Identification of QTL regions and SSR markers associated with resistance to reniform nematode in Gossypium barbadense L. accession GB713.
The identification of molecular markers that are closely linked to gene(s) in Gossypium barbadense L. accession GB713 that confer a high level of resistance to reniform nematode (RN), Rotylenchulus reniformis Linford & Oliveira, would be very useful in cotton breeding programs. Our objectives were to determine the inheritance of RN resistance in the accession GB713, to identify SSR markers linked with RN resistance QTLs, and to map these linked markers to specific chromosomes. We grew and scored plants for RN reproduction in the P(1), P(2), F(1), F(2), BC(1)P(1), and BC(1)P(2) generations from the cross of GB713 × Acala Nem-X. The generation means analysis using the six generations indicated that one or more genes were involved in the RN resistance of GB713. The interspecific F(2) population of 300 plants was genotyped with SSR molecular markers that covered most of the chromosomes of Upland cotton (G. hirsutum L.). Results showed two QTLs on chromosome 21 and one QTL on chromosome 18. One QTL on chromosome 21 was at map position 168.6 (LOD 28.0) flanked by SSR markers, BNL 1551_162 and GH 132_199 at positions 154.2 and 177.3, respectively. A second QTL on chromosome 21 was at map position 182.7 (LOD 24.6) flanked by SSR markers BNL 4011_155 and BNL 3279_106 at positions 180.6 and 184.5, respectively. Our chromosome 21 map had 61 SSR markers covering 219 cM. One QTL with smaller genetic effects was localized to chromosome 18 at map position 39.6 (LOD 4.0) and flanked by SSR markers BNL 1721_178 and BNL 569_131 at positions 27.6 and 42.9, respectively. The two QTLs on chromosome 21 had significant additive and dominance effects, which were about equal for each QTL. The QTL on chromosome 18 showed larger additive than dominance effects. Following the precedent set by the naming of the G. longicalyx Hutchinson & Lee and G. aridum [(Rose & Standley) Skovsted] sources of resistance, we suggest the usage of Ren (barb1) and Ren (barb2) to designate these QTLs on chromosome 21 and Ren (barb3) on chromosome 18.


Soil drying and its effect on leaf conductance and CO2 assimilation of Vigna unguiculata (L.) Walp : I. The response to climatic factors and to the rate of soil drying in young plants.
Well watered plants of Vigna unguiculata (L.) Walp cv. California Blackeye No. 5 had maximum photosynthetic rates of 16 μmol m-2 s-1 (at ambient CO2 concentration and environmental parameters optimal for high CO2 uptake). Leaf conductance declined with increasing water vapour concentration difference between leaf and air (Δw), but it increased with increasing leaf temperature at a constant small Δw. When light was varied, CO2 assimilation and leaf conductance were correlated linearly. We tested the hypothesis that g was controlled by photosynthesis via intercellular CO2 concentration (c i). No unique relationship between (1) c i, (2) the difference between ambient CO2 concentration (c a) and c i, namely c a-c i, or (3) the c i/c a ratio and g was found. g and A appeared to respond to environmental factors fairly independently of each other. The effects of different rates of soil drying on leaf gas exchange were studied. At unchanged air humidity, different rates of soil drying were produced by using (a) different soils, (b) different irrigation schemes and (c) different soil volumes per plant. Although the soil dried to wilting point the relative leaf water content was little affected. Different soil drying rates always resulted in the same response of photosynthetic capacity (A max) and corresponding leaf conductance (g(Amax)) when plotted against percent relative plant-extractable soil water content (W e %) but the relationship with relative soil water content (W e ) was less clear. Above a range of W e of 15%-25%, A max and g(Amax) were both high and responded little to decreasing W e . As soon as W e fell below this range, A max and g(Amax) declined. The data suggest root-to-leaf communication not mediated via relative leaf water content. However, g(Amax) was initially more affected than A max.


Emerging role for transcript elongation in plant development.
Transcript elongation by RNA polymerase II (RNAPII), once regarded as the simple extension of the initiated mRNA, is a complex and highly regulated phase of the transcription cycle. Many factors have been identified that contribute to the dynamic control of the elongation stage of transcription. There are elongation factors that modulate the activity of RNAPII and other factors that facilitate the transcription through chromatin. Recent studies of mutants defective in elongation factors have revealed the importance of proper transcript elongation for the development of higher eukaryotes. Here, the essentials of transcript elongation are briefly summarized to discuss its role in developmental processes.


Sloughage of the anus and lower rectum following aortic graft replacement: report of a case.
The successful management of a near-complete sloughage of the anal outlet following aortic graft replacement is reported. Oxygenation in the immediate postoperative period along with appropriate antibiotics may be beneficial in preventing such sloughage. Embolic phenomena or bacterial growth, or both, may have been factors in causing the extensive sloughage.


Impact of anthocyanin component and metabolite of Saskatoon berry on gut microbiome and relationship with fecal short chain fatty acids in diet-induced insulin resistant mice.
Previous studies demonstrated that oral administration of Saskatoon berry powder (SBp) reduced fasting plasma glucose (FPG), insulin resistance, lipids, and inflammatory markers in diet-induced insulin resistant rodents. Mechanism for the beneficial effects of SB remains unclear. The present study examined the effects of high fat-high sucrose (HFHS) diet supplemented with or without 5% SBp, cyanidin-3-glucoside (C3G, an anthocyanin rich in SBp) at a dosage of C3G in 5% SBp, or equimolar concentration of protocatechuic acid (PCA, a relatively stable metabolite of C3G) for 11 weeks on FPG, cholesterol, triglycerides, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), circulatory inflammatory markers, fecal microbiota, and short chain fatty acids in mice. HFHS diet significantly enhanced FPG, insulin, HOMA-IR, lipids and inflammatory markers, but reduced the abundance of fecal Bacteroidetes, Muribaculaceae and propionate compared to low fat diet. Supplementation of SBp, C3G or PCA significantly attenuated HFHS diet induced metabolic and inflammatory markers, and increased the abundances of fecal Muribaculaceae and propionate compared to HFHS diet alone. The abundances of fecal Muribaculaceae negatively correlated with FPG, lipids, HOMA-IR and inflammatory markers in the mice. The abundances of fecal propionate positively correlated with fecal Muribaculaceae and negatively correlated with the metabolic and inflammatory markers. The findings suggest that C3G in SBp and PCA contribute to the metabolic and anti-inflammatory effect of SBp in mice. The increases in fecal Muribaculaceae and propionate may play important regulatory roles in the anti-diabetic and anti-inflammatory benefits of SBp, C3G, and PCA in mice.


Uncollected Bones and Ambiguous Loss: Okinawan Mourning Rituals in the Northern Mariana Islands.
The study expounds upon the psychological concept of 'ambiguous loss,' proposed by Pauline Boss. The article attempts to broaden the concept's individualistic focus by offering a more ethnographically nuanced and socioculturally contextualized application of the concept. It examines how Okinawan WWII survivors, who repatriated from the Northern Mariana Islands after the war, relied on their belief system to make sense of 'abnormal' deaths during war, and the lack of proper mortuary rituals usually conducted for 'normal' deaths. The article argues that religio-spiritual rituals during their pilgrimages to the Marianas were the means with which those struggling with ambiguous loss attempt to deal with their psychological trauma and spiritual pain. It is also argued, however, that the uncollected bodies/bones continue to haunt the bereaved families, so their struggle with the loss cannot come to a complete 'closure,' resulting in their repeated visits to the sites of their loved ones' violent deaths.


Author Correction: MicroRNA-146a directs the symmetric division of Snail-dominant colorectal cancer stem cells.
In the version of Supplementary Fig. 6c originally published with this Article, the immunoprecipitation (IP) and immunoblotting (IB) tags in the top panel were mislabelled. In addition, in Supplementary Fig. 6e, the blot of the IP: Numb; IB: β-Trcp panel for HCT15 was mistakenly duplicated for HCT116. The correct versions of these figures are shown below. An independent repeat of the experiments presented in Supplementary Fig. 6c and e, showing results that are consistent with those reported in the unprocessed blots, have been deposited in figshare ( 10.6084/m9.figshare.7570685 ).


A chicken and egg scenario in psychoneuroimmunology: Bidirectional mechanisms linking cytokines and depression.
Cytokines are an important part of the immune system. Certain cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα), have well-described associations with depression. Various mechanisms exist that may explain bidirectional effects of cytokines on depression and vice versa. No recent reviews to our knowledge have comprehensively characterized both these mechanisms and the interaction of these mechanisms using evidence from the molecular level to the clinical level. The goal of this review is to both evaluate the present knowledge base and identify knowledge gaps to help guide future research. We conducted an extensive bibliographic search across multiple databases, using both general (e.g. "cytokine") and topic-specific (e.g. "kynurenine") keywords. We describe the most recent evidence outlining these mechanisms, including the role of the hypothalamic pituitary axis, the kynurenine pathway, and neural circuitry. For relevant topics, we outline the pathways by which cytokine activation may lead to depressive symptoms, and how depressive symptomology may lead to elevations in cytokines. We also identify key areas for future research, including the need for longitudinal clinical studies to examine causality in pertinent mechanisms and modulating factors in the cytokine-depression interaction. Given the numerous potential mechanisms associating cytokines and depressions, this review paper solely focuses on the most commonly described mechanisms at a basic level. Bidirectional evidence exists for several mechanisms in the relationship between cytokines and depression. However, more work is required to further elucidate the role of these mechanisms in specific clinical populations.


History of a suspected delirium is more common in dementia with Lewy bodies than Alzheimer's disease: a retrospective study.
Delirium is common and is associated with an increased risk of dementia. However, it is not clear whether delirium confers increased risk of any particular type of dementia. We performed a retrospective study of Alzheimer's disease (AD) and Dementia with Lewy bodies (DLB) to ascertain whether a suspected episode of preceding delirium was more common prior to diagnosis in either type of dementia. The study was carried out in a tertiary referral unit for the diagnosis of dementia. Clinic letters from the first presentation to the unit of 85 cases with DLB and 95 cases of AD were reviewed for documentation of any previous episodes of suspected delirium. In this study, 25% of DLB cases had at least one reported episode of suspected delirium as compared to 7% of AD cases (p = 0.001). For the DLB cases who had a prior suspected delirium, 23% had more than one episode compared with 14% of the AD group. The median time between most recent suspected episode of delirium and diagnosis of dementia in both groups was less than a year A greater proportion of those presenting and diagnosed with DLB had a documentation of a suspected delirium than those diagnosed with AD. Delirium may lead to a higher risk of DLB as opposed to other forms of dementia, or delirium may, at least in some cases, represent the early stages of DLB. These data suggest that a diagnosis of DLB should be specifically considered in those presenting with a delirium.


Theoretical study of the novel sandwich compound [Au3Cl3Tr 2]2+.
A theoretical study of a sandwich compound with a metal monolayer sheet between two aromatic ligands is presented. A full geometry optimization of the [Au(3)Cl(3)Tr(2)](2+) (1) compound, which is a triangular gold(I) monolayer sheet capped by chlorines and bounded to two cycloheptatrienyl (Tr) ligands was carried out using perturbation theory at the MP2 computational level and DFT. Compound (1) is in agreement with the 18-electron rule, the bonding nature in the complex may be interpreted from the donation interaction coming from the Tr rings to the Au array, and from the back-donation from the latter to the former. NICS calculations show a strong aromatic character in the gold monolayer sheet and Tr ligands; calculations done with HOMA, also report the same aromatic behavior on the cycloheptatrienyl fragments giving us an insight on the stability of (1). The Au -Au bond lengths indicate that an intramolecular aurophilic interaction among the Au(I) cations plays an important role in the bonding of the central metal sheet.


Selectivity aspects of activity-based (chemical) probes.
Selective chemical modulators are ideal tools to study the function of a protein. Yet, the poor ligandability of many proteins has hampered the development of specific chemical probes for numerous protein classes. Tools, such as covalent inhibitors and activity-based protein profiling, have enhanced our understanding of thus-far difficult-to-target proteins and have enabled correct assessment of the selectivity of small-molecule modulators. This also requires deeper knowledge of compound and target site reactivity, evaluation of binding to noncovalent targets and protein turnover. The availability of highly selective chemical probes, the evolution of activity-based probes, and the development of profiling methods will open a new era of drugging the undruggable proteome.


Neurodevelopmental origins of bipolar disorder: iPSC models.
Bipolar disorder (BP) is a chronic neuropsychiatric condition characterized by pathological fluctuations in mood from mania to depression. Adoption, twin and family studies have consistently identified a significant hereditary component to BP, yet there is no clear genetic event or consistent neuropathology. BP has been suggested to have a developmental origin, although this hypothesis has been difficult to test since there are no viable neurons or glial cells to analyze, and research has relied largely on postmortem brain, behavioral and imaging studies, or has examined proxy tissues including saliva, olfactory epithelium and blood cells. Neurodevelopmental factors, particularly pathways related to nervous system development, cell migration, extracellular matrix, H3K4 methylation, and calcium signaling have been identified in large gene expression and GWAS studies as altered in BP. Recent advances in stem cell biology, particularly the ability to reprogram adult somatic tissues to a pluripotent state, now make it possible to interrogate these pathways in viable cell models. A number of induced pluripotent stem cell (iPSC) lines from BP patient and healthy control (C) individuals have been derived in several laboratories, and their ability to form cortical neurons examined. Early studies suggest differences in activity, calcium signaling, blocks to neuronal differentiation, and changes in neuronal, and possibly glial, lineage specification. Initial observations suggest that differentiation of BP patient-derived neurons to dorsal telencephalic derivatives may be impaired, possibly due to alterations in WNT, Hedgehog or Nodal pathway signaling. These investigations strongly support a developmental contribution to BP and identify novel pathways, mechanisms and opportunities for improved treatments.


Gumpy: a Python toolbox suitable for hybrid brain-computer interfaces.
The objective of this work is to present gumpy, a new free and open source Python toolbox designed for hybrid brain-computer interface (BCI). Gumpy provides state-of-the-art algorithms and includes a rich selection of signal processing methods that have been employed by the BCI community over the last 20 years. In addition, a wide range of classification methods that span from classical machine learning algorithms to deep neural network models are provided. Gumpy can be used for both EEG and EMG biosignal analysis, visualization, real-time streaming and decoding. The usage of the toolbox was demonstrated through two different offline example studies, namely movement prediction from EEG motor imagery, and the decoding of natural grasp movements with the applied finger forces from surface EMG (sEMG) signals. Additionally, gumpy was used for real-time control of a robot arm using steady-state visually evoked potentials (SSVEP) as well as for real-time prosthetic hand control using sEMG. Overall, obtained results with the gumpy toolbox are comparable or better than previously reported results on the same datasets. Gumpy is a free and open source software, which allows end-users to perform online hybrid BCIs and provides different techniques for processing and decoding of EEG and EMG signals. More importantly, the achieved results reveal that gumpy's deep learning toolbox can match or outperform the state-of-the-art in terms of accuracy. This can therefore enable BCI researchers to develop more robust decoding algorithms using novel techniques and hence chart a route ahead for new BCI improvements.


Effect of long term organic amendments and vegetation of vineyard soils on the microscale distribution and biogeochemistry of copper.
In this study we evaluated the effect of the long term organic management of a vineyard-soil on the biogeochemistry of copper at the micro-aggregate scale. The model vineyard-soil (Mâcon-France) experienced a long-term field-experiment that consisted in amendments and vegetations with various materials and plants. We studied specifically the effect of Straw (S) and Conifer Compost (CC) organic amendments and Clover (Cl) and Fescue (F) vegetation on the fate of copper (fungicide) in the surface layer of this loamy soil, through a comparison with the Non Amended soil (NA). After collection the five soils were immediately physically fractionated in order to obtain 5 granulometric size-fractions. All soils and size-fractions were quantitatively characterized in terms of granulometry, chemical content and copper distribution, speciation and bioavailability to bacteria and plants. The results showed strong increases of soil-constituents aggregation for all treatments (Cl>CC>S>F>NA), in relation with the increased cementation of soil-constituents by organic matter (OM). The distribution patterns of all major elements and organic carbon were found highly variable within the soil sub-fractions and also between the 5 treatments. Due to their specific inorganic and organic composition, soil sub-fractions can thus be considered as a specific microbial habitat. Added OM accumulated preferentially in the 20-2 μm and in the >250 μm of the 5 soils. The distribution patterns of copper as well as its speciation and bioavailability to bacteria in the soil sub-fractions were shown to be strongly different among the five soils, in relation with OM distribution. Our results also suggest that Cu-bioavailability to plants is controlled by soil-rhizosphere structure. Altogether our results permitted to show that long-term organic management of a vineyard soil induced stable modifications of soil physical and chemical properties at both macro and micro-scales. These modifications affected in turn the micro-scale biogeochemistry of copper, and especially its bioavailability to bacteria and plants.


Distinct angiogenic and non-angiogenic growth patterns of lung metastases from renal cell carcinoma.
We have recently evaluated a classification of non-small-cell lung cancer based upon the presence of an angiogenic or a non-angiogenic growth pattern. The aim of the present study was to test the hypothesis that lung metastases of clear cell renal cell carcinoma (RCC) can grow without eliciting angiogenesis and give rise to the same set of growth patterns. Tissue sections of 24 patients with lung metastases from clear cell RCC were analysed. Haematoxylin and eosin and reticulin staining were performed to evaluate growth pattern. Double-labelling with antibodies to CD34 and proliferating cell nuclear antigen (PCNA) was performed to determine the endothelial cell proliferation fraction (ECPF) and the microvessel density (MVD). Three growth patterns were observed. In the destructive growth pattern (54%), the architecture of the lung was not preserved. In the alveolar (33%) and interstitial growth patterns (13%), the normal lung parenchyma was preserved within the metastases. MVD was higher in the destructive than in the alveolar growth pattern (P = 0.009). ECPF was higher in the destructive (mean 31.1 +/- 22.7%, median 30.0) than in the alveolar growth pattern (mean 3.6 +/- 2.8%, median 3.2; P = 0.005). The present study demonstrates that highly angiogenic primary tumours can give rise to non-angiogenic metastases. This type of metastasis may be resistant to antiangiogenic therapy.


Managing risks of neoplasia in inflammatory bowel disease.
Inflammatory bowel disease (IBD) has been linked with a variety of intestinal and extraintestinal cancers. This review summarizes the latest literature with regard to which cancers are truly linked with IBD and which are not, the absolute and relative risks of these cancers, how medications commonly prescribed for IBD affect this risk, and finally strategies for managing these risks. Physicians and health professionals may find this information useful for counseling and educating patients as well as for improving patient care.


Therapeutic effect of palbociclib in chondrosarcoma: implication of cyclin-dependent kinase 4 as a potential target.
Chondrosarcoma is a malignant cartilaginous neoplasm of the bone which resistant to radiation therapy and chemotherapy. Cyclin-dependent kinase 4 (CKD4) is highly expressed in human cancer, and palbociclib, the inhibitor of CDK4 has been used clinically under FDA approval for application in cancer therapeutic remedies. However, the level of CDK4 and the treatment possibility in chondrosarcoma require further exploration. Thus, we aim to investigate the level of CDK4 and accompanying therapeutic effects of palbociclib in chondrosarcoma. We used immunohistochemistric analysis to evaluate human CDK4 productions in chondrosarcoma tissues. The inhibitory expression of CDK4 by siRNA or palbociclib on cell proliferation, invasion, migration, apoptosis and cycle arrest of chondrosarcoma were determined by MTT, wound healing, transwell and flow cytometry. CDK4/Rb signaling pathway were determined by western blot and Immunofluorescence assay. The inhibition effect of palbociclib on tumor growth within the bone were determined by bioluminescence imaging in vivo. CDK4 was found to express significantly in human chondrosarcoma samples. The enhanced levels of CDK4 were interlinked with malignant metastasis and undesirable prognosis of chondrosarcoma patients. CDK4 was also highly expressed in human chondrosarcoma cell lines and its inhibition by specific siRNA and palbociclib lead to a decrease in cell proliferation, accompanied by the phosphorylation of Rb. Furthermore, palbociclib also induced cell cycle arrest in G1 phase and decreased cell migration and invasion via CDK4/Rb signaling pathway. Administration of palbociclib in vivo could reduce tumor burden in chondrosarcoma. In summary, these data highlight CDK4 inhibitors, such as palbociclib, as potential promising therapeutics in the treatment of human chondrosarcoma.


Suboptimal decision making by children with ADHD in the face of risk: Poor risk adjustment and delay aversion rather than general proneness to taking risks.
Suboptimal decision making in the face of risk (DMR) in children with attention-deficit hyperactivity disorder (ADHD) may be mediated by deficits in a number of different neuropsychological processes. We investigated DMR in children with ADHD using the Cambridge Gambling Task (CGT) to distinguish difficulties in adjusting to changing probabilities of choice outcomes (so-called risk adjustment) from general risk proneness, and to distinguish these 2 processes from delay aversion (the tendency to choose the least delayed option) and impairments in the ability to reflect on choice options. Based on previous research, we predicted that suboptimal performance on this task in children with ADHD would be primarily relate to problems with risk adjustment and delay aversion rather than general risk proneness. Drug naïve children with ADHD (n = 36), 8 to 12 years, and an age-matched group of typically developing children (n = 34) performed the CGT. As predicted, children with ADHD were not more prone to making risky choices (i.e., risk proneness). However, they had difficulty adjusting to changing risk levels and were more delay aversive-with these 2 effects being correlated. Our findings add to the growing body of evidence that children with ADHD do not favor risk taking per se when performing gambling tasks, but rather may lack the cognitive skills or motivational style to appraise changing patterns of risk effectively. (PsycINFO Database Record


Desmoglein-3 acts as a pro-survival protein by suppressing reactive oxygen species and doming whilst augmenting the tight junctions in MDCK cells.
Kidney disease prevalence increases with age, with a common feature of the disease being defects in the epithelial tight junctions. Emerging evidence suggests that the desmosomal adhesion protein Desmoglein-3 (Dsg3) functions beyond the desmosomal adhesion and plays a role in regulating the fundamental pathways that govern cell fate decisions in response to environmental chemical and mechanical stresses. In this study, we explored the role of Dsg3 on dome formation, reactive oxygen species (ROS) production and transepithelial electrical resistance (TER) in MDCK cells, a kidney epithelial cell model widely used to study cell differentiation and tight junction formation and integrity. We show that overexpression of Dsg3 constrained nuclear ROS production and cellular doming in confluent cell cultures and these features coincided with augmented TER and enhanced tight junction integrity. Conversely, cells expressing dominant-negative Dsg3ΔC mutants exhibited heightened ROS production and accelerated doming, accompanied by increased apoptosis, as well as cell proliferation, with massive disruption in F-actin organization and accumulation, and alterations in tight junctions. Inhibition of actin polymerization and protein synthesis was able to sufficiently block dome formation in mutant populations. Taken together, these findings underscore that Dsg3 has a role in controlling cellular viability and differentiation as well as the functional integrity of tight junctions in MDCK cells.


Nonablative Fractional Laser Resurfacing for Acne Scarring in Patients With Fitzpatrick Skin Phototypes IV-VI.
There is a paucity of studies investigating laser resurfacing in Fitzpatrick skin phototypes (SPT) IV to VI. To assess the efficacy and safety of fractional nonablative laser resurfacing in the treatment of acne scarring in patients with SPT IV to VI. The authors conducted a randomized, investigator-blinded and rater-blinded, split-face comparative study of adults with SPT IV to VI and facial acne scars treated with 2 different density settings and the same fluence. Quantitative global scarring grading system (QGSGS) scores were significantly improved from baseline at 16 and 24 weeks (p = .0277). Improvements in QGSGS scores after higher and lower density treatments were statistically similar (p = .96). The live-blinded dermatologist, the blinded dermatologist photoraters, and the patients rated scars as being significantly more improved by visual analog scale at weeks 16 and 24 compared with baseline (p < .001) for both treatment densities. Five of 7 and 3 of 7 patients in the higher and lower density group, respectively, experienced mild or moderate hyperpigmentation as an investigator observed site reaction. The nonablative 1550-nm fractional laser is safe and efficacious in treating acne scaring in Fitzpatrick skin types IV to VI. Self-limited postinflammatory hyperpigmentation was a common occurrence, especially with higher treatment densities.


[Glomangioma in the eyelid. A clinical and histological case report (author's transl)].
A glomangioma of the eyelid is presented. This localisation of such a tumor is considered to be an extremely exceptional one. Clinical and histological details are described. The differential diagnosis is discussed.


Successful diagnosis of diaphragmatic solitary fibrous tumor of the pleura by preoperative ultrasonography.
The diaphragm is an uncommon site for solitary fibrous tumors of the pleura (SFTPs). Diaphragmatic SFTPs are usually found as pedunculated tumors with a clear margin with their surrounding structures. However, preoperative diagnosis of the tumor is difficult because their morphological features are not well detected on radiological images. We presented a case of diaphragmatic SFTP that was successfully diagnosed by ultrasonography (US). The US revealed a well-circumscribed mass with the feeding arteries leading from the diaphragm. Subsequently, this finding was confirmed histopathologically after resection. US can be less invasive and more sensitive than radiological examinations for diagnosing diaphragmatic SFTPs. To our knowledge, this is the first report of a preoperative diagnosis of diaphragmatic SFTP by US.


Dissociation of antiplatelet effects from myocardial cytoprotective activity during acute myocardial ischemia in cats by a new carbacyclin derivative (ZK 36 375).
We studied the potential therapeutic value of the chemically stable carbacyclin analogue ZK 36 375 during acute myocardial ischemia and compared the cardiovascular and anti- and disaggregatory effects of the compound in vitro and ex vivo. In anesthetized cats the left anterior descending coronary artery was ligated, and 30 min later an intravenous infusion of ZK 36 375 (3.6 micrograms/kg X min) or vehicle was initiated and continued for 4.5 h. ZK 36 375 reduced the ST-segment elevation at 2-5 h (p less than 0.01) when compared to vehicle-treated cats. ZK 36 375 significantly inhibited both the loss of creatine phosphokinase--specific activity and the decrease in the percentage of bound cathepsin D in the infarcted area of the myocardium (p less than 0.05). ZK 36 375 did not reverse ischemia-induced formation of platelet aggregates in vivo and was found ex vivo to be two to three orders of magnitude less active in preventing platelet aggregation, redispersing platelet aggregates, and relaxing bovine coronary arteries than prostacyclin (PGI2) or its (5E) stereoisomer ZK 36 374. It is concluded that ZK 36 375 has a significant cardioprotective activity in acute myocardial ischemia of the cat that can be dissociated from antiplatelet effects in vivo.


Long-term impact of web-based tools, leadership feedback, and policies on inpatient antipsychotic polypharmacy.
This column describes a series of interventions to decrease antipsychotic polypharmacy in the New York State Office of Mental Health (NYSOMH) network of psychiatric hospitals. Phase 1 consisted of implementation of the Psychiatric Services Clinical Knowledge Enhancement System (PSYCKES), a Web-based application supporting clinical decision making and quality improvement, and a policy requiring approval by NYSOMH's medical director to prescribe more than two antipsychotics per patient. In phase 2 hospital leaders received feedback from the office of the medical director identifying specific patients on polypharmacy. In phase 3, access to PSYCKES continued, but the prior-approval policy and feedback were discontinued. Polypharmacy decreased significantly during phase 1, from 16.9 to 9.7 inpatients per 1,000, and decreased further in phase 2, to 3.9 inpatients per 1,000. In phase 3 the prevalence of antipsychotic polypharmacy remained low at six-month follow-up (3.1 inpatients per 1,000), despite the ending of state-level oversight. On long-term follow-up, polypharmacy increased, eventually rising to 9.2 inpatients per 1,000 after 36 months, but remained well below baseline levels.


Receptor-mediated internalization of fluorescent chemotactic peptide by human neutrophils.
Tetramethylrhodamine labeled N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys is a potent chemoattractant for human neutrophils. Binding of this peptide to living neutrophils was observed by means of video intensification microscopy. At 37 degrees C, diffuse membrane fluorescence was seen initially, followed by rapid aggregation and internalization of the fluorescent peptide. These processes are dependent on specific binding to the formal peptide chemotactic receptor.


Fatty acid biosynthesis in Mycobacterium tuberculosis var. bovis Bacillus Calmette-Guérin. Purification and characterization of a novel fatty acid synthase, mycocerosic acid synthase, which elongates n-fatty acyl-CoA with methylmalonyl-CoA.
A crude extract from Mycobacterium tuberculosis var. bovis Bacillus Calmette-Guérin was previously shown to incorporate methylmalonyl-CoA into mycocerosic acids, exemplified by 2,4,6,8-tetramethyloctacosanoic acid, and malonyl-CoA into n-fatty acids (Rainwater D. L., and Kolattukudy, P. E. (1983) J. Biol. Chem. 258, 2979-2985). The presence of several fatty acid synthases with differences in substrate preference and product chain length was detected in the crude extract of M. tuberculosis var. bovis. Among them was a mycocerosic acid synthase which was purified to homogeneity using anion-exchange chromatography, gel filtration, affinity chromatography, and hydroxylapatite chromatography. This fatty acid synthase elongated long-chain fatty acyl-CoA primers using methylmalonyl-CoA and NADPH to produce multimethyl-branched mycocerosic acids. The enzyme was specific for methylmalonyl-CoA and would not incorporate malonyl-CoA into fatty acids. It elongated n-C6 to n-C20 CoA esters to generate primarily the corresponding tetramethyl-branched mycocerosic acids. Exogenous [1-14C]acyl-CoA and trideuteromethylmalonyl-CoA were incorporated into the multimethyl-branched fatty acids. Dodecyl sulfate electrophoresis showed that the enzyme had a molecular weight of 238,000, whereas gel filtration showed a native molecular weight of 490,000, indicating that the enzyme is composed of two monomers of identical molecular weight. The enzyme contained an acyl carrier protein-like segment as indicated by incorporation of [1-14C] pantothenate into the 238-kDa protein and production of 1 mol of taurine/mol of the monomer upon hydrolysis of performic acid-oxidized enzyme. It is concluded that the mycocerosic acid synthase is a multifunctional enzyme similar to the well-characterized multifunctional fatty acid synthases except for the substrate specificity.


Spectroscopic identification of cyclic imide b2-ions from peptides containing Gln and Asn residues.
In mass-spectrometry based peptide sequencing, formation of b- and y-type fragments by cleavage of the amide C-N bond constitutes the main dissociation pathway of protonated peptides under low-energy collision induced dissociation (CID). The structure of the b2 fragment ion from peptides containing glutamine (Gln) and asparagine (Asn) residues is investigated here by infrared ion spectroscopy using the free electron laser FELIX. The spectra are compared with theoretical spectra calculated using density functional theory for different possible isomeric structures as well as to experimental spectra of synthesized model systems. The spectra unambiguously show that the b2-ions do not possess the common oxazolone structure, nor do they possess the alternative diketopiperazine structure. Instead, cyclic imide structures are formed through nucleophilic attack by the amide nitrogen atom of the Gln and Asn side chains. The alternative pathway involving nucleophilic attack from the side-chain amide oxygen atom leading to cyclic isoimide structures, which had been suggested by several authors, can clearly be excluded based on the present IR spectra. This mechanism is perhaps surprising as the amide oxygen atom is considered to be the better nucleophile; however, computations show that the products formed via attack by the amide nitrogen are considerably lower in energy. Hence, b2-ions with Asn or Gln in the second position form structures with a five-membered succinimide or a six-membered glutarimide ring, respectively. b2-Ions formed from peptides with Asn in the first position are spectroscopically shown to possess the classical oxazolone structure.


The differential effects of gender, anthropometry, and prior hormonal state on frontal plane knee joint stiffness.
Gender differences in passive frontal plane knee stiffness may contribute to the increased anterior cruciate ligament injury rate in females. Gender-based stiffness differences have been attributed to anthropometric variations, but little data exist describing this relationship. Furthermore, sex hormone levels appear to influence joint stiffness, but the differential effects of instantaneous and prior hormonal concentrations remain unknown. This study sought to explore the effect of gender, prior hormonal status, and anthropometry on passive frontal plane knee joint stiffness. Twelve males and 31 females participated. Females were grouped by hormonal contraceptive use (non users [n=11], monophasic contraceptive users [n=11], and triphasic contraceptive users [n=9]) and tested at the same point in the menstrual cycle. Subjects' right knee was passively stretched +/-7 degrees in the frontal plane at 3 degrees /s. Stiffness was estimated at three loading levels and normalized by body size to minimize anthropometric biases. A 4 (group)x3 (load) repeated measures analysis of variance was performed for both raw and normalized stiffness. Linear regression analyses were preformed between stiffness estimates and knee diameter and quadriceps femoris angle. Males displayed significantly greater (P<0.05) frontal plane stiffness than females. When normalized, males displayed significantly greater stiffness in valgus (P<0.05), but not varus (P>0.05) than females. No significant effect (P>0.05) of prior hormonal state was found; however, when normalized, varus stiffness was significantly less for triphasic contraceptive users than the other female groups (P<0.05). Quadriceps femoris angle was negatively correlated and knee diameter was positively correlated to knee stiffness. Consistent with earlier in vitro findings, our data may indicate that ligament material properties are gender specific. A deficit in passive knee joint stiffness may place a larger burden on the neuromuscular system to resist frontal plane loading in females.


Ligninolytic behavior of the white-rot fungus Stereum ostrea under influence of culture conditions, inducers and chlorpyrifos.
The production of three ligninolytic enzymes, laccase (LAC), manganese peroxidase (MnP) and lignin peroxidase (LiP) by the white-rot fungus, Stereum ostrea, was significantly more in Koroljova liquid medium in the presence of chlorpyrifos under shaking conditions than under stationary conditions. These enzymes were secreted into the broth to the extent of 214.37, 82.75 and 8.05 U/ml under influence of chlorpyrifos on 10th day of incubation in comparison with 138.06, 51.85 and 6.44 U/ml, respectively, under similar conditions in control. Maximum production of LAC, MnP and LiP on liquid medium with/without chlorpyrifos under stationary conditions did not exceed 80-85, 33-40, 0.6-0.7 U/ml, respectively. Among lignosulfonic acid, veratryl alcohol (VA), gallic acid (GA) and tannic acid tested, GA induced maximum production of LAC (300.53 U/ml) and MnP (181.66 U/ml) after 10 days of growth in the presence of chlorpyriphos, while maximum LiP (1.134 U/ml) was produced when grown with the inducer VA during this period. Our data suggest that chlorpyrifos and inducers interacted positively in producing higher amounts of the ligninolytic enzymes in S. ostrea.


Caffeine inhibition of GLUT1 is dependent on the activation state of the transporter.
Caffeine has been shown to be a robust uncompetitive inhibitor of glucose uptake in erythrocytes. It preferentially binds to the nucleotide-binding site on GLUT1 in its tetrameric form and mimics the inhibitory action of ATP. Here we demonstrate that caffeine is also a dose-dependent, uncompetitive inhibitor of 2-deoxyglucose (2DG) uptake in L929 fibroblasts. The inhibitory effect on 2DG uptake in these cells was reversible with a rapid onset and was additive to the competitive inhibitory effects of glucose itself, confirming that caffeine does not interfere with glucose binding. We also report for the first time that caffeine inhibition was additive to inhibition by curcumin, suggesting distinct binding sites for curcumin and caffeine. In contrast, caffeine inhibition was not additive to that of cytochalasin B, consistent with previous data that reported that these two inhibitors have overlapping binding sites. More importantly, we show that the magnitude of maximal caffeine inhibition in L929 cells is much lower than in erythrocytes (35% compared to 90%). Two epithelial cell lines, HCLE and HK2, have both higher concentrations of GLUT1 and increased basal 2DG uptake (3-4 fold) compared to L929 cells, and subsequently display greater maximal inhibition by caffeine (66-70%). Interestingly, activation of 2DG uptake (3-fold) in L929 cells by glucose deprivation shifted the responsiveness of these cells to caffeine inhibition (35%-70%) without a change in total GLUT1 concentration. These data indicate that the inhibition of caffeine is dependent on the activity state of GLUT1, not merely on the concentration.


Chromosomal mosaicism confined to chorionic tissue.
Chorionic villus samples from two healthy pregnant females were obtained for first trimester fetal diagnosis. The karyotypes were 46,XX/47,XX,+3 and 46,XX/47,XX,+15, respectively. In both cases fibroblast cultures after termination of pregnancy were shown to have normal karyotypes.


The effect of experimental warming on fine root functional traits of woody plants: Data synthesis.
Fine root traits are critical to plant nutrition and water uptake, and soil nutrient cycling. The impacts of climate warming on woody plants are predicted to be severe, but the effects on the fine root traits of woody plants remain unclear. To evaluate the effects of warming on fine-root traits of woody plants, we synthesized 431 paired observations of 13 traits from 78 studies. The result showed that warming increased the fine root nitrogen (N) concentration, root mortality, and root respiration, but decreased fine root phosphorus (P) concentration, root C:N and root nonstructural carbohydrates (NSC) concentration. However, warming had no significant effect on fine root biomass, root production and morphological traits. Warming effects on fine root biomass and root diameter decreased with warming magnitude, while root P concentration increased. Moreover, with increasing warming duration, the effect size of specific root length (SRL), root length, root C:N and root NSC increased. The effects size of root biomass, root diameter, root length and root C:N decreased with mean annual temperature (MAT) and mean annual precipitation (MAP) increase. However, the effect size of root N concentration increased with higher MAT and MAP. Furthermore, warming increased the fine root biomass of ectomycorrhiza (ECM) plants, but decreased that of plants associated with arbuscular mycorrhizal (AM) fungi. These results indicate that the effect of warming on fine root traits of woody plants was not only modulated by warming duration and magnitude, but also MAT and MAP. Our findings highlight the differential warming responses to fine root traits of woody plants, which have strong implications for shrubs and tree-dominated ecosystems soil nutrients cycling and carbon stocks.


Distinct effects on splicing of two monoclonal antibodies directed against the amino-terminal domain of galectin-3.
Previous experiments had established that galectin-3 (Gal3) is a factor involved in cell-free splicing of pre-mRNA. Addition of monoclonal antibody NCL-GAL3, whose epitope maps to the NH2-terminal 14 amino acids of Gal3, to a splicing-competent nuclear extract inhibited the splicing reaction. In contrast, monoclonal antibody anti-Mac-2, whose epitope maps to residues 48-100 containing multiple repeats of a 9-residue motif PGAYPGXXX, had no effect on splicing. Consistent with the notion that this region bearing the PGAYPGXXX repeats is sequestered through interaction with the splicing machinery and is inaccessible to the anti-Mac-2 antibody, a synthetic peptide containing three perfect repeats of the sequence PGAYPGQAP (27-mer) inhibited the splicing reaction, mimicking a dominant-negative mutant. Addition of a peptide corresponding to a scrambled sequence of the same composition (27-mer-S) failed to yield the same effect. Finally, GST-hGal3(1-100), a fusion protein containing glutathione-S-transferase and a portion of the Gal3 polypeptide including the PGAYPGXXX repeats, also exhibited a dominant-negative effect on splicing.


Laser etched bifilar fine wire electrode for skeletal muscle motor unit recording.
To selectively record a limited number of skeletal muscle motor unit action potentials, a bifilar fine wire electrode was developed. Two 8 micrometers wires were braided together, a hook formed, and ends insulated. A round beam, pulsed laser, etched a 5 micrometers piece of insulation from each wire near the hooked end. Bipolar recordings from a select number of skeletal muscle motor units were obtained from these two uninsulated 5 micrometers areas. Reactive and capacitative components for each set of electrodes were measured. These electrodes were selective in recording from 3 to 5 single motor unit action potentials at low isometric tension levels.


Does authoritarianism necessarily stifle creativity? The role of discipline-focused authoritarian leadership.
A burgeoning body of research has shown that authoritarian leadership (AL) embodies the characteristics of "light" and "dark," meaning that it does not always have a negative impact on employees' creative activities. However, studies explaining this potential positive effect are insufficient. To extend the AL and creativity literature, we draw on self-determination theory and event system theory, and elicit discipline-focused AL and appointment event criticality to examine whether, when, and how authoritarian leaders affect employee creativity positively. With time-lagged data collected from 435 employees and their direct leaders in China, we found that discipline-focused AL has an indirect positive effect on employee creativity through creative self-efficacy. Additionally, appointment event criticality strengthens the positive relationship between discipline-focused AL and creative self-efficiency, and the indirect impact of discipline-focused AL on employee creativity through creative self-efficiency. The theoretical and practical implications are discussed.


Hyperhomocyst(e)inemia and Chlamydia pneumoniae IgG seropositivity in patients with coronary artery disease.
Elevated levels of homocyst(e)ine and infection by Chlamydia pneumoniae have been hypothesized individually to play a role in coronary artery disease (CAD), but the mechanisms are unclear. Data on a possible association are not available. We investigated the correlation between IgG antibody titers against C. pneumoniae and fasting plasma homocyst(e)ine in 234 consecutive male patients with CAD. Chlamydial antibodies to a recombinant genus-specific lipopolysaccharide (LPS) were measured with ELISA. Total homocyst(e)ine (tHcy) concentrations were measured by high-performance liquid chromatography (HPLC). Thirty-seven subjects were classified hyperhomocyst(e)inemic (fasting homocyst(e)ine>14 micromol/l, group A), and 197 subjects were below cut-off (tHcy<14 micromol/l, group B). Prevalence of IgG seropositivity against C. pneumoniae was significantly higher in group A (68%) as compared to group B (39%, P=0.002). Antibody titers were also significantly higher in hyperhomocyst(e)inemic subjects than in cases with low homocyst(e)ine levels (P=0.002). Overall titers correlated significantly with tHcy levels (r(2)=0.222, P=0.001). Hyperhomocyst(e)inemia was associated with arterial hypertension (P=0.003), intake of lipid lowering drugs (P=0.022) and quite not with low folate concentration (P=0.052). No association was seen for IgG seropositivity or homocyst(e)ine and age, body mass index, smoking, diabetes, vitamin B(6) and B(12), cholesterol and triglycerides. These data indicate an association between elevated plasma homocyst(e)ine concentrations and chlamydial IgG antibody titers in patients with CAD.


Pseudocontinuous arterial spin labeling with optimized tagging efficiency.
The adiabatic inversion of blood in pseudocontinuous arterial spin labeling (PCASL) is highly sensitive to off-resonance effects and gradient imperfections and this sensitivity can lead to tagging efficiency loss and unpredictable variations in cerebral blood flow estimates. This efficiency loss is caused by a phase tracking error between the RF pulses and the flowing spins. This article introduces a new method, referred to as Optimized PCASL (OptPCASL), that minimizes the phase tracking error by applying an additional compensation RF phase term and in-plane gradients to the PCASL pulse train. The optimal RF phase and gradient amplitudes are determined using a prescan procedure, which consists of a series of short scans interleaved with automated postprocessing routines integrated to the scanner console. The prescan procedure is shown to minimize the phase tracking error in a robust and time efficient manner. As an example of its application, the use of OptPCASL for the improved detection of functional activation in the visual cortex is demonstrated and temporal signal-to-noise ratio (SNR), image SNR, and baseline cerebral blood flow measures are compared to those acquired from conventional PCASL.


The MTP -493TT genotype is associated with peripheral arterial disease: results from the Linz Peripheral Arterial Disease (LIPAD) Study.
Microsomal triglyceride transfer protein (MTP) transfers lipids into apoprotein B-containing lipoproteins for secretion from liver, intestine, and heart. We hypothesized the -493T single nucleotide polymorphism in the MTP promoter region to be associated with altered lipoprotein levels and with presence of peripheral arterial disease (PAD). 433 patients with symptomatic PAD and 433 controls matched for sex and age from the Linz Peripheral Arterial Disease (LIPAD) study were genotyped cross-sectionally for the -493T single nucleotide polymorphism in the promoter region of the MTP gene. The frequency of the -493T allele in patients with PAD was 0.320, whereas it was 0.255 in controls (p<0.001). The MTP -493TT genotype was independently associated with PAD, even after adjustment for LDL cholesterol. The odds ratio of the -493TT MTP genotype for PAD was 3.18 (95% CI, 1.76-5.71) when adjusted for current smoking, arterial hypertension, LDL cholesterol, triglycerides, glycohemoglobin, C-reactive protein, and homocysteine. Furthermore, we found an association between the MTP promoter polymorphism and the apolipoprotein B-containing lipoproteins total-cholesterol (p=0.011), LDL cholesterol (p=0.002) and apolipoprotein B (p=0.034). Our results provide preliminary evidence for a potential role of the MTP -493TT genotype in the pathogenesis of PAD.


Economic analysis for evidence-based policy-making on a national immunization program: a case of rotavirus vaccine in Thailand.
Severe diarrhea caused by rotavirus is a health problem worldwide, including Thailand. The World Health Organization has recommended incorporating rotavirus vaccination into national immunization programs. This policy has been implemented in several countries, but not in Thailand where the mortality rate is not high. This leads to the question of whether it would be cost-effective to implement such a policy. The Thai National Vaccine Committee, through the Immunization Practice Subcommittee, has conducted an economic analysis. Their study aimed to estimate the costs of rotavirus diarrhea and of a rotavirus vaccination program, and the cost-effectiveness of such a program including budget impact analysis. The study was designed as an economic evaluation, employing modeling technique in both provider and societal perspectives. A birth cohort of Thai children in 2009 was used in the analysis, with a 5-year time horizon. Costs were composed of cost of the illness and the vaccination program. Outcomes were measured in the form of lives saved and DALYs averted. Both costs and outcomes were discounted at 3%. The study found the discounted number of deaths to be 7.02 and 20.52 for vaccinated and unvaccinated cohorts, respectively (13.5 deaths averted). Discounted DALYs were 263.33 and 826.57 for vaccinated and unvaccinated cohorts, respectively (563.24 DALYs averted). Costs of rotavirus diarrhea in a societal perspective were US$6.6 million and US$21.0 million for vaccinated and unvaccinated cohorts, respectively. At base case, the costs per additional death averted were US$5.1 million and US$5.7 for 2-dose and 3-dose vaccines, respectively, in a societal perspective. Costs per additional DALYs averted were US$128,063 and US$142,144, respectively. In a societal perspective, with a cost-effectiveness threshold at 1 GDP per capita per DALYs averted, vaccine prices per dose were US$4.98 and US$3.32 for 2-dose and 3-dose vaccines, respectively; in a provider perspective, they were US$2.90 and US$1.93. One-way and probabilistic sensitivity analyses were included. The budget required for vaccine purchase was calculated for all scenarios.


The Wooden Skull: An Innovation through the Use of Local Materials and Technology to Promote the Teaching and Learning of Human Anatomy.
Skeleton models are important in facilitating a student's easy retention and recollection of information in the future. These may assist students carry out hands-on practice in order to acquire and practice new skills that are relevant to first aid. The increasing number of medical institutions and medical students attracts the challenge of inadequate facilitation of the teaching and learning processes. This warrants a study and/or an exploration of an alternative solution such as wooden models in order to solve the problem of scarce and ethically restricted human teaching aids. Wooden pieces (50 cm length × 20 cm diameter) from a Jacaranda mimosifolia tree were prepared for the carving process, and wooden replicas of human skulls were made. Two experimental groups of randomly selected medical students (60: active and 60: control) were separately taught using wooden and natural skull models, respectively. The two groups were assessed and evaluated using the natural skull models to compare their understanding of the anatomy of the skull. Additionally, opinion statements were collected from participants in the active group during the oral examination. Six (6) wooden skull models were produced and used for experimental study. Comparisons of academic scores (mean and median) between active (students using the wooden skull) and control (students using natural skull) groups showed no statistically significant difference (P ≥ 0.05). Concerning the enhancement of learning skills, the wooden model was constructed in a way that would be able to enhance learning as it would be the natural skull. The wooden skull model, with more improvement in structural formation, can adequately facilitate the teaching and learning of anatomy of the human skull. This project and the experimental study about utilization of the wooden skull model provide a good potential of using the wooden models to supplement the use of the natural human skull.


Biologically active glycosides from Asteroidea, 41. Isolation and structure determination of glucocerebrosides from the starfish Linckia laevigata.
A new glucocerebroside, linckiacerebroside A (1) and a known glucocerebroside S-2a-3 (2), have been isolated from the cerebroside molecular species obtained from the less polar fraction of the CHCl3/MeOH extract of the starfish Linckia laevigata, together with three pseudo homogeneous glucocerebroside, 3, 4, and 5. The structures of these cerebrosides were determined on the basis of chemical and spectroscopic evidence.


Biodegradation of clopidogrel bisulfate by Pseudomonas aeruginosa and Pseudomonas putida strains isolated from Algerian wastewater.
The clopidogrel bisulfate was degraded under aerobic conditions by two bacterial strains isolated from industrial effluents in El-Harrach, Algeria. The sequencing of their 16S rRNA revealed that these two strains are Pseudomonas aeruginosa and Pseudomonas putida. The experiments showed that this consortium could remove clopidogrel bisulfate at high concentrations (5-1500 mg·L-1) within 96 h incubation period. The HPLC analysis recorded 75.23% degradation of clopidogrel bisulfate at an initial concentration of 100 mg·L-1 after five days of incubation at pH 7.0 and a temperature of 30 °C. Also, a maximum degradation of 99.08% was carried out at a more basic pH (8.5). While only 41% was degraded at a temperature of 20 °C. Moreover, the presence of supplemental sources of carbon and nitrogen in the mixed culture media effectively improved the biodegradation of clopidogrel bisulfate by the stains. Finally, the morphology of the strains and the properties of the cell's surface were studied using a scanning electron microscope (SEM). This study reports, for the first time, the viability of the aerobic biodegradation of clopidogrel bisulfate in water in a wide range of concentrations.


Effect of dibutyryl cyclic AMP and analogs on the rate of contractions of myocytes in culture.
2O, 6N-butyryl, 3', 5'-cyclic monophosphate (dibu cAMP) when added to fetal rat heart cells in culture inhibits myocyte contraction. This inhibition is 100, 84 and 51% complete when the dibu cAMP concentration used is 2, 0.2 and 0.02 mM, respectively. The potency of dibu cAMP derivatives in myocyte contraction inhibition follows the order, dibu cAMP greater than 6N-bu cAMP greater than 2O-bu cAMP = AMP greater than butyrate. The inhibition caused by the first three chemicals is greater than 70%.


The intersection of community socioeconomic factors with gender on outcomes after thoracic aortic surgery.
We evaluated the relationship among community socioeconomic factors (poverty, income, and education), gender, and outcomes in patients who underwent ascending aortic, root, and arch surgery. For 2634 consecutive patients, we associated patients' ZIP codes with community socioeconomic factors. The composite adverse outcome comprised death, persistent neurological injury, and renal failure necessitating dialysis at discharge. Multivariable analysis and Kaplan-Meier survival curves were used. Men and women from the full cohort and from the elective patients were propensity matched. Median follow-up was 3.6 years (interquartile range, 1.2-9.3). Men lived in areas characterized by less poverty (P = .03), higher household income (P = .01), and more education (P = .02) than women; likewise, in the elective cohort, all community socioeconomic factors favored men (P ≤ .009). Female gender predicted composite adverse outcome (P = .006). In the propensity-matched women and men (820 pairs), the composite adverse outcome rates were 14.2% and 11%, respectively (P = .06). In 583 propensity-matched pairs of elective patients, men had less composite adverse outcome (P = .02), operative mortality (P = .04), and renal (P = .02) and respiratory failure (P = .0006). The 5- and 10-year survivals for these men and women were 74.2% versus 71.4% and 50.2% versus 48.2%, respectively (P = .06). All community socioeconomic factors in both propensity-matched groups nonsignificantly favored men. This study is among the first to examine the association among community socioeconomic factors, gender, and outcomes in patients who undergo proximal aortic surgery. Female gender predicted a composite adverse outcome. In the elective patients, most adverse outcomes were significantly less in men. In the propensity-matched patients, all community socioeconomic factors favored men, although not significantly. Larger studies with patient-level socioeconomic information are needed.


MORICE--new technology for mechanical oil recovery in ice infested waters.
Mechanical oil recovery in ice infested waters (MORICE) was initiated in 1995 to develop technology for the recovery of oil spills in ice. It has been a multinational effort involving Norwegian, Canadian, American and German organizations and researchers. Through a stepwise approach with the development organized in six separate phases, laboratory tests and field experiments have been conducted to study various ideas and concepts, and to refine the ideas that were considered to have the best potential for removing oil in ice. Put together in one unit, these concepts included ice processing equipment and two alternative oil recovery units installed on a work platform. In January 2002, the final oil and ice testing with MORICE concepts was conducted at the Ohmsett test facility in Leonardo, New Jersey. The unit has been referred to as a harbor version to indicate the size and operating conditions, but the concepts could be scaled up to increase the capacity of oil and ice processing. For heavier ice conditions it would also be necessary to increase the overall strength.


Enzymatic characterization of an active NDH complex from Thermosynechococcus elongatus.
Although type-1 NAD(P)H dehydrogenase (NDH) complex subunit constituents and physiological functions have been reported in plants and cyanobacteria, the biochemical properties of this enzyme are not clear. We used chromatographic isolation to purify and characterize a NADPH-active NDH from the cyanobacterium Thermosynechococcus elongatus. Ferredoxin (Fd) and ferredoxin-NADP(+) oxidoreductase (FNR) were co-eluted with NDH, implying the electron donation from NADPH to NDH via the interaction with FNR. We investigated the enzymatic properties of the complex. Furthermore, the activity is competitively inhibited by rotenone, suggesting that it possesses a quinone binding site, similar to mitochondria complex I.


Kinematic analysis of speed transitions within walking in younger and older adults.
The ability to adapt to environmental and task demands while walking is critical to independent mobility outside the home and this ability wanes with age. Such adaptability requires individuals to acutely change their walking speed. Regardless of age, changes between walking speeds are common in daily life, and are a frequent type of walking adaptability. Here, we report on older and younger adults when transitioning from preferred walking speed overground to either slower or faster walking. Specifically, we evaluated biomechanical parameters prior to, during, and post transition. Individuals approached the walking speed transition similarly, independent of whether the transition was to slower or faster walking. Regardless of age or walking speed, the step during which a walking speed transition occurred was distinct from those prior- and post- transition, with on average 0.15 m shorter step lengths, 3.6° more hip flexion, and 3.3° more dorsiflexion during stance. We also found that peak hip flexion occurred 22% later, and peak hip extension (39%), knee flexion (26%), and dorsiflexion (44%) occurred earlier in stance for both typical to slower and typical to faster walking. Older adults had altered timing of peak joint angles compared with younger adults across both acceleration and deceleration conditions, indicating age-dependent responses to changing walking speed. Our findings are an important first step in establishing values for kinematics during walking speed transitions in younger and typical older adults.


Ketorolac Use for Pain Management in Trauma Patients With Rib Fractures Does not Increase of Acute Kidney Injury or Incidence of Bleeding.
Ketorolac is useful in acute pain management to avoid opiate-related complications; however, some surgeons fear associated acute kidney injury (AKI) and bleeding despite a paucity of literature on ketorolac use in trauma patients. We hypothesized that our institution's use of intravenous ketorolac for rib fracture pain management did not increase the incidence of bleeding or AKI. Rib fracture patients aged 15 years and above admitted between January 2016-June 2018 were identified in our trauma registry along with frequency of bleeding events. AKI was defined as ≥ 1.5x increase in serum creatinine from baseline measured on the second day of admission (after 24 hours of resuscitation) or an increase of ≥ .3 mg/dL over a 48-hour period. Patients receiving ketorolac were compared to patients with no ketorolac use. Two cohorts of 199 control and 205 ketorolac patients were found to be similar in age, gender, admission systolic blood pressure (SBP), injury severity score, intravenous radiocontrast received, and transfusion requirements. Analysis revealed no difference in frequency of AKI using both definitions (8% vs. 7.3%, P = .79) and (19.6% vs. 15.1%, P = .24), respectively, or bleeding events (2.5% vs. 0%, P = .03). Logistic regression demonstrated that ketorolac use was not an independent predictor for AKI but age and admission SBP < 90 were. Use of ketorolac in this cohort of trauma patients with rib fractures did not increase the incidence of AKI or bleeding events.


The N-terminal and C-terminal domains of a receptor tyrosine phosphatase are associated by non-covalent linkage.
We have cloned the rat homolog of the human leukocyte common antigen-related gene (LAR), which encodes a transmembrane receptor phosphotyrosine phosphatase, and raised antibodies against its protein product. We present evidence here for a processing event resulting in a two-chain structure of the mature receptor on the cell surface. The LAR protein is synthesized as a 190-kDa precursor which is subsequently cleaved into 145-kDa and 85-kDa fragments. The 145-kDa fragment, representing the amino terminus of the protein, is exclusively extracellular and is modified by N-linked glycosylation. The 85-kDa component, derived from the C-terminus of the protein, contains the transmembrane region and intracellular phosphotyrosine phosphatase domains. The two products, associated in a non-covalent manner, comprise the functional LAR cell-surface receptor.


Silencing information regulator 1 ameliorates lipopolysaccharide-induced acute lung injury in rats via the upregulation of caveolin-1.
Acute lung injury (ALI) is an intractable medical problem linked with to high morbidity and mortality all over the worldglobally. The prognosis of advanced acute lung injury remains persistently poor due to its underlying mechanisms remain unclear.Despite advancements in medical research, the its prognosis of advanced ALI remains persistently poor due to unclear underlying mechanisms. We aimed to investigate the protective effects of silencing information regulator 1 (SIRT1) on lipopolysaccharide (LPS)-induced acute lung injuryALI and to reveal its underlying molecular mechanism. Male Sprague--Dawley rats were divided grouped into 4 groupsfour: normal saline group (group NS), lipopolysaccharide group (group L), SIRT1 activator SRT1720-pretreated group (group S), and SIRT1 inhibitor EX527- pretreated group (group E). Rats They were intranasally dripped with LPS to establish the model of ALI modelsacute lung injury respectively. We investigated the effect of SIRT1 on acute lung injury by analysing We analyzed the CT images of the rat lungs and used, HE staining, lung wet-to-dry ratio, inflammatory factor expression, lung injury marker expression, immunohistochemistry, and related mRNA expression to determine the effect of SIRT1 on ALI. Our results show that LPS induction produced resulted in acute lung injury, ALI and disrupting disrupted normal SIRT1 expression, which led to the overexpression of STAT3, TLR4, TNF-ɑ, and IL-6 and suppression of Cav-1 expression. Upregulation The upregulation of Cav-1 protein and mRNA following the administration of an SIRT1 agonist resulted in reduced lung injury. SRT1720 pretreatment was closely associated with reduced expressions of STAT3,TLR4, TNF-ɑ, and IL-6. ALI lung injury was more severeworsened after administration of SIRT1 inhibitors, and the changes in the above indicators were reversed. These results suggest that SIRT1 may protect against LPS-induced acute lung injuryALI via by counteracting inflammatory remissionion, and this protective effect might may be mediated by suppressing STAT3 to activate the expression ofinduce Cav-1 expression.


Study of structural and electronic origin of ambergris odor of some compounds.
The correlation between structural, stereochemical as well as electronic features and ambergris odor of some tricyclic ethers is established based on quantum chemical calculation method. A definite structural fragment (a "new ambergris triangle") with certain electronic properties determining the origin of the odor is revealed. The influence of HOMO-LUMO energy gaps and total energies of some ambergris compounds on their odor intensity is investigated.


CYP2J2/EET reduces vulnerability to atrial fibrillation in chronic pressure overload mice.
Growing evidence has well established the protective effects of CYP2J2/EET on the cardiovascular system. The aim of the present study was to determine whether CYP2J2/EET has a preventive effect on atrial fibrillation (AF) and to investigate the underlying mechanisms. Wild-type mice were injected with or without AAV9-CYP2J2 before abdominal aortic constriction (AAC) operation. After 8 weeks, compared with wild-type mice, AAC mice display higher AF inducibility and longer AF durations, which were remarkably attenuated with AAV9-CYP2J2. Also, AAV9-CYP2J2 reduced atrial fibrosis area and the deposit of collagen-I/III in AAC mice, accompanied by the blockade of TGF-β/Smad-2/3 signalling pathways, as well as the recovery in Smad-7 expression. In vitro, isolated atrial fibroblasts were administrated with TGF-β1, EET, EEZE, GW9662, SiRNA Smad-7 and pre-MiR-21, and EET was demonstrated to restrain the differentiation of atrial fibroblasts largely dependent on Smad-7, due to the inhibition of EET on MiR-21. In addition, increased inflammatory cytokines, as well as activated NF-κB pathways induced by AAC surgery, were also significantly blunted by AAV9-CYP2J2 treatment. These effects of CYP2J2/EET were partially blocked by GW9662, the antagonist of PPAR-γ. In conclusion, this study revealed that CYP2J2/EET ameliorates atrial fibrosis through modulating atrial fibroblasts activation by disinhibition of MiR-21 on Smad-7, and attenuates atrial inflammatory response by repressing NF-κB pathways, reducing the vulnerability to AF, and CYP2J2/EET exerts its role at least partially through PPAR-γ activation. Our findings might provide a novel upstream therapeutic strategy for AF.


Ondansetron orally disintegrating tablet versus placebo for the prevention of postdischarge nausea and vomiting after ambulatory surgery.
Ondansetron orally disintegrating tablet reduces postdischarge nausea and vomiting and improves patient satisfaction with postoperative nausea and vomiting management.


Point-of-care testing for streptomycin based on aptamer recognizing and digital image colorimetry by smartphone.
The rapid detection of antibiotic residual in everyday life is very important for food safety. In order to realize the on-site and visual detection of antibiotic, a POCT method was established by using digital image colorimetry based on smartphone. Streptomycin was taken as the analyte model of antibiotics, streptomycin aptamer preferentially recognized analyte, and the excess aptamer hybridized with the complementary DNA to form the dsDNA. SYBR Green I combined with the dsDNA and then emitted obvious green fluorescence, thus the fluorescence intensity decreased with the increasing of streptomycin concentration. Then a smartphone-based device was constructed as the fluorescence readout. The smartphone camera acquired the images of the fluorescence derived from the samples, and the Touch Color APP installed in smartphone read out the RGB values of the images. There was a linear relationship between the G values and the streptomycin concentrations in the range of 0.1-100µM. The detection limit was 94nM, which was lower than the maximum residue limit defined by World Health Organization. The POCT method was applied for determining streptomycin in chicken and milk samples with recoveries in 94.1-110%. This method had the advantages of good selectivity, simple operation and on-site visualization.


Gradient distribution pattern of muscarinic receptors in N1E 115 mouse neuroblastoma cells.
The distribution pattern of muscarinic receptors in N1E 115 mouse neuroblastoma cells after linear and non-linear gradient centrifugation was investigated. In untreated cells, at least two forms of the receptors, with different densities, were found.


Evaluation of restriction enzymes for standardizing pulsed-field gel electrophoresis protocol for rapid subtyping of Vibrio parahaemolyticus.
We evaluated the cost-effectiveness of the restriction enzymes with rare-cutting sites in the genome of Vibrio parahaemolyticus RIMD 2210633 for pulsed-field gel electrophoresis (PFGE) analysis. The evaluation indicated that PFGE with both NotI and SfiI was discriminatory, but NotI was more cost-effective. Based on the results of this study, we suggest using NotI and SfiI as the 1st and the 2nd restriction enzyme for standardizing the PulseNet PFGE protocol for molecular subtyping and global surveillance of V. parahaemolyticus.


Allergen-induced IL-6 trans-signaling activates γδ T cells to promote type 2 and type 17 airway inflammation.
A variant in the IL-6 receptor (IL-6R) gene increases asthma risk and is predicted to decrease IL-6 classic signaling and increase IL-6 trans-signaling. This suggests that inhibition of IL-6 trans-signaling, but not classic signaling, might suppress allergic airway inflammation. We sought to determine whether IL-6 signaling contributes to (1) acute experimental asthma induced by clinically relevant allergens and (2) variation in asthma clinical phenotypes in asthmatic patients. Mice were sensitized to house dust mite (HDM) or cockroach at day 0, treated with IL-6R inhibitors at day 13, and challenged with the same allergen at days 14 to 17. End points were measured 3 hours after the final challenge. IL-6 and soluble IL-6 receptor (sIL-6R) expression in induced sputum of asthmatic patients was correlated with asthma clinical phenotypes. Both HDM and cockroach induced a type 2/type 17 cytokine profile and mixed granulocytic inflammation in the airways. Both allergens increased IL-6 expression in the airways, but only cockroach induced sIL-6R expression. Therefore HDM challenge promoted IL-6 classic signaling but not trans-signaling; in this model treatment with anti-IL-6R did not suppress airway inflammation. In contrast, cockroach-induced inflammation involved activation of IL-6 trans-signaling and production of IL-17A by γδ T cells. Anti-IL-6R, selective blockade of sIL-6R, or γδ T-cell deficiency significantly attenuated cockroach-induced inflammation. Asthmatic patients with high airway IL-6 and sIL-6R levels were enriched for the neutrophilic and mixed granulocytic subtypes. Experimental asthma associated with both high IL-6 and high sIL-6R levels in the airways is attenuated by treatment with IL-6R inhibitors.


Relation between renal and hepatic excretion of drugs. VI. Influence of pretreatment with phenol red on renal excretion and accumulation capacity of kidney or liver slices of immature and adult rats.
Pretreatment with phenol red causes a significant increase in renal excretion of p-amino-hippurate (PAH) in adult rats. In vitro experiments have shown that phenol red pretreatment significantly enhances the accumulation of PAH in renal tubular cells of adult rats. Thus the stimulation of active renal tubular PAH transport is at least in part responsible for its accelerated excretion via urine. A similar phenol red administration does not enhance the renal excretion of this dye, neither in adult nor in immature rats. In accordance with these in vivo findings the renal accumulation of phenol red is not increased after pretreatment with this dye. Remarkably the repeated administration of phenol red causes a distinct reduction of phenol red accumulation capacity in liver tissue. The rate of accumulation of both PAH and phenol red in renal cortical slices increases significantly during maturation; in liver tissue slices such an intensification does not occur. Under anaerobic conditions an active energy requiring uptake of phenol red does not take place and an accumulation by active transport of the dye can also be excluded. Therefore a passive uptake of phenol red and a binding of the dye in renal tubular cells could explain the distinct accumulation of phenol red in tissue slices from the kidney under nitrogen atmosphere. In 55-day-old rats the anaerobic phenol red accumulation in the liver is diminished after pretreatment with this dye.


Chimera and cluster collective states in a dispersal ecological network under state-dependent feedback control and complex habitat structure.
Pest control based on an economic threshold (ET) can effectively prevent excessive pest control measures such as pesticide abuse and overharvesting. The instinctive dispersal of pest populations in biological network patches for better survival poses challenges for pest management. As long as the pest density is controlled below the economic threshold and no pest outbreak occurs, the aim of pest management can be achieved and it is not necessary to completely remove the pests. This study focuses on the issues of chimera states and cluster solutions in regular bidirectional biological networks with state-dependent impulsive pest management. We consider the influence of two different control modes on the system states, namely global control and local control. Local control is found to be more likely to induce the chimera state. In addition, in the local coupling mode, a higher coupling strength is more likely to generate a coherent state, whereas a lower coupling strength is more likely to generate chimera and incoherent states. Furthermore, the cluster size is inversely related to the coupling strength under local coupling and global control.


Prevalence of overweight and obesity among African primary school learners: a systematic review and meta-analysis.
The increasing trend in the global prevalence of childhood overweight and obesity presents a major public health challenge. This study reports the results of a systematic review and meta-analysis to estimate the prevalence of overweight and obesity among primary school learners residing in Africa according to the different body mass index criteria and population level characteristics. A search of multiple databases was conducted to identify relevant research articles published between January 1980 and February 2017. Random effects models were used to pool prevalence data within and across population level characteristics after variance stabilization through arcsine transformation (PROSPERO registration number CRD42016035248). Data from 45 studies across 15 African countries, and comprising 92,379 and 89,468 participants for overweight and obesity estimates were included. Estimated overweight and obesity prevalence differed significantly across criteria: 10.5% [95% confidence interval, CI: 7.1-14.3] and 6.1% [3.4-9.7] by World Health Organization; 9.5% [6.5-13.0] and 4.0% [2.5-5.9] by International Obesity Task Force; and 11.5% [9.6-13.4] and 6.9% [5.0-9.0] by Centre for Diseases Control, respectively (p = 0.0027 for overweight; p < 0.0001 for obesity). Estimates were mostly higher in urban, and private schools, but generally similar by gender, major geographic regions, publication year and sample size. Substantial heterogeneity in the estimates across and within criteria were not always explained by major study characteristics. Overweight and obesity are prevalent among African primary school learners, particularly those attending urban, and private schools. The results from this meta-analysis could be helpful in making informed decisions on childhood obesity prevention efforts in African countries.


Mastopexy with Autoaugmentation and Fat Transfer.
Patients have been requesting implant removal in revisional breast surgery and options for breast improvement without the use of breast implants in primary breast surgery. This article focuses on perioperative decision making and surgical technique in performing a mastopexy with autoaugmentation and fat grafting. The use of a lower island of breast parenchyma relocated to the upper pole through a central pedicle in primary surgery and a superior pedicle in postexplantation cases, along with fat grafting can provide improvement in global volume or simply additional volume in areas of deficiency, such as the upper poles and medial cleavage region.


Impacts of early smoking initiation: long-term trends of lung cancer mortality and smoking initiation from repeated cross-sectional surveys in Great Britain.
To show long-term trends of smoking initiation in Great Britain including unanalysed data and assess the impact of early smoking initiation on the lung cancer mortality in later ages focusing on birth cohorts. Reanalysis of repeated cross-sectional surveys conducted 13 times during 1965-1987. Great Britain. Men and women aged 16 years and over in each survey. Smoking initiation for 1898-1969 birth cohorts and lung cancer mortality in 1950-2009. In men, 1900-1925 birth cohorts showed high smoking initiation (>32%, >50% and >80% at 15, 17 and 29 years old, respectively). Correspondingly, the lung cancer mortality in these cohorts exceeded 1 per 1000 at a young age (50-54 years old). In women, smoking initiation increased clearly from the 1898 cohort to the 1925 cohort (2% to 12%, 4% to 24%, and 13% to 54% at 15, 17 and 29 years old, respectively). Correspondingly, the age at which the mortality exceeded 1 per 1000 became younger (75-79 to 60-64 years old). In both men and women, short-term decreases in initiation were seen from the late-1920s cohorts. Correspondingly, lung cancer mortality decreased. In women, initiation increased again after the mid-1930s cohorts, and mortality increased after they became 60-64 years old. Clear relationships between smoking initiation and lung cancer mortality across birth cohorts were observed. Countries with rapid increases in initiation in teens should not underestimate the risk in the distant future. Because of the long time lags within cohorts compared with rapid changes in smoking habits across cohorts, age-specific measures focusing on birth cohorts should be monitored.


[Identification of protein peroxiredoxin 2 related to crystalline NiS-induced neoplastic transformation].
To provide evidence for illustrating the molecular mechanism of nickel carcinogenesis, and to identify the differential expression of protein in crystalline NiS-induced neoplastic transformation of human bronchial epithelial cell by proteomics technology. Two dimensional electrophoresis (2-DE) and the ImageMaster 3.10 software were used to analyze the differential expression of protein, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) combined with database search was applied to identify protein peroxiredoxin 2 (PDX2) related to malignant transformation. The good 2-DE pattern including resolution and reproducibility was obtained. Nearly 700 expressed proteins per 2-D gel were isolated with molecular weights (MW) ranging from 14,400 to 94,000 KD and pI 3 - 10. A protein PDX2 with MW 21,890 KD, pI 5.66, which was highly expressed in malignantly transformed cell, was identified using MALDI-TOF-MS. PDX2 was involved in malignant transformation of human bronchial epithelial cell induced by crystalline nickel sulfide.


An abnormal plasma antithrombin with no apparent affinity for heparin.
Congenital antithrombin abnormality was found in several members of a French family. No history of thrombotic episodes was associated with this abnormality. Plasma antithrombin concentration as well as the rate of thrombin inactivation by defibrinated plasma in the absence of heparin were normal. However, the heparin cofactor activity was decreased by about 50% in plasma of affected patients. Accordingly, about half the amount of plasma antithrombin did not bind to gel bound heparin. Moreover the crossed immunoelectrophoretic pattern in the presence of heparin demonstrated two peaks of antithrombin, the slower one migrating as normal antithrombin when heparin was omitted from the first agarose gel. It was concluded that molecular alteration of the antithrombin molecule seemed to affect only the heparin binding site thus preventing from any rate enhancement of thrombin inactivation.


Revealing the role of the benzyloxy pharmacophore in the design of a new class of monoamine oxidase-B inhibitors.
The conceptual layout of monoamine oxidase (MAO) inhibitors has been modified to explore their potential biological application in the case of neurological disorders for the time being. The current review article is an effort to display the summation of innovative conceptual prospects of MAO inhibitors and their intriguing chemistry and bioactivity. Based on this scenario, we emphasize the pivotal role of the benzyloxy moiety attached to scaffolds like oxadiazolones, indolalkylamines, safinamide, caffeine, benzofurans, α-tetralones, β-nitrostyrene, benzoquinones, coumarins, indoles, chromones, and chromanone analogs, while acting as an MAO inhibitor.


1,25-Dihydroxyvitamin D deficiency induces sarcopenia by inducing skeletal muscle cell senescence.
To determine if 1,25(OH)2D deficiency can induce age-related sarcopenia, the skeletal muscular phenotype of male wild-type (WT) and Cyp27b1 knockout (KO) mice were compared at 3 and 6 months of age. We found that muscle mass, grip strength and muscle fiber size were significantly decreased in aging Cyp27b1 KO male mice. The expression levels of genes related to mitochondrial metabolic activity, and antioxidant enzymes including SOD1, catalase, Nqo1 and Gcs were significantly down-regulated in skeletal muscle tissue of Cyp27b1 KO male mice; in contrast, the percentage of p16+ and p21+ myofibers, and the expression of p16, p19, p21, p53, TNFα, IL6 and MMP3 at mRNA and/or protein levels were significantly increased. We then injected tibialis anterior muscle of WT and Cyp27b1+/- male mice with BaCl2, and analyzed the regenerative ability of skeletal muscle cells 7 days later. The results revealed that the numbers of newly formed regenerating central nucleated fibers (CNF), the percentage of BrdU+ cells and the expression of MyoD, MyHC and Myf5 at mRNA levels were significantly down-regulated in the injured skeletal muscle tissue of Cyp27b1+/- mice. In summary, our studies indicate that 1,25(OH)2D deficiency can result in the development of age-related sarcopenia by inducing oxidative stress, skeletal muscular cell senescence and SASP, and by inhibiting skeletal muscle regeneration. Cyp27b1 KO mice can therefore be used as an animal model of age-related sarcopenia in order to investigate the pathogenesis of age-related sarcopenia and potentially to test intervention measures for treatment of sarcopenia.


Urotensin II is an autocrine/paracrine growth factor for aortic adventitia of rat.
Urotensin II (UII) is a potent vasoconstrictive peptide; however, its significance in vascular adventitia has not been clearly elucidated. In this study, rat aortic adventitia showed mRNA expression and immunoreactivity of UII and its receptor (UT). Moreover, radioligand-binding assay showed that maximum binding capacity (Bmax) of [(125)I]-UII was higher in adventitia than in media (28.60+/-1.94 vs. 20.21+/-1.11 fmol/mg, P<0.01), with no difference in binding affinity (dissociation constant [Kd] 4.27+/-0.49 vs. 4.60+/-0.40 nM, P>0.05). Furthermore, in cultured adventitial fibroblasts, UII stimulated DNA synthesis, collagen synthesis and secretion in a concentration-dependent manner. These effects were inhibited by the UII receptor antagonist urantide (10(-6) mol/l), Ca(2+) channel blocker nicardipine (10(-5) mol/l), protein kinase C inhibitor H7 (10(-6) mol/l), and mitogen-activated protein kinase inhibitor PD98059 (10(-6) mol/l) but not the phosphatidyl inositol-3 kinase inhibitor wortmannin (10(-7) mol/l). UII may act as an autocrine/paracrine factor through its receptor and the Ca(2+) channel, protein kinase C, and mitogen-activated protein kinase signal transduction pathways, in the pathogenesis of vascular remodeling by activating vascular adventitia.


Use of Surgical Simulation by Underrepresented High School Students to Address Diversity Gaps in Surgery.
Recent tragedies have displayed systemic inequities in our society. Our institution has created a program for underrepresented high school students in our surgical simulation lab. The students have responded very favorably, and their interest in a surgical career and self-confidence increased significantly.


The function of GORASPs in Golgi apparatus organization in vivo.
In vitro experiments have shown that GRASP65 (GORASP1) and GRASP55 (GORASP2) proteins function in stacking Golgi cisternae. However, in vivo depletion of GORASPs in metazoans has given equivocal results. We have generated a mouse lacking both GORASPs and find that Golgi cisternae remained stacked. However, the stacks are disconnected laterally from each other, and the cisternal cross-sectional diameters are significantly reduced compared with their normal counterparts. These data support earlier findings on the role of GORASPs in linking stacks, and we suggest that unlinking of stacks likely affects dynamic control of COPI budding and vesicle fusion at the rims. The net result is that cisternal cores remain stacked, but cisternal diameter is reduced by rim consumption.


The effects of arm crank training on the physiological responses to submaximal wheelchair ergometry.
The purpose of this investigation was to examine the cardiovascular and metabolic effects of a 5 wk arm crank (AC) training program on submaximal wheelchair (WC) ergometry in able-bodied women. The 6 subjects in the training group (TG) and 4 in the control group (CG) performed a 10 min WC exercise prior to and following the training period at a power output (PO) that elicited 70% of the pre-training peak oxygen uptake (VO2). Steady state VO2, heart rate (HR), cardiac output (Qc) and stroke volume (Vs) were measured. Resting and post-exercise blood lactate concentrations (LA) were measured, the difference was recorded as net LA. The TG exercised on the AC 3 d.wk-1 at a PO that elicited 85% of each subject's recorded peak HR. Each session consisted of four 4 min exercise bouts preceded by a 2 min warm-up and interspersed with 2 min rest periods. After training, the TG had a significantly (p less than 0.05) lower HR, larger Vs and lower LA in response to the WC exercise. Qc and VO2 were not significantly altered. The results demonstrate that the AC exercise program used in this study produced a physiological training effect which was observed during submaximal WC exercise of an intensity frequently encountered during daily WC ambulation. It appears that short-term, moderate intensity AC training offers an adequate stimulus to reduce the stress imposed by wheelchair locomotion.


Synaptically released zinc: physiological functions and pathological effects.
In addition to its familiar role as a component of metalloproteins, zinc is also sequestered in the presynaptic vesicles of a specialized type of neurons called 'zinc-containing' neurons. Here we review the physiological and pathological effects of the release of zinc from these zinc-containing synaptic terminals. The best-established physiological role of synaptically released zinc is the tonic modulation of brain excitability through modulation of amino acid receptors; prominent pathological effects include acceleration of plaque deposition in Alzheimer's disease and exacerbation of excitotoxic neuron injury. Synaptically released zinc functions as a conventional synaptic neurotransmitter or neuromodulator, being released into the cleft, then recycled into the presynaptic terminal. Beyond this, zinc also has the highly unconventional property that it passes into postsynaptic neurons during synaptic events, functioning analogously to calcium in this regard, as a transmembrane neural signal. To stimulate comparisons of zinc signals with calcium signals, we have compiled a list of the important parameters of calcium signals and zinc signals. More speculatively, we hypothesize that zinc signals may loosely mimic phosphate 'signals' in the sense that signal zinc ions may commonly bind to proteins in a lasting manner (i.e., 'zincylating' the proteins) with consequential changes in protein structure and function.


In vitro embryo production in buffalo (Bubalus bubalis) using sexed sperm and oocytes from ovum pick up.
The objective was to explore the use of sexed sperm and OPU-derived oocytes in an IVP system to produce sex-preselected bubaline embryos. Oocytes were recovered from 20 fertile Murrah and Nili-Ravi buffalo cows by repeated (twice weekly) ultrasound-guided transvaginal ovum pick up (OPU), or by aspiration of abbatoir-derived bubaline ovaries, and subjected to IVF, using frozen-thawed sexed or unsexed bubaline semen. On average, 4.6 oocytes were retrieved per buffalo per session (70.9% were Grades A or B). Following IVF with sexed sperm, oocytes derived from OPU had similar developmental competence as those from abattoir-derived ovaries, in terms of cleavage rate (57.6 vs. 50.4%, P=0.357) and blastocyst development rate (16.0 vs. 23.9%, P=0.237). Furthermore, using frozen-thawed sexed versus unsexed semen did not affect rates of cleavage (50.5 vs. 50.9%, P=0.978) or blastocyst development (15.3 vs. 19.1%, P=0.291) after IVF using OPU-derived oocytes. Of the embryos produced in an OPU-IVP system, 9 of 34 sexed fresh embryos (26.5%) and 5 of 43 sexed frozen embryos (11.6%) transferred to recipients established pregnancies, whereas 7 of 26 unsexed fresh embryos (26.9%) and 6 out of 39 unsexed frozen embryos (15.4%) transferred to recipients established pregnancies. Eleven sex-preselected buffalo calves (10 females and one male) and 10 sexed buffalo calves (six females and four males) were born following embryo transfer. In the present study, OPU, sperm sexing technology, IVP, and embryo transfer, were used to produce sex-preselected buffalo calves. This study provided proof of concept for further research and wider field application of these technologies in buffalo.


Assignment of segments of the bacteriorhodopsin sequence to positions in the structural map.
Specific amino acid sequence segments have been assigned to locations in the structural map of bacteriorhodopsin using two-dimensional neutron diffraction data and a model building analysis. Models are constructed computationally by building specific regions of the amino acid sequence as alpha helices and then positioning the helices on axes indicated by the density map of Henderson and Unwin (Nature [Lond.]. 1975, 257:28-32). Neutron diffraction data were collected from samples of stacked, oriented "native" purple membranes as well as purple membranes containing different kinds of deuterated amino acids. Models differing in the assignments of helices to specific axes and in rotations of the helices about those axes were tested against the neutron data using a weighted residual factor to rank the models. This residual factor was calculated between observed and predicted intensity differences for pairs of data sets. Using this approach, a small set of related models has been found that predicts the observed intensity changes between five independent data sets. These models are inconsistent with the proposed locations of the retinal chromophore and the carboxyl terminus and with any of the previously proposed models for bacteriorhodopsin.


gamma-Hydroxybutyric acid is not a GABA-mimetic agent in the spinal cord.
gamma-Hydroxybutyric acid (GHB), a pharmacologically active central nervous system constituent, has been postulated to function as a gamma-aminobutyric acid (GABA) agonist. This hypothesis was tested directly on GABAergic synapses in isolated, superfused frog spinal cord. Addition of GHB to the superfusate produced effects on primary afferent terminals that were distinctly different from the effects of GABA. Thus, although both compounds depressed dorsal root potentials, GHB hyperpolarized terminals while GABA depolarized the same structures. The GABA responses were antagonized by bicuculline and picrotoxin, but these alkaloids did not change GHB's actions. In addition, GHB altered neither high-affinity uptake by cord slices, nor potassium-evoked release of tritiated GABA from them. GHB did not directly release GABA from spinal slices preloaded with [3H]GABA. These observations suggest that the central nervous system actions of GHB are not dependent upon its ability to activate GABAergic synapses or to modify GABAergic mechanisms.