0.05) as compared with sham-vaccinated mice, when challenged with a high-fat diet. Mice with very high plasma levels of aAb-IL6 developed elevated fasting plasma glucose (mM, 4.8+/-0.4 vs 3.3+/-0.1, P<0.001) and impaired glucose tolerance (AUC glucose, 1340+/-38 vs 916+/-25, P<0.001) as compared with sham-control mice on normal chow. In conclusion, the prevalence of plasma aAb-IL6 at levels known to impair IL6 signaling in vivo is increased 2.5-fold in people with type 2 diabetes. In mice, matching levels of aAb-IL6 cause obesity and hyperglycemia. These data suggest that a small subset of type 2 diabetes may in part evolve from an autoimmune attack against IL6.


Measurement and FEM/BEM simulation of transverse effects in SAW resonators on lithium tantalate.
It is well known that transverse effects contribute significantly to the loss of SAW resonators on lithium tantalate. In particular, for frequencies above resonance, the surface wave is not guided inside the transducer and radiates into the busbars. In addition, because bulk modes can also be excited, scalar models are not sufficient to accurately predict transverse effects. It is also known that the layout of a SAW resonator (electrode gaps and dummy electrodes) has a strong impact on the transverse effects. In this paper, a periodic FEM/BEM model is presented and is used to simulate the transverse effects for various SAW resonator layouts. Test devices matching those simulated are fabricated and measured; the measured results are compared with the simulated results and show good agreement. By analyzing the dispersion curves produced from the FEM/BEM model in the different regions of the device, several frequency bands corresponding to different transverse behaviors are identified. These results are consistent with the elastic displacements, also computed by the FEM/BEM model. It is further shown that guided conditions in the gap between the transducer and the busbar occur for a frequency range above resonance. This result is in agreement with measurements showing that resonators with smaller gaps exhibit smaller spurious responses in their admittance.


Multiconfigurational time-dependent Hartree calculations for tunneling splittings of vibrational states: Theoretical considerations and application to malonaldehyde.
Full-dimensional multiconfigurational time-dependent Hartree calculations on the tunneling splitting of the vibrational ground state and the low lying excited states of malonaldehyde are presented. Methodological developments utilizing the symmetry of double well systems for the efficient calculation of tunneling splittings are described and discussed. Important aspects of the theory underlying the previously communicated results for the ground state tunneling splitting [M. D. Coutinho-Neto et al., J. Chem. Phys. 121, 9207 (2004)] are detailed and further developments facilitating the calculation of tunneling splittings for vibrationally excited states are introduced. Utilizing these developments, the 14 lowest vibrational states of malonaldehyde, i.e., seven tunneling splittings, have been computed. The tunneling splittings are found to vary significantly depending on the particular vibrational excitation. This results in a complex pattern of vibrational levels. Studying the dependence of the tunneling splittings on the vibrational excitation, good agreement with available experimental results is found and intuitive interpretations of the results can be given.


Improvement of solubility and stability of the antimicrobial peptide nisin by protein engineering.
Nisin is a 3.4-kDa antimicrobial peptide that, as a result of posttranslational modifications, contains unsaturated amino acids and lanthionine residues. It is applied as a preservative in various food products. The solubility and stability of nisin and nisin mutants have been studied. It is demonstrated that nisin mutants can be produced with improved functional properties. The solubility of nisin A is highest at low pH values and gradually decreases by almost 2 orders of magnitude when the pH of the solution exceeds a value of 7. At low pH, nisin Z exhibits a decreased solubility relative to that of nisin A; at neutral and higher pH values, the solubilities of both variants are comparable. Two mutants of nisin Z, which contain lysyl residues at positions 27 and 31, respectively, instead of Asn-27 and His-31, were produced with the aim of reaching higher solubility at neutral pH. Both mutants were purified to homogeneity, and their structures were confirmed by one- and two-dimensional 1H nuclear magnetic resonance. Their antimicrobial activities were found to be similar to that of nisin Z, whereas their solubilities at pH 7 increased by factors of 4 and 7, respectively. The chemical stability of nisin A was studied in the pH range of 2 to 8 and at a 20, 37, and 75 degrees C. Optimal stability was observed at pH 3.0. Nisin Z showed a behavior similar to that of nisin A. A mutant containing dehydrobutyrine at position 5 instead of dehydroalanine had lower activity but was significantly more resistant to acid-catalyzed chemical degradation than wild-type nisin Z.


Acute cardiovascular effects of the alpha2-adrenoceptor antagonist, idazoxan, in rats: influence of the basal sympathetic tone.
Intravenous administration of the alpha2-adrenoceptor antagonist, idazoxan, elicits variable cardiovascular effects, depending on experimental conditions. In this study, the effects of idazoxan were investigated in rats with high, low, or no basal sympathetic tone. In a group of conscious Sprague-Dawley rats (n = 9), mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nervous activity (RSNA) were recorded. Idazoxan (250 microg/kg, i.v.) induced a transient decrease in MAP (-12+/-3 mm Hg) that was accompanied by increases in HR (49+/-14 beats/min) and RSNA (53+/-14%). In six of nine rats, a light pentobarbitone anesthesia was given. Basal RSNA was decreased (6.0+/-1.3 microV from 12.8+/-4.1 microV; p<0.05), and the depressor effect of idazoxan was reversed to a pressor effect (21+/-6 mm Hg) associated with bradycardia (-16+/-8 beats/min) and sympathoinhibition (-56+/-15%). In eight conscious intact rats, idazoxan (250 microg/kg, i.v.) attenuated by approximately 40% the pressor response to the selective alpha1-adrenoceptor agonist, cirazoline (0.5 microg/kg, i.v.). In three groups of six to seven ganglion-blocked (chlorisondamine, 2.5 mg/kg, i.v.) conscious rats, idazoxan dose-dependently increased mean arterial pressure (MAP: 39+/-2, 55+/-3, and 69+/-4 mm Hg at 125, 250, and 500 microg/kg, i.v., respectively) with minimal changes in HR. In contrast, the noradrenaline-releasing agent, tyramine (62.5, 125, and 250 microg/kg, i.v.), dose-dependently increased both MAP and HR. The alpha1-adrenoceptor antagonist, prazosin (1 mg/kg, i.v.; n = 8) blunted by approximately 70% (p<0.01) the pressor effect of 250 microg/kg idazoxan. It is concluded that in rats with high sympathetic tone, idazoxan has depressor effects, most likely related to its peripheral alpha-adrenoceptor antagonist properties. In rats with low or no sympathetic tone, idazoxan induced pressor responses mainly secondary to its partial agonist activity at vascular postjunctional alpha1-adrenoceptors.


Medicare program; criteria for Medicare coverage of heart transplants--HCFA. Notice of HCFA ruling.
This notice extends Medicare coverage to heart transplantations when furnished by participating facilities that meet specific criteria, including patient selection criteria. We are extending coverage to heart transplants based on the results of the National Heart Transplant Study and our subsequent determination that heart transplants are a medically reasonable and necessary service when specific criteria are met. Because the HCFA Ruling HCFAR 80-1 excluded heart transplants from coverage under that Medicare program, we are issuing this notice as a new HCFA ruling. It will rescind HCFAR 80-1 and set forth the new coverage policy for heart transplants.


Effect of H+ on ATP-regulated K+ channels in feline ventricular myocytes.
Using patch-clamp techniques, we examined the effects of pH on properties of ATP-regulated K+ channels in single myocytes isolated from cat left ventricles. ATP-K+ channels of inside-out patches were bilaterally exposed to 140 mM K+ solutions (22 degrees C). In the absence of ATP and Mg2+, the channels had a linear current-voltage relationship during hyperpolarizing pulses (20-100 mV negative to the reversal potential) at both intracellular pH (pHi) 7.4 and 6.5, but the slope conductance was 66 +/- 2 pS at pHi 7.4 and 46 +/- 2 pS at pHi 6.5. Lowering pHi from 7.4 to 6.5 increased the mean open time (from 15.9 +/- 4.6 to 35.9 +/- 7.9 ms, P less than 0.01) but decreased the open-state probability measured at 50 mV positive to the reversal potential (from 0.35 +/- 0.04 to 0.16 +/- 0.04, P less than 0.01). However, in the presence of both 0.2 mM ATP and 1 mM MgCl2, lowering pHi from 7.4 to 6.5 increased the mean open time (from 5.0 +/- 2.6 to 17.9 +/- 5.9 ms, P less than 0.01) and the open-state probability (from 0.025 +/- 0.010 to 0.098 +/- 0.024, P less than 0.01). These data indicate that increases in intracellular H+ concentration modulate cardiac ATP-K+ channel properties. Ischemia-associated decreases in pHi may enhance the opening of cardiac ATP-regulated K+ channels and resultant action potential shortening.


Beyond policy networks: policy framing and the politics of expertise in the 2001 Foot and Mouth Disease crisis.
For the past decade, the policy community/issue network typology of pressure group interaction has been used to explain policy outcomes and the policy-making process. To re-examine the validity of this typology, the paper focuses on the UK government's response to the 2001 Foot and Mouth Disease (FMD) crisis, and in particular the decision to pursue contiguous culling rather than vaccination to overcome the epidemic. Rather than illustrating the emergence of an issue network in agricultural policy, the decision-making process of the FMD outbreak demonstrates continuity with prior crises. In addition, the politicization of scientific expertise is identified as an emerging trend in crisis management. Policy framing is used to explain the impetus behind the contiguous cull decision, concluding that the legacy of previous policy choices conditioned the crisis response to a far greater degree than contemporaneous pressure group action.


A comparison study of detecting gold nanorods in living cells with confocal reflectance microscopy and two-photon fluorescence microscopy.
Two-photon fluorescence microscopy and confocal reflectance microscopy were compared to detect intracellular gold nanorods in rat basophilic leukaemia cells. The two-photon photoluminescence images of gold nanorods were acquired by an 800 nm fs laser with the power of milliwatts. The advantages of the obtained two-photon photoluminescence images are high spatial resolution and reduced background. However, a remarkable photothermal effect on cells was seen after 30 times continuous scanning of the femto-second laser, potentially affecting the subcellular localization pattern of the nanorods. In the case of confocal reflectance microscopy the images of gold nanorods can be obtained with the power of light source as low as microwatts, thus avoiding the photothermal effect, but the resolution of such images is reduced. We have noted that confocal reflectance images of cellular gold nanorods achieved with 50 microW 800 nm fs have a relatively poor resolution, whereas the 50 microW 488 nm CW laser can acquire reasonably satisfactory 3D reflectance images with improved resolution because of its shorter wavelength. Therefore, confocal reflectance microscopy may also be a suitable means to image intracellular gold nanorods with the advantage of reduced photothermal effect.


Cross-validation and reliability of the line-drill test of anaerobic performance in basketball players 14-16 years.
This study evaluates the validity and reliability of the line-drill (LD) test of anaerobic performance in 76 male basketball players 14.0-16.0 years of age. The Wingate Anaerobic Test (WAnT) was used as the reference for anaerobic performance. Wingate Anaerobic Test and LD test were moderately correlated (0.39 and 0.43, p < 0.01). Estimated age at peak height velocity (APHV) was moderately, negatively, and significantly (p < 0.01) correlated with WAnT peak (r = -0.69) and mean power (r = -0.71); earlier-maturing players had greater anaerobic power. Training experience was not associated with anaerobic performance, but chronological age (CA) and estimated APHV were significant covariates of the LD test (p < 0.05). National players were better than local players on the LD test (p < 0.01) after controlling for CA and body size. Short-term reliability of the LD test (n = 12, 1-week interval) was good: technical error of measurement = 0.44 seconds (95% confidence interval [CI] 0.31-0.75 seconds), intraclass correlation coefficient = 0.91 (95% CI 0.68-0.97), and coefficient of variation = 1.4% (95% CI 1.0-2.3%). Although the relationship between the LD test and WAnT was moderate, the LD test effectively distinguished local- and national-level adolescent basketball players. In contrast to WAnT, the LD test was not influenced by estimated biological maturity status. Thus, the LD test may be suitable for field assessment of anaerobic performance of youth basketball players.


The theoretical current-voltage dependence of a non-degenerate disordered organic material obtained with conductive atomic force microscopy.
We develop a simple continuum model for the current voltage characteristics of a material as measured by the conducting atomic force microscopy, including space charge effects. We address the effect of the point contact on the magnitude of the current and on the transition voltages between the different current regimes by comparing these with the corresponding expressions obtained with planar electrodes.


Sugar-sweetened soft drink consumption acutely decreases spontaneous baroreflex sensitivity and heart rate variability.
In healthy humans, fructose-sweetened water consumption increases blood pressure variability (BPV) and decreases spontaneous cardiovagal baroreflex sensitivity (cBRS) and heart rate variability (HRV). However, whether consuming commercially available soft drinks containing high levels of fructose elicits similar responses is unknown. We hypothesized that high-fructose corn syrup (HFCS)-sweetened soft drink consumption increases BPV and decreases cBRS and HRV to a greater extent compared with artificially sweetened (diet) and sucrose-sweetened (sucrose) soft drinks and water. Twelve subjects completed four randomized, double-blinded trials in which they drank 500 mL of water or commercially available soft drinks matched for taste and caffeine content. We continuously measured beat-to-beat blood pressure (photoplethysmography) and R-R interval (ECG) before and 30 min after drink consumption during supine rest for 5 min during spontaneous and paced breathing. BPV was evaluated using standard deviation (SD), average real variability (ARV), and successive variation (SV) methods for systolic and diastolic blood pressure. cBRS was assessed using the sequence method. HRV was evaluated using the root mean square of successive differences (RMSSD) in R-R interval. There were no differences between conditions in the magnitude of change from baseline in SD, ARV, and SV (P ≥ 0.07). There were greater reductions in cBRS during spontaneous breathing in the HFCS (-3 ± 5 ms/mmHg) and sucrose (-3 ± 5 ms/mmHg) trials compared with the water trial (+1 ± 5 ms/mmHg, P < 0.03). During paced breathing, HFCS evoked greater reductions in RMSSD compared with water (-26 ± 34 vs. +2 ± 26 ms, P < 0.01). These findings suggest that sugar-sweetened soft drink consumption alters cBRS and HRV but not BPV.


High altitude dives from 7000 to 14,200 feet in the Himalayas.
Indian Navy divers carried out no-decompression dives at altitudes of 7000 to 14,200 ft (2134-4328 m) in the Nilgiris and Himalayas from May to July 1988. Seventy-eight dives on air and 22 dives on oxygen were carried out at various altitudes. The final dives were at Lake Pangong Tso (4328 m) in Ladakh, Himalayas, to a maximum of 140 feet of sea water (fsw) [42.6 meters of sea water (msw)] equivalent ocean depth in minimum water temperature of 2 degrees C. Oxygen diving at 14,200 ft (4328 m) was not successful. Aspects considered were altitude adaptation, diminished air pressure diving, hypothermia, and remote area survival. Depths at altitude were converted to depths at sea level and were applied to the Royal Navy air tables. Altitude-related manifestations, hypoxia, hypothermia, suspected oxygen toxicity, and equipment failure were observed. It is concluded that stress is due to effects of altitude and cold on man and equipment, as well as changes in diving procedures when diving at high altitudes. Equivalent air depths when applied to Royal Navy tables could be considered a safe method for diving at altitudes.


Regulation and pathological role of p53 in cisplatin nephrotoxicity.
Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. However, its use is limited by side effects in normal tissues, particularly the kidneys. Recent studies, using both in vitro and in vivo experimental models, have suggested a critical role for p53 in cisplatin nephrotoxicity. The signaling pathways upstream and downstream of p53 are being investigated and related to renal cell injury and death. Along with the mechanistic studies, renoprotective approaches targeting p53 have been suggested. Further research may integrate p53 signaling with other nephrotoxic signaling pathways, providing a comprehensive understanding of cisplatin nephrotoxicity and leading to the development of effective renoprotective strategies during cancer therapy.


The Structure of Plant Cell Walls: I. The Macromolecular Components of the Walls of Suspension-cultured Sycamore Cells with a Detailed Analysis of the Pectic Polysaccharides.
This is the first in a series of papers dealing with the structure of cell walls isolated from suspension-cultured sycamore cells (Acer pseudoplatanus). These studies have been made possible by the availability of purified hydrolytic enzymes and by recent improvements in the techniques of methylation analysis. These techniques have permitted us to identify and quantitate the macromolecular components of sycamore cell walls. These walls are composed of 10% arabinan, 2% 3,6-linked arabinogalactan, 23% cellulose, 9% oligo-arabinosides (attached to hydroxyproline), 8% 4-linked galactan, 10% hydroxyproline-rich protein, 16% rhamnogalacturonan, and 21% xyloglucan.The structures of the pectic polymers (the neutral arabinan, the neutral galactan, and the acidic rhamnogalacturonan) were obtained, in part, by methylation analysis of fragments of these polymers which were released from the sycamore walls by the action of a highly purified endopolygalacturonase. The data suggest a branched arabinan and a linear 4-linked galactan occurring as side chains on the rhamnogalacturonan. Small amounts or pieces of a xyloglucan, the wall hemicellulose, appear to be covalently linked to some of the galactan chains. Thus, the galactan appears to serve as a bridge between the xyloglucan and rhamnogalacturonan components of the wall.The rhamnogalacturonan consists of an alpha-(1 --> 4)-linked galacturonan chain which is interspersed with 2-linked rhamnosyl residues. The rhamnosyl residues are not randomly distributed in the chain but probably occur in units of rhamnosyl- (1 --> 4)-galacturonosyl- (1 --> 2)-rhamnosyl. This sequence appears to alternate with a homogalacturonan sequence containing approximately 8 residues of 4-linked galacturonic acid. About half of the rhamnosyl residues are branched, having a substituent attached to carbon 4. This is likely to be the site of attachment of the 4-linked galactan.The hydroxyprolyl oligo-arabinosides of the hydroxyproline-rich glycoprotein contain 3-linked, 2-linked, and terminal arabinosyl residues. The structure of the hydroxyprolyl oligo-arabinosides deduced from our methylation studies agrees with the structure reported for similar oligosaccharides.


MicroRNA-103 promotes tumor growth and metastasis in colorectal cancer by directly targeting LATS2.
Colorectal cancer (CRC) has become the third most common cancer worldwide and leads to a high mortality rate. Although colorectal cancer has been studied widely, the underlying molecular mechanism remains unclear. Increasing evidence shows that the abnormal expression of microRNAs (miRNAs) is involved in tumorigenesis. Previous studies have reported that miRNA-103 (miR-103) is dysregulated in CRC; however, the expression, function and mechanism of miR-103 in CRC are not well known. The present study showed that miR-103 was overexpressed in the primary tumor tissues of patients with CRC and was significantly associated with a more aggressive phenotype of CRC in patients. Survival rate analysis demonstrated that CRC patients with high miR-103 expression had a poorer overall survival compared with CRC patients with low miR-103 expression. In CRC cell lines, miR-103 inhibition significantly decreased the proliferation, invasion and migration of the cells in vitro. Furthermore, miR-103 repressed large tumor suppressor kinase 2 (LATS2) expression by directly binding to the LATS2-3'-untranslated region, and an inverse correlation was identified between the expression of miR-103 and LATS2 messenger RNA in primary CRC tissues. In addition, the restoration of LATS2 led to suppressed proliferation, invasion and migration of CRC cells. In vivo, miR-103 promotes tumor growth in nude mice. In summary, miR-103 performs a critical role in the promotion of the invasive and metastatic capacities of CRC, possibly by directly targeting LATS2. This miRNA may be involved in the development and progression of CRC.


Treatment of "Gamekeeper's Thumb" by reconstruction of the ulnar collateral ligament.
This study examines the treatment of 22 thumbs with symptomatic laxity of the ulnar collateral ligament of the metacarpophalangeal joint by ligament reconstruction 1 week to 10 years after injury. The existing ligament remnants were repaired in 13 thumbs and were re-attached to bone, using a bone anchor, in seven cases. Two ligaments were reconstructed using the extensor pollicis brevis tendon. Patients were reviewed at a mean of 16 months. Functional stability was regained in all patients, but two thumbs had ongoing pain in the metacarpophalangeal joint. All but one patient returned to their original work and recreational pastimes. This study suggests that ligament reconstruction for chronic laxity of the ulnar collateral ligament is likely to achieve painless stability of the metacarpophalangeal joint even when reconstruction is delayed. This makes joint fusion unnecessary in most instances.


Functional analyses of nanoparticle toxicity: a comparative study of the effects of TiO2 and Ag on tomatoes (Lycopersicon esculentum).
Engineered nanoparticles (NPs), increasingly used in industry, enter and migrate through biological ecosystems. NPs may create some acute toxicity, but their overall effects on living organisms remain largely unknown. In particular, the behavior of NPs in natural conditions and their consequent ecological effects are still poorly understood. In this study, we developed methods to test the phytotoxicity of two distinctly different NPs, one aerosol (nano-TiO2), and the other colloidal silver (AgNP), by specifically considering their tendencies to agglomerate and form precipitates. First we examined effects of these NPs on germination and root elongation. While exposure to neither of these NPs resulted in acute toxicity on germination, silver NPs caused significantly decreased root elongation at every concentration we tested. We found that the hydrodynamic diameters of AgNPs were much smaller than those of nano-TiO2, which induced higher uptake and phytotoxicity. Based on the agglomeration behavior of the NPs, greenhouse trials were run using commercial soil, for nano-TiO2, and Hoagland's solution, for AgNP. Phytotoxicity of silver NPs in the mature plants was demonstrated by lower chlorophyll contents, higher superoxide dismutase activity and less fruit productivity, while nano-TiO2 resulted in higher superoxide dismutase activity at the highest concentration (5000mg/kg). Both nano-TiO2 and AgNPs were taken up into plant stems, leaves and fruits. Our results suggest that further studies of the ecological effects of nanoparticles and steps to mitigate appropriate management strategies are required.


No Increase in Fractures After Stopping Hormone Therapy: Results From the Women's Health Initiative.
The Women's Health Initiative (WHI) hormone therapy (HT) trials showed protection against hip and total fractures, but a later observational report suggested loss of benefit and a rebound increased risk after cessation of HT. The purpose of this study was to examine fractures after discontinuation of HT. Two placebo-controlled randomized trials served as the study setting. Study patients included WHI participants (N = 15,187) who continued active HT or placebo through the intervention period and who did not take HT in the postintervention period. Trial interventions included conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) in naturally menopausal women and CEE alone in women with prior hysterectomy. Total fractures and hip fractures through 5 years after discontinuation of HT were recorded. Hip fractures were infrequent (∼2.5 per 1000 person-years); this finding was similar between trials and in former HT and placebo groups. There was no difference in total fractures in the CEE + MPA trial for former HT vs former placebo users (28.9 per 1000 person-years and 29.9 per 1000 person-years, respectively; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.87 to 1.09; P = 0.63); however, in the CEE-alone trial, total fractures were higher in former placebo users (36.9 per 1000 person-years) compared with the former active group (31.1 per 1000 person-years), a finding that was suggestive of a residual benefit of CEE against total fractures (HR, 0.85; 95% CI, 0.73 to 0.98; P = 0.03). We found no evidence for increased fracture risk, either sustained or transient, for former HT users compared with former placebo users after stopping HT. There was residual benefit for total fractures in former HT users from the CEE-alone study.


Akt activation is necessary for growth factor-induced trafficking of functional K(Ca) channels in developing parasympathetic neurons.
The protein kinase Akt is a crucial regulator of neuronal survival and apoptosis. Here we show that Akt activation is necessary for mobilization of large-conductance K(Ca) channels in ciliary ganglion (CG) neurons evoked by beta-neuregulin-1 (NRG1) and transforming growth factor-beta1 (TGFbeta1). Application of NRG1 to embryonic day 9 (E9) CG neurons increased Akt phosphorylation, as observed previously for TGF(beta)1. NRG1- and TGF(beta)1-evoked stimulation of K(Ca) is blocked by inhibitors of PI3K by overexpression of a dominant-negative form of Akt, by overexpression of CTMP, an endogenous negative regulator of Akt, and by application of the Akt inhibitor 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO). Conversely, overexpression of a constitutively-active form of Akt was sufficient by itself to increase mobilization of functional K(Ca) channels. NRG1 and TGF(beta)1 evoked an Akt-dependent increase in cell-surface SLO alpha-subunits. These procedures have no effect on voltage-activated Ca2+ currents. Thus Akt plays an essential role in the developmental regulation of excitability in CG neurons.


Self-recognition in retarded children.
This study was designed to investigate the relationship between cognitive and affective development. Young preverbal retarded children watched TV images of themselves with faces marked or unmarked and of a peer whose face was marked. We used the objective technique of increased mark-directed responses as evidence of self-recognition and rated the children's reactions as they watched these images. The emergence of self-recognition was closely tied to the maturity of the children's general responsiveness to their reflections. The Down's syndrome children made a broad range of responses, including the curiosity and self-conscious behaviors characteristic of normal children during the second year of life, and all except one of these children showed evidence that they recognized their images. In contrast, the range of behaviors displayed by multihandicapped children was greatly restricted and similar to children in the first year of life. Less than half of these children showed an emergence of self-recognition.


Exploring the relationship between polymorphic (TG/CA)n repeats in intron 1 regions and gene expression.
The putative role of (TG/CA)n repeats in the regulation of transcription has recently been reported for several cancer- and disease-related genes, including the genes encoding the epidermal growth factor receptor (EGFR), hydroxysteroid (11-beta) dehydrogenase 2 (HSD11B2) and interferon-gamma (IFNG). These studies indicated a correlation between gene expression levels and the presence or length of (TG/CA)n repeats in their intron 1 regions. A genome-wide search for genes with similar features may provide evidence of whether these dinucleotide repeats represent a class of universal regulators of gene expression, which has recently begun to be investigated as a quantitative complex phenotype. Using a public database of simple repeats, we identified 330 genes containing potentially polymorphic long (TG/CA)n repeats (n >or= 12) in their intron 1 regions. One known physiological pathway, the calcium signalling pathway, was found to be enriched among the genes containing long repeats. In addition, certain biological processes, such as cation transport, signal transduction and ion transport, were found to be enriched in these genes. Genotyping of the long repeats showed that the majority of these dinucleotide repeats were polymorphic in the HapMap CEU (Caucasians from Utah, USA) samples of northern and western European ancestry. Evidence for a significant association between these repeats and gene expression was not observed in the genes selected based on their expression profiles in the HapMap CEU samples. Our current findings, therefore, do not support a role for these repeats as a class of universal gene expression regulators. A more comprehensive evaluation of the relationship between these repeats and gene expression, potentially in other tissues, may be necessary to illustrate their roles in gene regulation in the future.


Climate Change Influences Basidiome Emergence of Leaf-Cutting Ant Cultivars.
Maintaining symbiosis homeostasis is essential for mutualistic partners. Leaf-cutting ants evolved a long-term symbiotic mutualism with fungal cultivars for nourishment while using vertical asexual transmission across generations. Despite the ants' efforts to suppress fungal sexual reproduction, scattered occurrences of cultivar basidiomes have been reported. Here, we review the literature for basidiome occurrences and associated climate data. We hypothesized that more basidiome events could be expected in scenarios with an increase in temperature and precipitation. Our field observations and climate data analyses indeed suggest that Acromyrmex coronatus colonies are prone to basidiome occurrences in warmer and wetter seasons. Even though our study partly depended on historical records, occurrences have increased, correlating with climate change. A nest architecture with low (or even the lack of) insulation might be the cause of this phenomenon. The nature of basidiome occurrences in the A. coronatus-fungus mutualism can be useful to elucidate how resilient mutualistic symbioses are in light of climate change scenarios.