[Concept of tumor promoters in hepatocarcinogenesis].
Tumor promotion is defined as 1 step of carcinogenesis. Its intervention occurred when cell DNA was already damaged by a carcinogen and is the support of quiescent mutations. This leads to a complete malignant transformation of the cells by a non genotoxic mechanism. The presence of tumor promoters in our environment, although difficult to estimate, must be taken into account. This requires further research.


Human soil-transmitted helminths: implications of mass drug administration.
With the London Declaration on neglected tropical disease (NTD), we are entering a new era of combating NTDs. However, the worldwide prospects of increased mass drug administration (MDA) treatments warrant caution on the development of anthelmintic resistance. In this review, we discuss the practical implications of MDA programs on the development of anthelmintic resistance in human soil-transmitted helminths (STH). There is poor evidence of anthelmintic resistance in human STH. Moreover, there is presumptive evidence that the refugia in MDA programs to control human STH is currently large, suggesting that the development of anthelmintic resistance in STH will be slow or may not occur. It remains unclear whether the current MDA strategy to control STH will sufficiently delay or prevent the development of anthelmintic resistance. First, differences in efficacy across and within STH species, and seasonal transmission of STH have not yet been considered. Second, any surveillance system to monitor drug efficacy is lacking. Finally, there is still no agreed strategy on how to deal with anthelmintic resistance once it emerges. Although anthelmintic resistance in human STH is currently of limited concern, various actions should be put in place for its delay and monitoring, and strategies should be developed in case anthelmintic resistance occurs.


Comparative analysis of obesity-related cardiometabolic and renal biomarkers in human plasma and serum.
The search for biomarkers associated with obesity-related diseases is ongoing, but it is not clear whether plasma and serum can be used interchangeably in this process. Here we used high-throughput screening to analyze 358 proteins and 76 lipids, selected because of their relevance to obesity-associated diseases, in plasma and serum from age- and sex-matched lean and obese humans. Most of the proteins/lipids had similar concentrations in plasma and serum, but a subset showed significant differences. Notably, a key marker of cardiovascular disease PAI-1 showed a difference in concentration between the obese and lean groups only in plasma. Furthermore, some biomarkers showed poor correlations between plasma and serum, including PCSK9, an important regulator of cholesterol homeostasis. Collectively, our results show that the choice of biofluid may impact study outcome when screening for obesity-related biomarkers and we identify several markers where this will be the case.


On the mechanism of reduction of maleate and fumarate by Ni(I)(1,4,8,11-tetraazacyclotetradecane)+ in aqueous solutions.
Ni(I)(1,4,8,11-tetraazacyclotetradecane)(+), Ni(I)L(+), was produced in neutral aqueous solutions by radiolytic techniques. The mechanism and kinetics of the reaction of Ni(I)L(+) with maleate and fumarate were studied applying pulse-radiolysis and analysis of the final products. Surprisingly the mechanisms of reduction of maleate and fumarate differ considerably. Based on the results it was also shown that Ni(II)L(2+) is an electrocatalyst for the reduction of alkenes in aqueous solutions.


Tuning the Dipole-Dipole Interaction in a Quantum Gas with a Rotating Magnetic Field.
We demonstrate the tuning of the magnetic dipole-dipole interaction (DDI) within a dysprosium Bose-Einstein condensate by rapidly rotating the orientation of the atomic dipoles. The tunability of the dipolar mean-field energy manifests as a modified gas aspect ratio after time-of-flight expansion. We demonstrate that both the magnitude and the sign of the DDI can be tuned using this technique. In particular, we show that a magic rotation angle exists at which the mean-field DDI can be eliminated, and at this angle, we observe that the expansion dynamics of the condensate is close to that predicted for a nondipolar gas. The ability to tune the strength of the DDI opens new avenues toward the creation of exotic soliton and vortex states as well as unusual quantum lattice phases and Weyl superfluids.


Nanoparticle-based Point of Care Immunoassays for in vitro Biomedical Diagnostics.
In resource-limited settings, the availability of medical practitioners and early diagnostic facilities are inadequate relative to the population size and disease burden. To address cost and delayed time issues in diagnostics, strip-based immunoassays, e.g. dipstick, lateral flow assay (LFA) and microfluidic paper-based analytical devices (microPADs), have emerged as promising alternatives to conventional diagnostic approaches. These assays rely on chromogenic agents to detect disease biomarkers. However, limited specificity and sensitivity have motivated scientists to improve the efficiency of these assays by conjugating chromogenic agents with nanoparticles for enhanced qualitative and quantitative output. Various nanomaterials, which include metallic, magnetic and luminescent nanoparticles, are being used in the fabrication of biosensors to detect and quantify biomolecules and disease biomarkers. This review discusses some of the principles and applications of such nanoparticle-based point of care biosensors in biomedical diagnosis.


[A gradient-based direct aperture optimization].
Aiming at the disadvantages of traditional direct aperture optimization (DAO) method, such as slow convergence rate, prone to stagnation and weak global searching ability, a gradient-based direct aperture optimization (GDAO) is proposed. In this work, two different optimization methods are used to optimize the shapes and the weights of the apertures. Firstly, in order to improve the validity of the aperture shapes optimization of each search, the traditional simulated annealing (SA) algorithm is improved, the gradient is introduced to the algorithm. The shapes of the apertures are optimized by the gradient based SA method. At the same time, the constraints between the leaves of multileaf collimator (MLC) have been fully considered, the optimized aperture shapes are meeting the requirements of clinical radiation therapy. After that, the weights of the apertures are optimized by the limited-memory BFGS for bound-constrained (L-BFGS-B) algorithm, which is simple in calculation, fast in convergence rate, and suitable for solving large scale constrained optimization. Compared with the traditional SA algorithm, the time cost of this program decreased by 15.90%; the minimum dose for the planning target volume was improved by 0.29%, the highest dose for the planning target volume was reduced by 0.45%; the highest dose for the bladder and rectum, which are the organs at risk, decreased by 0.25% and 0.09%, respectively. The results of experiment show that the new algorithm can produce highly efficient treatment planning a short time and can be used in clinical practice.


What impact will the 'conversion' of two district general hospitals into teaching hospitals have? Views from the field.
To gather opinions from a variety of healthcare professionals in Birmingham and the Black Country as to the potential impact of 'converting' 2 district general hospitals into teaching hospitals. Thirty-three semi-structured interviews were conducted with healthcare professionals including Directors of Public Health, Community Health Council Chief Officers, Trust Chief Executives, medical directors, trust managerial and consultant staff, junior doctors and nurses. Interviewees were asked to outline what they felt the major impacts of the 'conversion' to teaching status were likely to be. Five main thematic areas were identified from the interviews. Three of these related to the medical students receiving their clinical training in the new teaching hospitals, the teachers undertaking new or additional teaching duties and the patients being treated in the new teaching settings. Interviewees also identified several organisational effects relating to the new, established and non-teaching hospitals in the locality and discussed potential impacts outside of health care settings. The majority of views expressed by participants were positive citing potential benefits from developments in teaching provision. Areas of concern generally related to the need for successful implementation of the changes within clinically focused environments rather than to the effects of teaching per se. The impacts consequent to the reconfiguration of district general hospitals to teaching hospitals should be evaluated by appropriately designed longitudinal studies.


Cutaneous clear cell sarcoma: a clinicopathologic, immunohistochemical, and molecular analysis of 12 cases emphasizing its distinction from dermal melanoma.
Clear cell sarcoma (CCS) of tendons and aponeuroses/malignant melanoma (MM) of soft parts is a rare tumor and in the majority of cases presents a characteristic reciprocal translocation t(12;22)(q13;q12) that results in fusion of the EWS and ATF1 genes. Although the melanocytic differentiation of CCS is indisputable, its precise lineage remains unclear. Typically, the slowly growing tumor affects the extremities of adolescents or young adults, especially around the ankle and foot. CCS is classically regarded as a deep soft tissue tumor associated with tendons or aponeuroses. This traditional view is put into perspective by the description of primary CCS of the gastrointestinal tract that may have a variant fusion gene EWSR1-CREB1. We describe 12 cases of cutaneous CCS and discuss the differential diagnoses. These 12 cases share an identical immunohistochemical profile with MM and thus can easily be confused with a dermal variant of spindle cell MM or metastasis of MM. The patients' ages ranged from 6 to 74 years (median: 25 y), and there was a female predominance (10 females, 2 males). Most tumors (n = 9) were located on the extremities, 2 tumors arose on the back, and 1 on the abdomen. The mean tumor size was 0.97 cm (range, 0.4 to 1.7 cm). Six cases showed invasion of the subcutis, the other 6 cases were entirely dermal. Tumor necrosis was evident in 2 cases, melanin pigment in 2 cases, and ulceration in 1 tumor. All cases showed uniform nests and fascicles of pale spindled or slightly epitheloid cells with finely granular eosinophilic or clear cytoplasm. There was fair pleomorphism with plump spindled nuclei and significantly prominent nucleoli. Multinucleated wreath-like tumor giant cells were observed in two-thirds of cases, but were usually present only focally. The dense cellular aggregates were encased by delicate fibrous septa. The stroma showed a sclerotic reticulated pattern. Partly, the nests of spindle cells bordered the epidermis, prima vista mimicking junctional nests of melanocytes. The specific translocation pattern was confirmed in all cases by fluorescence in situ hybridization. Local recurrences and metastases developed in 2 and 3 patients, respectively, and 1 patient died of the disease.


Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy.
In the general population with COVID-19, the male sex is an established risk factor for mortality, in part due to a more robust immune response to COVID-19 in women. Because patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants, we examined whether the male sex is still a risk factor for mortality among patients on KFRT with COVID-19. From the European Renal Association COVID-19 Database (ERACODA), we examined patients on KFRT with COVID-19 who presented between February 1st, 2020, and April 30th, 2021. 1204 kidney transplant recipients (male 62.0%, mean age 56.4 years) and 3206 dialysis patients (male 61.8%, mean age 67.7 years) were examined. Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (p = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (p = 0.001). The adjusted HR for the risk of 3-month mortality in males (vs females) was 0.89 (95% CI 65, 1.23, p = 0.49) in kidney transplant recipients and 1.33 (95% CI 1.13, 1.56, p = 0.001) in dialysis patients (pinteraction = 0.02). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (vs. dialysis patients) was 1.39 (95% CI 1.02, 1.89, p = 0.04) in males and 2.04 (95% CI 1.40, 2.97, p < 0.001) in females (pinteraction = 0.02). In patients on KFRT with COVID-19, the male sex is not a risk factor for mortality among kidney transplant recipients but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk.


Deciphering Molecular Mechanisms Involved in Salinity Tolerance in Guar (Cyamopsis tetragonoloba (L.) Taub.) Using Transcriptome Analyses.
Guar is a commercially important legume crop known for guar gum. Guar is tolerant to various abiotic stresses, but the mechanisms involved in its salinity tolerance are not well established. This study aimed to understand molecular mechanisms of salinity tolerance in guar. RNA sequencing (RNA-Seq) was employed to study the leaf and root transcriptomes of salt-tolerant (Matador) and salt-sensitive (PI 340261) guar genotypes under control and salinity. Our analyses identified a total of 296,114 unigenes assembled from 527 million clean reads. Transcriptome analysis revealed that the gene expression differences were more pronounced between salinity treatments than between genotypes. Differentially expressed genes associated with stress-signaling pathways, transporters, chromatin remodeling, microRNA biogenesis, and translational machinery play critical roles in guar salinity tolerance. Genes associated with several transporter families that were differentially expressed during salinity included ABC, MFS, GPH, and P-ATPase. Furthermore, genes encoding transcription factors/regulators belonging to several families, including SNF2, C2H2, bHLH, C3H, and MYB were differentially expressed in response to salinity. This study revealed the importance of various biological pathways during salinity stress and identified several candidate genes that may be used to develop salt-tolerant guar genotypes that might be suitable for cultivation in marginal soils with moderate to high salinity or using degraded water.


Serum antibodies to human enteric coronavirus-like particles in Australia, South Africa, Indonesia, Niue, and Papua New Guinea.
Relatively high levels of antibody to human enteric coronavirus-like particles were detected in the sera from rural Aborigines in Australia. Levels were generally much lower in the sera from urban Aborigines, and extremely low to not detectable in the sera from Europeans. Antibody to coronavirus-like particles was also detected in the sera from rural blacks from South Africa, in the sera from Indonesia and Niue, and also possibly in the sera from rural villagers from Papua New Guinea, but in the latter case at only very low level.


Sea sand disruption method (SSDM) as a valuable tool for isolating essential oil components from conifers.
Essential oils are one of nature's most precious gifts with surprisingly potent and outstanding properties. Coniferous oils, for instance, are nowadays being used extensively to treat or prevent many types of infections, modify immune responses, soothe inflammations, stabilize moods, and to help ease all forms of non-acute pain. Given the broad spectrum of usage of coniferous essential oils, a fast, safe, simple, and efficient sample-preparation method is needed in the estimation procedure of essential oil components in fresh plant material. Generally, the time- and energy-consuming steam distillation (SD) is applied for this purpose. This paper will compare SD, pressurized liquid extraction (PLE), matrix solid-phase dispersion (MSPD), and the sea sand disruption method (SSDM) as isolation techniques to obtain aroma components from Scots pine (Pinus sylvestris), spruce (Picea abies), and Douglas fir (Pseudotsuga menziesii). According to the obtained data, SSDM is the most efficient sample preparation method in determining the essential oil composition of conifers. Moreover, SSDM requires small organic solvent amounts and a short extraction time, which makes it an advantageous alternative procedure for the routine analysis of coniferous oils. The superiority of SSDM over MSPD efficiency is ascertained, as there are no chemical interactions between the plant cell components and the sand. This fact confirms the reliability and efficacy of SSDM for the analysis of volatile oil components.


High-Pressure Low-Temperature Optical Studies of BaWO4:Ce,Na Crystals.
We report detailed optical studies of BaWO4:Ce and BaWO4:Ce,Na single crystals. The material does not emit any luminescence at ambient pressure under near-UV (325 nm) excitation. Efficient green light is emitted only at high pressure (HP) and low temperature (LT). The luminescence is of excitonic character, since the lowest Ce3+ 5d level is degenerate with the conduction band also under hydrostatic pressures. To explain these phenomena, absorption measurements were made together with powder X-ray diffraction (XRD) and confocal micro-Raman and Fourier transform infrared (FTIR) spectroscopy. Raman experiments confirm the existence of a metastable phase, induced by certain nonhydrostatic conditions, before the reversible transition at a high-pressure range above 9 GPa, where efficient photoluminescence (PL) occurs. Although the phase transition is reversible, it proceeds with a prominent hysteresis observed in luminescence and Raman experiments. FTIR focuses on the existence of Ce3+ multisites observed during LT measurements.


The Intestinal Tract Brush Border in Young Children Uniformly Expresses Guanylate Cyclase C.
The present study examined staining of guanylate cyclase C (GCC/GUCY2C) in the small and large intestines of children younger than age 7 years. Normal intestinal tissue from children aged 0 to 7 years was stained using GCC, uroguanylin, and villin antibodies and scored for staining intensity. A subset underwent quantitative real-time polymerase chain reaction. Data were analyzed using t test of independent means, descriptive statistics, and logistic regression. Four hundred sixty-four specimens underwent immunohistochemistry; 291 specimens underwent real-time polymerase chain reaction. GCC, villin, and uroguanylin were detected across age groups and anatomic sites. No significant differences were identifiable across age groups. GUCY2C and uroguanylin mRNA was detected in all samples, with no variability of statistical significance of either target-to-villin normalization between any age cohorts. A gradient of expression of GCC across age groups does not seem to exist.


[Down regulation of mitogen activated protein kinase phosphatase-1 mediate acquired multidrug resistance in pancreatic adenocarcinoma cell line SW1990/Fu].
To investigate the role of mitogen activated protein kinase phosphatase-1 (MKP-1) in mediating acquired multidrug resistance in pancreatic adenocarcinoma cell line SW1990/Fu. To detect MKP-1 mRNA expression, Northern blot analysis was carried out in well established drug resistant pancreatic adenocarcinoma cell line SW1990/Fu, SW1990 and MiaPaCa-2 cell lines. To further elucidate the exact role of MKP-1, Western blot hybridization was performed in these three cell lines. Northern blot analysis of total RNA isolated from SW1990/Fu, SW1990 and MiaPaCa-2 cell lines revealed the presence of the 2400 bp MKP-1 transcript 7 at relatively high levels in pancreatic cancer cell lines SW1990 and MiaPaCa-2. In the SW1990/Fu, the MKP-1 transcript was detectable at very low level. Densitometric analysis with normalization to 7S indicated that MKP-1 mRNA expression level was significantly decreased in SW1990/Fu in comparison with the parental and MiaPaCa-2 cell lines. MKP-1 protein expression level in SW1990/Fu detected by Western blot was coincident with mRNA level. MKP-1 may be involved in acquired multidrug resistance in pancreatic adenocarcinoma, and we could hypothesized that alterations of intra-cellular transduction signal system acts as an important role in multidrug resistance of tumor cells.


Comprehensive microsurgical anatomy of the jugular foramen and review of terminology.
The microsurgical anatomy of the jugular foramen was studied in 12 formalin preserved cadavers (24 foramina) and 40 dry-skulls (80 foramina). The jugular foramen was exposed by microsurgical dissection with drilling from a superior to inferior direction. Observations regarding dural architecture of the jugular foramen and relationships between neurovascular structures passing through the foramen were noted in cadavers. Normal bony construction of the foramen and its variational anatomy were examined in dry-skull specimens. Using photographs and drawings, the anatomy of the jugular foramen is presented and related terminology is discussed in the light of a literature review.


[Prostaglandins E1 and psychopathogeny of schizophrenia].
The authors assess the results of several studies, fundamental or clinical with therapeutic tests, to demonstrate a possible role of prostaglandins--specially of a possible lack of PGE1--in the pathogeny of certain forms of schizophrenia. The heterogeneousness of the results leads one to think there's heterogeneousness of the illness. Meanwhile, in certain cases, the contribution of a direct precursor of PGE1 the GLA, has given possible noticeable clinical results, mainly with deficiency symptoms.


Lower Education and Household Income Contribute to Advanced Disease, Less Treatment Received and Poorer Prognosis in Patients with Hepatocellular Carcinoma.
Understanding the ways in which socioeconomic status affects prognosis of hepatocellular carcinoma (HCC) is important for building up strategies eliminating the inequalities in cancer diagnosis and treatments among different groups, which, remains undetermined. In the present study, 1485 newly diagnosed HCC patients with complete demographic and clinical data were included. Socioeconomic data, including education, annual household income and residency was also reported by patients or families. In the present study, less educated patients were older, more female involved, poorly paid, more living in rural places, had more advanced tumor burden, received less curative and loco-regional therapies, and thus showed poorer short-term and long-term outcomes (in total or after surgical resection) than the highly educated. Patients with lower income were less educated, less treated, and more likely to live in rural places, had more advanced stages of HCC and thus poorer long-term survival (in total or after surgical resection) than higher income groups. In Cox regression analysis, lower household income was independently associated with poorer outcome (HR=1.2, 95% CI: 1.0-1.4, p=0.036). These results indicate that education and income are critically associated with early diagnosis, treatments and prognosis of HCC. Much more efforts should be taken to support the patients with less education and lower income to improve the outcomes of HCC.


Unmet Needs in Psoriasis Patients.
Psoriasis can greatly impact patients' quality of life. The introduction of new treatments has improved treatment outcomes, but treatment gaps may still exist. Identify unmet treatment needs in patients with psoriasis. Participants aged 18 years or older, with an Amazon Mechanical Turk account, who reported diagnosis of psoriasis and correctly answered an attention check question were included. Results were analyzed using descriptive and inferential statistics. Of the 417 participants who met study inclusion criteria, 51.1% were female, and 39.3% were 31-40 years of age; 61.2% reported mild, 25.4% moderate, and 13.4% severe psoriasis. Most (74.8%) were currently under treatment; half (51.6%) were mostly or completely satisfied with treatment, while 24.5% were slightly or not at all satisfied. Respondents were most satisfied with topical (59.5%), followed by oral (46%), and injectable treatments (19.9%). Most (78.7%) slightly or strongly felt there should be more cost-effective options. Gaps in current psoriasis treatment options included more affordable topical and oral treatments that work faster and require less frequent use. The use of an English survey and Amazon Mechanical Turk precludes certain populations from this study. Participants were not asked to provide their current form of psoriasis treatment. Despite advances in psoriasis treatment, there remains a desire for more effective, faster, longer acting, and less costly, more accessible treatments. J Drugs Dermatol. 2022;21(8):839-844. doi:10.36849/JDD.6589.


The Emerging Role of Long Non-Coding RNAs in Development and Function of Gilthead Sea Bream (Sparus aurata) Fast Skeletal Muscle.
Long non-coding RNAs (lncRNAs) are an emerging group of ncRNAs that can modulate gene expression at the transcriptional or translational levels. In the present work, previously published transcriptomic data were used to identify lncRNAs expressed in gilthead sea bream skeletal muscle, and their transcription levels were studied under different physiological conditions. Two hundred and ninety lncRNAs were identified and, based on transcriptomic differences between juveniles and adults, a total of seven lncRNAs showed potential to be important for muscle development. Our data suggest that the downregulation of most of the studied lncRNAs might be linked to increased myoblast proliferation, while their upregulation might be necessary for differentiation. However, with these data, as it is not possible to propose a formal mechanism to explain their effect, bioinformatic analysis suggests two possible mechanisms. First, the lncRNAs may act as sponges of myoblast proliferation inducers microRNAs (miRNAs) such as miR-206, miR-208, and miR-133 (binding energy MEF < -25.0 kcal). Secondly, lncRNA20194 had a strong predicted interaction towards the myod1 mRNA (ndG = -0.17) that, based on the positive correlation between the two genes, might promote its function. Our study represents the first characterization of lncRNAs in gilthead sea bream fast skeletal muscle and provides evidence regarding their involvement in muscle development.


Primary thoracoscopic repair of diaphragmatic hernia with pericostal sutures.
The surgical management of congenital diaphragmatic hernias has traditionally been via laparotomy or thoracotomy. Although laparoscopic and thoracoscopic repairs have been described, most reports are in older infants. We describe a method for primary thoracoscopic repair applied in the immediate neonatal period when no posterolateral rim of diaphragm exists. This simple technique for placing the pericostal sutures is a useful adjunct in the thoracoscopic management of diaphragmatic hernias.


Effect of antigen-induced synovitis on the extensor tendons within the retinacular compartment of the dog.
Antigen-induced proliferative synovitis was produced within the extensor retinacular compartment of one forepaw of young littermate dogs. The extensor tendons within the synovitis compartment were compared with the tendons in control compartments of the opposite forepaw. At 7 days following challenge, the tendons from the proliferative synovitis compartment showed increased uptake of [3H]proline at 5 min after pulse labeling. At 7, 14, and 28 days following challenge, the tendons within the proliferative synovitis compartment showed a significant increase in metabolic activity compared with control tendons after radioactive labeling for 6 h, with no associated difference in total collagen content of the control and synovitis tendons. These results indicate an increase in protein synthesis and degradation by the synovitis-surrounded tendons.


Practical application of the concept of mean times in biopharmaceutics.
The "concept of mean times" (1) in combination with the "method of moments" (3, 4) provides a practical basis for handling biopharmaceutical problems. This holds for in vitro, in vitro/in vivo and in vivo situations. Using several examples, it was demonstrated that questions concerning the comparability of in vitro dissolution models and their in vivo relevance can be answered, and that the rate of bioavailability can be evaluated exactly.


Proteomics for cancer drug design.
Introduction: Signal transduction cascades drive cellular proliferation, apoptosis, immune, and survival pathways. Proteins have emerged as actionable drug targets because they are often dysregulated in cancer, due to underlying genetic mutations, or dysregulated signaling pathways. Cancer drug development relies on proteomic technologies to identify potential biomarkers, mechanisms-of-action, and to identify protein binding hot spots. Areas covered: Brief summaries of proteomic technologies for drug discovery include mass spectrometry, reverse phase protein arrays, chemoproteomics, and fragment based screening. Protein-protein interface mapping is presented as a promising method for peptide therapeutic development. The topic of biosimilar therapeutics is presented as an opportunity to apply proteomic technologies to this new class of cancer drug. Expert opinion: Proteomic technologies are indispensable for drug discovery. A suite of technologies including mass spectrometry, reverse phase protein arrays, and protein-protein interaction mapping provide complimentary information for drug development. These assays have matured into well controlled, robust technologies. Recent regulatory approval of biosimilar therapeutics provides another opportunity to decipher the molecular nuances of their unique mechanisms of action. The ability to identify previously hidden protein hot spots is expanding the gamut of potential drug targets. Proteomic profiling permits lead compound evaluation beyond the one drug, one target paradigm.


Discotricha papillifera: structure and morphogenesis of a marine interstitial ciliate.
Discotricha papillifera Tuffrau, a marine interstitial ciliate, is redescribed with the aid of light, scanning, and transmission electron microscopy from cells collected at a New Hampshire beach. Presence of primitive membranelles as well as an advanced stomatogenesis is demonstrated. The ultrastructure, including a unique membrane-bounded septate structure, is described. The cell is tentatively placed in the nassulid suborder Microthoracina, but affinities with other groups are discussed.


Transcriptomic and Ectoine Analysis of Halotolerant Nocardiopsis gilva YIM 90087T Under Salt Stress.
The genus Nocardiopsis is an unique actinobacterial group that widely distributed in hypersaline environments. In this study, we investigated the growth conditions, transcriptome analysis, production and accumulation of ectoine by Nocardiopsis gilva YIM 90087T under salt stress. The colony color of N. gilva YIM 90087T changed from yellow to white under salt stress conditions. Accumulation of ectoine and hydroxyectoine in cells was an efficient way to regulate osmotic pressure. The ectoine synthesis was studied by transferring the related genes (ectA, ectB, and ectC) to Escherichia coli. Transcriptomic analysis showed that the pathways of ABC transporters (ko02010) and glycine, serine, and threonine metabolism (ko00260) played a vital role under salt stress environment. The ectABC from N. gilva YIM 90087T was activated under the salt stress. Addition of exogenous ectoine and hydroxyectoine were helpful to protect N. gilva YIM 90087T from salt stress.


Self-Powered Ultraviolet Photodetectors Driven by Built-In Electric Field.
Self-powered ultraviolet (UV) photodetectors, which have vast applications in the military and for civilian purposes, have become particularly attractive in recent years due to their advantages of high sensitivity, ultrasmall size, and low power consumption. In particular, self-powered UV photodetectors driven by a built-in electric field cannot only detect UV signals but also be powered by the incident signals instead of external power. In this concept, the key issues and most recent developments on photovoltaic type UV photodetectors driven by p-n homojunction, heterojunction, and Schottky junction are surveyed. This should generate extensive interest in this field and encourage more researchers to engage in and tackle the scientific challenges.


Step-by-step synthesis of the endohedral stannaspherene [Ir@Sn12]3- via the capped cluster anion [Sn9Ir(cod)]3-.
The endohedral stannaspherene cluster anion [Ir@Sn(12)](3-) was synthesized in two steps. The reaction of K(4)Sn(9) with [IrCl(cod)](2) (cod: 1,5-cyclooctadienyl) in ethylenediamine (en) solution first yielded the [K(2,2,2-crypt)](+) salt (2,2,2-crypt: 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane) of the capped cluster anion [Sn(9)Ir(cod)](3-). Subsequently, crystals of this compound were dissolved in en, followed by the addition of triphenylphosphine or 1,2-bis(diphenylphosphino)ethane and treatment at elevated temperatures. [Ir@Sn(12)](3-) was obtained and characterized as the [K(2,2,2-crypt)](+) salt. The isolation of [Sn(9)Ir(cod)](3-) as an intermediate product establishes that the formation of the stannaspherene [Ir@Sn(12)](3-) occurs through the oxidation of [Sn(9)Ir(cod)](3-). Among the structurally characterized tetrel cluster anions, [Ir@Sn(12)](3-) is a unique example of a stannaspherene, and one of the rare spherical clusters encapsulating a metal atom that is not a member of Group 10. Single-crystal structure determination shows that the novel Zintl ion cluster has nearly perfect icosahedral I(h) point symmetry.


Fluorescence Assay for Ribonuclease H Based on Nonlabeled Substrate and DNAzyme Assisted Cascade Amplification.
As a highly conserved damage repair protein, RNase H can specifically hydrolyze RNA in DNA-RNA chimeric strands. DNAzyme, a synthetic single-stranded DNA consisting of binding and catalytic sites, can cleave RNA in the presence of cofactors. In this study, we establish a highly sensitive RNase H assay assisted with DNAzyme's cleavage property. A DNA-RNA chimeric strand, which contains DNAzyme sequences, is used as the hydrolysis substrate of RNase H. The RNase H hydrolysis of the chimeric substrate results in the release of DNAzyme. Subsegment DNAzyme digest, a molecular beacon, causes a "turn-on" fluorescence signal by disrupting its hairpin structure. Furthermore, the fluorescence signal is amplified by cyclic digestion of DNAzyme to the substrate of molecular beacon. Under the optimal conditions, the detection limit of RNase H is 0.01 U/mL, which is superior to those of several alternative approaches. Additionally, the method was further used for RNase H detection in heterogeneous biological samples as well as to investigate the effects of natural compounds on this enzyme. In summary, these results show that the method not only provides a universal platform for monitoring RNase H activity but also shows great potential in biomedical studies and drug screening.


Pleomorphic adenoma of lateral nasal wall presenting with epiphora.
We report a rare case of pleomorphic adenoma arising from the lateral nasal wall which was incidentally detected at a very early stage. A 38-year-old man presented to the ophthalmology department with a 2-year history of epiphora from the left eye. He was referred to otorhinolaryngology department as a candidate for endoscopic dacryocystorhinostomy. Nasal endoscopy revealed a polypoid mass on the left lateral nasal wall arising near the uncinate process and protruding into the middle meatus. Endoscopic excision of the mass and a concomitant endoscopic dacryocystorhinostomy and functional endoscopic sinus surgery were done. Histopathological examination was compatible with pleomorphic adenoma having tumour-negative surgical margins. He was free from the disease 24 months after the surgery.


Strategic application of convective cooling to maximize the thermal gradient and reduce heat stress response in dairy cows.
This study determined the effectiveness of convective cooling at different times of day when air temperature (Ta) was cycled from day to night. Mid-lactation Holstein cows (n = 12) were placed in 3 environmental chambers (4 cows per chamber) and acclimated to Ta 19.9°C (thermoneutral; TN) for 7 d followed by an incremental increase over 3 d to a heat stress (HS) condition. Conditions were maintained for 11 d at high and low daily Ta of 33 and 23°C, respectively. To determine adaptive HS response, the HS period was divided into early (E: d 11 to 14) and late (L: d 17 to 20) periods. During HS, cows were exposed to continuous fan (convective) cooling (CC), 8-h day fan cooling (1100 to 1900 h; DC), or 8-h night fan cooling (2300 to 0700 h; NC). Compared with DC, the NC treatment maximized the thermal gradient during the convective cooling. Each animal received all treatments within 3 trials using a repeated 3 × 3 Latin square design. Cows were fed a total mixed ration and milked twice daily. Thermal status was assessed by using thermal conductance and average daily values for mean, minimum, and maximum rectal temperature (Tre), skin temperatures, and respiration rate. Percent reduction in dry matter intake from TN to HS was less for CC than DC and NC, with no change from E to L periods. The DC group exhibited the greatest trend for a percent reduction in total milk yield below CC due to the significantly lower morning milk production. All values for total daily milk production decreased from E to L periods, with E to L reductions in both morning and afternoon milk production. Minimum Tre for CC and NC cows was 0.4°C below DC. In contrast, maximum Tre was similar for NC and DC groups, at 0.5 to 0.6°C above the CC group. Skin temperature for CC cows was always less than DC cows. Skin temperature for NC cows was equal to CC for minimum skin temperature, but exceeded both CC and DC cows for maximum skin temperature. Average skin temperature decreased from E to L, which suggested heat adaptation. The thermal advantage of night (lowest Ta and greatest thermal gradient) versus day cooling (greatest Ta and lowest thermal gradient) was increased heat transfer via thermal conductance with NC. The higher thermal strain of DC cows caused a larger percent decrease in morning milk yield than for NC cows. In contrast, use of convective cooling at night in the absence of elevated humidity could sufficiently reduce heat strain beyond DC to maintain milk production at a level that is closer to that of CC cows.


[Effect of hyperthermic irrigation with bleomycin on prophylaxis of recurrence of bladder cancer].
Hyperthermic irrigation with Bleomycin of bladder at 43 approximately 44 degrees C for 3 hours after operation was performed in about 80 cases of bladder cancer from 1978, in our hospital. Bleomycin (90 mg) in 3,000 ml saline solution, was irrigated for 10 days postoperatively. No severe side effect was observed, while the complaint of a local side effect (bladder irritability) was made in 57.8%. Non-recurrence rate was calculated by the actual method, in 54 patients with bladder cancer which occurred initially. Non recurrence rate was 88.0% after 1 year, 73.3% after 2 and 3 years, and 63.5% after 4 years or more. Recurrence rate per 100 patient-month was 0.98. On the basis of our observations, it was concluded that hyperthermic irrigation with Bleomycin was useful for the prophylaxis for recurrence of bladder cancer after removal of the tumor.


Genetic and phenotypic characterization of the heat shock response in Pseudomonas putida.
Molecular chaperones function in various important physiological processes. Null mutants of genes for the molecular chaperone ClpB (Hsp104), and those that encode J-domain proteins (DnaJ, CbpA, and DjlA), which may act as Hsp40 co-chaperones of DnaK (Hsp70), were constructed from Pseudomonas putida KT2442 (KT) to elucidate their roles. The KTΔclpB mutant showed the same heat shock response (HSR) as the wild-type, both in terms of heat-shock protein (Hsp) synthesis (other than ClpB) and in hsp gene expression; however, the mutant was quite sensitive to high temperatures and was unable to disaggregate into thermo-mediated protein aggregates, indicating that ClpB is important for cell survival after heat stress and essential for solubilization of protein aggregates. On the other hand, the KTΔdnaJ mutant was temperature-sensitive, and formed more protein aggregates (especially of high molecular weight) upon heat stress than did KT. P. putida CbpA, a probable Hsp, partially substituted the functions of DnaJ in cell growth and solubilization of thermo-mediated protein aggregates, and might be involved in the HSR which was regulated by a fine-tuning system(s) that could sense subtle changes in the ambient temperature and control the levels of σ(32) activity and quantity, as well as the mRNA levels of hsp genes.


Expression of transient receptor potential mRNA isoforms and Ca(2+) influx in differentiating human stem cells and platelets.
Store-regulated Ca(2+) entry (SOCE) is an important mechanism of elevating cytosolic [Ca(2+)]i in platelets, though the Ca(2+) influx channels involved are still unclear. We screened human platelets and their precursor cells (human stem cells and megakaryocytes) for the presence of candidate influx channels, i.e., isoforms of the Trp family of proteins. Primary stem cells were cultured with thrombopoietin to allow differentiation into megakaryocytes. The undifferentiated stem cells (CD34(+)) showed mRNA expression of only a spliced variant Trp1A. Immature (CD61(+)/CD42b(low)) and mature (CD61(+)/CD42b(high)) megakaryocytes as well as platelets expressed in addition unspliced Trp1 as well as Trp4 (less abundant) and Trp6 isoforms. This unspliced isoform appeared to be specific for cells of the megakaryocyte/platelet lineage, since immature (CD14(+)/CD61(-)/CD42b(-)) and mature monocytes expressed only the Trp1A isoform. This conclusion was confirmed by the presence of Trp1A, 3, 4 and 6 transcripts in the immature megakaryocytic Dami cell line, and of Trp1, 1A, 4 and 6 transcripts in the more mature CHRF-288 cell line. The up-regulation of Trp1, 4 and 6 in the lineage from primary stem cells to mature megakaryocytes and platelets was accompanied by increased influx of extracellular Ca(2+) after pretreatment of the cells with thapsigargin or thrombin. Expression of new Trp isoforms in the differentiated cells is thus accompanied by increased SOCE.


Multiple Sclerosis: New Aspects of Immunopathogenesis.
Multiple sclerosis (MS) is a multicomponent disease characterized by inflammation, neurodegeneration, and cancellation of the central nervous system recovery mechanisms. The cause of MS is still unknown, but it is undeniable that genetic, environmental and immune factors are involved in the etiopathogenesis of this complex and heterogeneous disease. From the aspect of immunopathogenesis, until recently the opinion prevailed that autoreactive T lymphocytes played a major role, the activation of which is a key step in MS. The knowledge of the effector and regulatory roles of B cells supports a new concept of MS immunopathogenesis that is based on the highly com-plex interaction of T and B cells, with B cells actively participating in cellular immunity by directing the intensity and quality of cellular immune response. The mechanisms of B cell activity in MS immunopathogenesis are multiple and include antigen presentation and T cell costimulation, cytokine secretion, antibody synthesis, and formation of ectopic lymphoid B cell aggregates in the intrameningeal spaces. The importance of B cells has been confirmed by modern therapeutic options for the treatment of MS.


Chronic partial ureteral obstruction in the neonatal guinea pig. I. Influence of uninephrectomy on growth and hemodynamics.
Although obstructive nephropathy is a frequent cause of renal insufficiency in infancy, factors influencing adaptation to chronic partial ureteral obstruction (CPUO) are poorly understood. Guinea pigs were subjected to unilateral CPUO within the first 2 days of life (Group I) and microsphere studies were performed at 23 +/- 3 days of age. To also investigate the role of functional renal mass on growth and hemodynamics, contralateral nephrectomy was performed in Group II at the time of ureteral constriction. Compared to sham-operated controls (ureteral diameter = 1 mm) CPUO caused impaired somatic growth in both groups. Resulting hydroureteronephrosis was variable and most severe (ureteral diameter greater than 3 mm) in azotemic animals of Group II, which demonstrated reduced compensatory renal hypertrophy and poorest somatic growth. Mean arterial blood pressure was not affected by CPUO or uninephrectomy. Renal blood flow (RBF) was higher in Group II than Group I, and did not fall significantly with severity of CPUO in Group II, in which number of perfused glomeruli was similar to controls. In contrast, renal vascular resistance (RVR) increased by 172% in animals of Group I with severe CPUO, and was associated with 34% fewer perfused glomeruli than in the hypertrophied contralateral kidney. With increasing severity of CPUO, RBF tended to be distributed to outer cortical regions in the obstructed kidney of Group I, while the shift in RBF distribution was from outer to inner cortex in the remaining kidney of Group II. Filtration fraction fell as a result of CPUO in both groups, such that reduction in the glomerular filtration rate was due in large part to factors other than RBF.(ABSTRACT TRUNCATED AT 250 WORDS)


Reliability and criterion validity of the "Gyroscope" application of the iPod™ for measuring lumbar range of motion.
Recent technologies, such as the iPod, are often equipped with an accelerometer and magnetometer, which, through software applications, can perform various inclinometric functions. These applications have the potential to measure and quantify range of motion (ROM). The purpose of this study was to estimate the iPod "Gyroscope" application intra- and inter-rater reliability as well as its criterion validity in healthy participants lumbar ROM assessment. The sample consisted of 29 healthy participants. For the estimation of intra- and inter-reliability, two examiners measured the lumbar ROM of each participant twice using the iPod. To estimate the criterion validity, the measures were compared to those obtained with the Back Range of Motion Device (BROM; lateral flexion) and the double inclinometer (flexion and extension). Reliability and validity were then established using the intraclass correlation coefficient (ICC). We observed a moderate to high intra-rater reliability (ICCs = 0.67-0.91) and a moderate to high inter-rater reliability for each movement (ICCs = 0.72-0.89). For the criterion validity, the ICCs were all high (ICCs = 0.65-0.89). Our results provide evidence that the iPod "Gyroscope" application can be used to assess lumbar ROM for all movements.


Cellulose-Chitosan-Nanohydroxyapatite Hybrid Composites by One-Pot Synthesis for Biomedical Applications.
The development of organic-inorganic hybrid materials deserves special interest for bone tissue engineering applications, where materials must have properties that induce the survival and activation of cells derived from the mesenchyme. In this work, four bio-nanocomposites based on cellulose and variable content of chitosan, from 15 to 50 w% based on cellulose, with nanohydroxyapatite and β-Glycerophosphate as cross-linking agent were synthesized by simplified and low-energy-demanding solvent exchange method to determine the best ratio of chitosan to cellulose matrix. This study analyzes the metabolic activity and survival of human dermal fibroblast cells cultivated in four bio-nanocomposites based on cellulose and the variable content of chitosan. The biocompatibility was tested by the in vitro cytotoxicity assays Live/Dead and PrestoBlue. In addition, the composites were characterized by FTIR, XRD and SEM. The results have shown that the vibration bands of β-Glycerophosphate have prevailed over the other components bands, while new diffraction planes have emerged from the interaction between the cross-linking agent and the biopolymers. The bio-nanocomposite micrographs have shown no surface porosity as purposely designed. On the other hand, cell death and detachment were observed when the composites of 1 and 0.1 w/v% were used. However, the composite containing 10 w% chitosan, against the sum of cellulose and β-Glycerophosphate, has shown less cell death and detachment when used at 0.01 w/v%, making it suitable for more in vitro studies in bone tissue engineering, as a promising economical biomaterial.


Mast cells in fracture healing: an experimental study using rat model.
To investigate the role of mast cells in wound healing process, the time course of appearance and distribution of mast cells were examined during fracture healing in rats. In the early phase of fracture healing, mast cells appeared in the original marrow adjacent to the internal callus. In later phases, mast cells appeared in the newly formed marrow in the external callus. In the external callus the number of mast cells reached a peak at around 5 weeks after fracture when remodeling was progressing. At this phase, the number of mast cells in the convex side of the fracture was significantly greater than that in the concave side. These results suggest that mast cells promote bone resorption, especially during remodeling of callus formed at the fractured site.


Chromene-Containing Aromatic Sulfonamides with Carbonic Anhydrase Inhibitory Properties.
Carbonic anhydrases (CAs, EC 184.108.40.206) catalyze the essential reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. A series of chromene-based sulfonamides were synthesized and tested as possible CA inhibitors. Their inhibitory activity was assessed against the cytosolic human isoforms hCA I, hCA II and the transmembrane hCA IX and XII. Several of the investigated derivatives showed interesting inhibition activity towards the tumor associate isoforms hCA IX and hCA XII. Furthermore, computational procedures were used to investigate the binding mode of this class of compounds, within the active site of hCA IX.


Idiopathic sclerosing peritonitis in a man.
Idiopathic sclerosing peritonitis is a rare disease described in young adolescent women, characterized by fibrosis and adhesions of the peritoneum to loops of the small bowel. Here we describe a 35-year-old man who underwent exploratory laparotomy for repeated small bowel obstruction. Only partial resection of the terminal ileum was possible because of adhesions; recurrent abdominal infections and leakage from anastomosis required further resection, which ultimately resulted in short bowel syndrome and malabsorption. The clinical and pathological findings were characteristic for idiopathic sclerosing peritonitis. We review the relevant literature, to confirm, to the best of our knowledge, that this is the first report of a male patient who has developed this rare disease.


Computational design of environmental sensors for the potent opioid fentanyl.
We describe the computational design of proteins that bind the potent analgesic fentanyl. Our approach employs a fast docking algorithm to find shape complementary ligand placement in protein scaffolds, followed by design of the surrounding residues to optimize binding affinity. Co-crystal structures of the highest affinity binder reveal a highly preorganized binding site, and an overall architecture and ligand placement in close agreement with the design model. We use the designs to generate plant sensors for fentanyl by coupling ligand binding to design stability. The method should be generally useful for detecting toxic hydrophobic compounds in the environment.


Optimization of variable number tandem repeat typing set for differentiating Mycobacterium tuberculosis strains in the Beijing family.
Variable number tandem repeat (VNTR) typing of Mycobacterium tuberculosis, as presently used, has often failed to differentiate clonal strains especially in areas where the Beijing family genotype is predominant. We have evaluated mycobacterial interspersed repetitive units (MIRUs), Queen's University of Belfast (QUB) loci and exact tandem repeat (ETR) loci individually for their abilities to differentiate the Beijing and non-Beijing genotype families of M. tuberculosis. The best locus was QUB 3232 followed by QUB 11b. Available MIRU, QUB and ETR loci were then consecutively arranged in declining order of discriminatory power, and combined to form an optimal set of 12-loci VNTR typing (MIRU 10, 26, 39, 40; QUB 11a, 11b, 15, 18, 26, 3232, 3336; ETR A) that possessed comparable discriminatory ability to IS6110 restriction fragment length polymorphism. This optimized 12-loci VNTR typing set can become an important tool for tracking M. tuberculosis of the Beijing family.


Cupping for treating neck pain in video display terminal (VDT) users: a randomized controlled pilot trial.
This was a randomized controlled pilot trial to evaluate the effectiveness of cupping therapy for neck pain in video display terminal (VDT) workers. Forty VDT workers with moderate to severe neck pain were recruited from May, 2011 to February, 2012. Participants were randomly allocated into one of the two interventions: 6 sessions of wet and dry cupping or heating pad application. The participants were offered an exercise program to perform during the participation period. A 0 to 100 numeric rating scale (NRS) for neck pain, measure yourself medical outcome profile 2 score (MYMOP2 score), cervical spine range of motion (C-spine ROM), neck disability index (NDI), the EuroQol health index (EQ-5D), short form stress response inventory (SRI-SF) and fatigue severity scale (FSS) were assessed at several points during a 7-week period. Compared with a heating pad, cupping was more effective in improving pain (adjusted NRS difference: -1.29 [95% CI -1.61, -0.97] at 3 weeks (p=0.025) and -1.16 [-1.48, -0.84] at 7 weeks (p=0.005)), neck function (adjusted NDI difference: -0.79 [-1.11, -0.47] at 3 (p=0.0039) and 7 weeks (p<0.0001)) and discomfort (adjusted MYMOP2 difference score: -0.72 [-1.04 to -0.40] at 3 weeks and -0.92 [-1.24, -0.60] at 7 weeks). Significant improvement in EQ-5D was observed at 7 weeks (1.0 [0.88, 1.0] with cupping and 0.91 [0.86, 0.91] with heating pad treatment, p=0.0054). Four participants reported mild adverse events of cupping. Two weeks of cupping therapy and an exercise program may be effective in reducing pain and improving neck function in VDT workers.


Bridging the gap in heart failure prevention: rationale and design of the Nurse-led Intervention for Less Chronic Heart Failure (NIL-CHF) Study.
The primary objective of the Nurse-led Intervention for Less Chronic Heart Failure (NIL-CHF) Study is to develop a programme of care that cost-effectively prevents the development of chronic heart failure (CHF). Methods NIL-CHF is a randomized controlled trial of a hybrid, home- and clinic-based, nurse-led multidisciplinary intervention targeting hospitalized patients at risk of developing CHF. A target of 750 patients aged >/=45 years will be exposed to usual post-discharge care or the NIL-CHF intervention. The composite primary endpoint is all-cause mortality or CHF-related admission during 3-5 years of follow-up. After 12 months recruitment, approximately 300 eligible patients (40% of target) have been randomized. Overall, 73% are male and the mean age is 65 +/- 10 years. The most common antecedents for CHF thus far are hypertension (70%, 95% CI, 64-75%), coronary artery disease (51%, 95% CI, 31-41%), and type 2 diabetes (26%, 95% CI, 21-31%), whereas 76% (95% CI, 69-82%) of patients have diastolic dysfunction, 29% (95% CI, 23-36%) left ventricular hypertrophy, 71% (95% CI, 64-78%) mitral valve dysfunction, and 7% (95% CI, 4-12%) have a left ventricular ejection fraction </=45%. As one of the largest randomized studies of its kind, NIL-CHF will ultimately provide important insights into the potential to prevent CHF via prolonged and intensive disease management.


The distribution and expression of S100A8 and S100A9 in gingival epithelium of mice.
Gingival epithelium protects against bacterial infection by producing antimicrobial peptides such as calprotectin. Calprotectin consists of proteins S100A8 and S100A9. Although in vitro assay has shown that neutrophils and gingival epithelial cells express calprotectin, the expression of S100A8 and S100A9 and colocalization of both S100 proteins in gingival tissue in vivo are not fully understood. The aim of this study was to investigate the distribution of S100A8 and S100A9 expression in gingival epithelium of mice in the presence and absence of infection. A quantitative analysis of S100A8 and S100A9 mRNA in junctional epithelium (JE) and oral gingival epithelium (OGE) of both germ-free mice and conventional mice was performed using laser microdissection and real-time polymerase chain reaction (PCR). Confirmation of S100A8 and S100A9 mRNA expression in the JE was conducted by fluorescent immunohistochemistry. Real-time PCR analysis indicated that S100A8 and S100A9 expressions were mainly detected in JE and only slightly or not detected in OGE. Levels of both S100A8 and S100A9 mRNA expression in JE of conventional mice were significantly higher than those in JE of germ-free mice. Additionally, fluorescent immunohistochemistry showed that S100A8 expression was observed in the JE of both conventional and germ-free mice, whereas S100A9 was expressed in the JE of conventional but not germ-free mice. S100A8 protein is expressed in JE cells of mice in the presence and in the absence of infection with oral bacteria. S100A9 expression in JE cells in the presence of microflora is significantly increased compared with the absence of microflora, which suggests that S100A9 expression may be induced by infection of microflora. The production of calprotectin in gingival epithelial cells may be mediated through S100A9 induction by bacterial infection.


High-order multiblock copolymers via iterative Cu(0)-mediated radical polymerizations (SET-LRP): toward biological precision.
We report a new approach for the facile synthesis of high-order multiblock copolymers comprising very short blocks. The approach entails sequential addition of different monomers via an iterative single electron transfer-living radical polymerization technique, allowing nearly perfect control of the copolymer microstructure. It is possible to synthesize high-order multiblock copolymers with unprecedented control, i.e., A-B-C-D-E-etc., without any need for purification between iterative 24 h block formation steps. To illustrate this concept, we report the synthesis of model P(MA-b-MA...) homopolymer and P(MA-b-nBuA-b-EA-b-2EHA-b-EA-b-nBuA) copolymer in extremely high yield. Finally, the halide end-group can be modified via "click chemistry", including thiol-bromide click chemistry, sodium methanethiosulfonate nucleophilic substitution, and atom transfer radical nitroxide coupling reaction, to yield functional, structurally complex macromolecules.


Host migration strategy and blood parasite infections of three sparrow species sympatrically breeding in Southeast Europe.
Mobile hosts like birds occupy a wide array of habitats in which they encounter various vector and parasite faunas. If the infection probability for vector-borne parasites varies among seasons and biomes, a migratory life can critically influence the infections of a host. The growing body of literature on avian blood parasites suggests that host migrations do not only influence prevalence of infection but can also evoke higher infection intensities and increased parasite diversity in migrant compared to resident host species. We investigated the prevalence, intensity and diversity of Plasmodium and Haemoproteus infections in three closely-related and sympatrically breeding sparrow species with different migration strategies ranging from residential house sparrow and partially migratory tree sparrow to the obligate migratory Spanish sparrow. With a prevalence of 49%, the migratory Spanish sparrows were significantly less frequently infected than the resident house sparrows (82%). The partially migratory tree sparrow showed an intermediate prevalence of 60%. The parasitaemias were similar in all three host species and indicated mostly chronic but also few acute infections. While we found Plasmodium parasites in all three sparrow species, only Spanish sparrows were infected with Haemoproteus parasites in our study. With nine clearly identified parasite lineages in our study and the highest number of lineages per infected individuals (i.e. relative diversity), Spanish sparrows harboured the most diverse parasite fauna. Our results suggest that migration strategies can affect Plasmodium and Haemoproteus infections of sparrows resulting in a lower parasite prevalence and higher parasite diversity in migratory hosts-at least during our host's breeding period. A general scope for all annual cycle periods and across various bird taxa remains to be elucidated.


Self-assessed learning style correlates to use of supplemental learning materials in an online course management system.
The benefit of online learning materials in medical education is not well defined. The study correlated certain self-identified learning styles with the use of self-selected online learning materials. First-year osteopathic medical students were given access to review and/or summary materials via an online course management system (CMS) while enrolled in a pre-clinical course. At the end of the course, students completed a self-assessment of learning style based on the Index of Learning Styles and a brief survey regarding their usage and perceived advantage of the online learning materials. Students who accessed the online materials earned equivalent grades to those who did not. However, the study found that students who described their learning styles as active, intuitive, global, and/or visual were more likely to use online educational resources than those who identified their learning style as reflective, sensing, sequential, and/or verbal. Identification of a student's learning style can help medical educators direct students to learning resources that best suit their individual needs.


Direct-to-consumer advertising skepticism and the use and perceived usefulness of prescription drug information sources.
This study investigates advertising skepticism in the context of consumers' prescription drug information seeking behavior. Results of a telephone survey found that: (a) the overall level of direct-to-consumer advertising (DTCA) skepticism among consumers was neutral; (b) DTCA skepticism was unrelated to age, positively related to education and income, and varied by race; (c) however, when all the antecedent variables were considered concurrently, only education emerged as a significant predictor (consumers with higher education were more skeptical of DTCA); (d) DTCA skepticism was not significantly related to perceived importance of prescription drug information; (e) DTCA skepticism was not associated with use of advertising and interpersonal sources of prescription drug information; and (f) DTCA skepticism was negatively related to perceived usefulness of advertising sources but unrelated to perceived usefulness of professional interpersonal sources (i.e., physicians and pharmacists). The article concludes with a discussion of findings and directions for future research.


Brain DNA methylomic analysis of frontotemporal lobar degeneration reveals OTUD4 in shared dysregulated signatures across pathological subtypes.
Frontotemporal lobar degeneration (FTLD) is an umbrella term describing the neuropathology of a clinically, genetically and pathologically heterogeneous group of diseases, including frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP). Among the major FTLD pathological subgroups, FTLD with TDP-43 positive inclusions (FTLD-TDP) and FTLD with tau-positive inclusions (FTLD-tau) are the most common, representing about 90% of the cases. Although alterations in DNA methylation have been consistently associated with neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, little is known for FTLD and its heterogeneous subgroups and subtypes. The main goal of this study was to investigate DNA methylation variation in FTLD-TDP and FTLD-tau. We used frontal cortex genome-wide DNA methylation profiles from three FTLD cohorts (142 FTLD cases and 92 controls), generated using the Illumina 450K or EPIC microarrays. We performed epigenome-wide association studies (EWAS) for each cohort followed by meta-analysis to identify shared differentially methylated loci across FTLD subgroups/subtypes. In addition, we used weighted gene correlation network analysis to identify co-methylation signatures associated with FTLD and other disease-related traits. Wherever possible, we also incorporated relevant gene/protein expression data. After accounting for a conservative Bonferroni multiple testing correction, the EWAS meta-analysis revealed two differentially methylated loci in FTLD, one annotated to OTUD4 (5'UTR-shore) and the other to NFATC1 (gene body-island). Of these loci, OTUD4 showed consistent upregulation of mRNA and protein expression in FTLD. In addition, in the three independent co-methylation networks, OTUD4-containing modules were enriched for EWAS meta-analysis top loci and were strongly associated with the FTLD status. These co-methylation modules were enriched for genes implicated in the ubiquitin system, RNA/stress granule formation and glutamatergic synaptic signalling. Altogether, our findings identified novel FTLD-associated loci, and support a role for DNA methylation as a mechanism involved in the dysregulation of biological processes relevant to FTLD, highlighting novel potential avenues for therapeutic development.


[Early diagnosis of dentomaxillary disharmony].
In permanent dentition diagnostic problems are certainly simplified, because of the stability of the occlusal and skeletal relationship; on the contrary in deciduous and mixed dentition diagnostic and therapeutic problems are more complex. That's why precocious clinical signs of dento-maxillary discrepancy must be known and observed, since the first years of life, following the modification of the dental arch. From deciduous dentition to the mixed till the permanent, in order to guide and create the condition for a correct setting of permanent teeth.


Highly thermosensitive Ca dynamics in a HeLa cell through IP(3) receptors.
Intracellular Ca(2+) distribution and its dynamics are essential for various cellular functions. We show with single HeLa cells that a microscopic heat pulse induces Ca(2+) uptake into intracellular stores during heating and Ca(2+) release from them at the onset of recooling, and the overshoot of Ca(2+) release occurs above the critical value of a temperature change, which decreases from 1.5 to 0.2 degrees C on increasing the experimental temperature from 22 to 37 degrees C. This highly thermosensitive Ca(2+) dynamics is probably attributable to the altered balance between Ca(2+) uptake by endoplasmic reticulum Ca(2+)-ATPases and Ca(2+) release via inositol 1,4,5-trisphosphate receptors. These results suggest that Ca(2+) signaling is extremely sensitive to temperature changes, especially around body temperature, in cells expressing inositol 1,4,5-trisphosphate receptors.


High Fat Activates O-GlcNAcylation and Affects AMPK/ACC Pathway to Regulate Lipid Metabolism.
A high-fat diet often leads to excessive fat deposition and adversely affects the organism. However, the mechanism of liver fat deposition induced by high fat is still unclear. Therefore, this study aimed at acetyl-CoA carboxylase (ACC) to explore the mechanism of excessive liver deposition induced by high fat. In the present study, the ORF of ACC1 and ACC2 were cloned and characterized. Meanwhile, the mRNA and protein of ACC1 and ACC2 were increased in liver fed with a high-fat diet (HFD) or in hepatocytes incubated with oleic acid (OA). The phosphorylation of ACC was also decreased in hepatocytes incubated with OA. Moreover, AICAR dramatically improved the phosphorylation of ACC, and OA significantly inhibited the phosphorylation of the AMPK/ACC pathway. Further experiments showed that OA increased global O-GlcNAcylation and agonist of O-GlcNAcylation significantly inhibited the phosphorylation of AMPK and ACC. Importantly, the disorder of lipid metabolism caused by HFD or OA could be rescued by treating CP-640186, the dual inhibitor of ACC1 and ACC2. These observations suggested that high fat may activate O-GlcNAcylation and affect the AMPK/ACC pathway to regulate lipid synthesis, and also emphasized the importance of the role of ACC in lipid homeostasis.


[Growth factors and gene therapy for erectile dysfunction].
Growth factors have a universal bioactivity. Gene therapy is a new strategy in dealing with erectile dysfunction (ED). This paper presents an overview on the value of growth factors, particularly the vascular epithelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1), in the treatment of ED.


Lung adenocarcinomas with micropapillary components.
Micropapillary adenocarcinoma is becoming increasingly recognized as a prognostically important histological subtype of carcinoma in various organs. This report presents the clinicopathological findings of lung adenocarcinomas with micropapillary components. A total of 15 patients with micropapillary components were selected between April 2005 and December 2008. The results of their clinical presentation, metastasis to lymph nodes, pleural invasion, pathological stage, and clinical outcomes were evaluated. In all, 12 patients underwent a lobectomy or bilobectomy with a regional lymph node dissection; 8 showed metastases to the regional lymph nodes at the time of the operation. Altogether, 14 of 15 cases showed lymphovascular invasion; 10 cases were up-staged after the operation because of lymph node metastases or pleural invasion. The duration of follow-up ranged from 1 to 42 months (median 16 months). Seven patients are alive without disease, whereas seven are alive with disease and one patient died of disease. These results suggest that the micropapillary components are a manifestation of aggressive behavior, as shown by the frequent lymph node metastases and pleural invasion. Surgeons should search more carefully for metastases and conduct a closer follow-up on these patients when this feature is present with lung adenocarcinoma.


Thoracic mesothelioma associated with abdominal mesenteric panniculitis.
Mesenteric panniculitis (MP) is characterized by an abdominal inflammatory reaction and mesenteric fat necrosis. Clinically, MP manifests as recurrent abdominal pain, pyrexia, and space-occupying peritoneal masses. We report a patient with MP, severe enough to require immunosuppressant treatment, who developed a recurrent pleural effusion. Malignant mesothelioma was identified in the pleural space 3 yr after initial pleural investigation. This case is the second report of pleural effusion associated with MP. It is the first report in which thoracic mesothelioma and MP occurred together. MP has been associated with other malignancies.


Drug induced esophageal lesions studied in vitro.
This paper describes an in vitro method of studying the esophago-irritant potential of oral formulations of drugs. Porcine esophagus was used. The method offers the possibility of studying muscle activity and enzyme leakage (e.g. LDH) and of performing histomorphology of the exposed preparations. Examples of drugs which were tested are alprenolol (Aptin), propranolol (Inderal), doxycycline (Idocyklin) and (Vibramycin) and emepronium bromide (Cetiprin). Concerning effects on muscle activity, Aptic caused a marginal contraction while Cetiprin caused a relaxation of the esophagus preparation. Increased LDH-leakage was noted during exposure with the above mentioned pills in comparison with concurrent control preparations. Histopathological examination disclosed morphological changes such as softening and necrosis of the squamous epithelium of the esophageal mucosa after exposure to drugs like Idocyklin and Aptin.


Immature mouse granulocytic myeloid cells are characterized by production of ficolin-B.
Ficolins activate the lectin pathway of the complement system upon binding to carbohydrate patterns on pathogens. To characterize the producer cells of ficolin-B the expression of mouse ficolin-B, the orthologue of human M-ficolin, was studied in macrophages and dendritic cells during differentiation from bone marrow cells, in primary granulocytes, and during differentiation of granulocytes derived from ER-Hoxb8 cells. Expression of ficolin-B mRNA declined in all myeloid cell types to low levels during terminal differentiation. However, in contrast to macrophages and dendritic cells, ficolin-B expression was enhanced upon activation in granulocytes. High expression of ficolin-B was observed in primary immature neutrophilic CD11b(+) Ly-6C(int) Ly-6G(high) granulocytes when isolated from the bone marrow, in particular during sepsis. Ficolin-B was demonstrated in lysates of primary granulocytes, ER-Hoxb8-derived granulocytes, bone marrow-derived macrophages, and dendritic cells. Native ficolin-B from cell lysates and supernatants of granulocytes activated the lectin pathway as measured by binding to MASP-2 and inducing C4 deposition. Specific staining demonstrated intra-cellular or cell associated ficolin-B protein in activated immature granulocytes deposited in a granular fashion. This study shows that ficolin-B is stored in and set free from immature granulocytic myeloid cells indicating a role in the early infection-induced cellular response of these inflammatory cells.


Genome-wide association analyses identify new loci influencing intraocular pressure.
Elevated intraocular pressure (IOP) is a significant risk factor for glaucoma, the leading cause of irreversible blindness worldwide. While previous studies have identified numerous genetic variants associated with IOP, these loci only explain a fraction of IOP heritability. Recently established of biobank repositories have resulted in large amounts of data, enabling the identification of the remaining heritability for complex traits. Here, we describe the largest genome-wide association study of IOP to date using participants of European ancestry from the UK Biobank. We identified 671 directly genotyped variants that are significantly associated with IOP (P < 5 × 10-8). In addition to 103 novel loci, the top ranked novel IOP genes are LMX1B, NR1H3, MADD and SEPT9. We replicated these findings in an external population and examined the pleiotropic nature of these loci. These discoveries not only further our understanding of the genetic architecture of IOP, but also shed new light on the biological processes underlying glaucoma.


Therapeutic effects of quetiapine on memory deficit and brain β-amyloid plaque pathology in a transgenic mouse model of Alzheimer's disease.
Our previous study has shown the preventive effects of quetiapine, an atypical antipsychotic drug, on memory impairment and brain pathological changes in a mouse model of Alzheimer's disease (AD). The aim of the present study was to evaluate the therapeutic effects of quetiapine on memory deficit and neuropathology in an amyloid precursor protein (APP)/presenilin-1 (PS1) double transgenic mouse model of AD. The APP/PS1 mice started to have detectable brain β-amyloid (Aβ) at 3 months of age. Non-transgenic and transgenic mice were treated with quetiapine (0, 2.5, or 5 mg/(kg day)) in drinking water from the age of 4 months. After 8 months of continuous quetiapine administration, memory deficit was reversed and brain Aβ plaque pathology was attenuated in the AD mice. Quetiapine also decreased the soluble Aβ peptide levels in brain and cerebrospinal fluid (CSF), and attenuated the decreased synaptic protein levels in the AD mice. Furthermore, quetiapine normalized the abnormal activity of glycogen synthase kinase-3β (GSK-3β), an AD-involved kinase, in the AD mice. These results suggest that quetiapine can treat and alleviate the neuropathology in an APP/PS1 transgenic mouse model of AD, and indicate that quetiapine may have therapeutic effects in the treatment of AD.


Computational study of inclusion complexes of V-type nerve agents (VE, VG, VM, VR and VX) with β-cyclodextrin.
The effective detoxification of organophosphate (OP) nerve agents (OPNAs) is a challenging issue for scientists. The host-guest inclusion complexes of five V-type nerve agents (VE, VG, VM, VR and VX) with β-cyclodextrin (β-CD) have been studied by combining quantum mechanical (QM) calculations and molecular dynamics (MD) simulations. The frontier molecular orbital (FMO) and molecular electrostatic potential (MEP) have been analyzed to describe the reactivity parameters and electronic properties. The obtained results clearly reveal that stable complexes were formed in both vacuum and water media, and the complexation process occurred spontaneously. To understand non-covalent interactions, natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) have been used. IR and Raman spectra have been calculated to confirm the formation of complexes and also thermodynamic parameters have been investigated. It was demonstrated that in addition to van der Waals interactions, the presence of intermolecular hydrogen bonds enhances the stability of these complexes. Furthermore, MD simulations were carried out to get a better insight into the inclusion process of the above complexes. From MD simulations, all simulated systems reached full equilibration at 1000 ps and the V-agent molecules consistently remained in the β-CD cavity and only had vibrational motion inside the cavity. More importantly, MD simulations support the findings of QM calculations and indicate that hydrogen bonding can help the leaving groups of V-agents to be released and them to be hydrolyzed. All results have shown that the VR agent formed the most stable complex with β-CD molecule than that of other agents.Communicated by Ramaswamy H. Sarma.


Optical versus virtual: teaching assistant perceptions of the use of virtual microscopy in an undergraduate human anatomy course.
Many studies that evaluate the introduction of technology in the classroom focus on student performance and student evaluations. This study focuses on instructor evaluation of the introduction of virtual microscopy into an undergraduate anatomy class. Semi-structured interviews were conducted with graduate teaching assistants (TA) and analyzed through qualitative methods. This analysis showed that the teaching assistants found the virtual microscope to be an advantageous change in the classroom. They cite the ease of use of the virtual microscope, access to histology outside of designated laboratory time, and increasing student collaboration in class as the primary advantages. The teaching assistants also discuss principal areas where the use of the virtual microscope can be improved from a pedagogical standpoint, including requiring students to spend more time working on histology in class.


Evidence for anatomical but not functional asymmetry in the hemidecorticate rat.
Rats with unilateral ablation of the left or right cerebral neocortex or left or right hippocampus were studied in a battery of tests of spatial orientation, motor coordination, and social behavior, including Morris water task, radial arm maze, feeding, narrow beam traversing, puzzle latches, hoarding, grooming, nest building, running wheel activity, male--male interaction, and shock-induced aggression. Comparison of the brains of operated and control rats confirmed previous suggestions that the right hemisphere of the rat is bigger and may have different connections than the left hemisphere. Despite the morphological asymmetries, comparison of the behavior of rats with right hemidecortication with that of rats with left hemidecortication, and of rats with right and of those with left hippocampal lesions, failed to show a single instance of functional asymmetry in the rat brain. These behavioral results stand in marked contrast to previous reports of functional asymmetry in the control of activity, orientation, and rotation.


Incidence of otitis media in children with deformational plagiocephaly.
In the past decade, deformational plagiocephaly has seen a staggering increase attributed to the Back to Sleep Campaign of April 1992. With this increase, the possible clinical associations need to be fully understood. The anatomic changes seen include ipsilateral occipital flattening, ipsilateral frontal bossing, ipsilateral anterior ear displacement, contralateral occipital bossing, and contralateral frontal flattening [J Craniofac Surg 2004;15:368-372, erratum in J Craniofac Surg 2004;15:705; Fig. l]. Children with deformational plagiocephaly can have malpositioned ears affecting normal drainage of the eustachian tube as it shifts with this deformity. The eustachian tube plays an important role in draining the middle ear. As evidenced by children with cleft palates, structural differences in the anatomy of the middle ear and eustachian tube can result in an increased susceptibility to otitis media. An institutional review board-approved retrospective study was conducted on all patients whose conditions were diagnosed as deformational plagiocephaly from a cleft and craniofacial deformities clinic for a 2-year period. Parents of patients self-reported the number of ear infections on a questionnaire. The questionnaire results were compared to age-matched patient data available from the Center for Disease Control. There were 1259 patients who fit the inclusion criteria for the questionnaire part of the study, and of these, 634 (50.4%) reported at least 1 ear infection by 1 year of age. In addition to the questionnaire, a subset of infants with deformational plagiocephaly up to 1 year of age were administered a tympanogram, to assess the state of the middle ear. There were 124 patients who fit the inclusion criteria for the tympanometry part of the study, and of these 121 had an abnormal tympanogram at 1 or more clinic visits. The questionnaire did not show deformational plagiocephaly to be a significant risk factor for otitis media in our patient population; however, a trend directly correlating otitis media and the severity level of deformational plagiocephaly was observed. Although this trend lacked statistical significance, further studies should explore these differences. Tympanogrametry showed a marked percentage of infants with deformational plagiocephaly to have eustachian tube dysfunction. Future studies will focus on the significance of these findings.


Aetiology of childhood acute leukaemias: current status of knowledge.
Acute leukaemia is a consequence of malignant transformation of a haematopoetic progenitor cell. Molecular studies have revealed a prenatal origin of many childhood leukaemias. According to current models, a preleukaemic stem cell clone is generated by a first mutation in utero which, in a minority of children, progresses to leukaemia after receiving further postnatal genetic hits. The nature of pre- and postnatal events involved in leukaemogenesis in children is not well understood. Although genetic predisposition and specific environmental exposures may account for individual cases, the bulk of childhood leukaemia cannot be explained by any of these factors. The higher incidence of the most common leukaemia subtype in affluent societies, as well as the age peak between 2-5 y, suggest a contributory role of socioeconomic factors. An abnormal immune response during delayed exposure to common infections provides a plausible mechanism for malignant progression of preleukaemic clones in a subgroup of children. As highlighted in this review, a common cause for all types and subtypes of childhood leukaemia is highly unlikely. Deeper insights into the pathogenesis of childhood leukaemia will rely on large-scale and combined epidemiological and biomolecular studies.


Erythropoietic protoporphyria. The problem of a suitable screening test.
Erythropoietic protoporphyria (EPP) is characterized by increased red cell protoporphyrins and is included in the differential diagnosis of children presenting with photosensitivity. In the past 20 years, using the traditional solvent extraction qualitative screening test for blood porphyrins, the diagnosis of EPP had been missed in 9 out of 10 patients but recently, using fluorescence microscopy of erythrocytes, no patients with EPP have been missed. All 14 patients in Northern Ireland known to have EPP were recalled and it was found that fluorescence microscopic determination was positive in all cases. We recommend fluorescence microscopy as the screening test of choice for the detection of increased red cell porphyrins.


Is field intubation useful?
The establishment and maintenance of an adequate airway is often the single most important initial therapy provided to a victim of severe injury. This may be accomplished by simple techniques such as placement of an oral or nasopharyngeal airway as well as bag-mask ventilation techniques. More advanced techniques such as endotracheal intubation require a higher level of training and expertise for both prehospital and hospital providers. Although paramedics routinely practice endotracheal intubation in the field, there are increasing reports on the many potential risks associated with these procedures as well as increased morbidity and mortality in both pediatric and adult patients. These data have important implications for field airway management in the critically ill trauma patient.


Alternate deacylating specificities of the archaeal sirtuins Sir2Af1 and Sir2Af2.
Sirtuins were originally shown to regulate a wide array of biological processes such as transcription, genomic stability, and metabolism by catalyzing the NAD(+) -dependent deacetylation of lysine residues. Recent proteomic studies have revealed a much wider array of lysine acyl modifications in vivo than was previously known, which has prompted a reevaluation of sirtuin substrate specificity. Several sirtuins have now been shown to preferentially remove propionyl, succinyl, and long-chain fatty acyl groups from lysines, which has changed our understanding of sirtuin biology. In light of these developments, we revisited the acyl specificity of several well-studied archaeal and bacterial sirtuins. We find that the Archaeoglobus fulgidus sirtuins, Sir2Af1 and Sir2Af2, preferentially remove succinyl and myristoyl groups, respectively. Crystal structures of Sir2Af1 bound to a succinylated peptide and Sir2Af2 bound to a myristoylated peptide show how the active site of each enzyme accommodates a noncanonical acyl chain. As compared to its structure in complex with an acetylated peptide, Sir2Af2 undergoes a conformational change that expands the active site to accommodate the myristoyl group. These findings point to both structural and biochemical plasticity in sirtuin active sites and provide further evidence that sirtuins from all three domains of life catalyze noncanonical deacylation.


Differential mRNA and miRNA Profiles Reveal the Potential Roles of Genes and miRNAs Involved in LPS Infection in Chicken Macrophages.
Lipopolysaccharide (LPS) is a component of the cell wall of Gram-negative bacteria, and triggers an inflammatory response both in vitro and in vivo. Here, we used LPS from Escherichia coli serotype enteritidis to stimulate chicken macrophages (HD11) and conducted the transcriptome analysis using a bioinformatics approach to explore the functions of immune-related genes and miRNAs. In total, 1759 differentially expressed genes (DEGs) and 18 differentially expressed (DE)-miRNAs were detected during LPS infection. At 6 h post infection, 1025 DEGs and 10 miRNAs were up-regulated, and 734 DEGs and 8 DE-miRNAs were down-regulated. Based on both RNA hybrid and miRanda systems, 55 DEGs could be targeted by 14 DE-miRNAs. The target genes were related to the immune response, such as IRF8, STAT3, TRAF7, and other potential candidate genes. The DE-miRNAs miR146a-3p, miR6583-5p, and miR30c-2-3p were investigated further. They were predicted to target 34 genes that may also be candidates for immune-related miRNAs and genes. Our results enhanced our understanding of the pathogenic mechanisms of Gram-negative bacteria in chickens.


[Cardioprotective effect of remote ischemic preconditioning].
Authors of review analyze papers published in 1993-2008 on problem of remote ischemic preconditioning of the heart. The main manifestations of preconditioning at a distance are a decrease in infarct size, an improvement of cardiac contractility in reperfusion period, an enhancement of cardiac tolerance to arrhythmogenic impact of ischemia-reperfusion. The published data demonstrate that the humoral factors (endogenous opioids, bradykinin, calcitonin gene-related peptide, endogenous cannabinoids) play the main role in preconditioning at a distance. In the review, it is presented data that protein kinase C, mitochondrial ATP-sensitive K+ -channel, mitochondrial permeability transition pore, NO-synthase, reactive oxygen species are involved in signaling cascade of remote preconditioning.


Fat-free mass estimation by the two-electrode impedance method.
In 202 healthy subjects (81 men, 121 women) aged 12-71 y, impedance (Z) was measured with a two-electrode analyzer. Fat-free mass was assessed by hydrodensitometry (FFMd). This population was randomized into two groups for cross-validation. In group 1 the relationship between ht2/Z at 1 MHz and FFMd was highly significant (r = 0.85, P less than 0.001). The equation for predicting FFMd from impedance, height2, weight, and age obtained in group 1 (r = 0.97) was applied to group 2 (r = 0.96) without reduction in r value. The accuracy of this equation was not different between men and women or between active and sedentary people. These data indicate that the two-electrode impedance method is a reliable and valid approach not only for the determination of extracellular water (as previously shown) but also for that of FFM.


A dual role for EDEM1 in the processing of rod opsin.
Mutations in rod opsin, the archetypal G-protein-coupled receptor, cause retinitis pigmentosa. The majority of mutations, e.g. P23H, cause protein misfolding, resulting in ER retention, induction of the unfolded protein response and degradation by ERAD. If misfolded rod opsin escapes degradation, it aggregates and forms intracellular inclusions. Therefore, it is important to identify the chaperones that mediate the folding or degradation of rod opsin. ER degradation enhancing alpha-mannosidase-like 1 (EDEM1) can enhance the release of terminally misfolded glycoproteins from the calnexin chaperone system. Here, we identify EDEM1 as a novel chaperone of rod opsin. EDEM1 expression promoted the degradation of P23H rod opsin and decreased its aggregation. By contrast, shRNA-mediated knockdown of EDEM1 increased both the amount of P23H rod opsin and its aggregation into inclusions. EDEM1 was detected in rod photoreceptor inner segments and EndoH-sensitive rod opsin co-immunoprecipitated with EDEM1 from retina, suggesting that rod opsin is a physiological EDEM1 client. Unexpectedly, EDEM1 binding to rod opsin was independent of mannose trimming and EDEM1 promoted the cell-surface expression of mutant rod opsin. Collectively, the data suggest that EDEM1 is a chaperone for rod opsin and that expression of EDEM1 can be used to promote correct folding, as well as enhanced degradation, of mutant proteins in the ER to combat protein-misfolding disease.


Using bioassays and species sensitivity distributions to assess herbicide toxicity towards benthic diatoms.
Although benthic diatoms are widely used in ecological studies of aquatic systems, there is still a dearth of data concerning species sensitivities towards several contaminants. Within the same community, different species may respond differently depending on their physiological and ecological characteristics. This lack of knowledge makes specific appropriate risk assessment impossible. To find out whether species sensitivity distribution (SSD) could be used to estimate the risk of herbicide toxicity for diatoms, we need to know whether their sensitivity depends on their physiological and ecological characteristics. We carried out single-species bioassays on 11 diatom species exposed to 8 herbicides. Dose-responses relationships were used to extrapolate the Effective Concentration 5 (EC(5)) and the Effective Concentration 50 (EC(50)) for each exposure. These data were used to fit a SSD curve for each herbicide, and to determine the Hazardous concentration 5 (HC(5)) and 50 (HC(50)). Our results revealed a high level of variability of the sensitivity in the set of species tested. For photosystem-II inhibitor (PSII) herbicides, diatoms species displayed a typical grouping of sensitivity levels consistent with their trophic mode and their ecological guild. N-heterotroph and "motile" guild species were more tolerant of PSII inhibitors, while N-autotroph and "low profile" guild species were more sensitive. Comprehensive SSD curves were obtained for 5 herbicides, but not for sulfonylurea herbicides or for dimetachlor, which had toxicity levels that were below the range of concentration tested. The SSD curves provided the following ranking of toxicity: diuron> terbutryn> isoproturon> atrazine> metolachlor. The HC that affected 5% of the species revealed that, even at the usual environmental concentrations of herbicides, diatom assemblages could be affected, especially by isoproturon, terbutryn, and diuron.


Using elemental profiles and stable isotopes to trace the origin of green coffee beans on the global market.
A broad elemental profile incorporating 54 elements (Li, Be, B, Na, Mg, Al, P, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Y, Mo, Pd, Ag, Cd, Sn, Sb, Te, Cs, Ba, La, Ce, Pr, Nd, Sm, Eu, Gd, Dy, Er, Tm, Yb, Re, Ir, Pt, Au, Hg, Tl, Pb, Bi and U) in combination with δ(2) H, δ(13) C, δ(15) N and δ(18) O was used to characterise the composition of 62 green arabica (Coffea arabica) and robusta (Coffea canephora) coffee beans grown in South and Central America, Africa and Asia, the four most internationally renowned areas of production. The δ(2) H, Mg, Fe, Co and Ni content made it possible to correctly assign 95% of green coffee beans to the appropriate variety. Canonical discriminant analysis, performed using δ(13) C, δ(15) N, δ(18) O, Li, Mg, P, K, Mn, Co, Cu, Se, Y, Mo, Cd, La and Ce correctly traced the origin of 98% of coffee beans.


A new labdanic norditerpene from Pinus sylvestris.
A new labdanic norditerpene and six known labdanic diterpenes were isolated from the petroleum ether extract of the needles of Pinus sylvestris. By spectroscopic methods, the isolated compounds were determined as 15-norpinifolic acid (1), pinifolic acid (2), 4-eplimbricataloic acid (3), monomethyl pinifolate (4), 18α-acetoxylabd-8(17)-en-15-oic acid (5), 2-pentenoic acid (6) and 3β-hydroxy-8(17),E-13-labdadien-15-oic acid (7), respectively. Compound 1 showed significant anti-tumour activity.


Factors influencing the variation in tenderness of seven major beef muscles from three Angus and Brahman breed crosses.
Beef carcasses (n=30) from 3/4 Angus (A)×1/4 Brahman (B), 1/4A×3/4B, and 1/2A×1/2B F(1) crosses were used to evaluate breed type, electrical stimulation, and postmortem aging on the M. semimembranosus (SM), M. semitendinosus (ST), M. biceps femoris (BF), M. vastus lateralis (VL), M. gluteus medius (GM), M. longissimus dorsi lumborum (LD), and M. triceps brachii (TB). Shear force values decreased with increased postmortem aging to a greater extent in steaks from 3/4A×1/4B than steaks from the other breed types. Shear force values for steaks from the round (SM, ST, BF, VL) were higher than steaks from the loin (LD, GM) and chuck (TB) for both electrically stimulated and non-electrically stimulated muscles. In the LD muscle, calpastatin activities were similar among breed types. Muscle type played the greatest role in determining tenderness.


Bowel management with antegrade colonic enema using a Malone or a Monti conduit--clinical results.
During this last decade, major surgical improvements have been proposed for the treatment of patients suffering from faecal incontinence or intractable constipation. Between 1996 and 1999, 12 patients mainly presenting with spina bifida were operated for antegrade colonic enema (ACE). In seven cases, a Malone procedure was performed. In 5 cases we used a Monti plasty to create a continent catheterisable conduit. In 4 cases the neoconduit was placed between the transverse colon and the umbilicus. The mean follow-up was 15 months. Bowel control and continence were obtained in 11 cases, postoperatively. One early complete stenosis of the cutaneous stoma occurred, after which the patient did not wish to carry on. Another patient stopped using his ACE stoma after several months because he was able to manage his bowel evacuation voluntarily without requiring an enema. The other ten patients have greatly improved their quality of life. Complications included principally stomal stenosis which can be regularly dilated by the patient himself using the Hegar dilator. Patients with umbilical stoma have a result comparable to patients with Malone procedure. Our series shows that ACE can be performed without an appendix using a Monti plasty. Implantation of the continent conduit in the caecum or in the transverse colon does not modify the overall results of ACE.