Signal peptide hydrophobicity is critical for early stages in protein export by Bacillus subtilis.
Signal peptides that direct protein export in Bacillus subtilis are overall more hydrophobic than signal peptides in Escherichia coli. To study the importance of signal peptide hydrophobicity for protein export in both organisms, the alpha-amylase AmyQ was provided with leucine-rich (high hydrophobicity) or alanine-rich (low hydrophobicity) signal peptides. AmyQ export was most efficiently directed by the authentic signal peptide, both in E. coli and B. subtilis. The leucine-rich signal peptide directed AmyQ export less efficiently in both organisms, as judged from pulse-chase labelling experiments. Remarkably, the alanine-rich signal peptide was functional in protein translocation only in E. coli. Cross-linking of in vitro synthesized ribosome nascent chain complexes (RNCs) to cytoplasmic proteins showed that signal peptide hydrophobicity is a critical determinant for signal peptide binding to the Ffh component of the signal recognition particle (SRP) or to trigger factor, not only in E. coli, but also in B. subtilis. The results show that B. subtilis SRP can discriminate between signal peptides with relatively high hydrophobicities. Interestingly, the B. subtilis protein export machinery seems to be poorly adapted to handle alanine-rich signal peptides with a low hydrophobicity. Thus, signal peptide hydrophobicity appears to be more critical for the efficiency of early stages in protein export in B. subtilis than in E. coli.


Denoising time-resolved microscopy image sequences with singular value thresholding.
Time-resolved imaging in microscopy is important for the direct observation of a range of dynamic processes in both the physical and life sciences. However, the image sequences are often corrupted by noise, either as a result of high frame rates or a need to limit the radiation dose received by the sample. Here we exploit both spatial and temporal correlations using low-rank matrix recovery methods to denoise microscopy image sequences. We also make use of an unbiased risk estimator to address the issue of how much thresholding to apply in a robust and automated manner. The performance of the technique is demonstrated using simulated image sequences, as well as experimental scanning transmission electron microscopy data, where surface adatom motion and nanoparticle structural dynamics are recovered at rates of up to 32 frames per second.


Encapsulation of large dye molecules in hierarchically superstructured metal-organic frameworks.
Microporous metal-organic frameworks (MOFs) represent a new family of microporous materials, offering potential applications in gas separation and storage, catalysis, and membranes. The engineering of hierarchical superstructured MOFs, i.e., fabricating mesopores in microporous frameworks during the crystallization stage is expected to serve a myriad of applications for molecular adsorption, drug delivery, and catalysis. However, MOFs with mesopores are rarely studied because of the lack of a simple, effective way to construct mesoscale cavities in the structures. Here, we report the use of a perturbation-assisted nanofusion technique to construct hierarchically superstructured MOFs. In particular, the mesopores in the MOF structure enabled the confinement of large dye species, resulting in fluorescent MOF materials, which can serve as a new type of ratiometric luminescent sensors for typical volatile organic compounds.


Development of new core competencies for Taiwanese Emergency Medical Technicians.
Core competencies are considered the foundation for establishing Emergency Medical Technician (EMT) and paramedic curricula, and for ensuring performance standards in the delivery of prehospital care. This study surveyed EMT instructors and medical directors to identify the most desirable core competencies for all levels of EMTs in Taiwan. A principal components analysis with Varimax rotation was conducted. An online questionnaire was distributed to obtain perspectives of EMT instructors and medical directors on the most desirable core competencies for EMTs. The target population was EMT training-course instructors and medical directors of fire departments in Taiwan. The questionnaire comprised 61 competency items, and multiple-choice and open-ended questions were used to obtain respondents' perspectives of the Taiwanese EMT training and education system. The results identified three factors at EMT-1 and EMT-2 levels and five factors at the EMT-Paramedic level. The factors for EMT-1 and EMT-2 were similar, and those for EMT-Paramedics identified further comprehensive competence perspectives. The key factors that appear to influence the development of the Taiwanese Emergency Medical Services (EMS) education system are the attitude of authorities, the licensure system, and legislation. The findings present new core competencies for the Taiwanese EMT system and provide capacity to redesign curricula and reconsider roles for EMT-1 and EMT-2 technicians. At the EMT-Paramedic level, the findings demonstrate the importance of incorporating competency standards in the current skills-based curriculum. Moreover, the core-competencies gap that exists between Taiwanese EMT-1s, EMT-2s, and EMT-Paramedics and internationally recognized core competencies needs to be addressed. By identifying the key factors that potentially impact the development of the EMS education system, such as the attitude of authorities, the licensure system, and legislation, these findings will inform future curricula design in Taiwan.


Determination of caffeine and identification of undeclared substances in dietary supplements and caffeine dietary exposure assessment.
Caffeine is one of the most consumed stimulants in the world, and is a frequent ingredient of dietary supplements. The aims of this work were to validate a GC-MS method for the quantitation of caffeine and identification of other substances in supplements, mainly weight loss products, and to estimate the caffeine intake by consumers. Sample preparation included extraction with chloroform:water in ultrasonic bath, centrifugation and analysis of the organic layer for caffeine quantitation, and extraction with methanol for identification of other substances. A total of 213 samples of 52 supplement products not registered in Brazil and seized by the Brazilian Federal Police were analyzed. From the 109 samples that declared the amount of caffeine present, 26.6% contained more than 120% of the specified content. Considering the maximum recommended dose stated on the product labels, the consumption of 47.9% of the samples would lead to a daily intake of caffeine above the safe limit of 400 mg. Undeclared drugs, including sibutramine, phenolphthalein, amphepramone and femproporex were found in 28 samples. These results show that consumers of dietary supplements should be aware that these products might contain caffeine at levels that could represent potential health risks, in addition to undeclared pharmaceutical drugs.


ISOLATING MECHANISMS IN SEABIRDS.
In most species of birds, differences in plumage coloration or song structure act as isolating mechanisms. In seabirds, plumages are generally drab, and vocal repertoires are limited so that other phenotypic attributes must act as isolating mechanisms. One classic study of gulls suggests that the contrast between eye color and head color acts as a reproductive isolating mechanism, but this idea has been largely refuted by widespread evidence of hybridization in gulls in the last 20 years. An examination of more than 100 species of seabirds that breed sympatrically with congeners reveals that species with bills and feet similar in color hybridize in all areas where they breed sympatrically. Species that have bills or feet of different colors either do not hybridize or they produce rare hybrids that are unable to obtain mates as adults. This suggests that bill and foot coloration act as the primary isolating mechanisms in all surface-nesting seabirds and some burrow nesters. It may be a general pattern in birds that foot color acts to supplement bill color in reproductive isolation and mate choice.


[Association of the neprilysin and apolipoprotein E gene polymorphisms with Alzheimer's disease in Xinjiang Uygur population].
To assess the association between the neprilysin (NEP) gene and apolipoprotein E (ApoE) gene polymorphisms and sporadic Alzheimer's disease (SAD) in Xinjiang Uygur population. The polymorphisms of the NEP and ApoE gene were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 111 SAD patients and 117 healthy controls. (1) The frequency of the T allele in the NEP gene was significantly higher in the SAD patients than that in the controls (Chi-square= 5.005, P< 0.05); and there was higher risk to develop SAD in the T allele carriers. (2) The frequency of the ApoE 4 epsilon 4 allele was higher in the SAD patients than in the controls (Chi-square= 4.218, P< 0.05); and the ApoE 4 epsilon 4 carriers had significantly increased risk of developing SAD. (3) No significant interaction was found between the NEP and ApoE polymorphisms in SAD patients. The NEP and ApoE gene polymorphisms may be associated with SAD. NEP gene may be an independent genetic risk factor for SAD in Xinjiang Uygur population.


Preoperative evaluation and preparation in pancreatic carcinoma.
The preoperative evaluation in patients with pancreatic carcinoma includes ultrasonography or CT to diagnose and localize the tumour, to rule out metastases and to guide biopsy for cytological and/or histological verification. In patients with jaundice direct cholangiography, either transhepatic (PTC) or endoscopic (ERC), is necessary to give exact anatomical delineation of the tumour. Further, these procedures may be used to establish preoperative biliary drainage or to insert an endoprosthesis for permanent biliary drainage in inoperable cases. In patients without jaundice endoscopic pancreaticography (ERP) may delineate the pathology. Selective arteriography, both of the coeliac and superior mesenteric artery, visualize possible variations in arterial anatomy and tumour invasion. Stricture of one of the main arteries is usually a sign of inoperability. As venous phase portography only in some cases gives precise visualization of both the splenic, superior mesenteric and portal vein, transhepatic portography with selective catheterization of the splenic and superior mesenteric vein should be performed to diagnose strictures or invasion of the portal venous system. Only a few cases with invasion of these veins will be operable. The preoperative preparation in patients with pancreatic carcinoma includes correction of electrolytes, hypoalbuminemia, anemia, and, in patients with jaundice, treatment of K-vitamin deficiency. All patients should have prophylactic anti-thromboembolic treatment. Whether preoperative biliary drainage in jaundiced patients is of any benefit is still controversial, but may be indicated in patients with heavy jaundice and/or septic cholangitis.


Molecular Mechanisms for Altered Glucose Homeostasis in HIV Infection.
A complete understanding of the molecular mechanisms leading to HIV-associated insulin resistance remains elusive. Complex interrelationships between genetic predisposition, disease-related body changes and multidrug therapy all contribute to alterations in glucose homeostasis. These abnormalities can be differentiated between acute and reversible changes directly induced by HAART medications and more chronic and less reversible changes due to the development of lipodystrophy and hyperlipidemia. Implicated pathways include changes in adipokine secretion, insulin signaling, lipid homeostasis and disease-related increases in inflammatory mediators. The insulin responsive facilitative glucose transporter GLUT4 is the first molecule to have been identified as a direct target of HIV protease inhibitors. Efforts to elucidate the mechanisms directly responsible for the evolution of insulin resistance during HIV infection and therapy will be greatly assisted by the further identification and characterization of direct molecular targets amenable to pharmacologic therapy and/or the development of newer antiretroviral agents that do not adversely affect these target proteins.


Adenosine as an endogenous mediator of hypoxia for induction of vascular endothelial growth factor mRNA in U-937 cells.
Adenosine induced by hypoxia exerts various effects via different types of receptors. Recently, hypoxia was shown to be a strong inducer of vascular endothelial growth factor, a secreted endothelial cell specific mitogen. In this report, we studied on effects of adenosine on inducibility of VEGF and possible mediation of hypoxia for its induction in U-937 cells. Hypoxia induced expression of VEGF mRNA with an early peak at 1 hour. 5'-N-ethylcarboxamidoadenosine, an adenosine analog, strongly induced VEGF mRNA, which was inhibited by 3,7-dimethyl-1-propargylxanthine (DMPX), an A2-antagonist. The hypoxic induction was inhibited by adenosine deaminase, 7-(beta-hydroxyethyl)theophylline, a non-selective adenosine receptor antagonist and DMPX. These results suggest that the hypoxic induction of VEGF mRNA is mediated by adenosine via A2-receptor in U-937 cells.


Artificial ribozyme and antisense gene expression in Saccharomyces cerevisiae.
A sensitive, quantitative reporter gene-based experimental system for the in vivo analysis of hammerhead ribozyme and antisense gene function in Saccharomyces cerevisiae is described. The system was constructed to test the activity of ribozyme and antisense genes targeting the chloramphenicol acetyltransferase gene (CAT) in both a cis and trans configuration relative to the target. When both target and ribozyme or antisense genes were transcribed in the same mRNA from an expression vector, CAT expression was reduced by up to 90%. Although the cis-positioned ribozyme molecule cleaved the target RNA in vitro, the steady state RNA levels of these chimeric transcripts were increased several fold relative to control mRNAs. This observation indicates a mechanism of suppression of CAT gene expression other than duplex-dependent degradation of mRNA. When the ribozyme or antisense genes were transcribed in trans from a plasmid-based expression vector, expression of a CAT gene integrated into a chromosome was unaffected. The effect of the cis-located RNA molecules may be dependent on an interaction requiring co-localization of ribozyme or antisense and target mRNAs during or immediately after target gene transcription. The failure of such a co-localization of these RNAs when synthesized in trans may contribute to the lack of efficacy seen in the trans-acting ribozymes or antisense RNAs. These observations are consistent with other studies reporting inefficient trans-acting ribozyme and antisense activity in S. cerevisiae.


Longitudinal Changes in Structural Connectivity in Young People at High Genetic Risk for Bipolar Disorder.
Recent studies of patients with bipolar disorder or at high genetic risk reveal structural dysconnections among key brain networks supporting cognitive and affective processes. Understanding the longitudinal trajectories of these networks across the peak age range of bipolar disorder onset could inform mechanisms of illness onset or resilience. Longitudinal diffusion-weighted MRI and phenotypic data were acquired at baseline and after 2 years in 183 individuals ages 12-30 years in two cohorts: 97 unaffected individuals with a first-degree relative with bipolar disorder (the high-risk group) and 86 individuals with no family history of mental illness (the control group). Whole-brain structural networks were derived using tractography, and longitudinal changes in these networks were studied using network-based statistics and mixed linear models. Both groups showed widespread longitudinal changes, comprising both increases and decreases in structural connectivity, consistent with a shared neurodevelopmental process. On top of these shared changes, high-risk participants showed weakening of connectivity in a network encompassing the left inferior and middle frontal areas, left striatal and thalamic structures, the left fusiform, and right parietal and occipital regions. Connections among these regions strengthened in the control group, whereas they weakened in the high-risk group, shifting toward a cohort with established bipolar disorder. There was marginal evidence for even greater network weakening in those who had their first manic or hypomanic episode before follow-up. Neurodevelopment from adolescence into early adulthood is associated with a substantial reorganization of structural brain networks. Differences in these maturational processes occur in a multisystem network in individuals at high genetic risk of bipolar disorder. This may represent a novel candidate to understand resilience and predict conversion to bipolar disorder.


Geochemical niches of iron-oxidizing acidophiles in acidic coal mine drainage.
A legacy of coal mining in the Appalachians has provided a unique opportunity to study the ecological niches of iron-oxidizing microorganisms. Mine-impacted, anoxic groundwater with high dissolved-metal concentrations emerges at springs and seeps associated with iron oxide mounds and deposits. These deposits are colonized by iron-oxidizing microorganisms that in some cases efficiently remove most of the dissolved iron at low pH, making subsequent treatment of the polluted stream water less expensive. We used full-cycle rRNA methods to describe the composition of sediment communities at two geochemically similar acidic discharges, Upper and Lower Red Eyes in Somerset County, PA, USA. The dominant microorganisms at both discharges were acidophilic Gallionella-like organisms, "Ferrovum" spp., and Acidithiobacillus spp. Archaea and Leptospirillum spp. accounted for less than 2% of cells. The distribution of microorganisms at the two sites could be best explained by a combination of iron(II) concentration and pH. Populations of the Gallionella-like organisms were restricted to locations with pH>3 and iron(II) concentration of >4 mM, while Acidithiobacillus spp. were restricted to pH<3 and iron(II) concentration of <4 mM. Ferrovum spp. were present at low levels in most samples but dominated sediment communities at pH<3 and iron(II) concentration of >4 mM. Our findings offer a predictive framework that could prove useful for describing the distribution of microorganisms in acid mine drainage, based on readily accessible geochemical parameters.


Detergents as probes of reconstituted rat liver cytochrome P-450 function.
A series of 16 ionic, zwitterionic, and nonionic detergents have been used to perturb the catalytic activities of major cytochrome P-450 (P-450) forms from untreated (UT-A), phenobarbital-treated (PB-B) and beta-naphthoflavone-treated (BNF-B) rats in reconstituted systems with NADPH--P-450 reductase Detergent effects on R warfarin hydroxylase activities were correlated with detergent effects on the quaternary structures of P-450 and reductase, and on their 1:1 complexes as determined by gel exclusion chromatography using sodium cholate as a prototype detergent. The detergent concentrations used did not in most cases affect rates of NADPH-dependent reduction of cytochrome c by the reductase. With P-450 BNF-B, ionic and zwitterionic detergents enhanced warfarin hydroxylase activities at low concentrations and produced marked inhibition at higher concentrations, while nonionic detergents only inhibited. With P-450 UT-A, some nonionic and zwitterionic detergents increased rates at low concentrations and inhibited at higher concentrations. P-450 PB-B was inhibited by detergents of all three classes at low and high concentrations. The concentrations of a detergent required to affect 50% inhibition differed for the three P-450s, suggesting, together with the differential susceptibilities to detergent-mediated rate enhancing effects, that the reductase interacts functionally differently with the three P-450s. Chromatographic studies demonstrated that concentrations of sodium cholate which optimally enhanced metabolic rates with P-450 BNF-B facilitated the uptake of the P-450 into the functional reductase/P-450 complex, and higher concentrations of cholate, which completely inhibited activity, produced profound disruptions of the complex. The data have provided insight into the functional interactions required for monooxygenase activity.


Extreme-ultraviolet-induced oxidation of Mo/Si multilayers.
The extreme-ultraviolet (EUV)-induced oxidation of Mo/Si multilayer mirrors was characterized by several methods: EUV reflectivity, x-ray photoelectron spectroscopy, small-angle x-ray reflectometry, atomic force microscopy, and EUV scattering measurements. Based on the results of the different investigation techniques, an oxidation model was developed to explain the degradation of the mirrors under EUV radiation.


Comparative studies on antioxidant activity and polyphenolic content of Lycium barbarum L. and Lycium chinense Mill. leaves.
The purpose of this research was to bring new data regarding the phenolic composition and the antioxidant activity of L. barbarum L. and L. chinense Mill. leaves. The determination of the main polyphenolic compounds was performed using a HPLC-UV-MS method. The dominant compound found for both species was rutin, with its highest amount registered in L. chinense (24141.90±21.3 μ/g plant material) leaves. Among the flavonoidic aglycones, quercetin was found in both samples, being quantified in a higher amount in L. chinense. In the antioxidant assays, both extracts exhibited important antioxidant activities, as witnessed by the three methods, both correlated with their total polyphenolic content.


Modeling DNA structure, elasticity, and deformations at the base-pair level.
We present a generic model for DNA at the base-pair level. We use a variant of the Gay-Berne potential to represent the stacking energy between the neighboring base pairs. The sugar-phosphate backbones are taken into account by semirigid harmonic springs with a nonzero spring length. The competition between these two interactions and the introduction of a simple geometrical constraint lead to a stacked right-handed B-DNA-like conformation. The mapping of the presented model to the Marko-Siggia and the stack-of-plates model enables us to optimize the free model parameters so as to reproduce the experimentally known observables such as persistence lengths, mean and mean-squared base-pair step parameters. For the optimized model parameters, we measured the critical force where the transition from B- to S-DNA occurs to be approximately 140 pN. We observe an overstretched S-DNA conformation with highly inclined bases which partially preserves the stacking of successive base pairs.


The MRI characteristics of non-mass enhancement lesions of the breast: associations with malignancy.
The American College of Radiology updated the terms used for expressing the imaging characteristics of non-mass enhancement (NME) lesions in the fifth edition of the breast imaging-reporting data system (BI-RADS) lexicon. Both the distribution and internal enhancement descriptors were revised for NME lesions. Our aim was to determine the MRI characteristics of NME lesions and to investigate their association with malignancy. The MRI results of 129 NME lesions were retrospectively evaluated. The medical files, biopsy results and follow-up findings of lesions were recorded. Patients who had benign biopsy and those who had stable or regressed lesions during follow-up were classified as benign. All MRI results had been obtained with a 1.5 Tesla Signa HDx MR system (GE Healthcare). Segmental and diffuse distribution along with clustered-ring internal enhancement were significantly associated with malignancy, while linear distribution and homogeneous enhancement pattern were associated with benignancy. Additionally, the plateau type (Type II) curve was significantly more frequent in malignant lesions. There was no association between the presence of cystic structures and the benign/malignant nature of the lesion. However, multivariate logistic regression showed that only segmental distribution and diffusion restriction were associated with malignancy. In the current study, segmental distribution, clustered-ring enhancement, Type II dynamic curve and the presence of diffusion restriction were found to be associated with malignancy. There is a requirement for multicenter studies which include higher numbers of patients in order to better evaluate lesions with rarer characteristics for distribution and enhancement pattern. Our aim in this study was to investigate the MRI characteristics of NME lesions. We have reported the MRI findings of NME lesions and have found that segmental distribution and clustered-ring enhancement patterns are significantly more frequent in malignant lesions.


Genotoxicity Induced by Dental Materials: A Comprehensive Review.
Genotoxicity is the capacity of an agent to produce damage in the DNA molecule. Considering the strong evidence for a relationship between genetic damage and carcinogenesis, evaluation of genotoxicity induced by dental materials is necessary for elucidating the true health risks to patients and professionals. The purpose of this article was to provide a comprehensive review of genotoxicity induced by dental materials. All published data showed some evidence of genotoxicity, especially related to dental bleaching, restorative materials and endodontic compounds. Certainly, such information will be added to that already established for regulatory purposes as a safe way to promote oral healthcare and prevent oral carcinogenesis.


Bilateral maxillary and mandibular fourth molars: a case report and literature review.
Supernumerary teeth are those present in addition to the normal set of teeth. These teeth are found in both the primary and the permanent dentitions, and are most frequently seen in the maxillary anterior and molar regions. Supernumerary molars are divided into two types, depending on their location: distomolars and paramolars. Distomolars usually occur in the form of a fourth molar distal to the third molar, while paramolars are rudimentary supernumerary teeth that might develop buccally or lingually to the molar series. The management of a supernumerary tooth should be part of a comprehensive treatment plan. This paper reports a rare case of a male patient with bilateral maxillary and mandibular fourth molars, and reviews the literature on supernumerary teeth.


Persistent arthralgia, vomiting and hypercalcemia as the initial manifestations of hyperthyroidism: A case report.
A 53-year-old woman presented with persistent edema and pain of the metacarpophalangeal and proximal interphalangeal joints and the wrist, knee and ankle joints, with more recent intermittent nausea and vomiting. Treatment for rheumatoid arthritis and osteoarthritis was ineffective. No clinical manifestations typical of hyperthyroidism were observed. The results of the thyroid function tests were as follows: Thyroid-stimulating hormone, 0.003 µIU/ml; triiodothyronine (T3), 4.44 ng/ml;, thyroxine (T4) >30 µg/dl; free T3, 14.03 pg/ml; and free T4, 8.84 ng/dl. The laboratory tests revealed an elevated serum calcium level (2.96 mmol/l); moderate hypophosphatemia (0.84 mmol/l); significantly reduced serum intact parathyroid hormone (4.8 pg/ml); normal 25-hydroxy vitamin D (52.13 nmol/l) and bone-specific alkaline phosphatase (22.1 ng/ml); and elevated osteocalcin (128.8 ng/ml). X-ray and quantitative ultrasound examinations revealed extensive osteoporosis of the hands, skull, knees and pelvis, with a bone mineral density of 0.254 g/cm2 (T-score, -3.2). Anti-thyroid therapy (methimazole, 30 mg/day; salmon calcitonin, 50 IU/day; and alendronate, 70 mg/week) was initiated. After 2 weeks, the serum calcium and phosphate levels were normalized (2.44 and 1.19 mmol/l, respectively) and calcitonin was discontinued. After 3 months, the patient had no nausea, vomiting or joint pain, and her appetite was normal, with a weight gain of ~10 kg. Euthyroidism was achieved and the serum calcium and phosphate levels were normalized (2.31 and 1.12 mmol/l, respectively) and maintained for 6 months, by which time the osteocalcin level had diminished (80.40 ng/ml). This rare case of arthralgia, hypercalcemia and extensive osteoporosis as the first manifestations of hyperthyroidism suggests that, even without typical symptoms, hyperthyroidism should be considered in the differential diagnosis of patients with persistent arthralgia.


One-year prospective three-center study comparing the outcome of a "soft bone implant" (prototype Mk IV) and the standard Brånemark implant.
Oral implant treatment ad modum Brånemark has been used for decades in the rehabilitation of edentate and partially dentate patients. Posterior jaw regions frequently exhibit bone of poor texture, and it is often difficult to obtain primary stability. Thus, it may prove beneficial to deviate from the original protocol and to use implants with a modified design, for example, with a slightly tapered geometry. The purpose of the investigation was to compare the early behavior of a modified (prototype Mk IV, Brånemark System, Nobel Biocare AB, Gothenburg, Sweden; test) implant with that of the standard Brånemark implant (control) in regions of mainly type 4 bone. Three Swedish centers participated, and a total of 44 patients were treated with oral implants for 39 maxillas and 5 mandibles. The study focused on the most distal right and left implant sites (88 implants), which were randomized to receive either a test or a control implant. Various parameters were recorded, such as registered insertion torque (OsseoCare), Nobel Biocare AB), wobbling during insertion, primary and secondary stability (as measured with resonance frequency), and marginal bone loss. The implants were followed up for 1 year. The test implant more frequently required a higher insertion torque and showed a significantly higher primary stability than the control implant. This difference in stability leveled out over time, and test and control implants exhibited similar secondary stability at abutment operation and at the 1-year visit. Wobbling during insertion was rarely recorded for either of the implant designs. The 1-year cumulative success rate was 93.1% for test implants and 88.4% for control implants. The modified implant design resulted in an increased primary stability, which may be important when placing implants in jaw regions of type 4 bone. However, independent of the achieved primary stability, successful implants tended to approach similar secondary stability in the two designs tested.


[Successful curative resection after chemotherapy for initially unresectable advanced gallbladder cancer with rectal metastasis:a case report].
A 42-year-old male was referred to our hospital with bloody feces and lower back pain. He was diagnosed with unresectable gallbladder cancer with rectal metastasis (T3aN1M1, Stage IVB). The patient was administered gemcitabine plus cisplatin (GC). After nine courses of GC, computed tomography showed regression of the tumor and the patient's tumor marker levels had decreased. Therefore, curative resection was performed. Ten months after the operation, recurrence was observed in the rectal margin and GC was restarted. Because the total dose of cisplatin was 1040mg, we stopped cisplatin and continued to administer only gemcitabine (at the same dose). A follow-up examination 2 years after the operation showed no evidence of recurrence. Conversion therapy might be an effective multidisciplinary treatment for advanced gallbladder cancer that is initially unresectable. Herein, we report the case of a patient with advanced gallbladder cancer and rectal metastasis who was successfully treated by curative resection after chemotherapy;we also review the relevant literature.


Ultraeffective ZnS nanocrystals sorbent for mercury(II) removal based on size-dependent cation exchange.
We report a novel nanocrystals (NCs) sorbent, which shows an extraordinary adsorption capacity to aqueous Hg(2+) based on cation exchange and allows for the utmost removal of mercury from water. The NCs sorbent was synthesized by direct coating ZnS NCs on the surface of the α-Al2O3 nanoparticles. The as-prepared ZnS NCs sorbent can efficiently remove over 99.9% Hg(2+) in 1 min, and lower the Hg(2+) concentration from 297.5 mg/L (ppm) to below 1.0 μg/L (ppb) within 5 min. The saturated adsorption capacity of ZnS NCs for Hg(2+) is about 2000 mg/g, which is close to the theoretic saturated adsorption capacity. The mechanism of Hg(2+) removal by ZnS NCs sorbent, the influences of pH value and other cations on Hg(2+) removal were investigated, respectively. Meanwhile, it is found the size-dependent cation exchange plays a critical role in the removal of Hg(2+) by ZnS NCs. Small size ZnS NCs shows better performance than the big size ZnS NCs in the adsorption capacity and adsorption rate for Hg(2+). Furthermore, the mercury adsorbed by the ZnS NCs sorbent is readily recycled by extraction with aqueous sodium sulfide.


Using a Community-based Participatory Research Approach to Implement a Health Fair for Children.
When devising strategies to combat obesity, strategies focusing on children should be utilized since health-related behaviors track into adulthood. One strategy that begins to address, and brings awareness to, the rising obesity rates and other health disparities in adults is the utilization of community health fairs. Previous literature has described how to conduct an adult health fair using a community-based participatory research (CBPR) approach, but no study has shown how to conduct a health fair for children. This article explains how a CBPR approach was used to develop a health fair focused on obesity prevention for children. A partnership between the community and a local university was formed to assist in the planning and implementation of a health fair. While the data obtained from the health fair served as a needs assessment for future projects, the health fair was also a good first step in developing relationships and trust among the partners.


A rapid purification procedure for pyruvate kinase from the hyphal fungus Aspergillus nidulans.
Pyruvate kinase was purified from the filamentous fungus Aspergillus nidulans with a 45-55% yield. The procedure involved dye-affinity chromatography and fast protein liquid chromatography, resulting in highly active and pure enzyme in milligram quantities within 2 days. The purified enzyme, a tetramer with a subunit molecular weight of 65,000 and an isoelectric point of 4.7, was used to determine the amino acid composition.


Surgical treatment of pancreatic cancer: Currently debated topics on morbidity, mortality, and lymphadenectomy.
This review will examine several aspects of pancreatic surgery. Over the past twenty years, the need for a standardized postoperative complication report after resective pancreatic surgery has led to the definition both of a postoperative complication severity score, a postoperative pancreatic fistula (POPF) severity grading, a fistula risk score (FRS) and a postoperative morbidity index to establish the burden of complications. Unfortunately, three problems have hindered the success of standardization: first, the failure to define a minimum postoperative follow-up period that needs to be reported; second, the lack of a clear definition of POPF-related morbidity and mortality; third, the often-incomplete reporting of postoperative complications. The debate on the extent of lymphadenectomy to associate to pancreaticoduodenectomy started in the late 1980s when, based on retrospective studies, Japanese surgeons reported better survival after extended" than after "standard" lymphadenectomy. Subsequently, eight prospective randomized controlled trials showed that "extended" lymphadenectomy offers no advantage over "standard" lymphadenectomy. Several consensus conference and reviews tried to define the optimal extent of lymphadenectomy to be associated to pancreaticoduodenectomy and distal pancreatectomy (DP). At least nineteen lymph nodes (LN) are required for optimal tumor staging, but eleven LN are considered the minimum to prevent under staging. There is no general agreement about aborting PD in LN16-positive patients; some authors perform PD in fit patients. Based on retrospective studies, a significant increase of R0 resections, a decrease of recurrence rate, a decrease of local recurrence rate and an increase of median or overall disease-free survival were reported after mesopancreas excision.


Chronic diabetic complications in patients with MODY3 diabetes.
MODY3 diabetes, which is caused by a mutation in the hepatocyte nuclear factor-1alpha gene (HNF-1alpha) on chromosome 12, represents a relatively common monogenic form of diabetes in Finland. Age at onset of the disease can vary from 10 to 60 years, but little is known about the natural course of the disease, particularly the development of diabetes-related chronic complications. The availability of genetic markers now allows description of the clinical course of the disease. In order to examine the prevalence of chronic diabetic complications in MODY3, we examined 57 carriers with HNF-1alpha mutations for the presence of micro- and macrovascular complications. Thirty-four percent of the MODY patients had mild and 13% had severe non-proliferative or proliferative retinopathy; this figure did not differ from the figures in insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) patients matched for duration and glycaemic control but not for age. Neither did the prevalence of microalbuminuria differ between MODY3 and IDDM or NIDDM patients (19 vs 24 and 23%). Neuropathy was observed with the same frequency as previously reported in IDDM. Hypertension was less frequent in MODY3 and IDDM than in NIDDM (24.5 and 19 vs 53.7%; p < 0.001). Coronary heart disease was more common in MODY3 than in IDDM (16 vs 4.5%; p < 0.02) but less common than in the older NIDDM patients (33.3%; p < 0.02). In a multiple logistic regression analysis, poor glycaemic control was an independent risk factor for retinopathy (p = 0.03), microalbuminuria (p < 0.04) and neuropathy (p = 0.03). In conclusion, microangiopathic complications are observed with the same frequency in patients with MODY3 diabetes as in IDDM and NIDDM and are strongly related to poor glycaemic control.


Severe intracranial haemorrhage in neonatal alloimmune thrombocytopenia.
Neonatal alloimmune thrombocytopenia is a rare (1/1000-5000 births) life-threatening disorder, caused by fetomaternal incompatibility for a fetal human platelet alloantigen inherited from the father, with production of maternal alloantibodies against fetal platelets, leading to severe thrombocytopenia and potential bleeding. Intracranial haemorrhage is the most feared complication. This report presents the case of a term newborn infant, born from caesarean section after a normal pregnancy, presenting signs of skin bleeding with different ages. Obstetric history included a previous spontaneous abortion after amniocentesis. Severe thrombocytopenia (4×10(9)/l platelets) was found and brain ultrasound showed multiple intracranial haemorrhages. Human platelet antigen (HPA) phenotyping showed maternal negative HPA-1a and paternal positive HPA-1a platelets. Strongly positive anti-HPA-1a and weakly positive anti-human leukocyte antigen class I alloantibodies were found in the mother. Multiple platelet transfusions, intravenous immunoglobulin and corticosteroid were given but favourable response was accomplished only after a compatible platelet transfusion. Brain MRI showed multiple subacute and chronic haemorrhages.


Both WFIKKN1 and WFIKKN2 have high affinity for growth and differentiation factors 8 and 11.
WFIKKN1 and WFIKKN2 are large extracellular multidomain proteins consisting of a WAP, a follistatin, an immunoglobulin, two Kunitz-type protease inhibitor domains, and an NTR domain. Recent experiments have shown that WFIKKN2 protein binds mature GDF8/myostatin and myostatin propeptide and inhibits the biological activity of myostatin (Hill, J. J., Qiu, Y., Hewick, R. M., and Wolfman, N. M. (2003) Mol. Endocrinol. 17, 1144-1154). Here we show that the paralogue of this protein, WFIKKN1, also binds to both myostatin and myostatin propeptide and that both WFIKKN1 and WFIKKN2 bind GDF11, the growth and differentiation factor most closely related to myostatin, with high affinity. Structure-function studies on WFIKKN1 have revealed that the follistatin domain is primarily responsible for the binding of mature growth factor, whereas the NTR domain contributes most significantly to the interaction with myostatin propeptide. Analysis of the evolutionary histories of WFIKKN1/WFIKKN2 and GDF8/GDF11 proteins indicates that the functional association of an ancestral WFIKKN protein with an ancestor of GDF8/11 may date back to cephalochordates/urochordates. Although duplication of the corresponding genes gave rise to WFIKKN1/WFIKKN2 and GDF8/GDF11 in early vertebrates, the data presented here suggest that there is significant functional overlap of the paralogous proteins.


Interleukin-1.
Interleukin-1 (IL-1) is a polypeptide that is produced following infection, injury, or antigenic challenge. Although the macrophage is a primary source of IL-1, epidermal, epithelial, lymphoid, and vascular tissues synthesize IL-1. When IL-1 gains access to the circulation, it induces a broad spectrum of systemic changes in neurologic, metabolic, hematologic, and endocrinologic systems. However, because IL-1 lacks a signal peptide, a considerable amount of the IL-1 that is synthesized may remain associated with the cell, particularly as part of the plasma membrane; moreover, membrane-associated IL-1 is biologically active, especially in its ability to participate in lymphocyte activation and mesenchymal tissue remodeling. There are two gene products coding for IL-1:IL-1-beta and IL-1-alpha. The spectrum of biologic activities of IL-1 are induced by both forms. IL-1 activates lymphocytes and plays an important role in the initiation of the immune response. Receptors for IL-1 recognize both forms, but receptors are scare and their affinities often do not match the potency of the biologic response. The most consistent property of IL-1 is up-regulation of cellular metabolism and increased expression of several genes coding for biologically active molecules. IL-1 is a highly inflammatory molecule and stimulates the production of arachidonic acid metabolites. IL-1 also acts synergistically with other cytokines, particularly tumor necrosis factor. The multitude of biologic responses to IL-1 is an example of the rapid adaptive changes that take place to increase the host's defensive mechanisms.


Antral and fundic D-cell numbers in Helicobacter pylori infection.
Helicobacter pylori infection is associated with an exaggeration of gastrin release following meals or bombesin stimulation attributed to a defect of somatostatin secretion of antral D-cells. Nevertheless, these modifications of gastric physiology do not explain the increase of gastric acid secretion which is only observed in duodenal ulcer patients. The inhibitory effect of somatostatin secretion of fundic D-cells on parietal cells is well known. The aim of our prospective study was to compare the number of fundic D-cells and likewise the number of antral G-cells and D-cells between patients with duodenal ulcer and healthy subjects with and without H. pylori infection. The numbers of D-cells and G-cells were compared between 19 infected patients with duodenal ulcer and 20 healthy subjects, 10 with and 10 without H. pylori infection. Fundic mucosal biopsy specimens were examined using immunohistochemical techniques specific for the presence of somatostatin, antral mucosal biopsy specimens for the presence of gastrin and somatostatin. The number of G-cells was significantly lower (P = 0.0012) in duodenal ulcer patients by comparison with infected subjects and controls. The number of antral D-cells was significantly less (P < 0.0001) in duodenal ulcer patients (mean of 10 random fields = 0.45 +/- 0.04) than in either asymptomatic infected patients (0.65 +/- 0.07) or uninfected controls (0.88 +/- 0.10). The number of fundic D-cells was significantly lower (P < 0.0001) in duodenal ulcer patients (mean = 0.20 +/- 0.03) than in either asymptomatic infected subjects (0.29 +/- 0.05) or controls (0.73 +/- 0.09); here the difference between the two groups of infected subjects was not significant. Multivariate analysis showed that the presence of H. pylori infection of the fundic mucosa did not influence the number of fundic D-cells. Changes in the number of fundic and antral D-cells induced by H. pylori infection did not explain abnormalities of gastric acid secretion usually observed in duodenal ulcer patients; it is suggested that pre-existing abnormalities in the regulation of parietal cell or increase of parietal cell mass are involved.


Taxonomy and distribution of the salamander genus Bolitoglossa Duméril, Bibron & Duméril, 1854 (Amphibia, Caudata, Plethodontidae) in Brazilian Amazonia.
For nearly 40 years Bolitoglossa paraensis has been synonymized with Bolitoglossa altamazonica. This fact has been mainly related to taxonomic ambiguities arising from the morphological similarities between these species and the scarcity of material deposited in collections. However, during the past 30 years new material of Bolitoglossa has been collected in many places throughout the Brazilian Amazonia, including the type locality of B. paraensis, Santa Isabel do Pará. In this article we designate the neotype of B. paraensis based on new material from the type locality, correct misinterpretations about this name. We determined how many species of the genus Bolitoglossa occur in Brazilian Amazonia, described three new species, B. caldwellae sp. nov., B. madeira sp. nov., and B. tapajonica sp. nov., provide a key for identifying Brazilian salamanders. Were analyzed two hundred and seventy eight specimens of Bolitoglossa from the Brazilian states of Acre, Amapá, Amazonas, Pará, and Rondonia; morphological data ofB. altamazonica from Colombia were used for comparison purposes. We confirm the presence of B. altamazonica in extreme western Brazil, and expand the number of species occurring in Brazilian Amazonia to five.


Training and detraining effects of the resistance vs. endurance program on body composition, body size, and physical performance in young men.
The purpose of this study was to investigate the changes in the body composition, body size, muscle strength, and VO2max after 24 weeks of resistance or endurance training and detraining in young men. Thirty healthy college-aged men (20.4 ± 1.36 years) participated in the study. Subjects were assigned to resistance training group (RTG, n = 10), endurance training group (ETG, n = 10), and control group (CG, n = 10). The training program consisted of running or weight-resistance exercise for 3 sessions per week under supervision. VO2max, upper and lower body strength (UBS, LBS), body fat, lean body mass, and body circumference were measured at baseline and after training and detraining. After the training period, the exercise groups demonstrated significant increases in VO2max and LBS (p < 0.05). The UBS, lean mass (LM), and body size of arm and calf were significantly greater in the RTG than in the other 2 groups (p<0.05). In addition, the strength and LM of the RTG were still greater than the baseline values after 24 weeks of detraining (p < 0.05). The conclusions of this study are (a) that endurance or resistance training alone led to training-specific improvements in physical performance, body composition, and body size of the arms for the young men examined and (b) that the RTG maintained the gains in strength and LM for more prolonged periods after training ceased than the endurance training group.


Association of assisted reproductive technology (ART) treatment and parental infertility diagnosis with autism in ART-conceived children.
Are assisted reproductive technology (ART) treatment factors or infertility diagnoses associated with autism among ART-conceived children? Our study suggests that the incidence of autism diagnosis in ART-conceived children during the first 5 years of life was higher when intracytoplasmic sperm injection (ICSI) was used compared with conventional IVF, and lower when parents had unexplained infertility (among singletons) or tubal factor infertility (among multiples) compared with other types of infertility. Some studies found an increased risk of autism among ART-conceived infants compared with spontaneously-conceived infants. However, few studies, and none in the USA, have examined the associations between types of ART procedures and parental infertility diagnoses with autism among ART-conceived children. Population-based retrospective cohort study using linkages between National ART Surveillance System (NASS) data for 1996-2006, California Birth Certificate data for 1997-2006, and California Department of Developmental Services (DDS) Autism Caseload data for 1997-2011. All live born ART-conceived infants born in California in 1997-2006 (n = 42 383) with 5-year observation period were included in the study. We assessed the annual incidence of autism diagnosis documented in DDS, which includes information on the vast majority of persons with autism in California, and the association of autism diagnosis with ART treatment factors and infertility diagnoses. Among ART-conceived singletons born in California between 1997 and 2006, the incidence of autism diagnosis remained at ∼0.8% (P for trend 0.19) and was lower with parental diagnosis of unexplained infertility (adjusted hazard risk ratio [aHRR]; 95% confidence interval: 0.38; 0.15-0.94) and higher when ICSI was used (aHRR 1.65; 1.08-2.52), when compared with cases without these patient and treatment characteristics. Among ART-conceived multiples, the incidence of autism diagnosis between 1997 and 2006 remained at ∼1.2% (P for trend 0.93) and was lower with parental diagnosis of tubal factor infertility (aHRR 0.56; 0.35-0.90) and higher when ICSI was used (aHRR 1.71; 1.10-2.66). Study limitations include imperfect data linkages, lack of data on embryo quality and possible underestimation of autism diagnosis cases. Limitations of the observational study design could affect the analysis by the possibility of residual confounders. Since information about ICSI use was missing for most frozen/thawed embryo transfer cycles, our findings of association of ICSI use and autism diagnosis can only be generalizable to fresh embryo transfer cycles. Our study provides additional evidence of the association between some types of ART procedures with autism diagnosis. Additional research is required to explain the increased risk of autism diagnosis with ICSI use, as well as studies on the effectiveness and safety of ICSI.


Influence of hypothyroidism duration on developmental changes in the hypothalamic factors implicated in growth hormone secretion in the male rat.
The effects of hypothyroidism duration on several factors implicated in GH secretion control were studied in the male rat at different maturity stages, ranging from the peripuberal period to adulthood. Thyroid ablation was performed on 22-day-old Wistar male rats maintained on a low iodine diet (T group). Age-paired controls (C group) were fed with the same diet, supplemented with potassium iodide. Subgroups of T and C animals (aged 32, 42, 52, 82 and 112 days) were studied 10, 20, 30, 60 and 90 days after surgery. After pentobarbital anesthesia, jugular blood was withdrawn before and 5 min after an intravenous TRH stimulus, for GH assay. Hypothalamic and pituitary tissues were obtained in order to measure GH, immunoreactive somatostatin (IR-SRIF) and growth hormone-releasing factor (IR-GRF). Growth rate and serum testosterone confirmed that C rats reached sexual maturity by day 30 of the study. Mean +/- SE serum GH (ng/ml) increased (p less than 0.05) in C animals from day 10 (38.5 +/- 5) to day 30 (67.4 +/- 7.3), with no significant variations thereafter. The same time sequence pattern was observed in pituitary GH concentrations. In T rats, both serum and pituitary GH decreased progressively from day 10 to 90, being significantly lower than in C at all times of the study. No GH response to TRH could be found in C groups. In contrast, GH increased significantly (p less than 0.05) in T animals after TRH at days 20 and 30.(ABSTRACT TRUNCATED AT 250 WORDS)


The occurrence and fate of chemicals of emerging concern in coastal urban rivers receiving discharge of treated municipal wastewater effluent.
To inform future monitoring and assessment of chemicals of emerging concern (CECs) in coastal urban watersheds, the occurrence and fate of more than 60 pharmaceuticals and personal care products (PPCPs), commercial/household chemicals, current-use pesticides, and hormones were characterized in 2 effluent-dominated rivers in southern California (USA). Water samples were collected during 2 low-flow events at locations above and below the discharge points of water reclamation plants (WRPs) and analyzed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. Approximately 50% of targeted CECs were detectable at stations downstream from WRPs, compared with <31% and <10% at the reference stations above the WRPs. Concentrations of chlorinated phosphate flame retardants were highest among the CECs tested, with mean total aggregate concentrations of tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCPP), and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) of 3400 ng/L and 2400 ng/L for the 2 rivers. Maximum in-stream concentrations of pyrethroids (bifenthrin and permethrin), diclofenac, and galaxolide exceeded risk-based thresholds established for monitoring of CECs in effluent-dominated receiving waters. In contrast, maximum concentrations of PPCPs commonly detected in treated wastewater (e.g., acetaminophen, N,N,diethyl-meta-toluamide [DEET], and gemfibrozil) were less than 10% of established thresholds. Attenuation of target CECs was not observed downstream of WRP discharge until dilution by seawater occurred in the tidal zone, partly because of the short hydraulic residence times in these highly channelized systems (<3 d). In addition to confirming CECs for future in-stream monitoring, these results suggest that conservative mass transport is an important boundary condition for assessment of the input, fate, and effects of CECs in estuaries at the bottom of these watersheds.


Can experience modulate handler responses to boxes designed to decrease musculoskeletal load?
Biomechanical load during the handling of commercial (cardboard box with and without cut out) and non-commercial boxes (cardboard box with a retreat on the bottom edges), on experienced compared to inexperienced subjects was evaluated. Thirty-seven inexperienced and 21 experienced workers handled all boxes at shoulder and ground levels. Biomechanical load on upper limb was investigated through posture and electromyography (EMG) recordings. Comfort and effort were assessed immediately after each handling. In general, experienced workers had low range of motion. On the other hand, EMG was similar between both groups, except when non-commercial boxes were handled in non-favourable heights. Comfort was higher when a non-commercial box was handled versus a commercial one, regardless of the group. Both groups had a lower biomechanical load when handling the non-commercial boxes compared to the commercial ones. However, experienced workers did not have the same advantage as inexperienced subjects when handling those new boxes. Practitioner Summary: Box designs favouring intuitive hand coupling and more efficient postures have potential to reduce the risk of upper-limb musculoskeletal disorders in inexperienced subjects. However, ergonomist has to deal with workers on different levels of experience. Results of this study can support the development of effective recommendations for the working context.


WP-1034, a novel JAK-STAT inhibitor, with proapoptotic and antileukemic activity in acute myeloid leukemia (AML).
Cytokine stimulation induces proliferation and growth of acute myeloid leukemia (AML) blasts and high levels of cytokines have been associated with poor prognosis in AML. The Jak-Stat pathway constitutes a major mediator of cytokine activity. We investigated whether WP-1034, a novel Jak-Stat inhibitor, is active against AML blasts. OCIM2 and fresh AML cells were incubated with 1 to 6 microM WP-1034 to determine its effect on proliferation. WP-1034 effectively inhibited proliferation of OCIM2 cells and fresh AML samples. We then analyzed the expressions of Stat 1, 3, and 5, as well as Phospho-Stat 1, 3, and 5 by Western immunoblotting after incubation of OCIM2 cells without and with 1 to 10 microM WP-1034 for 2 hours, and at 5 microM from 20 minutes up to 4 hours and found that WP-1034 blocked Stat 3 and 5 activation. Analysis of cell cycle status by PI staining and flow cytometry showed that WP-1034 caused cell cycle arrest of OCIM2 cells in sub-Go phase. We then evaluated the induction of apoptosis of OCIM2 cells following incubation with WP-1034 at 3 to 6 microM by annexin V-CY5 assay and analyzed caspase 3 and PARP cleavage using Western immunoblotting. We found that WP-1034 induced apoptosis of OCIM2 cells and that induction of apoptosis involved cleavage of caspase 3 and the DNA repair enzyme poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP). Taken together, our data suggest that WP-1034 is a potent inhibitor of AML cell proliferation by inhibition of Stat 3 and 5 and induction of caspase-dependent apoptosis.


beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds.
Fibroproliferative processes are a group of disorders in which there is excessive proliferation of spindle (mesenchymal fibroblast-like) cells. They range from hypertrophic scars to neoplasms such as aggressive fibromatosis. Cells from these disorders share cytologic similarity with fibroblasts present during the proliferative phase of wound healing, suggesting that they represent a prolonged wounding response. A critical role for beta-catenin in mesenchymal cells in fibroproliferative processes is suggested by its high rate of somatic mutation in aggressive fibromatosis. Using a Tcf-reporter mouse we found that beta-catenin protein level and Tcf-transcriptional activity are elevated in fibroblasts during the proliferative phase of healing. We generated a transgenic mouse in which stabilized beta-catenin is expressed in mesenchymal cells under control of a tetracycline-regulated promoter. Fibroblasts from the transgenic mice exhibited increased proliferation, motility, and invasiveness when expressing stabilized beta-catenin and induced tumors after induction of the transgene when grafted into nude mice. Mice developed aggressive fibromatoses and hyperplastic gastrointestinal polyps after 3 months of transgene induction and healed with hyperplastic cutaneous wounds compared with control mice, which demonstrates an important function for beta-catenin in mesenchymal cells and shows a central role for beta-catenin in wound healing and fibroproliferative disorders.


Effect of miR-200c on migration and proliferation of breast cancer MDA-MB-231 cells and BT-549 cells and the possible mechanism.
The article "Effect of miR-200c on migration and proliferation of breast cancer MDA-MB-231 cells and BT-549 cells and the possible mechanism, by Y. Lei, Y. Ma, Y. Liu, X.-F. Wang, published in Eur Rev Med Pharmacol Sci 2020; 24(2):735-739. DOI: 10.26355/eurrev_202001_20053. PMID: 32016976" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause.


Tapping the promise of genomics in species with complex, nonmodel genomes.
Genomics is enabling a renaissance in all disciplines of plant biology. However, many plant genomes are complex and remain recalcitrant to current genomic technologies. The complexities of these nonmodel plant genomes are attributable to gene and genome duplication, heterozygosity, ploidy, and/or repetitive sequences. Methods are available to simplify the genome and reduce these barriers, including inbreeding and genome reduction, making these species amenable to current sequencing and assembly methods. Some, but not all, of the complexities in nonmodel genomes can be bypassed by sequencing the transcriptome rather than the genome. Additionally, comparative genomics approaches, which leverage phylogenetic relatedness, can aid in the interpretation of complex genomes. Although there are limitations in accessing complex nonmodel plant genomes using current sequencing technologies, genome manipulation and resourceful analyses can allow access to even the most recalcitrant plant genomes.


Lignin Hydrogenolysis: Phenolic Monomers from Lignin and Associated Phenolates across Plant Clades.
The chemical complexity of lignin remains a major challenge for lignin valorization into commodity and fine chemicals. A knowledge of the lignin features that favor its valorization and which plants produce such lignins can be used in plant selection or to engineer them to produce lignins that are more ideally suited for conversion. Sixteen biomass samples were compositionally surveyed by NMR and analytical degradative methods, and the yields of phenolic monomers following hydrogenolytic depolymerization were assessed to elucidate the key determinants controlling the depolymerization. Hardwoods, including those incorporating monolignol p-hydroxybenzoates into their syringyl/guaiacyl copolymeric lignins, produced high monomer yields by hydrogenolysis, whereas grasses incorporating monolignol p-coumarates and ferulates gave lower yields, on a lignin basis. Softwoods, with their more condensed guaiacyl lignins, gave the lowest yields. Lignins with a high syringyl unit content released elevated monomer levels, with a high-syringyl polar transgenic being particularly striking. Herein, we distinguish phenolic monomers resulting from the core lignin vs those from pendent phenolate esters associated with the biomass cell wall, acylating either polysaccharides or lignins. The basis for these observations is rationalized as a means to select or engineer biomass for optimal conversion to worthy phenolic monomers.


Immunohistochemical localization of cyclic guanosine monophosphate (cGMP) on mouse fetal chromosomes.
In previous immunohistochemistry studies, cyclic guanosine monophosphate (cGMP) has been found in polytene chromosomes of D. melanogaster, cGMP has not been found in mammalian metaphase chromosomes, but this could be due to loss of cGMP during staining. Thus the effect of different fixation techniques on the immunohistochemically detectable cGMP associated with metaphase chromosomes from mouse fetal tissue was examined. In chromosomes from cells fixed in 2% formalin, or unfixed cells dropped on slides preheated to 60 degrees C, there was diffuse cGMP staining. When cells were fixed in methanol:glacial acetic acid, 3:1, no chromosomal cGMP immunofluorescence was observed, whereas chromosomes from cells fixed in methanol:glacial acetic acid, 6:1, had different patterns of cGMP immunofluorescence depending on the temperature of the slides onto which the fixed cells were dropped. On slides prechilled to 4 degrees C, cGMP immunofluorescence outlined the chromosomes; on room temperature slides, faint chromosomal cGMP staining was observed, and on slides preheated to 68 degrees C or room temperature slides blown dry with hot air, the chromosomes had more intense diffuse cGMP immunofluorescence or distinct symmetrical bands of cGMP immunofluorescence. We have demonstrated the presence of cGMP in mammalian metaphase chromosomes. The different patterns of cGMP immunofluorescence observed may reflect variable preservation of chromosomal proteins that have binding sites for cGMP.


How Do Video Games Elicit Guilt in Players? Linking Character Morality to Guilt Through a Mediation Analysis.
Research has consistently found that committing immoral actions in video games is capable of eliciting feelings of guilt in players. This study aimed to investigate the mediating role of theoretically-relevant psychological mechanisms: Perceived morality of the player-controlled character and self-attribution of virtual behavior. Based in psychological and communication theory, we derived a model that links these variables to character portrayal and guilt. A between-subjects experiment manipulated the portrayal of the player-controlled character (immoral vs. moral) and measured the mediating variables and self-reported guilt. The hypothesized model was tested using a path model. Data were generally consistent with hypotheses. Controlling an immoral character reduced perceived character morality. Perceived character morality positively predicted self-attribution of character behavior and negatively predicted guilt. Self-attribution positively predicted guilt but self-attribution and perceived character morality did not interact. Our findings suggest novel directions for continued research into how game features elicit emotional responses in players.


Health Information From Web Search Engines and Virtual Assistants About Pre-Exposure Prophylaxis for HIV Prevention in Adolescents and Young Adults: Content Analysis.
Adolescents and young adults are disproportionately affected by HIV, suggesting that HIV prevention methods such as pre-exposure prophylaxis (PrEP) should focus on this group as a priority. As digital natives, youth likely turn to internet resources regarding health topics they may not feel comfortable discussing with their medical providers. To optimize informed decision-making by adolescents and young adults most impacted by HIV, the information from internet searches should be educational, accurate, and readable. The aims of this study were to compare the accuracy of web-based PrEP information found using web search engines and virtual assistants, and to assess the readability of the resulting information. Adolescent HIV prevention clinical experts developed a list of 23 prevention-related questions that were posed to search engines (Ask.com, Bing, Google, and Yahoo) and virtual assistants (Amazon Alexa, Microsoft Cortana, Google Assistant, and Apple Siri). The first three results from search engines and virtual assistant web references, as well as virtual assistant verbal responses, were recorded and coded using a six-tier scale to assess the quality of information produced. The results were also entered in a web-based tool determining readability using the Flesch-Kincaid Grade Level scale. Google web search engine and Google Assistant more frequently produced PrEP information of higher quality than the other search engines and virtual assistants with scores ranging from 3.4 to 3.7 and 2.8 to 3.3, respectively. Additionally, the resulting information generally was presented in language at a seventh and 10th grade reading level according to the Flesch-Kincaid Grade Level scale. Adolescents and young adults are large consumers of technology and may experience discomfort discussing their sexual health with providers. It is important that efforts are made to ensure the information they receive about HIV prevention methods, and PrEP in particular, is comprehensive, comprehensible, and widely available.


[Clinical significance of matrix metalloproteinase-9 and tissue factors secreted by cultured monocyte-derived macrophage of patients with coronary heart disease in vitro and the intervenient effect of puerarin on them].
To investigate the clinical significance of matrix metalloproteinase-9 (MMP-9) and tissue factor (TF) secreted by cultured monocyte-derived macrophages (HMDM) from patients with coronary heart disease (CHD) in vitro, and to evaluate the intervenient effect of puerarin (Pur) on them. A total of 40 patients were enrolled, including 12 patients with acute myocardial infarction (AMI), 16 patients with unstable angina pectoris (UAP), 12 patients with stable angina pectoris (SAP). Besides, 8 healthy subjects with normal coronary arteriograph were set as controls. Monocytes acquired from their peripheral blood were incubated for 48 h and induced to differentiate into macrophages by phorbolester 12-myristate 13-acetate (PMA), the contents of MMP-9 and TF in supernatant were assayed, and the relationship of them with patients' age, risk factors of CHD and coronary artery lesion scores were analyzed. HMDMs randomly from selected 12 patients with acute coronary syndrome (ACS) were arranged for observing the intervenient effects of different concentrations of Pur on the levels and activity of MMP-9 and TF. The levels of MMP-9 and TF in UAP and AMI patients were significantly higher than those in SAP patients and healthy subjects (P < 0.01), but no statistical correlation was found between levels of MMP-9 and TF with different CHD risk factors, as well as patients' age and coronary artery lesion scores. The levels and activity of MMP-9 and TF in the 12 ACS patients were significantly decreased in a dose-dependent manner after Pur intervention when compared with the controt group. The levels of MMP-9 and TF secreted in vitro by HMDM from CHD patients could be taken as indexes for evaluating patient's condition of ACS. Pur can inhibit the expression and the activity of MMP-9 and TF secreted by HMDM, stabilize the plaque and improve the vulnerability of blood to certain extent.


Microwave-induced synthesis of carboxymethyl hemicelluloses and their rheological properties.
In this article, a facile, rapid, and efficient method was developed for the preparation of carboxymethyl hemicelluloses using microwave-induced organic reaction enhancement chemistry. The influences of the factors including reaction time, temperature, and the amount of sodium monochloroacetate and sodium hydroxide on the degree of substitution (DS) of the products were investigated. The rheological properties and the chemical structure of the resulting polymers were also studied. It was found that microwave irradiation could significantly promote the chemical reaction efficiency and accelerate the carboxymethylation of hemicelluloses with sodium monochloroacetate. Therefore, carboxymethyl hemicelluloses with higher DS of 1.02 could be obtained in much shorter time scales as compared to the conventional heating method. Results from rheological analysis indicated that carboxymethyl hemicellulose solutions exhibited shear-thinning behavior in the range of shear rates tested and showed lower viscosity and modulus in comparison with those of the native hemicelluloses due to lower molecular weight and the role of carboxymethyl groups in reducing the entanglements between hemicelluloses chains.


[The remarkable debate during the beginning of the nineteenth century concerning the aetiology of scabies].
The scabies mite (acarus or sarcoptes scabiei) was known already to Aristoteles, to the Arabic medicine during the early and to European physicians as well as laymen during the later Middle Ages, depicted in 1687 by Bonomo in Italy and by Schwiebe in Germany during the beginning of the eighteenth century. Later in the middle of the century three pupils to Linnaeus in their doctor's theses stated that the scabies mite (Acarus humanus subcutaneus) was the cause of scabies. The best pictures of the scabies-mite as well as of the flour- and cheese-mite was given by the Swedish entomologist Charles de Geer in 1778. In spite of all these facts the real aetiology of scabies seemed to be unknown in France and in most parts of Europe. This was probably due to the fact that no one had learned the rather simple method to extract the mite from the skin with a needle and thereby verify its existence. In the beginning of the twentieth century scabies was a real problem for the health authorities. In Paris l'Académie de Médecine even offered a reward to the person who could solve the enigma of the itch. Jean Chrysanthe Galés was the pharmacist at l'Hôpital St. Louis, the famous skin hospital in Paris, where at this time about 65 percent of the beds were occupied by patients suffering from scabies. Galés also studied medicine and wanted to write a doctor's thesis. As the theme of a dissertation he was given the cause of the itch. In 1812 he published his thesis ("Essai sur la Gale") including a plate with sketches of mites that he claimed to have extracted from vesicules on the skin of his scabies patients. His findings could not be verified by other investigators. Galés however refused to take part in any control experiments and left the hospital. The debate concerning the supposed cause of the itch continued for two decades both inside and outside the hospital. F.C. Raspail, a famous natural scientist, was interested. After having studied the literature and especially the drawings by de Geer he was convinced that the mites depicted by Galés were similar to de Geers' flour-and cheese mite and that they had no resemblence to his picture of scabies-mite. In a control experiment Raspail could show how Galés had cheated by contaminating his slide with cheese-mites. However, a Corsican student at l'Hôpital St. Louis named S.F. Renucci knew the answer to the riddle. He had long ago been taught by peasant women of his home island how to extract the mite and he could now show the method to the doctors at l'Hôpital St. Louis. this was on August 13 in 1834, which usually in the literature is looked upon as the day when the discovery of the aethiology of scabies was made. Maybe we have a different view in Sweden.


A model-driven approach for the german health telematics architectural framework and the related security infrastructure.
Shared care concepts such as managed care and continuity of care are based on extended communication and co-operation either between different health professionals, or between them and the patient. Health information systems and their components, which are very different in their structure, their behaviour, the respective data, and their semantics as well as regarding implementation details used in different environments for different purposes, have to provide intelligent interoperability. Therefore, flexibility, portability, and future-orientation must be guaranteed using the newest development of model driven architecture. The ongoing work for the German health telematics platform based on an architectural framework and a security infrastructure is described in some detail. This concept of future-proof health information networks with virtual Electronic Health Records as core application starts with multifunctional Electronic Health Cards. It fits into developments currently performed by many other developed countries in Europe and beyond.


High-intensity focused ultrasound-triggered nanoscale bubble-generating liposomes for efficient and safe tumor ablation under photoacoustic imaging monitoring.
High-intensity focused ultrasound (HIFU) is widely applied to tumors in clinical practice due to its minimally invasive approach. However, several issues lower therapeutic efficiency in some cases. Many synergists such as microbubbles and perfluorocarbon nanoparticles have recently been used to improve HIFU treatment efficiency, but none were determined to be effective and safe in vivo. In this study, nanoscale bubble-generating liposomes (liposomes containing ammonium bicarbonate [Lip-ABC]) were prepared by film hydration followed by sequential extrusion. Their stable nanoscale particle diameter was confirmed, and their bubble-generating capacity after HIFU triggering was demonstrated with ultrasound imaging. Lip-ABC had good stability in vivo and accumulated in the tumor interstitial space based on the enhanced permeability and retention effect evaluated by photoacoustic imaging. When used to synergize HIFU ablation to bovine liver in vitro and implanted breast tumors of BALB/c nude mice, Lip-ABC outperformed the control. Importantly, all mice survived HIFU treatment, suggesting that Lip-ABC is a safe HIFU synergist.


Capillary electrophoretic study of amine/carboxylic acid-functionalized carbon nanodots.
Capillary zone electrophoresis (CZE) coupled with UV absorption and laser-induced fluorescence detections has been applied to study the complexity of carbon nanodots (C-dots) products synthesized with microwave-assisted pyrolysis of citric acid (CA) and 1,2-ethylenediamine (EDA). The effects of pH and concentration of run buffer on the CZE separation of C-dots are studied in detail. The optimal acetate run buffer (30mM, pH 3.6) is subsequently employed to investigate the effect of reaction time and mole ratio of amine (NH2) to carboxylic acid (COOH) moieties of the precursors on the C-dots species present in C-dots products. Our results confirm that the synthesis of C-dots could be improved by lengthening the microwave irradiation time and optimizing the initial mole ratio of NH2/COOH in the precursors. Negatively charged C-dots are obtained only when the amount of CA exceeds that of EDA, i.e., the mole ratio of NH2/COOH is 0.25-0.80. By contrast, when the quantity (mole) of NH2 in EDA is equal to or larger than that of COOH in CA, only positively charged and neutral C-dots species are formed, inferring that the C-dots species are predominantly covered by the surface-attached ammonium and amido moieties. This work highlights the merit of CZE to identify the composition of an as-prepared C-dots product which is pretty much dependent on the mole ratio of NH2/COOH. It is anticipated that our CZE methodology will open a new avenue in optimizing the synthetic conditions for producing specific C-dots of desired composition.


Congenital syphilis: A contemporary update on an ancient disease.
Congenital syphilis (CS) rates reached a 20-year high in the United States in 2018. Unlike previous years, most babies diagnosed with CS were born to mothers who received prenatal care, indicative of the need for better provider education and guideline adherence. Current rates suggest that screening for syphilis should be performed at the first prenatal care visit and twice during the third trimester. There are two diagnostic algorithms available for use in the United States (traditional and reverse) and providers must understand how to perform each algorithm. Treatment should be administered according to stage of syphilis per Centers for Disease Control recommendations with best neonatal outcomes seen when treatment is initiated >30 days before delivery. Benzathine Penicillin G remains the only recommended treatment of syphilis during pregnancy. In viable pregnancies, a pretreatment ultrasound is recommended to identify sonographic evidence of fetal infection and treatment should be initiated with continuous fetal monitoring to evaluate for the Jarisch-Herxheimer reaction which can cause preterm labor and fetal distress. After adequate syphilotherapy, a fourfold decline in maternal nontreponemal titers may not be observed by delivery and does not correlate with rates of CS.


[Trends in the incidence of tuberculosis in the area of Seville-South (Spain) during the 1990s].
To describe the incidence of tuberculosis (TB) in the hospital area of Seville-South between 1990 and 1999. Study of the incidence of TB in the area's population between 1990 and 1999 by way of periodic survey of informants who were likely to see cases. The annual incidence of TB rose from 1990 (26.64/105) to its peak in 1992 (38.3/105), stabilized between 1992 and 1995, and later fell to 15.7/105 in 1999. Bacillary cases followed a similar pattern, with a peak of 13.76/105 in 1992 and a low of 6.06/105 in 1998. The annual incidence of TB-AIDS rose between 1990 (2.63/105) and 1995 (9.08/105), and then fell to 4.13/105 by 1999. The highest incidences were in the 25-to-34-year-old range in the periods from 1990 to 1993 (50.74/105) and 1994 to 1996 (61.49/105), whereas the incidence decreased among 55-to-64-year-olds (28.55/105) from 1997 to 1999. The age distribution was affected by rates in the TB-AIDS group, which contributed 48%, 50% and 55% in each period, respectively, for individuals in the 25-to-34-year-old range. The annual incidence of TB was 41,1% lower in 1999 than in 1990, as a result of the marked decrease beginning in the middle of the decade. The impact of TB-AIDS patients on the evolution of annual incidence and on age distribution was considerable throughout the decade.


Enhanced induction of cell cycle arrest and apoptosis via the mitochondrial membrane potential disruption in human U87 malignant glioma cells by aloe emodin.
Aloe emodin, one of the active compounds found in Aloe vera leaves, plays an important role in the regulation of cell growth and death. It has been reported to promote the anti-cancer effects in various cancer cells by inducing apoptosis. However, the mechanism of inducing apoptosis by this agent is poorly understood in glioma cells. This research is to investigate the apoptosis and cell cycle arrest inducing by aloe emodin on U87 human malignant glioma cells. Aloe emodin showed a time- and dose-dependent inhibition of U87 cells proliferation and decreased the percentage of viable U87 cells via the induction of apoptosis. Characteristic morphological changes, such as the formation of apoptotic bodies, were observed with confocal microscope by Annexin V-FITC/PI staining, supporting our viability study and flow cytometry analysis results. Our data also demonstrated that aloe emodin arrested the cell cycle in the S phase and promoted the loss of mitochondrial membrane potential in U87 cells that indicated the early event of the mitochondria-induced apoptotic pathway.


Note: Simultaneous measurement of surface plasmon resonance and surface-enhanced Raman scattering.
A surface plasmon resonance (SPR)-surface enhanced Raman scattering (SERS) microspectrometer was designed to obtain the incident angle dependence of SERS signals excited by the evanescent field. By simultaneous measurement of the SERS and SPR spectra of analytes, the highest SERS signal intensities were found to appear at the vicinity of the resonance angle. The enhancement factor was about 2.0x10(6). The simulated angle of the maximal SERS intensity based on Fresnel equation was found to be in good agreement with the experimental results. The SERS and SPR spectra captured simultaneously not only directly confirm the correlation between the SERS and SPR but also present a potential technique for obtaining the structure information about the analytes in molecule level with recording their SPR curves.


Cryo-EM Structure of the Fork Protection Complex Bound to CMG at a Replication Fork.
The eukaryotic replisome, organized around the Cdc45-MCM-GINS (CMG) helicase, orchestrates chromosome replication. Multiple factors associate directly with CMG, including Ctf4 and the heterotrimeric fork protection complex (Csm3/Tof1 and Mrc1), which has important roles including aiding normal replication rates and stabilizing stalled forks. How these proteins interface with CMG to execute these functions is poorly understood. Here we present 3 to 3.5 Å resolution electron cryomicroscopy (cryo-EM) structures comprising CMG, Ctf4, and the fork protection complex at a replication fork. The structures provide high-resolution views of CMG-DNA interactions, revealing a mechanism for strand separation, and show Csm3/Tof1 "grip" duplex DNA ahead of CMG via a network of interactions important for efficient replication fork pausing. Although Mrc1 was not resolved in our structures, we determine its topology in the replisome by cross-linking mass spectrometry. Collectively, our work reveals how four highly conserved replisome components collaborate with CMG to facilitate replisome progression and maintain genome stability.


Utilising the Delphi Process to Develop a Proficiency-based Progression Train-the-trainer Course for Robotic Surgery Training.
As the role of robot-assisted surgery continues to expand, development of standardised and validated training programmes is becoming increasingly important. To provide guidance on an optimised "train-the-trainer" (TTT) structured educational programme for surgical trainers, in which delegates learn a standardised approach to training candidates in skill acquisition. We aim to describe a TTT course for robotic surgery based on the current published literature and to define the key elements within a TTT course by seeking consensus from an expert committee formed of key opinion leaders in training. The project was carried out in phases: a systematic review of the current evidence was conducted, a face-to-face meeting was held in Philadelphia, and then an initial survey was created based on the current literature and expert opinion and sent to the committee. Thirty-two experts in training, including clinicians, academics, and industry, contributed to the Delphi process. The Delphi process underwent three rounds of survey in total. Additions to the second- and third-round surveys were formulated based on the answers and comments from the previous rounds. Consensus opinion was defined as ≥80% agreement. There was 100% consensus that there was a need for a standardized TTT course in robotic surgery. A consensus was reached in multiple areas, including the following: (1) definitions and terminologies, (2) qualifications to attend, (3) course objectives, (4) precourse considerations, (5) requirement of e-learning, (6) theory and course content, and (7) measurement of outcomes and performance level verification. The resulting formulated curriculum showed good internal consistency among experts, with a Cronbach alpha of 0.90. Using the Delphi methodology, we achieved an international consensus among experts to develop and reach content validation for a standardised TTT curriculum for robotic surgery training. This defined content lays the foundation for developing a proficiency-based progression model for trainers in robotic surgery. This TTT curriculum will require further validation. As the role of robot-assisted surgery continues to expand, development of standardised and validated training programmes is becoming increasingly important. There is currently a lack of high-level evidence on how best to train trainers in robot-assisted surgery. We report a consensus view on a standardised "train-the trainer" curriculum focused on robotic surgery. It was formulated by training experts from the USA and Europe, combining current evidence for training with experts' knowledge of surgical training.


Effects of comorbid alcohol use disorder on bipolar disorder: Focusing on neurocognitive function and inflammatory markers.
Alcohol use disorder (AUD) is a highly prevalent comorbid disorder in patients with bipolar disorder (BD). Both BD and AUD were found to be associated with inflammation and cognitive deficits, but few study has been done on BD comorbid with AUD (BD+AUD). We aimed to investigate the impacts of comorbid AUD and BD on cognitive function, inflammatory and neurotrophic markers. We recruited 641 BD patients, 150 patients with BD+AUD, and 185 healthy controls (HC). Neuropsychological tests [Wisconsin card sorting test (WCST), continuous performance test (CPT), and Wechsler memory scale - third edition (WMS-III)] and cytokine plasma levels [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-β1 (TGF-β1), and brain-derived neurotrophic factor (BDNF)] were assessed. BD+AUD patients had worse cognitive performance than those without AUD. There was a significant difference in the plasma levels of TNF-α, IL-8, and BDNF (P < 0.001, <0.001, and 0.01, respectively) between the patients and the HC groups. Post hoc analysis showed that BD+AUD patients had higher levels of TNF-α and IL-8 than BD-only patients (P < 0.001). Additionally, plasma IL-8 levels were negatively associated with number of completed categories in WCST (P = 0.02), and TNF-α levels were negatively associated with visual immediate index in WMS-III (P = 0.05). Our results suggest that comorbid AUD and BD might worsen cognitive impairments and inflammatory processes. Further longitudinal studies on BD+AUD may be needed.


Experimental measurement of proton, Cd, Pb, Sr, and Zn adsorption onto the fungal species Saccharomyces cerevisiae.
Proton, Cd, Pb, Sr, and Zn adsorption onto the fungal species Saccharomyces cerevisiae were measured in bulk adsorption experiments as a function of time, pH, surface: metal ratio, and ionic strength, and we measured the electrophoretic mobility of the cells as a function of pH. We modeled the acid/base properties of the fungal cell wall by invoking a nonelectrostatic surface complexation model with four discrete surface organic acid functional group types, with average pKa values (with 1 sigma uncertainties) of 3.4 +/- 0.4, 5.0 +/- 0.2, 6.8 +/- 0.4, and 8.9 +/- 0.6. The affinity of the fungal cells for the metal ions follows the following trend: Pb > Zn > Cd > Sr. We used the metal adsorption data to determine site-specific stability constants for the important metal fungal surface complexes. Our results suggest that S. cerevisiae may represent a novel biosorbent for the removal of heavy metal cations from aqueous waste streams.


Early and late outcomes after primary percutaneous coronary intervention by radial or femoral approach in patients presenting in acute ST-elevation myocardial infarction and cardiogenic shock.
Although radial approach is increasingly used in percutaneous coronary interventions (PCIs) including in acute myocardial infarction (MI), patients with cardiogenic shock have been excluded from comparisons with femoral approach. The aim of our study was to compare clinical outcomes in patients undergoing primary PCI with cardiogenic shock by radial and femoral approach. From 2,663 patients presenting with ST-elevation MI in 2 large volume radial centers, we identified 197 patients (7.4%) with signs of cardiogenic shock immediately before undergoing primary PCI. Radial approach was used in 55% of cases when at least 1 radial artery was weakly palpable, either spontaneously or after intravenous noradrenaline bolus. Patients in the radial group were older (69 ± 12 vs 64 ± 12 years, P = .010), had less diabetes (13% vs 26%, P = .028), and required less often intubation prior PCI (42% vs 66%, P = .0006) or intraaortic balloon pump (36% vs 55%, P = .0096). Mortality at 1 year was 44% in the radial group and 64% in the femoral group (P = .0044). Independent predictors of late mortality included radial approach (hazard ratio [HR] 0.65, 95% CI 0.42-0.98, P = .041), the use of glycoprotein IIb-IIIa receptor inhibitors (HR 0.63, 95% CI 0.40-0.96, P = .032), baseline creatinine ≥110 μmol/L (HR 3.34, 95% CI 2.20-5.12, P < .0001), initial glycemia >200 mg/dL (HR 2.02, 95% CI 1.34-3.11, P = .0008), and age >65 years (HR 1.80, 95% CI 1.18-2.79, P = .006). Radial approach was safe and feasible in more than half of the patients with ST-elevation MI and cardiogenic shock treated by primary PCI. After adjustment for baseline and procedural characteristics, radial approach remained associated with better survival. However, prognosis of patients undergoing primary PCI in cardiogenic shock remains poor.


Influence of variable hydrodynamic interaction strength on the transport properties of coiled polymers.
We have computed the hydrodynamic radius Rh and intrinsic viscosity [eta] of a large number of random coil polymer models by path integration. We examine the effects of chain length, solvent quality, monomer size and shape, and chain stiffness on the approach of these transport properties to the limit of large molecular mass. For many of the models, we have also calculated the ensemble-averaged solvent velocity field in the vicinity of the coil as it moves with constant drift velocity under the action of an external force. Naive scaling arguments predict alpha=nu and beta=3(nu-1) , where alpha , beta , and nu are the exponents controlling the chain length behavior of Rh , [eta] , and Rg , respectively. We present evidence for a "draining crossover" that quantifies the slow convergence of the transport properties to their asymptotic scaling behavior. Indeed, the convergence is so slow that effective alpha and beta exponents rarely agree with the naive predictions at typical molecular masses. For the same chain models, Rg converges rapidly to its asymptotic behavior, indicating that the effect is not due to a crossover from theta to swollen behavior, as often stated. Solvent quality, monomer size, and chain stiffness all influence the draining crossover. Our results call into question the common practice of extracting metrical data, e.g., characteristic ratios, directly from polymer solution transport properties.


Genetic insights into familial tumors of the nervous system.
Nervous system tumors represent unique neoplasms that arise within the central and peripheral nervous system. While the vast majority of nervous system neoplasm occur sporadically, most of the adult and pediatric forms have a hereditary equivalent. In a little over a decade, we have seen a tremendous increase in knowledge of the primary genetic basis of many of the familial cancer syndromes that involve the nervous system, syndromes that are mostly inherited as autosomal dominant traits. In this review, we discuss the most recent findings on the genetic basis of hereditary nervous system tumors. The identification of genes associated with familial cancer syndromes has in some families enabled a "molecular diagnosis" that complements clinical assessment and allows directed cancer surveillance for those individuals determined to be at-risk for disease.


Hyperbaric oxygen toxicity and ribosome destruction in Escherichia coli K12.
The viability of resting suspensions of Escherichia coli K12 Ymel exposed to air plus 300 psi (1 psi = 6.895 kPa) oxygen (hyperbaric oxygen) decreased as an apparent first-order process after an initial period of constant viability. Control suspensions exposed to air plus 300 psi nitrogen (hyperbaric nitrogen) did not lose viability over the 96 h of the experiment. It was observed that a decrease in the refractive index of the cells preceded the loss of viability in hyperbaric oxygen. This finding together with electron micrographs, which showed extensive loss of ribosomal particles in bacteria incubated in hyperbaric oxygen, led us to suspect that ribosome injury or disassociation might be important in hyperbaric oxygen toxicity. In support of this we found that cellular RNA, labeled with [5-3H]uridine, was much more rapidly and more completely degraded in hyperbaric oxygen than in hyperbaric nitrogen. Furthermore, a far greater proportion of RNA was degraded than was DNA or protein. A direct assay for ribosome particles by sucrose gradient centrifugation showed that only 34% of the 70S ribosome particles was lost during the first 24 h in hyperbaric nitrogen whereas in hyperbaric oxygen 99.6% of the 70S particles was degraded during the same period. In hyperbaric oxygen the rate of viability loss between 24 and 72 h was equal to the rate of 70S ribosome degradation during the first 24 h. If 70S ribosome disassociation in hyperbaric oxygen continues at the same rate after first 24 h, then cumulative 70S ribosome disassociation or injury may lead to and provide an explanation for irreversible bacterial cell injury and the loss of viability.


External chirality-triggered helicity control promoted by introducing a beta-Ala residue into the N-terminus of chiral peptides.
The noncovalent chiral domino effect (NCDE), defined as chiral interaction upon an N-terminus of a 3(10)-helical peptide, will provide a unique method for structural control of a peptide helix through the use of external chirality. On the other hand, the NCDE has not been considered to be effective for the helicity control of peptides strongly favoring a one-handed screw sense. We here aim to promote the NCDE on peptide helicity using two types of nonapeptides: H-beta-Ala-Delta(Z)Phe-Aib-Delta(Z)Phe-X-(Delta(Z)Phe-Aib)(2)-OCH(3) [Delta(Z)Phe = alpha,beta-didehydrophenylalanine, Aib = alpha-aminoisobutyric acid], where X as the single chirality is L-leucine (1) or L-phenylalanine (2). NMR, IR, and CD spectroscopy as well as energy calculation revealed that both peptides alone form a right-handed 3(10)-helix. The original CD amplitudes or signs in chloroform, irrespective of a strong screw-sense preference in the central chirality, responded sensitively to external chiral information. Namely added Boc-L-amino acid stabilized the original right-handed helix, while the corresponding d-isomer destabilized it or transformed it into a left-handed helix. These peptides were also shown to bind more favorably to an L-isomer from the racemate. Although similar helicity control was observed for analogous nonapeptides bearing an N-terminal Aib residue (Inai, Y.; et al. Biomacromolecules 2003, 4, 122), the present findings demonstrate that the N-terminal replacement by the beta-Ala residue significantly improves the previous NCDE to achieve more effective control of helicity. Semiempirical molecular orbital calculations on complexation of peptide 2 with Boc-(L or D)-Pro-OH reasonably explained the unique conformational change induced by external chirality.