Plant biomass and seed production of the legumes Aeschynomeme histrix and Stylosanthes hamata and the potential of endozoochory by cattle and sheep in semi-arid native pastures.
Endozoochory is a substantial vector for seed dispersal and plays an important role in vegetation dynamics, mainly in colonisation processes through seed input to the vegetation and soil seed bank. We investigated the endozoochorous seed input by cattle and sheep on a pasture located in the western region of Burkina Faso. Through germination experiments, we assessed viable seed content of the dung of these grazing animals to estimate their suitability and efficiency for seed dispersal of fodder legumes. Cattle and sheep were daily fed seeds of Sthylosanthes hamata and Aeschynomene histrix, mixed with cotton seed cake. Faeces containing seeds of both legumes were collected 24 h after feeding. One part of faeces samples was spread in buckets of soil for direct germination in the greenhouse to evaluate germinating seed content. To improve pastures, a randomized completed design with 6 replications was conducted with both legumes and phosphorus fertilization (0 and 100 kg/ha of P2O5) and year as experimental factors. Recovery of A. histrix seeds was better than that of S. hamata with cattle (18 and 9%, respectively) compared to sheep. Seed recovered from faeces had higher germination with sheep than cattle. Thus, S. hamata seed recovered from faeces germinated well (12 and 45% with cattle and sheep, respectively, than fresh seeds used as control. However, A. histrix's seeds recovered from faeces germinated less than control (P < 0.001). The findings confirmed that ruminants could be used for targeted legume seed dispersal in natural pastures. A. histrix and S. hamata have high potential for plant biomass and seed production when phosphorus is applied. Seed ingestion by ruminants should be undertaken for improving natural pastures in semi-arid zones as lower cost practice.


Obstructive sleep apnea and increased risk of glaucoma: a population-based matched-cohort study.
Previous studies had reported an increased prevalence of glaucoma in patients with obstructive sleep apnea (OSA). However, the risk of open-angle glaucoma (OAG) among patients with OSA remains unclear. Using a nationwide, population-based dataset in Taiwan, this study aimed to examine the prevalence and risk of OAG among patients with OSA during a 5-year follow-up period after a diagnosis of OSA. A retrospective, matched-cohort study. This study used data sourced from the Longitudinal Health Insurance Database 2000. We included 1012 subjects with OSA in the study cohort and randomly selected 6072 subjects in the comparison group. Each subject in this study was individually traced for a 5-year period to identify those subjects who subsequently received a diagnosis of OAG. Cox proportional hazards regression was performed to calculate the 5-year risk of OAG between the study and comparison cohorts. The incidence and risk of OAG between the study and comparison groups. During the 5-year follow-up period, the incidence rate per 1000 person-years was 11.26 (95% confidence interval [CI], 8.61-14.49) and 6.76 (95% CI, 5.80-7.83) for subjects with and without OSA, respectively. After adjusting for monthly income, geographic region, diabetes, hypertension, coronary heart disease, obesity, hyperlipidemia, renal disease, hypothyroidism, and the number of outpatient visits for ophthalmologic care during the follow-up period, stratified Cox proportional hazards regression revealed that the hazard ratio for OAG within the 5-year period for subjects with OSA was 1.67 (95% CI, 1.30-2.17; P<0.001) that of comparison subjects. Our results suggest that OSA is associated with an increased risk of subsequent OAG diagnosis during a 5-year follow-up period. The authors have no proprietary or commercial interest in any of the materials discussed in this article.


Does the presence of nuclear vacuoles in human sperm selected for ICSI affect pregnancy outcome?
To verify whether or not microinjection of sperm with a normal nuclear shape but large vacuoles affects IVF-ICSI pregnancy outcome. A comparative study testing IVF outcome parameters of IVF-ICSI, based on morphological selection of spermatozoa with normal nuclei against those based on microinjection of sperm with a normal nuclear shape but large vacuoles. An experimental group, including 28 IVF-ICSI cycles, where only embryos obtained from microinjection of spermatozoa with a normal nuclear shape but large vacuoles were transferred, was matched with a control group, including 28 IVF-ICSI cycles, where only embryos obtained from microinjection of spermatozoa with a strictly defined morphologically normal nuclear shape and content were transferred. The main outcome was IVF-ICSI pregnancy rate. The experimental group exhibited a significantly lower pregnancy rate per cycle and significantly higher abortion rate per pregnancy compared to the control group (18 versus 50%, and 80 versus 7%, respectively, P=0.01). Microinjection of vacuolated sperm appears to reduce the pregnancy rate and appears to be associated with early abortion.


Human Immunodeficiency Virus in Pregnancy.
Approximately 5000 people living with human immunodeficiency virus (HIV) give birth each year. Perinatal transmission of HIV will occur in about 15% to 45% of pregnancies without treatment. With appropriate antiretroviral therapy for pregnant people as well as appropriate intrapartum and postpartum interventions, the rate of perinatal transmission can be reduced to less than 1%. Antiretroviral therapy will also reduce health risks for pregnant patients living with HIV. All pregnant people should be offered the opportunity to learn their HIV status and access treatment as needed.


Detection of tumor vascularity in hepatocellular carcinoma with contrast-enhanced Dynamic Flow imaging: Comparison with contrast-enhanced power Doppler imaging.
To compare the effectiveness of contrast-enhanced Dynamic Flow imaging and contrast-enhanced power Doppler imaging using Levovist(®) as a microbubble contrast agent in evaluating intratumoral vascularity in hepatocellular carcinoma (HCC). Twenty-nine patients with 54 hepatocellular carcinoma nodules (before treatment, 31; after treatment, 23) were studied with both Dynamic Flow and power Doppler imaging with intravenous injection of Levovist(®). Tumor vascularity was categorized as 0, no blood flow signals within the tumor; 1, dotlike blood flow signals within the tumor; 2, moderate blood flow signals within the tumor; and 3, abundant blood flow signals within the tumor. Detectability of intratumoral vascularity of hepatocellular carcinoma in three groups based on tumor depth, blooming and noise artifacts on contrast-enhanced Dynamic Flow and contrast-enhanced power Doppler imaging were also compared with results obtained using dynamic CT as a the gold standard. The effectiveness of contrast-enhanced Dynamic Flow and contrast-enhanced power Doppler imaging in assessing therapeutic effect were compared at the same time. The ability of contrast-enhanced Dynamic Flow Doppler imaging to detect tumor vascularity in the superficial and intermediate hepatocellular carcinoma groups was close to that of contrast-enhanced power Doppler imaging (p>0.05). However, contrast-enhanced Dynamic Flow imaging demonstrated tumor parenchymal stain in 28 hepatocellular carcinoma nodules (61%), which was not detected by contrast-enhanced power Doppler imaging. Further, significantly fewer artifacts appeared in contrast-enhanced Dynamic Flow imaging than in contrast-enhanced power Doppler imaging (p<0.001). In assessing therapeutic response, the sensitivity of contrast-enhanced Dynamic Flow imaging was similar to that of dynamic CT. In deep areas, however, those more than 6 cm below the surface of the body, contrast-enhanced Dynamic Flow imaging was less sensitivity than contrast-enhanced power Doppler imaging (p=0.005). Contrast-enhanced Dynamic Flow imaging provides an effective approach to assessing intratumoral vascularity and therapeutic response in HCC lesions situated less than 6 cm from the surface of the body. It is superior to contrast-enhanced power Doppler imaging in its ability to detect tumor parenchymal stain and production of fewer artifacts.


The impact of environmental regulation on firm exports: evidence from environmental information disclosure policy in China.
As an important environmental regulation tool, does the environmental information disclosure have the pollution haven effect and adversely affect Chinese export? Research on such topics can provide implications for Chinese policymakers to formulate realistic environmental policies and employ information disclosure environmental regulation tools to coordinate the economic-environmental development. Using the 2003-2013 Annual Survey of Industrial Firms Database and difference-in-difference identification, we examine the effect of environmental information disclosure policy on firm exports and its impacting mechanisms. The empirical results show that the Chinese environmental information disclosure policy has reduced the scale of industrial firms' exports in the regulated regions, indicating the existence of the pollution heaven effect in China. And also, we find that this policy mainly inhibits export activities of enterprises in coastal areas. Considering enterprise heterogeneity, the policy plays an inhibitory role in the exports of the non-state-owned firms, large firms, and low-productivity firms. Furthermore, the impact mechanism test shows that corporate financing constraint and production costs are important channels for environmental information disclosure policy affecting corporate export activities. It implies that, in developing countries such as China, policymakers and enterprises need to adopt forward-looking strategies to reduce the negative influence of environmental constraints on corporate exports and coordinate environmental governance and sound development of enterprises.


Novel bisphosphonate inhibitors of phosphoglycerate kinase.
A series of novel, conformationally-restrained bisphosphonate analogues of 1,3-bisphosphoglyceric acid 1 have been synthesised and evaluated as inhibitors of 3-PGK. They are competitive inhibitors of the human enzyme and, especially for certain alpha-halophosphonic acid analogues, both Ki and IC50 values extend into the submicromolar range.


Genome Sequences of Allochromatium palmeri and Allochromatium humboldtianum Expand the Allochromatium Family Tree of Purple Sulfur Photosynthetic Bacteria within the Gammaproteobacteria and Further Refine the Genus.
New genomes of two Allochromatium strains were sequenced. Whole-genome and average nucleotide identity based on BLAST (ANIb) comparisons show that Allochromatium humboldtianum is the nearest relative of Allochromatium vinosum (ANIb, 91.5%), while both Allochromatium palmeri and Thermochromatium tepidum are more distantly related (ANIb, <87%). These new sequences firmly establish the position of Allochromatium on the family tree.


Atraumatic dislocation of a modern rotating hinge total-knee prosthesis. A rare but devastating complication.
The number of total knee arthroplasties (TKA) is rising in many countries along with the numbers of the revision TKA. Rotating hinge knee (RHK) implants have a fundamental role in the revision TKA and their design has evolved during the last years becoming appealing to many surgeons worldwide. They are mainly used in cases where large bone defects and severe soft tissue imbalance exist. However, despite their recent advancements, they are still associated with high complication rates such as infection, periprosthetic fractures and insufficiency of the extensor apparatus. An uncommon complication of the latest rotating hinge implants is their mechanical component failure. Here we present a rare case of such a devastating complication where a modern RHK prosthesis dislocated without a preceding traumatic event, a review of the corresponding literature and a potential cause for the failure of the mechanism. Moreover, insight on key aspects that need to be addressed is provided, like intrinsic and extrinsic factors which play a crucial role and shouldn't be overlooked for a successful outcome.


A preliminary study of the interaction of glass-ionomer dental cements with amino acids.
The aim of the study was to determine how the presence of low concentrations of the amino acids glycine and alanine affected the interaction of restorative glass-ionomer cements with water. For each material (Fuji IX and Ketac Molar, both handmixed), sets of six cylindrical specimens of 4 mm diameter x 6 mm height were prepared and weighed; then stored individually in one of: deionized water, 0.1% by mass glycine, 0.5% glycine, 0.1% alanine (Sigma Aldrich) and 0.5% alanine. After 1 week, the specimens were re-weighed and the pH of each solution determined. The solutions were then bulked and analyzed for ion content (Na, Ca, Al, Si and P) using ICP-OES. In a separate series of experiments, disks (12 mm diameter x 1 mm thick) were prepared, and exposed to similar solutions for periods of a week, after which Vicker's hardness was determined. Differences were analysed by one-way ANOVA, followed by Neumann-Keuls post-hoc analysis (P<0.05). All specimens increased in weight, and altered pH of the storage solution to similar values. Both cements released less aluminum, but generally more sodium, calcium and silicon in the presence of amino acids. Little or no phosphorus was found to be released under any conditions. Surface hardness of Fuji IX was not influenced by the presence of amino acids, but for Ketac Molar it was generally lower in the presence of amino acids. These results show that the interaction of glass-ionomer cements with water is influenced by the presence of low concentrations of amino acids, and that this may alter surface hardness.


Early diagnosis of bladder cancer by photoacoustic imaging of tumor-targeted gold nanorods.
Detection and removal of bladder cancer lesions at an early stage is crucial for preventing tumor relapse and progression. This study aimed to develop a new technological platform for the visualization of small and flat urothelial lesions of high-grade bladder carcinoma in situ (CIS). We found that the integrin α5β1, overexpressed in bladder cancer cell lines, murine orthotopic bladder cancer and human bladder CIS, can be exploited as a receptor for targeted delivery of GNRs functionalized with the cyclic CphgisoDGRG peptide (Iso4). The GNRs@Chit-Iso4 was stable in urine and selectively recognized α5β1 positive neoplastic urothelium, while low frequency ultrasound-assisted shaking of intravesically instilled GNRs@Chit-Iso4 allowed the distribution of nanoparticles across the entire volume of the bladder. Photoacoustic imaging of GNRs@Chit-Iso4 bound to tumor cells allowed for the detection of neoplastic lesions smaller than 0.5 mm that were undetectable by ultrasound imaging and bioluminescence.


Surgical treatment of trans-scaphoid, transcapitate, transtriquetral, perilunate fracture-dislocation with open reduction, internal fixation and lunotriquetral ligament repair.
This paper presents a rare case of trans-scaphoid, transcapitate, transtriquetral, perilunate fracture-dislocation of the right wrist as a result of a motorcycle accident. Open reduction and internal fixation of the scaphoid and capitate with one screw was performed and the lunotriquetral ligament was repaired using a suture anchor.


Partial control of hepatitis delta virus superinfection by immunisation of woodchucks (Marmota monax) with hepatitis delta antigen expressed by a recombinant vaccinia or baculovirus.
We have successfully limited the level of hepatitis delta viraemia occurring after superinfection of hepadna-virus infected woodchucks by prior immunisation with the short form of the hepatitis delta virus antigen expressed by a recombinant baculovirus or vaccinia virus. This phenomenon occurred in the absence of detectable circulating antibody to hepatitis delta virus antigen and in the absence of evidence of priming of the humoral immune response and may reflect the induction of a cytotoxic T-cell response. The latter would control viraemia by rapid lysis of delta antigen expressing hepatocytes. It is suggested that the T-cell epitopes involved may be located on the carboxyl end of the delta protein (amino acids 77-195).


Predictive value of amniotic acetylcholinesterase analysis in the diagnosis of fetal abnormality in 3700 pregnancies.
The value of acetylcholinesterase (AChE) analysis as an adjunctive test to amniotic alpha fetoprotein (amAFP) for the diagnosis of fetal abnormality has been investigated in a series of 3785 amniotic fluid samples. Quantitative analysis of AChE performed retrospectively on a selected group of 541 amniotic fluid samples failed to discriminate between normal and open neural tube defect pregnancies. Qualitative analysis of AChE by polyacrylamide gel (PAG) electrophoresis in the same series of 541 fluids correctly identified 251 of the 255 pregnancies with open neural tube defect and 29 of the 31 pregnancies with false positive amAFP results. The failure of the test to diagnose 4 cases of open neural tube defect was probably attributable to the age and condition of the stored AF samples. Routine diagnostic testing of AChE isoenzymes in a further 3244 AF samples successfully identified all 170 cases of open neural tube defect and 20 cases with other fetal defects. Thirteen fluids gave false positive AChE results (0.4 per cent) compared to 59 of the series in which there were false positive amAFP results (1.8 per cent). Six of the 13 false positive AChE cases had AChE bands of low intensity which would not be regarded as diagnostic of fetal abnormality, and in five the AChE band may have been the result of significant blood contamination. False positive AChE results contributed to the decision to abort three apparently normal fetuses, but a normal AChE result undoubtedly helped to save a number of pregnancies with false positive amAFP results. Our experience suggests that repeating the amniocentesis may help in resolving the rare diagnostic difficulty of a positive AChE result with or without an elevated amAFP in the absence of ultrasound evidence of fetal abnormality, particularly where there is blood contamination of the amniotic fluid sample.


Median Nerve Entrapment in the Ulna in a Both-Bone Pediatric Forearm Fracture: Case Report and Review of the Literature.
This case report presents entrapment with subsequent complete disruption of the median nerve in the distal ulna in a both-bone fracture of the forearm in a 9-year-old girl. Closed fractures of the radius and ulna commonly occur in pediatric populations. Postinjury nerve dysfunction is often seen. Severe nerve injury is rare. There are only 3 reports of the median nerve becoming entrapped in an ulnar fracture in a child, with no reports of entrapment in the distal forearm. Features seen on examination and the radiographs supported possible nerve entrapment. Although uncommon, nerve entrapment or transection should be considered in all forearm fractures with sensory or motor nerve dysfunction. If suspicions are high, an early diagnosis of nerve entrapment may be obtained with magnetic resonance imaging evaluation.


Electrochromic absorbance changes of photosynthetic pigments in Rhodopseudomonas sphaeroides. I. Stimulation by secondary electron transport at low temperature.
Light-induced absorbance changes were measured at temperatures between --30 and --55 degrees C in chromatophores of Rhodopseudomonas sphaeroides. Absorbance changes due to photooxidation of reaction center bacteriochlorophyll (P-870) were accompanied by a red shift of the absorption bands of a carotenoid. The red shift was inhibited by gramicidin D. The kinetics of P-870 indicated electron transport from the "primary" to a secondary electron acceptor. This electron transport was slowed down by lowering the temperature or increasing the pH of the suspension. Electron transport from soluble cytochrome c to P-870+ occurred in less purified chromatophore preparations. This electron transport was accompanied by a relatively large increase of the carotenoid absorbance change. This agrees with the hypothesis that P-870 is located inside the membrane, so that an additional membrane potential is generated upon transfer of an electron from cytochrome to P-870+. A strong stimulation of the carotenoid changes (more than 10-fold in some experiments) and pronounced band shifts of bacteriochlorophyll B-850 were observed upon illumination in the presence of artifical donor-acceptor systems. Reduced N-methylphenazonium methosulphate (PMS) and N,N,N',N'-tetramethyl-p-phenylene-diamine (TMPD) were fairly efficient donors, whereas endogenous ubiquinone and oxidized PMS acted as secondary acceptor. These results indicate the generation of large membrane potentials at low temperature, caused by sustained electron transport across the chromatophore membrane. The artificial probe, merocyanine MC-V did not show electrochromic band shifts at low temperature.


Adverse events of lipoprotein apheresis and immunoadsorption at the Apheresis Center at the University Hospital Dresden.
Lipoprotein apheresis and immunoadsorption methods have a firm place among therapeutic approaches in order to treat disorders of lipoprotein metabolism or anti-body induced diseases. The extracorporeal treatment is associated with adverse effects, we wanted to report the Dresden experience. In this study we retrospectively analyzed the adverse events of several lipoprotein apheresis and immunoadsorption methods at the Apheresis Center in Dresden (Germany). We carefully looked into all available documents. The first extracorporeal lipoprotein apheresis was performed in 1990 and the first extracorporeal immunoadsorption was executed in 1995. Throughout the 23 years study period, 10 different methods were employed in treating 268 patients for a total of 25,293 treatments. Adverse events of varying severity occurred in 1948 of the treatments (7.7%). We subdivided them into mild (61.3% no treatment was necessary), moderate (37.0% oral medication or infusion was given) and severe (1.7% emergency hospitalization was necessary). Therapy had to be stopped prematurely in 1.5% of the treatments. We compared adverse events profiles among the different methods and evaluated for differences by gender. Females were found to have a significantly higher risk of adverse events than male patients. In males, the rate of adverse events ranged from 3.3% (Liposorber(®) D) to 11% (Therasorb™ Ig); in females the minimum rate was 7.8% (DALI) and the maximum 30% (rheopheresis). Adverse events were evenly distributed between the ages of 30-69, the age range at which most of the therapies were performed. We also found that all methods had a higher rate of adverse events during the first year of treatment. Puncture problems and hypotension were the most common adverse events. It can be stressed that in general the extracorporeal methods used can be regarded as safe.


Assessment of genetic and non-genetic risk factors for venous thromboembolism in glioblastoma - The predictive significance of B blood group.
Venous thromboembolism (VTE) is a common problem among patients with glioblastoma multiforme (GBM) and with some other cancers. Here, we evaluated genetic and non-genetic potential risk factors for VTE among GBM patients. A cohort of 139 patients treated with concomitant radiotherapy and temozolomide were included in the study. Next generation sequencing and genotyping approaches were applied to assess genetic risk factors in the haemostatic system. Clinical data including surgery, reoperation as well as blood group and patient information such as age and gender were available from patient records. Logistic regression analysis was performed to asses VTE risk. In the study 47 patients (34%) were diagnosed for VTE during the course of their disease. When genetic and non-genetic potential risk factors were evaluated, only B blood group was found to be significantly associated with VTE incidence (odds ratio [OR] = 6.91; confidence interval [CI] = 2.19-24.14; P = 0.001). In contrast, A and O blood groups did not correlate with VTE risk. Frontal lobe tumor location also seemed to slightly increase VTE risk compared to other brain sites (OR = 3.14; CI = 1.1-10.7) although the significance level was at borderline (P = 0.05). Current study identified B blood group as the component in non-O blood groups that is responsible for increased VTE risk. In conclusion, these results suggest for the first time that B blood group is predictive for VTE incidence among patients with glioblastoma, information that may be potentially valuable when selecting GBM patients who are at risk for VTE for anticoagulant prophylaxis.


Microcirculatory flow changes during tissue growth.
Red blood cell (RBC) velocities, lumen diameters, and volumetric flow rates were determined as functions of position and time in the microvessels of repairing tissue grown in a transparent rabbit ear chamber. By making repeated measurements in the same region, and in many instances, in exactly the same vessel over the entire growth period, we have discerned a distinct microcirculatory flow trend. The flow to a particular region (vessel) increases rapidly after an initial lag time, peaks out, and eventually decays to a steady-state level. This behavior is analogous to the vessel density pattern previously observed in this laboratory, but is delayed in time 1 to 2 weeks. These observations are consistent with mechanical, biochemical, and physiological mechanisms underlying neovascularization, tissue growth, and blood flow regulation, and provide a quantitative understanding of these processes.


Phosphorus Doping in Si Nanocrystals/SiO2 multilayers and Light Emission with Wavelength compatible for Optical Telecommunication.
Doping in semiconductors is a fundamental issue for developing high performance devices. However, the doping behavior in Si nanocrystals (Si NCs) has not been fully understood so far. In the present work, P-doped Si NCs/SiO2 multilayers are fabricated. As revealed by XPS and ESR measurements, P dopants will preferentially passivate the surface states of Si NCs. Meanwhile, low temperature ESR spectra indicate that some P dopants are incorporated into Si NCs substitutionally and the incorporated P impurities increase with the P doping concentration or annealing temperature increasing. Furthermore, a kind of defect states will be generated with high doping concentration or annealing temperature due to the damage of Si crystalline lattice. More interestingly, the incorporated P dopants can generate deep levels in the ultra-small sized (~2 nm) Si NCs, which will cause a new subband light emission with the wavelength compatible with the requirement of the optical telecommunication. The studies of P-doped Si NCs/SiO2 multilayers suggest that P doping plays an important role in the electronic structures and optoelectronic characteristics of Si NCs.


Tracheal bronchus: classification, endoscopic analysis, and airway management.
Tracheal bronchus (bronchus suis) is an unusual congenital anomaly in which the right upper lobe has its origin in the trachea rather than distal to the carina. We sought to analyze the anatomy, presentation, and airway management principles of tracheal bronchi, and we present the first endoscopically documented tracheal diverticulum. Retrospective case series. The tracheal bronchus is located at the junction of the mid and distal thirds of the right lateral trachea, is more common in males and children with other congenital anomalies, and may be associated with right main bronchus stenosis. Bronchoscopy provides a clear definitive view of the anomaly, which we found in 5 children during a 12-year period (0.5% of pediatric bronchoscopy procedures). We illustrate 3 types of tracheal bronchi: (1) vestigial tracheal diverticulum (newly described), (2) high apical lobe, and (3) fully developed supranumerary aerated tracheal bronchus. Endoscopic documentation of each type is presented. Children with tracheal bronchi may present with stridor, cough, and/or recurrent right-sided pneumonia and/or to have foreign body aspiration ruled out. Treatment is based on the severity of symptoms and ranges from observation to right upper lobectomy. Otolaryngologists should be aware of the tracheal bronchus, to include classification, endoscopic analysis, and airway management of this uncommon anomaly. Bronchoscopy with selected radiographic imaging allows the otolaryngologist to fully evaluate the child with a tracheal bronchus and to present timely therapeutic options.


A six-domain structural model for Escherichia coli translation initiation factor IF2. Characterisation of twelve surface epitopes.
The Escherichia coli translation initiation factor IF2 is a 97 kDa protein which interacts with the initiator fMet-tRNAfMet, GTP and the ribosomal subunits during initiation of protein biosynthesis. For structural and functional investigations of the factor, we have raised and characterised monoclonal antibodies against E. coli IF2. Twelve epitopes have been localised at the surface of the protein molecule by three different methods: Interactions of the monoclonal antibodies with nested deletion mutants of IF2, comparison of the relative location of the epitopes in a competition immunoassay and cross-reactivity analyses of the monoclonal antibodies towards IF2 from Salmonella typhimurium, Klebsiella oxytoca, Enterobacter cloacae, Proteus vulgaris, and Bacillus stearothermophilus. These data are combined with predicted secondary structure and discussed in relation to a six-domain structural model for IF2. The model describes IF2 as a slightly elongated molecule with a structurally compact C-terminal domain, a well-conserved central GTP-binding domain, and a highly charged, solvent exposed N-terminal with protruding alpha-helical structures.


Action of indapamide on excitation-contraction coupling in vascular smooth muscle.
The effects of indapamide on electrophysiological and mechanical parameters of longitudinal smooth muscle strips isolated from mammalian portal vein were studied by means of a double sucrose gap method associated with a photoelectric device for recording contraction. Indapamide (10(-4) M) reduced both the amplitude of the action potential and the contraction. The calcium inward current decreased and consequently the phasic contraction was also reduced. The potassium outward current was diminished while the tonic contraction was not modified significantly. The depressant nature of the indapamide response could counterbalance the stimulating action of angiotensin II but not that of noradrenaline. The results suggest that indapamide acts primarily on the plasma membrane of vascular smooth muscle by reducing the transmembrane calcium current, although a secondary decrease in the intracellular bound calcium could not be completely excluded.


Design, synthesis and biological evaluation of novel diarylacylhydrazones derivatives for the efficient treatment of idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized with high mortality, unknown etiology, and lack of effective treatment. Many evidences validate that inhibiting the activation of STAT3 is an attractive therapeutic strategy for IPF. Herein, based on our previous findings that nifuroxazide (NIF) could effectively attenuate pulmonary fibrosis by inhibiting STAT3 activation, a series of diarylacylhydrazones derivatives have been designed and synthesized. Among them, compounds 44 and 52 could inhibit TGF-β1-induced abnormal activation of NIH-3T3 and A549 cells, as well as migration and EMT of A549 cells. In a bleomycin-induced mouse pulmonary fibrosis model, the oral administration of 44 and 52 (bioavailability F = 31.75% and 42.08%) improved mouse lung function and slowed the progression of IPF. Moreover, 52 could reverse the pulmonary fibrosis in treatment model. Collectively, this work shows 44 and 52 could be a potential lead compound for the treatment of IPF, and it is worthy of further study.


Immunity to melanoma mediated by 4-1BB is associated with enhanced activity of tumour-infiltrating lymphocytes.
4-1BB costimulates T cells to carry out effector functions such as eradication of established tumours. 4-1BB (CD137) is a member of the TNF receptor family, and its triggering by either 4-1BB ligand or antibody ligation induces T-cell activation and growth. We analysed tumour-infiltrating lymphocytes (TIL) in the experimental B16F10 melanoma model to determine the mechanisms involved in 4-1BB-mediated tumour suppression. 4-1BB(+/+) mice survived longer than 4-1BB(-/-) mice, and survival was further prolonged by triggering 4-1BB with an agonistic mAb. The number of metastatic B16F10 colonies in the lung was much greater in 4-1BB(-/-) mice than in their 4-1BB(+/+) littermates. Administration of agonistic anti-4-1BB mAb increased the number of TIL in the tumour masses in the lungs of 4-1BB(+/+) mice. The numbers of CD4(+) T, CD8(+) T and CD11b(+) TIL increased in these mice. Anti-4-1BB mAb induced not only CD8(+) 4-1BB(+) T cells but also a CD8(+) IFN-gamma(+) T-cell population. B16F10 cells from the lungs of anti-4-1BB-treated mice showed enhanced expression of MHC class Iota and IotaIota antigens compared with the same cells from control IgG-treated mice. Thus, the increase in number of CD8(+) T cells and enhanced MHC Iota and IotaIota expression in B16F10 cells that result from augmented IFN-gamma production in response to anti-4-1BB mAb may lead to suppression of tumour growth and metastasis.


Influence of graphene oxide and reduced graphene oxide on the activity and conformation of lysozyme.
The dramatically different bio-effects of graphene and graphene oxide (GO) have been widely observed in diverse biological systems, which determine the applications and toxicity of graphene materials. To elucidate the mechanism at molecular level, it is urgent to investigate the enzyme-graphene interaction and its consequences. In this study, we comparatively studied the influence of GO and reduced GO (RGO) on the activity and conformation of lysozyme to provide better understandings of their different bio-effects. Both GO and RGO adsorbed large quantities of lysozyme after incubation. GO inhibited lysozyme activity seriously, while RGO nearly had no influence on the enzyme activity. The different inhibitions of enzyme activity could be explained by the lysozyme conformational changes, where GO induced more changes to the protein conformation according to UV-vis absorbance, far-UV circular dichroism spectra, intrinsic fluorescence quenching, and infrared spectra. Based on the spectroscopic changes of lysozyme, GO induced the loss of secondary structure and exposed the active site of lysozyme more to the aqueous environment. In addition, neither GO nor RGO induced the fibrillation of lysozyme after 12d incubation. The results collectively indicated that the oxidation degree significantly impacted the enzyme-graphene interaction. The implications to the designs of enzyme-graphene system for bio-related applications and the toxicological effects of graphene materials are discussed.


Pulse charge and not waveform affects M-wave properties during progressive motor unit activation.
The aim of this study was to investigate changes in experimentally recorded M-waves with progressive motor unit (MU) activation induced by transcutaneous electrical stimulation with different pulse waveforms. In 10 subjects, surface electromyographic signals were detected with a linear electrode array during electrically elicited contractions of the biceps brachii muscle. Three different monophasic waveforms of 304-micros duration were applied to the stimulation electrode on the main muscle motor point: triangular, square, and sinusoidal. For each waveform, increasing stimulation current intensities were applied in 10 s (frequency: 20 Hz). It was found that: (a) the degree of MU activation, as indicated by M-wave average rectified value, was a function of the injected charge and not of the stimulation waveform, and (b) MUs tended to be recruited in order of increasing conduction velocity with increasing charge of transcutaneous stimulation. Moreover, the subjects reported lower discomfort during the contractions elicited by the triangular waveform with respect to the others. Since subject tolerance to the stimulation protocol must be considered as important as MU recruitment in determining the effectiveness of neuromuscular electrical stimulation (NMES), we suggest that both charge and waveform of the stimulation pulses should be considered relevant parameters for optimizing NMES protocols.


Non-invasive in vivo MRI detects long-term microstructural brain alterations related to learning and memory impairments in a model of inflammation-induced white matter injury.
Magnetic resonance imaging (MRI) is currently under investigation as a non-invasive tool to monitor neurodevelopmental trajectories and predict risk of cognitive deficits following white matter injury (WMI) in very preterm infants. In the present study, we evaluated the capacity of multimodal MRI (high-resolution T2-weighted imaging and diffusion tensor imaging)to assess changes following WMI and their relationship to learning and memory performance in Wistar rats as it has been demonstrated for preterm infants. Multimodal MRI performed at P31-P32 shown that animals exposed to neonatal LPS could be classified into two groups: minimal and overt injury. Animals with overt injury had significantly enlarged ventricles, hippocampal atrophy, diffusivity changes in hippocampal white and gray matter, in the striatum and the cortex. Following neonatal LPS exposure, animals presented learning and memory impairments as shown at the fear conditioning test at P36-P38. The severity of learning and memory deficits was related to increased mean diffusivity in the hippocampal region. In conclusion, non-invasive multimodal MRI (volumetric and DTI) assessed and classified the extent of injury at long-term following neonatal LPS exposure. Microstructural changes in the hippocampus at DTI were associated to learning and memory impairments. This further highlights the utility of multimodal MRI as a non-invasive quantitative biomarker following perinatal inflammation.


Exuberant clear cell odontogenic carcinoma of the mandible harboring EWSR1 rearrangement: Report of a rare case and a literature review.
Clear cell odontogenic carcinoma (CCOC) is a rare malignant odontogenic tumour (MOT) that mainly affects the mandible, with a slight female predominance in adult patients. In this study, we described an exuberant CCOC in mandible of a 22-year-female patient. On radiographic examination, a radiolucent lesion in the region of tooth 36 to 44 with tooth displacement and alveolar cortical resorption was observed. Histopathological study revealed a malignant neoplasm of the odontogenic epithelium, composed of PAS-positive clear cells and immunoreactivity for CK5, CK7, CK19, p63. The Ki-67 index was low (<10 %). Fluorescent in situ hybridization revealed EWSR1 gene rearrangement. The diagnosis of CCOC was established and the patient was referred for surgical treatment.


A rapid and sensitive LC/MS/MS assay for quantitative determination of digoxin in rat plasma.
Digoxin is a cardiac glycoside that is widely used for the treatment of congestive heart failure. To evaluate pharmacokinetics of digoxin in rats, a sensitive LC/MS/MS assay was developed and validated for the determination of digoxin concentration in rat plasma. For detection, a Sciex API3000 LC/MS/MS with atmospheric pressure ionization (API) mass spectrometry turbo ion spray inlet in the positive ion-multiple reaction monitoring mode was used to monitor precursor-->product ions of m/z 798.6-->651.6 for digoxin and m/z 577.6-->433.3 for oleandrin, the internal standard (IS). The standard curve was linear (r(2)>or=0.999) over the digoxin concentration range of 0.1-100 ng/ml in plasma for digoxin. The mean predicted concentrations of the quality control samples deviated by <5.8% from the corresponding nominal values; the intra-assay and inter-assay precision of the assay were within 8.6% relative standard deviation. At the lower limit of quantitation (LLQ) of 0.1 ng/ml, the mean deviation of predicted concentrations from the nominal value was within 3.7%. The extraction recoveries of digoxin and internal standard were 82.7+/-3.9 and 105.9+/-2.3%, respectively. The present method was successfully applied to characterization of pharmacokinetic profiles of digoxin in rats after oral administration.


The pathogenesis of renal cortical tumours in rats fed 2% trisodium nitrilotriacetate monohydrate.
To help assess the relationship between the renal toxicity and tumorigenicity associated with the administration of high doses of nitrilotriacetate (NTA) we have reviewed slides of sections from the kidneys of rats used in the National Cancer Institute bioassay of NTA. Trisodium NTA fed to Fischer 344 rats at 2% in the diet for 2 yr exerts a persistent toxic effect on the renal cortex which is manifested morphologically as vacuolation of proximal convoluted tubular epithelium and exacerbation of age-related nephrosis. Additionally, two pathogenic pathways leading to tumour formation in NTA-treated rats are suggested. A specific pathway initiated by vacuolation of proximal convoluted tubular epithelium leads to hyperplasia; reasons are advanced for the view that hyperplasia progresses to neoplasia. A possible concomitant pathway, which we suggest is nonspecific, is associated with regenerative proliferation in kidneys affected by severe age-related nephrosis. These data support the concept that there is a causal relationship between NTA-associated tubular toxicity and tumorigenicity. Doses of NTA that do not induce toxicity do not induce tubular tumours as demonstrated in this and in two other major long-term studies. Hence studies to investigate the pathogenesis of the toxic response provide an insight that suggests the basis for the development of NTA-associated tumours.


Meningeal carcinomatosis secondary to neurenteric cysts with malignant transformation: a case report.
Meningeal carcinomatosis is mainly associated with breast cancer, lung cancer, and melanoma. However, meningeal carcinomatosis secondary to a neurenteric cyst with malignant features is extremely rare. We report the case of a 35-year-old woman who was admitted to the hospital with a 10-month history of headache, 6-month history of diplopia, 4-month history of hearing loss, and 1-month history of back pain, suggesting a diagnosis of chronic meningitis. Notably, enhanced brain and spinal cord magnetic resonance imaging (MRI) revealed extensive lesions with enhancement signals in the pia mater of the pons and cervical, thoracic, and lumbar spinal cord. The cerebral spinal fluid profile showed that pressure was significantly elevated, with a slight increase in leukocytes that mostly comprised mononuclear cells and decreased glucose concentration. Cytology evaluation showed a small cluster of atypical nuclei, which were suspected to be tumor cells arising from the epithelium. However, no primary tumor was found through comprehensive body and skin screening. After a histopathological biopsy of subarachnoid meninx of the thoracic spinal canal, the cause of meningeal carcinomatosis of this patient was determined as neurenteric cysts with malignant features, which is extremely rare. This is the first case to ever report neurenteric cysts as a cause of leptomeningeal carcinomatosis and the first ever report of neurenteric cysts presenting as leptomeningeal carcinomatosis without typical cyst visible on brain MRI. This extremely rare case provided a novel view on the pathogenesis of meningeal carcinomatosis and clinical presentation of neurenteric cysts, highlighting the value of meningeal biopsy in chronic meningitis of unknown causes.


An empirically based simulation of group foraging in the harvesting ant, Messor pergandei.
We present an empirically based group model of foraging interactions in Messor pergandei, the Sonoran desert harvesting ant. M. pergandei colonies send out daily foraging columns consisting of tens of thousands of individual ants. Each day, the directions of the columns may change depending on the resource availability and the neighbor interactions. If neighboring columns meet, ants fight, and subsequent foraging is suppressed. M. pergandei colonies face a general problem which is present in many systems: dynamic spatial partitioning in a constantly changing environment, while simultaneously minimizing negative competitive interactions with multiple neighbors. Our simulation model of a population of column foragers is spatially explicit and includes neighbor interactions. We study how different behavioral strategies influence resource exploitation and space use for different nest distributions and densities. Column foraging in M. pergandei is adapted to the spatial and temporal properties of their natural habitat. Resource and space use is maximized both at the colony and the population level by a model with a behavioral strategy including learning and fast forgetting rates.


Canine olfactory detection of trained explosive and narcotic odors in mixtures using a Mixed Odor Delivery Device.
Like using a substandard calibrant to test and calibrate an instrumental detector, when detection canines are regularly exposed to less than optimal training material, their detection proficiency is diminished, risking the lives of their handlers and civilians they are intended to protect. This research examined canine detection proficiency to odor mixtures and the use of mixture training to improve said proficiency. Trained detection canines were tested on their ability to correctly locate their trained target odors, explosives or narcotics, in various mixtures from a series of blanks and distractor odors. After making base measurements, canines were trained on the target odor in mixtures using the Mixed Odor Delivery Device (MODD), which was previously developed to safely contain separated explosive components and deliver the mixed odor to a canine detector for training purposes. Headspace measurements, made using solid phase microextraction with gas chromatography/mass spectrometry (SPME-GC/MS), were also taken of mixture components in and out of the MODD to confirm that odor mixtures were accurately portrayed to the canines during MODD training. Following mixture training, canines were retested on the same mixtures. Results of the headspace analysis showed that the MODD did not alter the delivery of the odorants from the mixture components. As such, canines showed an improved proficiency in detection of target mixtures following mixture training, increasing the detection rate from 63% to 72% for pseudo cocaine mixtures and from 19% to 100% for explosive mixtures.


Hypersecretion of biliary fatty acids in patients with exocrine pancreatic disease.
The fatty acid composition of bile secreted into the duodenum in the first 10 min after an intravenous (i.v.) injection of Boots secretin (2 CHRu kg-1) has been analysed by gas liquid chromatography in 11 healthy volunteers, 8 patients without pancreatic disease, 27 patients with exocrine pancreatic disease who had not altered their diet substantially (acute pancreatitis 8; chronic pancreatitis 16; cancer 3) and 11 patients with exocrine pancreatic disease on low fat intakes (40 g/day) for at least 6 months. The mean values for total fatty acid outputs (after back transformation of the logged data) were significantly higher in each subgroup of patients with pancreatic disease on their usual diets (acute 134, chronic 189, cancer 235 mg) than in the two subgroups of controls (30 and 55 mg), due to significant increases in the outputs of every fatty acid, C16:0 through to C22:5. This finding, which was usually not apparent in patients with pancreatic disease on low-fat diets, may reflect the combined influence of dietary fat intakes and hepatic enzyme induction. Comparison of the fatty acid outputs in endoscopically collected bile and duodenal juice after separate injections of secretin three hours apart indicate that: (a) analysis of duodenal juice within 10 min of stimulation by Boots secretin provides valuable information on the composition of hepatic bile; (b) the increased phospholipid output in the untreated patients is due to hypersecretion and does not merely represent a 'washout' phenomenon.


Utilization of Lung Cancer Screening in the Medicare Fee-for-Service Population.
A number of organizations, including the US Preventive Services Task Force (USPSTF), recommend lung cancer screening (LCS) with low-dose CT (LDCT) imaging for high-risk current and former smokers. In 2015, Medicare issued a decision to cover LCS as a preventive health benefit; however, utilization by the Medicare population has not been thoroughly examined. Our objective was to evaluate the early use of LCS in the Medicare fee-for-service (FFS) population and determine the relationship(s) among beneficiary sociodemographic characteristics, geographic location, and use. This cross-sectional observational study used 100% Medicare FFS claims files for Medicare beneficiaries receiving LCS between January 1, 2016 and December 31, 2016. We estimated the LCS-eligible Medicare population using population and smoking data from the US Census Bureau and Centers for Disease Control and Prevention. We assessed variation in LCS rates by beneficiary characteristics and geography, using univariate and multivariate regression, the latter also including how interactions between geographic location and race/ethnicity influence screening. A total of 103,892 Medicare FFS beneficiaries received LCS in 2016, comprising 4.1% (95% CI, 3.9%-4.3%) of the estimated LCS-eligible Medicare population. Accounting for the interactions between race/ethnicity and US region, nonwhite (black, Hispanic) beneficiaries in all US regions were screened with lower frequency than white beneficiaries (P < .001). Screening rates in the Northeast were significantly higher than in other regions (adjusted rate ratio [95% CI] of Northeast relative to South: 1.83 [1.36-2.46]). The early adoption of LCS among Medicare beneficiaries was low. Our results suggest geographic and racial disparities in screening use, with populations in the South and those of nonwhite race/ethnicity being screened with lower frequency. Further work is needed to improve LCS uptake and ensure consistent use by all at-risk populations.


Prevalence and risk factors for visual impairment among elderly patients attending the eye clinic at Mulago National Referral Hospital, Uganda: a cross-sectional study.
The elderly have an increased risk of developing visual impairment (VI). Due to the increase in life expectancy of individuals in Sub-Saharan Africa, the population of the elderly is projected to increase. It is thus postulated that the prevalence of VI will increase which is currently unknown in Uganda. To determine the prevalence and risk factors for VI among the elderly at Mulago National Referral Hospital eye clinic in Uganda. This was a cross-sectional study carried out in 2020 with consecutive enrolment of patients aged 60 years and above. Obtaining history was followed by systemic and ocular examination. Statistical analysis was performed to determine the prevalence and factors associated with VI. Of 346 elderly participants examined, 174 (50.3%) were males and median age was 67 (IQR 63-74). Prevalence of VI was 32.1%. Cataract was the leading cause of blindness 54.1%, followed by refractive error (21.6%), glaucoma (11.7%), and corneal opacities (5.4%). Age (adjusted Prevalence Ratio (aPR): 1.05, 95% CI (1.02, 1.06)), history of diabetes mellitus (aPR 1.46, 95%CI (1.04, 2.05)), history of hypertension (aPR 1.46, 95%CI (1.10, 1.93)), having completed primary level of education (aPR 0.74, 95%CI (0.55, 0.98)) and secondary level of education (aPR 0.47, 95%CI (0.30,0.73)), presence of a cataract at examination (aPR: 2.28, 95%CI (1.66, 3.13)) were statistically significantly associated with VI. In Mulago hospital, the prevalence of VI among the elderly is high with majority of the causes being correctable. We recommend that efforts towards early case identification of causes of VI among the elderly should be a priority.


Magnetic resonance imaging detection of mesial temporal sclerosis in children.
The objective of this study was to investigate the prevalence and clinical characteristics of mesial temporal sclerosis as diagnosed by brain magnetic resonance imaging in children. A total of 390 consecutive brain magnetic resonance imaging studies in children were reviewed for evidence of mesial temporal sclerosis. Subsequently, the magnetic resonance imaging scans and charts of patients with mesial temporal sclerosis were reviewed and their clinical details were evaluated. The magnetic resonance imaging studies had been performed for multiple indications, including seizures, headache, and developmental problems. In children, the prevalence of mesial temporal sclerosis among all brain magnetic resonance imaging studies was 3.1% (12 of 390 studies) and 12.1% (12 of 99 studies) among all brain magnetic resonance imaging studies performed for seizures. These children all presented with a history of seizure disorder, often had other medical problems, and histopathology (when available) nearly always (5 of 6 patients) confirmed their magnetic resonance imaging diagnosis of mesial temporal sclerosis. The prevalence of mesial temporal sclerosis is low among all pediatric patients who had magnetic resonance imaging brain studies. All our mesial temporal sclerosis patients had clinical seizures; i.e., it was never an "incidental finding". Children with mesial temporal sclerosis often had comorbid conditions, and the diagnosis of mesial temporal sclerosis made by magnetic resonance imaging was accurate when compared with the available histopathology.


Phylogenetic diversity of actinobacteria associated with soft coral Alcyonium gracllimum and stony coral Tubastraea coccinea in the East China Sea.
Actinobacteria are widely distributed in the marine environment. To date, few studies have been performed to explore the coral-associated Actinobacteria, and little is known about the diversity of coral-associated Actinobacteria. In this study, the actinobacterial diversity associated with one soft coral Alcyonium gracllimum and one stony coral Tubastraea coccinea collected from the East China Sea was investigated using both culture-independent and culture-dependent approaches. A total of 19 actinobacterial genera were detected in these two corals, among which nine genera (Corynebacterium, Dietzia, Gordonia, Kocuria, Microbacterium, Micrococcus, Mycobacterium, Streptomyces, and Candidatus Microthrix) were common, three genera (Cellulomonas, Dermatophilus, and Janibacter) were unique to the soft coral, and seven genera (Brevibacterium, Dermacoccus, Leucobacter, Micromonospora, Nocardioides, Rhodococcus, and Serinicoccus) were unique to the stony coral. This finding suggested that highly diverse Actinobacteria were associated with different types of corals. In particular, five actinobacterial genera (Cellulomonas, Dermacoccus, Gordonia, Serinicoccus, and Candidatus Microthrix) were recovered from corals for the first time, extending the known diversity of coral-associated Actinobacteria. This study shows that soft and stony corals host diverse Actinobacteria and can serve as a new source of marine actinomycetes.


Differentiating Tumor Progression from Pseudoprogression in Patients with Glioblastomas Using Diffusion Tensor Imaging and Dynamic Susceptibility Contrast MRI.
Early assessment of treatment response is critical in patients with glioblastomas. A combination of DTI and DSC perfusion imaging parameters was evaluated to distinguish glioblastomas with true progression from mixed response and pseudoprogression. Forty-one patients with glioblastomas exhibiting enhancing lesions within 6 months after completion of chemoradiation therapy were retrospectively studied. All patients underwent surgery after MR imaging and were histologically classified as having true progression (>75% tumor), mixed response (25%-75% tumor), or pseudoprogression (<25% tumor). Mean diffusivity, fractional anisotropy, linear anisotropy coefficient, planar anisotropy coefficient, spheric anisotropy coefficient, and maximum relative cerebral blood volume values were measured from the enhancing tissue. A multivariate logistic regression analysis was used to determine the best model for classification of true progression from mixed response or pseudoprogression. Significantly elevated maximum relative cerebral blood volume, fractional anisotropy, linear anisotropy coefficient, and planar anisotropy coefficient and decreased spheric anisotropy coefficient were observed in true progression compared with pseudoprogression (P < .05). There were also significant differences in maximum relative cerebral blood volume, fractional anisotropy, planar anisotropy coefficient, and spheric anisotropy coefficient measurements between mixed response and true progression groups. The best model to distinguish true progression from non-true progression (pseudoprogression and mixed) consisted of fractional anisotropy, linear anisotropy coefficient, and maximum relative cerebral blood volume, resulting in an area under the curve of 0.905. This model also differentiated true progression from mixed response with an area under the curve of 0.901. A combination of fractional anisotropy and maximum relative cerebral blood volume differentiated pseudoprogression from nonpseudoprogression (true progression and mixed) with an area under the curve of 0.807. DTI and DSC perfusion imaging can improve accuracy in assessing treatment response and may aid in individualized treatment of patients with glioblastomas.


LPA/LPAR1 signaling induces PGAM1 expression via AKT/mTOR/HIF-1α pathway and increases aerobic glycolysis, contributing to keratinocyte proliferation.
Psoriasis is a chronic inflammatory skin disease and lysophosphatidic acid (LPA) has recently been reported to contribute to its pathogenesis through keratinocyte proliferation. In this study, we investigated the metabolic changes in the LPA-induced keratinocyte hyperproliferation and underlying mechanisms. HaCaT or HEKa cells were treated with LPA in the presence or absence of various chemical inhibitors. The glycolysis stress was measured using the Seahorse extracellular flux analyzer. Gene knockdown by siRNA transfection was used to investigate the role of LPAR1, PGAM1, and HIF-1α in LPA-induced metabolic changes. We confirmed the expression of PGAM1 and HIF-1α in imiquimod (IMQ)-induced psoriasis-like BALB/c mice. LPA increased aerobic glycolysis; however, treatment with ki16425, or LPAR1 knockdown inhibited LPA-induced glycolysis in HaCaT cells. LPA increased the expression of glycolytic enzyme PGAM1 through LPAR1. PGAM1 knockdown in HaCaT cells suppressed LPA-induced cell proliferation, changes in cell cycle factor expression, and inhibited LPA-induced aerobic glycolysis. LPA sequentially activated AKT, mTOR, its downstream target, p70 S6K, and increased HIF-1α expression through LPAR1. HIF-1α knockdown inhibited LPA-induced PGAM1 expression and aerobic glycolysis. A6730 also decreased LPA-induced activation of mTOR and p70 S6K and LPA-induced increases in HIF-1α and PGAM1 expression. Ki16425 suppressed the increased expression of PGAM1 and HIF-1α in the lesions of IMQ-induced psoriasis-like mice. In primary keratinocytes, LPA/LPAR1 signaling also induced AKT-mediated aerobic glycolysis. Collectively, the results demonstrated that LPA induces aerobic glycolysis via AKT/mTOR/HIF-1α-dependent PGAM1 expression during keratinocytes proliferation and this might be one of the mechanisms of psoriasis development.


Contribution of postsynaptic T-type calcium channels to parallel fibre-Purkinje cell synaptic responses.
At the parallel fibre-Purkinje cell glutamatergic synapse, little or no Ca(2+) entry takes place through postsynaptic neurotransmitter receptors, although postsynaptic calcium increases are clearly involved in the synaptic plasticity. Postsynaptic voltage-gated Ca(2+) channels therefore constitute the sole rapid postsynaptic Ca(2+) signalling mechanism, making it essential to understand how they contribute to the synaptic signalling. Using a selective T-type calcium channel antagonist, we describe a T-type component of the EPSC that is activated by the AMPA receptor-mediated depolarization of the spine and thus will contribute to the local calcium dynamics. This component can amount up to 20% of the EPSC, and this fraction is maintained even at the high frequencies sometimes encountered in sensory processing. Modelling based on our biophysical characterization of T-type calcium channels in Purkinje cells suggests that the brief spine EPSCs cause the activated T-type channels to deactivate rather than inactivate, enabling repetitive activation. In the cerebellum, sensory information is conveyed to Purkinje cells (PC) via the granule cell/parallel fibre (PF) pathway. Plasticity at the PF-PC synapse is considered to be a mechanism of information storage in motor learning. The induction of synaptic plasticity in the cerebellum and elsewhere usually involves intracellular Ca(2+) signals. Unusually, postsynaptic Ca(2+) signalling in PF-PC spines does not involve ionotropic glutamatergic receptors because postsynaptic NMDA receptors are absent and the AMPA receptors are Ca(2+) -impermeable; postsynaptic voltage-gated Ca(2+) channels therefore constitute the sole rapid Ca(2+) signalling mechanism. Low-threshold activated T-type calcium channels are present at the synapse, although their contribution to PF-PC synaptic responses is unknown. Taking advantage of 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide, a selective T-type channel antagonist, we show in the mouse that inhibition of these channels reduces PF-PC excitatory postsynaptic currents and excitatory postsynaptic potentials by 15-20%. This contribution was preserved during sparse input and repetitive activity. We characterized the biophysical properties of native T-type channels in young animals and modelled their activation during simulated dendritic excitatory postsynaptic potential waveforms. The comparison of modelled and observed synaptic responses suggests that T-type channels only activate in spines that are strongly depolarized by their synaptic input, a process requiring a high spine neck resistance. This brief and local activation ensures that T-type channels rapidly deactivate, thereby limiting inactivation during repetitive synaptic activity. T-type channels are therefore ideally situated to provide synaptic Ca(2+) entry at PF-PC spines.


[New molecules in the treatment of inflammatory bowel disease].
Inflammatory bowel disease (IBD) is a disorder of unknown aetiology that provokes chronic inflammation of the gastrointestinal tract. Anti-tumor necrosis factor drugs have represented a major advance in the treatment of IBD patients in the last few years and also have a good safety profile. Nevertheless, these treatments are not effective in all patients and, in initial responders, there can be a loss of response in the long-term. Consequently, new treatments are needed for IBD, aimed at distinct therapeutic targets. In the last few years, new molecules have been incorporated into the therapeutic armamentarium of IBD patients. Golimumab is an anti-tumor necrosis factor monoclonal antibody with demonstrated effectiveness in the treatment of ulcerative colitis. The use of CT-P13 (biosimilar infliximab) has been approved in Europe for the same indications as the original infliximab. More recently, vedolizumab, an anti-α4β7 integrin monoclonal antibody, has been approved for the treatment of Crohn's disease and ulcerative colitis. A large number of molecules are currently under development, some of which will, in the future, broaden the therapeutic options available in the treatment of IBD patients. Finally, in the next few years, studies should aim to identify factors predictive of response to the distinct biological agents for IBD in order to allow personalized selection of the best therapeutic alternative for each patient.


Arsenite-oxidizing Hydrogenobaculum strain isolated from an acid-sulfate-chloride geothermal spring in Yellowstone National Park.
An arsenite-oxidizing Hydrogenobaculum strain was isolated from a geothermal spring in Yellowstone National Park, Wyo., that was previously shown to contain microbial populations engaged in arsenite oxidation. The isolate was sensitive to both arsenite and arsenate and behaved as an obligate chemolithoautotroph that used H(2) as its sole energy source and had an optimum temperature of 55 to 60 degrees C and an optimum pH of 3.0. The arsenite oxidation in this organism displayed saturation kinetics and was strongly inhibited by H(2)S.


Atherogenesis in two strains of obese rats. The fatty Zucker and LA/N-corpulent.
Two strains of obese rats, the fatty Zucker and the LA/N-corpulent have been compared at 6 months age for the presence of vascular and myocardial disease. Both strains, when obese, exhibit a VLDL hyperlipidemia with elevated triglycerides and moderate elevations of plasma cholesterol concentrations compared to the lean rats of the same strain. The hyperlipidemia is more modest in the fatty Zucker than the corpulent LA/N, and the serum lipid concentrations of the lean Zucker are lower than those of the lean LA/N. Apolipoprotein concentrations were similar and elevated in the two obese genotypes compared to the lean genotypes which were also similar to each other. Male and female obese animals of both strains exhibited hyperinsulinemia under fasting conditions and after oral glucose, with obese male LA/N rats exhibiting the most severe hyperinsulinemia. Glucose tolerance was impaired in obese LA/N animals but was normal in lean rats of both strains and fatty Zucker rats of both sexes. The glucose intolerance observed in obese LA/N animals was more severe in the male than in the female rats. Unlike the corpulent rat, which develops atherosclerotic lesions, the fatty Zucker shows no evidence of advanced vascular lesions on scanning electron microscopy. The fatty Zucker also does not develop the myocardial lesions that are frequent in the male corpulent LA/N rat. It is suggested that the initiation of the atherogenic process is dependent upon elevated insulin levels or transient hyperglycemia. Development of the advanced lesions appears to require the presence of hyperlipidemia.


[Normal tissue tolerance to external beam radiation therapy: Bone marrow and cortical bone structures].
In patients undergoing external radiation therapy, bone marrow and cortical bone structures are all often neglected as organs at risk. Still, from increased febrile neutropenia risk in patients undergoing chemoradiation for a pelvic tumour to increased risk of vertebral fracture when undergoing hypofractioned stereotactic radiotherapy of a spinal metastasis, adverse effects are frequent and sometimes serious. This literature review first defines the rules for contouring these structures, then the dose constraints currently recommended. This article focuses first on conventional irradiation or intensity modulation radiotherapy considering classical fractionation. Secondly, it focuses on stereotactic radiotherapy. The considered organs will be haematopoietic structures, and bone cortical structures. Current recommendations are summarised in a table.


Evaluation of the topical spray containing Centella asiatica extract and its efficacy on excision wounds in rats.
Centella asiatica was extracted by methanol. The assay content of triterpenes in the extract was 0.12 % asiatic acid, 0.54 % madecassic acid, 0.25 % asiaticoside and 1.02 % madecassoside. The extract was complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD) and formulated with Eudragit E100, glycerol, PEG 400, copovidone, ethanol and purified water. A clear yellowish solution (F1-F8) was obtained. The formulations had a pH of 5.5-6.0 with viscosity in the range of 20-60 mPa s, surface tension 20.3-24.6 mN m-1 and contact angle less than 20°. The amount of PEG 400 and copovidone affected the film and spreadability. The content of triterpenes in the spray formulation was close to 100 % compared to triterpenes in the extract. The skin irritation study indicated that the formulation was non-irritating in a rat model. An in vivo excision wound healing model showed that wound excision was completely healed after 14 days.


Malignant transformation and mutagenesis in mammalian cells induced by vicinal diol-epoxides derived from benzo(a)pyrene.
Benzo[a] pyrene and the syn- and anti-isomers of the 7,8-diol 9,10-oxide and of the 9,10-diol 7,8-oxide derived from this hydrocarbon have been tested for their abilities to induce malignant transformation in M2 mouse fibroblasts and mutagenesis in V79 Chinese hamster cells. The anti-isomer of the 7,8-diol 9,10-oxide induced more mutations and transformation than did the other three vicinal diol-epoxides. The two 9,10-diol 7,8-oxides were moderately mutagenic but did not induce any transformation. In contrast, benzo[a]-pyrene induced transformation in M2 fibroblasts but was not mutagenic in the V79 cells.


Neural gallops across auditory streams.
We continually rely on our ability to segregate the myriad sounds in our environment--phones ringing, people talking--into separate "auditory streams," each originating from a different source. In this issue of Neuron, Micheyl et al. provide the most direct evidence to date linking single-unit spiking responses from auditory cortex to the perception of distinct auditory streams.


Stability of reagents used for chiral amino acid analysis during spaceflight missions in high-radiation environments.
The search for biosignatures on spaceflight missions requires in situ instrumentation capable of highly selective and sensitive organic analyses. To this end, CE-LIF is a uniquely promising technique, capable of determining the type, abundance, and chirality of amino acids present in environmental samples at nanomolar concentrations. However, this type of assay requires several reagents that have not yet been used on spaceflight missions. A key concern, particularly for future missions to Europa, is the survivability of these critical components for CE separation and LIF detection under high levels of radiation. Here we present an investigation of the chemical stability of the reagents and associated fused silica capillary after a total ionizing dose of 300 krad, exceeding the predicted total ionizing dose for the potential Europa Lander Mission payload by two-fold. Neither the fused silica capillary nor the fluorescent dye (5-carboxyfluorescein succinimidyl ester) showed significant change in performance following irradiation. Following the irradiation of the pre-mixed background electrolyte, both migration time and resolution were affected. However, when the reagents (sodium tetraborate, sodium taurocholate, and γ-cyclodextrin) and the acetonitrile solution were irradiated separately and mixed afterwards, there was no change in the separation performance.


Platelet activating factor and tracheobronchial respiratory glycoconjugate release in feline and human explants: involvement of the lipoxygenase pathway.
It has been suggested that platelet activating factor (PAF) may participate in many aspects of bronchial asthma, including stimulation of mucus secretion. Feline tracheal and human bronchial explant production of respiratory glycoconjugates (RGC) in response to platelet activating factor (PAF) was investigated, in order to differentiate the actions of this putative mediator on mucus secretion. PAF caused a dose-dependent increase in RGC release in concentrations ranging from 100-0.5 microM during a 1-2 hours incubation with either feline or human explants, and the effect was inhibited by the PAF receptor antagonists Ro 19-3704. Several lines of evidence suggest that PAF enhances RGC release indirectly through stimulation of the production of lipoxygenase metabolites of arachidonic acid. 1) Incubation of 10 microM PAF together with arachidonic acid (100 micrograms/ml) enhances PAF's stimulatory effect on RGC release in cats. 2) The cyclooxygenase inhibitor ibuprofen (65 and 420 microM) either failed to effect or slightly enhanced PAF induced RGC release in both species. 3) The combined cyclooxygenase and lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) as well as the putatively specific 5-lipoxygenase inhibitor L-651,392 (both at 50 microM) inhibited the response to PAF in both species. 4) The putative LTD4 receptor antagonists (L-660,711, 100 microM) slightly reduced the PAF secretory response in human bronchi. We conclude that PAF causes specific receptor mediated RGC release. This response is indirectly mediated through the generation of lipoxygenase metabolite formation including 5-lipoxygenase pathway metabolites.


Ferrocyanide as electron donor to cytochrome aa3. Cytochrome c requirement for oxygen uptake.
1. In the absence of cytochrome c, ferrocyanide or ferrous sulphate reduces cytochrome c oxidase (EC 22.214.171.124), but no continuous oxygen uptake ensues, as it does with N,N,N',N'-tetramethyl-p-phenylenediamine or reduced phenazine methosulphate as reductants, unless a substoichiometric amount of cytochrome c or an excess of clupein is present. Cytochrome c cannot be replaced by porphyrin cytochrome c. 2. Cytochrome c, porphyrin cytochrome c and clupein all stimulate the reduction of cytochrome aa3 by ferrocyanide. 3. A model is proposed to explain these findings in which a high-affinity site for cytochrome c on the oxidase regulates the access of hydrophilic electron donors to a low-affinity site, and reduction via the high-affinity site is required for continuous oxygen uptake. 4. Furthermore, it is shown that upon reaction of oxidase with ferrocyanide, cyano-oxidase is formed.


Isotope effects and their implications for the covalent binding of inhaled [3H]- and [14C]formaldehyde in the rat nasal mucosa.
DNA-protein crosslinks were formed in the nasal respiratory mucosa of Fischer-344 rats exposed for 3 hr to selected concentrations of [3H]- and [14C]formaldehyde (3HCHO and H14CHO) (M. Casanova and H. d'A. Heck (1987). Toxicol. Appl. Pharmacol. 89, 105-121). In rats depleted of glutathione (GSH) and exposed to 10 ppm of 3HCHO and H14CHO, the 3H/14C ratio of the fraction of the DNA that was crosslinked to proteins was significantly (39 +/- 6%) higher than that of the inhaled gas. This suggests an isotope effect, either on the formation of DNA-protein crosslinks by labeled HCHO or on the oxidation of labeled HCHO catalyzed by formaldehyde (FDH) or aldehyde dehydrogenase (AldDH). The possibility of an isotope effect on the formation of crosslinks was investigated using rat hepatic nuclei incubated with [3H]- and [14C]formaldehyde (0.1 mM, 37 degrees C). A small (3.4 +/- 0.9%) isotope effect was detected on this reaction, which slightly favored 3HCHO over H14CHO in binding to DNA. The magnitude of this isotope effect cannot account for the high isotope ratio observed in the crosslinked DNA in vivo. The possibility of an isotope effect on the oxidation of 3HCHO and H14CHO catalyzed by FDH was investigated using homogenates of the rat nasal mucosa incubated with [3H]- and [14C]formaldehyde at total formaldehyde concentrations ranging from 0.1 to 11 microM, NAD+ (1 mM), GSH (15 mM), and pyrazole (1 mM). The experiments showed that 3HCHO is oxidized significantly more slowly than H14CHO under these conditions (Vmax/Km (H14CHO) divided by Vmax/Km (3HCHO) = 1.82 +/- 0.11). A similar isotope effect was observed in the absence of GSH, presumably due to the oxidation of 3HCHO and H14CHO catalyzed by AldDH. These results suggest that the residual (unoxidized) formaldehyde present in the nasal mucosa of rats exposed to [3H]- and [14C]formaldehyde may be "enriched" in 3HCHO relative to H14CHO, which can bind to DNA resulting in an isotope ratio higher than that of the inhaled gas. The isotope effect on the oxidation of 3HCHO and H14CHO suggests that previous estimates of the amount of HCHO covalently bound to nasal mucosal DNA (M. Casanova-Schmitz, T. B. Starr, and H. d'A. Heck (1984). Toxicol. Appl. Pharmacol. 76, 26-44) may have been too large, especially at low airborne concentrations and that the shape of the concentration-response curve for DNA-protein crosslinking is more nonlinear than reported previously.


In vitro and in vivo effect of proglumide on cholecystokinin-stimulated amylase release in mouse pancreatic acini.
The effect of proglumide on cholecystokinin (CCK)-stimulated amylase release was studied in vitro and in vivo in dispersed acini from mouse pancreas. In an in vitro study, proglumide at concentrations between 0.3-10 mM inhibited CCK-stimulated amylase release dose-dependently, while proglumide did not influence the basal amylase release at concentrations between 0-3 mM. Dose-response curves to CCK for amylase release shifted to the right with increase in proglumide concentration. This inhibition by proglumide was reversible. In addition, the effect of proglumide was selective for CCK and its related peptide, and this drug did not inhibit other secretagogues such as carbachol or gastrin releasing peptide in mouse acini. In contrast to its inhibitory effect in vitro, in vivo administration of proglumide (500 mg/kg/day, i.p., for 5 days) to mice did not cause the rightward shift of the dose-response curve to CCK for amylase release from dispersed acini.


Effect of tellurite-mediated oxidative stress on the Escherichia coli glycolytic pathway.
To unveil the metabolic impact of tellurite in the bacterial cell, the effect of this toxicant on the expression and activity of key enzymes of the Escherichia coli glycolytic pathway was analyzed. E. coli exposure to tellurite results in: (i) increased glucose consumption, which was paralleled by an increased expression of the glucose transporter-encoding gene ptsG, (ii) augmented phosphoglucoisomerase activity and pgi transcription, (iii) decreased activity of the enzymatic regulators phosphofructokinase and pyruvate kinase. In spite of these observations, increased intracellular pyruvate, phosphoenol pyruvate and phosphorylated sugars was observed. E. coli lacking key glycolytic enzymes was considerably more sensitive to tellurite than the parental, isogenic, wild type strain. Taken together, these results suggest that increasing the availability of key metabolites (pyruvate, phosphoenol pyruvate, NADPH), required to respond to tellurite mediated-stress, E. coli shifts the carbon flux towards the pentose phosphate pathway thus facilitating the functioning of the Entner-Doudoroff pathway and/or the glycolytic productive phase.


Contribution to the genus Omalus Panzer, 1801 of China, with descriptions of two new species (Hymenoptera, Chrysididae).
In spite of that Chinese species of the genus Omalus Panzer, 1801 were recently revised by Wei et al. (2014), the study of more material has revealed the presence of other four species: two of them are new, O. corrugatus Rosa, Wei & Xu, sp. nov. (China, Guangdong) and O. hainanensis Rosa, Wei & Xu, sp. nov. (China, Hainan); the other two are newly recorded from China, O. stella (Semenov & Nikol'skaya, 1954) and O. timidus (Nurse, 1902), comb. nov. (from the genus Holophris Mocsáry, 1890). An update key to Chinese species and illustrations are provided.


Nephron-specific expression of components of the renin-angiotensin-aldosterone system in the mouse kidney.
The renin-angiotensin-aldosterone system (RAAS) plays an integral role in the regulation of blood pressure, electrolyte and fluid homeostasis in mammals. The capability of the different nephron segments to form components of the RAAS is only partially known. This study therefore aimed to characterize the nephron-specific expression of RAAS components within the mouse kidney. Defined nephron segments of adult C57B/16 mice were microdissected after collagenase digestion. The gene expression of renin, angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin II receptors 1a (AT1a), 1b (AT1b), and 2 (AT2) was assessed by reverse transcriptase polymerase chain reaction (RT-PCR). Renin mRNA was present in glomeruli, in proximal tubules, in distal convoluted tubules (DCT) and cortical collecting ducts (CCD). AGT mRNA was found in proximal tubules, descending thin limb of Henle's loop (dTL) and in the medullary part of the thick ascending limb (mTAL). ACE mRNA was not detectable in microdissected mouse nephron segments. AT1a, AT1b and AT2 mRNA was detected in glomeruli and proximal convoluted tubules. Our data demonstrate a nephron-specific distribution of RAAS components. All components of the local RAAS - except ACE - are present in proximal convoluted tubules, emphasizing their involvement in sodium and water handling.


Teaching Undergraduates Beyond the Classroom: Use of WhatsApp.
WhatsApp is a popular platform for social interaction. We used it as an e-learning platform for medical education. We discussed five clinical cases on a WhatsApp group with undergraduates; it increased their knowledge in the subject significantly (P<0.001). Participants accepted it well and perceived that it has improved their problem solving skill and stimulated them for self-study.


Uptake of ozone in human lungs and its relationship to local physiological response.
To investigate whether intersubject variations in the dose of inhaled ozone (O(3)) cause corresponding variations in the physiological response, 28 female and 32 male nonsmokers participated in a 1-h continuous inhalation of clean air or 0.25 ppm O(3) while exercising on a cycle ergometer at a constant ventilation rate of 30 L/min. The exposure protocols included continuous monitoring of respiratory flow rate and O(3) concentration from which O(3) uptake (OZU) and fractional uptake efficiency (UE) were computed. Pre-to-post changes in forced expired volume in 1 s (%DeltaFEV(1)), peripheral cross section for carbon dioxide diffusion (%Delta A(P)), and Fowler dead space volume (V(D)) were also measured for each exposure. Individual values of UE ranged from .70 to .98 among all the subjects, with significant differences (p<.05) existing between men and women. These intersubject differences were inversely correlated with breathing frequency and directly correlated with tidal volume. The mean +/- SD values of %Delta FEV(1), %Delta A(P), and %Delta V(D) were all significantly more negative in the O(3) exposure session (-13.31 +/- 13.40, -8.14 +/- 7.62, and -4.20 +/- 5.12, respectively) than in the air exposure session (-0.06 +/- 4.56, 0.22 +/- 10.82, and -0.70 +/- 6.88, respectively). Finally, our results showed that neither %DeltaFEV(1) nor %Delta V(D) was correlated OZU, whereas there was a significant relationship (rho = -0.325, p = .0257) between %Delta A(P) and OZU. We conclude that the overall uptake of O(3) is a weak predictor of intersubject variations in distal airspace response, but is not a predictor of intersubject variations in conducting airway responses.


Pharmacokinetic and pharmacodynamic aspects of antimicrobial agents for the treatment of uncomplicated urinary tract infections.
Uncomplicated urinary tract infections (UTI) are treated with beta-lactams, co-trimoxazole, quinolones and fosfomycin tromethamine. Due to increasing resistance of causative pathogens, antibiotics should be used by considering their pharmacodynamic and pharmacokinetic characteristics. beta-lactams have time-dependent activity and should not be used once-daily. Co-trimoxazole should be restricted due to increasing chemoresistance. Fluoroquinolones play a primary role in the treatment of serious and complicated infections. Fosfomycin tromethamine is active against most urinary tract pathogens. In vitro time-kill kinetics of fosfomycin against Escherichia coli and Proteus mirabilis showed primarily concentration-dependent activity, with a prolonged post-antibiotic effect (3.4 to 4.7h). Based on these results a single 3g dose of fosfomycin guarantees optimal efficacy against common uropathogens with an AUC(urine)/MIC ratio of 500.


Reprogramming Porcine Fibroblast to EPSCs.
The development of porcine expanded potential stem cells (pEPSCs) provides an invaluable tool for investigation of porcine stem cell pluripotency and opens a venue for research in biotechnology, agriculture, and regenerative medicine. Since the derivation of pEPSC from porcine pre-implantation embryos has been demanding in resource supply and technical challenges, it is more feasible and convenient for most laboratories to derive this new type of porcine stem cells by reprogramming somatic cells. In this chapter, we describe the detailed procedures for reprogramming porcine fetal fibroblast cells to EPSCiPSC with the eight reprogramming factors cloned on the piggyBac vectors followed by a selection for pluripotent cells independent of transgene expression using the EPSC media. This technique allows the generation of pEPSCs for stem cell research, genome editing, biotechnology, and agriculture.


Long-Lived Charge-Transfer State in Spiro Compact Electron Donor-Acceptor Dyads Based on Pyromellitimide-Derived Rhodamine: Charge Transfer Dynamics and Electron Spin Polarization.
We observed a long-lived charge transfer (CT) state in a novel orthogonal compact electron donor-acceptor dyads, with closed form of rhodamine (Rho) as electron donor and pyromellitimide (PI),or thionated PI, as electron acceptor. The two parts in the dyads are connected via a spiro quaternary carbon atom, thus the torsion between the donor and acceptor is completely inhibited, which is beneficial to reduce the reorganization energy and to exploit the Marcus inverted region effect to prolong the CT state lifetime. Femtosecond transient absorption spectra show that the charge separation is rather fast, while nanosecond transient absorption spectra confirmed the formation of long-lived CT state (2.6 μs). Time-resolved electron paramagnetic resonance (TREPR) spectra determined the spin multiplicity of the long living state and assigned it to a 3 CT state. Replacement of an oxygen atom in the PI part with a sulfur atom favoring classical intersystem crossing processes, causes a consistently shortening of the lifetime of the 3 CT state (0.29 μs).


Feeding selectivity in relation to territory size in a herbivorous reef fish.
Territory size in the herbivorous reef fish, Parma victoriae, (Pisces: Pomacentridae) is primarily determined by local density patterns and is independent of changes in food levels (Norman and Jones 1984). However, while individual readily expand territories in response to having their neighbours removed, they appear not to increase total food consumption. Individuals with large territories may benefit from improved food quality. Here we test the hypothesis that expanded territories increase access to preferred food types.A preliminary comparison of the relative proportions of algal species consumed and those present in the field indicated that feeding was highly selective. Strong feeding preferences were indicated by a field 'cafeteria' experiment, in which algal species were presented to individuals in equal amounts. Selectivity indices calculated from diet and availability measures were positively correlated with the feeding preference rankings.Individuals examined from two territory size categories (<10 m2 and > 10 m2) did not exhibit significant differences in feeding prefernces. However, they differed greatly in terms of the makeup of their diets. Higher ranking algae such as Champia zostricola and Rhodoglossum sp. were consumed in greater proportions on large territories. Algal abundances within territories also differed for the two groups. Some of the less abundant, high ranking food species were found in greater quantities per unit area on large territories. The differences in diet were not solely explained by changes in availability. The appropriate comparison showed that whereas individuals on large territories fed in a highly selective manner, those on small territories consumed algae in proportion to their availability. A neighbour removal experiment supported the hypothesis that territory expansion results in an increase in the consumption of preferred algal species.


Pro- and antiatherogenic effects of a dominant-negative P465L mutation of peroxisome proliferator-activated receptor-γ in apolipoprotein E-Null mice.
The dominant-negative mutation, P467L, in peroxisome proliferator-activated receptor-γ (PPARγ) affects adipose tissue distribution, insulin sensitivity, and blood pressure in heterozygous humans. We hypothesized that the equivalent mutation, PPARγ-P465L, in mice will worsen atherosclerosis. Apolipoprotein E-null mice with and without PPARγ-P465L mutation were bred in 129S6 inbred genetic background. Mild hypertension and lipodystrophy of PPARγ-P465L persisted in the apolipoprotein E-null background. Glucose homeostasis was normal, but plasma adiponectin was significantly lower and resistin was higher in PPARγ-P465L mice. Plasma cholesterol and lipoprotein distribution were not different, but plasma triglycerides tended to be reduced. Surprisingly, there were no overall changes in the atherosclerotic plaque size or composition. PPARγ-P465L macrophages had a small decrease in CD36 mRNA and a small yet significant reduction in very-low-density lipoprotein uptake in culture. In unloaded apolipoprotein E-null macrophages with PPARγ-P465L, cholesterol uptake was reduced whereas apolipoprotein AI-mediated efflux was increased. However, when cells were cholesterol loaded in the presence of acetylated low-density lipoprotein, no genotype difference in uptake or efflux was apparent. A reduction of vascular cell adhesion molecule-1 expression in aorta suggests a relatively antiatherogenic vascular environment in mice with PPARγ-P465L. Small, competing pro- and antiatherogenic effects of PPARγ-P465L mutation result in unchanged plaque development in apolipoprotein E-deficient mice.


Manganese and copper promote the binding of dopamine to "serotonin binding proteins" in bovine frontal cortex.
The authors previously reported that Fe2+ is capable of increasing the binding of dopamine and of serotonin to "serotonin binding proteins" which are present in soluble extracts from calf brain. In this study, it is shown that Mn2+ and Cu2+ are also capable of increasing the binding, but for dopamine only. As for Fe2+, Mn2+ and Cu2+ are likely to promote the binding by virtue of their ability to enhance the oxidation of dopamine into dopamine-O-quinone, a derivative which is known to undergo covalent association with sulfhydryl groups of proteins. Data such as the irreversible nature of the majority of the binding, the inhibitory action of reducing agents (sodium ascorbate) and of reagents which contain, or modify sulfhydryl groups (reduced glutathione) are compatible with such a mechanism. The three metal ions are also capable of inactivating part of the binding sites on SBP directly; this effect is more pronounced for Cu2+ than for Fe2+ and it is only weak for Mn2+. The Fe(2+)-mediated binding of dopamine is inhibited by the superoxide dismutase enzyme, and it was therefore suggested that Fe2+ enhances the oxidation of dopamine by virtue of its ability to produce superoxide radicals out of dissolved molecular oxygen. Such a mechanism does not appear to take place in the case of Mn2+ and Cu2+. Instead, it is likely that Cu2+ and dopamine form a complex which is highly susceptible towards oxidation by dissolved molecular oxygen. Mn2+, on the other hand, can easily be oxidized into Mn3+, which is capable to oxidize dopamine by itself.(ABSTRACT TRUNCATED AT 250 WORDS)


The erasable Western blot.
A method for successfully removing primary and secondary antibodies from nitrocellulose blots while preserving the originally immobilized polypeptides was developed. Polypeptides were separated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and electrophoretically transferred to nitrocellulose. Nonspecific binding sites were blocked with 5% (w/v) nonfat dried milk. After blots were reacted sequentially with antibodies directed against the antigen of interest and with radiolabeled secondary antibody, a 10-min wash in 5% (w/v) milk was required prior to drying and autoradiography. A 30-min incubation at 70 degrees C in 2% (w/v) sodium dodecyl sulfate containing 100 mM beta-mercaptoethanol quantitatively removed the antibodies and allowed reuse of the blot. A modification of this method similarly allowed reuse of Western blots when proteins were immobilized on nylon. Potential applications and limitations of this method are discussed.


Accessory nerve neurinoma mimicking a brain stem tumor on angiography: report of a case.
A case of accessory nerve neurinoma presenting with a so-called "intraaxial mass sign" on the angiograms is reported. The tumor originated from the intracranial portion of the accessory nerve and displaced the lateral medullary segment of the posterior inferior cerebellar artery posterolaterally. The displacement of the artery can be understood by the microanatomical relations.


Raloxifene in breast cancer prevention.
Raloxifene is a benzothiophene, selective estrogen receptor modulator with estrogen-agonist effects in the skeleton and the cardiovascular system but estrogen-antagonist effects in the uterus and the mammary gland. This compound was first approved in different countries for the prevention and treatment of osteoporosis. We performed a literature search to review available preclinical and clinical data that has led to the recent FDA approval of raloxifene as a chemopreventive agent for breast cancer in postmenopausal women. Different placebo-controlled trials indicated that raloxifene is effective in reducing invasive breast cancer risk in postmenopausal women. In a recent comparative study, a similar efficacy between raloxifene and tamoxifen for breast cancer prevention was demonstrated, but raloxifene showed a more favorable safety profile.


Probing the heterogeneous structure of eumelanin using ultrafast vibrational fingerprinting.
Eumelanin is a brown-black biological pigment with sunscreen and radical scavenging functions important to numerous organisms. Eumelanin is also a promising redox-active material for energy conversion and storage, but the chemical structures present in this heterogeneous pigment remain unknown, limiting understanding of the properties of its light-responsive subunits. Here, we introduce an ultrafast vibrational fingerprinting approach for probing the structure and interactions of chromophores in heterogeneous materials like eumelanin. Specifically, transient vibrational spectra in the double-bond stretching region are recorded for subsets of electronic chromophores photoselected by an ultrafast excitation pulse tuned through the UV-visible spectrum. All subsets show a common vibrational fingerprint, indicating that the diverse electronic absorbers in eumelanin, regardless of transition energy, contain the same distribution of IR-active functional groups. Aggregation of chromophores diverse in oxidation state is the key structural property underlying the universal, ultrafast deactivation behavior of eumelanin in response to photoexcitation with any wavelength.


Correlations between anti-dsDNA antibodies, complement levels and clinical course in SLE patients treated with steroid pulse therapy.
In patients with SLE dsDNA binding activity, C3 and C4 levels are correlated with the clinical course of the nephritis. In fact the study of these serological parameters has a prognostic value in patients treated with methylprednisolone pulse therapy. This treatment can rapidly normalize an acute phase.


Pathological features of vascular wall in Dieulafoy's disease.
Although there are many clinical reports on Dieulafoy's disease, there are few studies on the pathological structure of vascular wall in Dieulafoy's disease. In this study, the main structural changes of the intima and media of the vascular wall were observed by special staining and immunohistochemical methods in the subjects of Dieulafoy's disease of stomach and intestine. There were many vessels of different sizes in the submucosa, with uneven wall thickness of the vessels. Compared with the normal control group, the content of blue collagen fibers between the vascular smooth muscle cells in the lesion group was increased, the elastic fibers were thickened, and the internal elastic plate was arranged stiff or even interrupted. The increase of collagen and elastic fibers between the smooth muscle cells of the medium membrane and the destruction of the structure of the inner elastic plate may be the structural basis of vascular lesions leading to Dieulafoy's disease.