[Behavior therapy. Bases and criticism].
Our first concern is a general characterization of behaviour therapy. It cannot be produced by means of the description of its methods and techniques, since it includes a wide gamut of them, ranging from systematic desensitization to assertive training and aversive conditioning. It is necessary then to resort to the theoretical basis common to the different methods and techniques. The reciprocal inhibition principle, as stated by John Wolpe, is likely to provide a sound starting point. To Wolpe's mind, a neurosis is an anxiety response deeply rooted through conditioning. Most behaviour therapists share this conception. The therapist task is, according to it, to unchain the circuit between anxiety producing stimulus and neurotic responses. In order to achieve the disjunction, an antagonistic response is used, that reciprocally inhibits the anxiety response. Systematic desensitization based on relation is a typical application of the reciprocal inhibition principle. Nevertheless, other usual techniques, such as negative practice (used by Yates for the treatment of tics) or Skinner's operant conditioning are not based on that principle. A wider basis is thus required. Behaviour therapists claim that the theoretical basis is to be found in learning theory laws. The reciprocal inhibition principle is the counterpart of the counter-conditioning law, the negative practice principle is similar to the extinction law, and so on. However, there is not one single learning theory, but several ones, mutually contradictory. And they are not fit to provide the needed theoretical basis. That disagreement can be overcome looking for the common principle of all learning laws, namely, that the need is to create definite circuits that can operate in front of adequate stimulus. Still another set of criticisms to behaviour therapy comes from dynamic psychology and psychoanalysis. The fact is stressed that suppressing symptoms does not modify structural maladjustments. Behavior therapists acknowledge their treatments are kept at symptom level, but they claim it is the right approach, since the symptom is the neurosis, according to their conceptions.


Structure and organization of the murine band 3 gene.
The Band 3 protein mediates the reversible exchange of chloride and bicarbonate anions across the plasma membrane of erythrocytes, and probably, certain epithelial cells. It also serves to anchor the spectrin cytoskeleton to the plasma membrane via its association with ankyrin. We have isolated and largely sequenced the 17-kilobase murine Band 3 gene. We show that this gene is present in a single copy in the mouse genome and have identified and mapped the 19 intervening sequences. The locations of the intron/exon junctions in the Band 3 mRNA correlate with predicted structural features of the erythrocyte Band 3 protein structure and membrane topology. One of the introns within this gene contains a single copy of a murine Alu-type high dispersed sequence, in addition to several unusual tandemly repeated sequences.


[Research on preparation process of andrographolide-glycyrrhizic acid polymeric micelles].
This study aimed to prepare andrographolide (AP)-loaded glycyrrhizic acid (GA) micelles (AP-GA)-PMs to enhance the solubility and anti-tumor effect of andrographolide. Firstly, andrographolide (AP) was used as the model drug and glycyrrhizic acid (GA) as carriers to prepare (AP-GA)-PMs. Then the preparation methods and the ratios of drug and carrier were screened and optimized based on particle size, encapsulation efficiency (EE) and loading capacity of micelles. Finally, the pharmaceutical characters and the inhibition rate on HepG2 cells were evaluated on the (AP-GA)-PMs prepared by optimal process. The results showed that the prepared micelles under the optimal process had a nanosize of (127.11±1.38) nm, zeta potential of (-24.01±0.55) mV, the entrapment efficiency rate of (92.01±4.02)% , the drug loading rate of (51.44±1.24)% and high storage stability at 4 °C in 30 d, with slow but highly stable in vitro release. Moreover, (AP-GA)-PMs with the IC₅₀ value of 19.25 mg·L⁻¹ had a more synergistic and better anti-tumor effect in comparison with AP (IC₅₀=122.40 mg·L⁻¹) on HepG2 cells (P<0.01). In conclusion, the (AP-GA)-PMs prepared with glycyrrhizic acid as a carrier had a small particle size, large drug loading capacity, and high stability, and could significantly improve the anti-tumor effects of AP.


Overview of quinapril, a new ACE inhibitor.
Quinapril has been extensively studied for efficacy and safety in patients with hypertension or congestive heart failure (CHF) in the United States and Europe. Thirty-nine clinical pharmacology studies involving 383 patients have been completed. Moreover, 12 controlled, multicenter clinical studies and 3 single-center studies involving 1,793 patients have been conducted in hypertension. Three hemodynamic trials, two of which included both acute and long-term phases, and one placebo-controlled, dose-response study have been conducted in 333 patients with CHF. An additional 519 patients who completed studies on comparative agents were started on quinapril at the initiation of six long-term, open-label trials, which extended for up to 3 years. Twelve of 15 hypertension trials evaluated quinapril as first-line monotherapy in 1,452 patients with hypertension. Comparative agents included placebo in five trials (524 patients), enalapril in three trials (339 patients), captopril in four trials (335 patients), and chlorthalidone in one trial (74 patients). A total of 510 patients received quinapril in addition to a diuretic in double-blind trials: 341 patients with moderate to severe hypertension participated in three trials, and 169 patients with CHF participated in one trial. Quinapril administered once daily (o.d.) was evaluated in four placebo-controlled studies and in two studies of o.d. vs. twice-daily doses. The safety of quinapril has been evaluated in almost 2,700 patients in controlled, double-blind studies or in open-label extensions, for a total of more than 1,600 patient-years of exposure to quinapril. More than one-half of all patients participated in long-term trials: 980 patients were studied for 1 year and 315 patients were studied for 2 years at the time of data analysis. Safety data are available for 451 older patients (aged greater than or equal to 65 years), and comparative safety data from other compounds in the controlled studies are available for 1,058 patients. Quinapril's efficacy is comparable to that of other angiotensin-converting enzyme (ACE) inhibitors, and it has a lower incidence of adverse events or withdrawals due to adverse events than has been associated with captopril or enalapril.


Blood cultures in acute surgical admissions.
Obtaining blood cultures prior to the administration of antimicrobial therapy was a key recommendation of the 2012 UK Surviving Sepsis Campaign. Few studies have examined the effect blood cultures have on clinical management and there have been none on acute surgical admissions. This retrospective study sought to evaluate the effect of blood cultures on clinical management in acute surgical admissions. Data on acute surgical patients admitted between 1 January and 31 December 2012 were extracted from hospital records. Patients given intravenous antibiotics within 24 hours of admission were identified. Data collected included antibiotics administered, blood culture results, admission observations and white blood cell count. Case notes were reviewed for patients with positive cultures to establish whether the result led to a change in management. Of 5,887 acute surgical admissions, 1,346 received intravenous antibiotics within 24 hours and 978 sets of blood cultures were taken in 690 patients. The recommended two sets of cultures were obtained in 246 patients (18%). Patients who had blood cultures taken had the same in-hospital mortality as those who had none taken (3.6% vs 3.5%, p=0.97). Blood cultures were positive in 80 cases (11.6%). The presence of systemic inflammatory response syndrome did not increase positivity rates (12.9% vs 10.3%, p=0.28). Overall, cultures altered management in two patients (0.3%). Blood cultures rarely affect clinical management. In order to assess the additional value that blood cultures bring to sepsis management in acute surgical admissions, a prospective randomised trial focusing on outcome is needed.


The effect of hyperinflation, inspiratory hold, and oxygenation on cardiopulmonary status during suctioning in a lung-injured model.
This study determined the effects of a 5-second inspiratory hold during ventilatory maneuvers on cardiopulmonary status before, during, and after endotracheal suctioning in an acute lung-injured model. Eight mongrel dogs were anesthetized, paralyzed, mechanically ventilated, and given intravenous oleic acid to produce pulmonary edema. Four protocols were tested in alternate order in which either tidal volume inflations or hyperinflations at an FiO2 of 0.6 were given with and without an inspiratory hold of 5 seconds before and after each of three sequential suctioning passes. In those protocols in which an inspiratory hold was used, statistically significant changes occurred in right atrial, pulmonary arterial, and aortic systolic and diastolic pressures (p less than 0.04). The use of an inspiratory hold with hyperinflation maintained PaO2 during suctioning (range of 81 to 91 mm Hg), but had the greatest decrease in PaO2 (8%) after return to the ventilator. In all protocols, with the exception of the one in which hyperinflations without an inspiratory hold were used, there was a cumulative increase in PaCO2 with tidal volume inflation protocols reaching peak PaCO2 values of 49 (+/- 7.5) mm Hg. In protocol 4 in which hyperinflation without inspiratory hold was used, PaO2 ranged from 75 (+/- 16) to 92 (+/- 34) mm Hg, and PaCO2 ranged from 37 (+/- 7) to 42 (+/- 6) mm Hg. In conclusion, the use of hyperinflation without an inspiratory hold resulted in the least undesirable changes in the variables studied. However, this protocol needs to be replicated in an acutely ill clinical population before recommended for practice.


International evolution in AYA oncology: Current status and future expectations.
Adolescents and Young Adults (AYAs) contribute approximately 1 million incident cases globally, but the great majority are underserved. In high-income countries, overall survival exceeds 80%, but the needs of this population during and after their treatment experience are poorly met, though specialized clinical programs are evolving. Engagement of national governments is advantageous and deployment of multidisciplinary teams essential. Collaboration between pediatric and adult healthcare providers is mandatory and AYAs must be given a strong voice in program development. Building and sharing international experience will hasten advances in clinical care, education, and research, while a focus on developing countries is a worthy challenge.


Estimating FVC from FEV2 and FEV3: assessment of a surrogate spirometric parameter.
In the context that accurate measurement of FVC is important in diagnosing airflow obstruction and in assessing restriction, strategies to achieve reliable and accurate FVC measurement have drawn much attention. Because the rate of achieving end-of-test criteria during spirometry has been shown to be low, with resultant under-recording of the FVC, the current study proposes a regression equation for estimating FVC from measured values of the forced expiratory volume in 2 s (FEV2) and forced expiratory volume in 3 s (FEV3). The predictive equation for the estimated FVC from volume measurements within the first 3 s of exhalation (estimated FVC3) was generated based on 330 consecutive acceptable spirograms performed in the Cleveland Clinic Foundation Pulmonary Function Laboratory. The equation was applied to an independent validation set comprised of spirometry measurements on 370 different consecutive patients. In the validation spirometry sample, in which the prevalence of obstruction was 34% (based on values of the measured FEV1/FVC compared to National Health and Nutrition Examination Survey III values), the sensitivity, specificity, and positive and negative predictive values of FEV1/estimated FVC3 for obstruction were 93.8%, 89.1%, 81.2%, and 96.9%, respectively. The misclassification rate was 9.2%. In the same cohort, the mean difference (+/- SD) between estimated FVC3 and measured FVC was 24.7 +/- 237 mL. Given that FVC is frequently under-recorded, with resultant overestimation of FEV1/FVC and underdiagnosis of airflow obstruction, we believe that estimating FVC from FEV2 and FEV3 can offer practical diagnostic advantages.


Racial inequality and child neglect: findings in a metropolitan area.
Despite contradictory evidence, child neglect is often believed to occur more frequently in the African American than in the Caucasian population. This article reports findings on the racial differences among 182 families referred for neglect in a large metropolitan area. Although almost all of the families were poor, African American families in the neglect sample suffered even more from economic inequality than those in the general population. Implications of the findings for social welfare policy and child welfare practice are discussed.


PCR Based Molecular Detection of the Gyr-B-2 Gene from the Klebsiella Sp. Isolates from Patients who were Suffering with Pneumonia and Urinary Tract Infections (UTIs).
Detection of the virulence gene is a key component in determining the pathogenicity of any isolates, because these genes act multi-functionally and multi-factorially. A gyrase specific gene primer, in combination with the PCR technology, allows the precise detection of the DNA gyrase subunit B2 gene (gyr-B-2) from different virulent microorganisms. In the present study, forward and reverse primers with lengths of 20bp and 21bp were used for the detection of the gyr-B-2 genes in the clinical isolates of the Klebsiella sp. which were collected from patients who were suffering from pneumonia and urinary tract infections (UTIs). A total of 14 isolates viz., K1, K2, K3, K4, K5, K6, K7, K8, K9, K10, K11, K12, K13 and K14 were isolated from 3 different private medical colleges of Sylhet city. The gyr-B-2 gene which was amplified in 12 isolates viz., K1, K2, K3, K4, K5, K6, K7, K8, K10, K11, K12 and K14 gave the expected 411bp PCR product after its visualization under a gel documentation system in a 1.2% agarose gel. The present study was undertaken to detect the gyrB2 gene from Klebsiella sp, which will be helpful for further scientific studies. This PCR was outstanding in the detection of the gyb-B-2 gene in pneumonia and urinary tract infections in patients, which were caused by the Klebsiella species.


Grapefruit juice and orange juice effects on the bioavailability of nifedipine in the rat.
Previous studies with rats indicate that nifedipine undergoes both hepatic and extrahepatic presystemic metabolism after peroral (po) administration, and that its bioavailability is increased and absorption delayed by concomitant administration of grapefruit juice concentrate (GJC). Hence, the effects of GJC could be to delay stomach emptying and inhibit nifedipine metabolism in the small-intestinal wall and liver or, alternatively, to impede nifedipine absorption until reaching the large intestine where gut wall presystemic metabolism is not a factor. The mechanism(s) of action of GJC might be partially resolved by comparison with orange juice concentrate (OJC), which has a similar consistency but lacks inhibitory effects on nifedipine presystemic metabolism, and also by giving regular-strength solutions of the two juices, both on which should not significantly affect stomach emptying. This study compared the po bioavailability of nifedipine (6 mg kg-1) in male Sprague-Dawley rats coadministered GJC, OJC, grapefruit juice regular strength (GJRS), orange juice regular strength (OJRS), or (tap) water. Nifedipine plasma concentration-time profiles in the GJRS, OJRS, and (tap) water groups displayed a single peak. Both GJC and OJC groups have double-peak profiles (indicating delayed gastric emptying); however, the majority of the nifedipine dose in both cases was absorbed during the interval of the second peak, which occurred several hours postdosing. GJC significantly increased nifedipine bioavailability (relative bioavailability 2.02, compared with (tap) water), indicating that GJC may affect both extrahepatic and hepatic first-pass metabolism, although a reduction in systemic nifedipine clearance cannot be ruled out. Surprisingly, GJRS had no significant effect on nifedipine bioavailability. OJC did not increase nifedipine bioavailability, further suggesting that the delay in nifedipine absorption by GJC or OJC results from delayed gastric emptying.


Gestational exposure to nonylphenol causes precocious mammary gland development in female rat offspring.
This study examined whether or not exposure to 4-nonylphenol (NP) during late gestation affects reproductive and mammary development in the offspring of female rats. Time pregnant Long Evans rats were gavaged with NP (10 or 100 mg/kg), atrazine (ATR, 100 mg/kg), or corn oil on gestation days 15-19. The uterus weights of the NP (100 mg/kg/d)-exposed pups were higher than those of the controls but the weights of the other organs were unchanged. Delayed mammary gland (MG) development was detected in the ATR pups on PND 4 and persisted through to PND 66. The high dose NP pups had advanced lobular development of their MG on PND 22, while the glands from the low dose NP pups were no different morphologically from the controls. Immunohistochemical comparisons of the mammary sections from PND 41 demonstrated low levels of estrogen receptor (ER) staining in the control gland stroma and epithelium but higher levels in the tissue of the pups exposed to NP and ATR. ATR also elevated ER in the stroma surrounding the epithelial layer of the terminal end buds. The level of progesterone receptor (PR) staining was markedly lower in the epithelium of the 100 mg/kg NP glands vs. the control glands. However, PR was present at high levels in the epithelium of the 10 mg/kg NP glands and was even more prominent in the ATR-exposed ductal epithelium and fat cell nuclei. The level of prolactin staining was only elevated in glands containing lobule areas (NP-exposed) compared with the control levels. These results suggest that NP and ATR have opposite effects on the development of MG after gestational exposure. Exposure to them during the critical period of epithelial outgrowth altered the receptor levels of mammary progesterone and prolactin and might contribute to the differences in the mammary morphology at PND 41.


Product inhibition of cellulases studied with 14C-labeled cellulose substrates.
As a green alternative for the production of transportation fuels, the enzymatic hydrolysis of lignocellulose and subsequent fermentation to ethanol are being intensively researched. To be economically feasible, the hydrolysis of lignocellulose must be conducted at a high concentration of solids, which results in high concentrations of hydrolysis end-products, cellobiose and glucose, making the relief of product inhibition of cellulases a major challenge in the process. However, little quantitative information on the product inhibition of individual cellulases acting on cellulose substrates is available because it is experimentally difficult to assess the hydrolysis of the heterogeneous polymeric substrate in the high background of added products. The cellobiose and glucose inhibition of thermostable cellulases from Acremonium thermophilum, Thermoascus aurantiacus, and Chaetomium thermophilum acting on uniformly 14C-labeled bacterial cellulose and its derivatives, 14C-bacterial microcrystalline cellulose and 14C-amorphous cellulose, was studied. Cellulases from Trichoderma reesei were used for comparison. The enzymes most sensitive to cellobiose inhibition were glycoside hydrolase (GH) family 7 cellobiohydrolases (CBHs), followed by family 6 CBHs and endoglucanases (EGs). The strength of glucose inhibition followed the same order. The product inhibition of all enzymes was relieved at higher temperatures. The inhibition strength measured for GH7 CBHs with low molecular-weight model substrates did not correlate with that measured with 14C-cellulose substrates. GH7 CBHs are the primary targets for product inhibition of the synergistic hydrolysis of cellulose. The inhibition must be studied on cellulose substrates instead of on low molecular-weight model substrates when selecting enzymes for lignocellulose hydrolysis. The advantages of using higher temperatures are an increase in the catalytic efficiency of enzymes and the relief of product inhibition.


Dietary cholesterol alters Na+/K+ selectivity at intracellular Na+/K+ pump sites in cardiac myocytes.
A modest diet-induced increase in serum cholesterol in rabbits increases the sensitivity of the sarcolemmal Na+/K+ pump to intracellular Na+, whereas a large increase in cholesterol levels decreases the sensitivity to Na+. To examine the mechanisms, we isolated cardiac myocytes from controls and from rabbits with diet-induced increases in serum cholesterol. The myocytes were voltage clamped with the use of patch pipettes that contained osmotically balanced solutions with Na+ in a concentration of 10 mM and K+ in concentrations ([K+]pip) ranging from 0 to 140 mM. There was no effect of dietary cholesterol on electrogenic Na+/K+ current (Ip) when pipette solutions were K+ free. A modest increase in serum cholesterol caused a [K+]pip-dependent increase in Ip, whereas a large increase caused a [K+]pip-dependent decrease in Ip. Modeling suggested that pump stimulation with a modest increase in serum cholesterol can be explained by a decrease in the microscopic association constant KK describing the backward reaction E1 + 2K+ --> E2(K+)2, whereas pump inhibition with a large increase in serum cholesterol can be explained by an increase in KK. Because hypercholesterolemia upregulates angiotensin II receptors and because angiotensin II regulates the Na+/K+ pump in cardiac myocytes in a [K+]pip-dependent manner, we blocked angiotensin synthesis or angiotensin II receptors in vivo in cholesterol-fed rabbits. This abolished cholesterol-induced pump inhibition. Because the epsilon-isoform of protein kinase C (epsilonPKC) mediates effects of angiotensin II on the pump, we included specific epsilonPKC-blocking peptide in patch pipette filling solutions. The peptide reversed cholesterol-induced pump inhibition.


Testicular cancer in nine northern European countries.
The incidence of testicular cancer was examined in the Nordic and Baltic countries, Poland and Germany by collaboration among 10 cancer registries. Population-based registers were used to analyze a total of 34,309 cases, diagnosed from the start of registration (varying from 1943 in Denmark to 1980 in Latvia and Lithuania) through 1989. An approximately 10-fold geographical variation was found in 1980, with the highest age-standardized incidence rate (7.8 per 10(5); world standard population) in Denmark and the lowest (0.9) in Lithuania. During the entire period of registration, incidence increased rapidly in all countries, by 2.3 to 3.4 per cent annually in the Nordic countries and by about 5 per cent in Poland and Germany; there was some evidence of a slower increase in Denmark and Poland after 1975. The rising trend was more pronounced for ages below 30. The age-specific incidence peaked in all countries at ages 25 to 34, but the geographical variation was considerable. Our data indicate that environmental influences on testicular cancer are strong. Exposure to causal factors mostly takes place early in life, shows substantial geographical variation, and increases over time, so that the age-standardized incidence doubles every 15 to 25 years. New aetiological hypotheses are needed to accommodate these salient features of the descriptive epidemiology, since risk factors considered so far cannot explain the observed pattern.


The colorful versatility of adipocytes: white-to-brown transdifferentiation and its therapeutic potential in humans.
Brown and brite adipocytes contribute to energy expenditure through nonshivering thermogenesis. Though these cell types are thought to arise primarily from the de novo differentiation of precursor cells, their abundance is also controlled through the transdifferentiation of mature white adipocytes. Here, we review recent advances in our understanding of the regulation of white-to-brown transdifferentiation, as well as the conversion of brown and brite adipocytes to dormant, white-like fat cells. Converting mature white adipocytes into brite cells or reactivating dormant brown and brite adipocytes has emerged as a strategy to ameliorate human metabolic disorders. We analyze the evidence of learning from mice and how they translate to humans to ultimately scrutinize the relevance of this concept. Moreover, we estimate that converting a small percentage of existing white fat mass in obese subjects into active brite adipocytes could be sufficient to achieve meaningful benefits in metabolism. In conclusion, novel browning agents have to be identified before adipocyte transdifferentiation can be realized as a safe and efficacious therapy.


Analysis of the interface pressure exerted by the Chêneau brace in patients with double-curve adolescent idiopathic scoliosis.
The Chêneau brace has proven its effectiveness in treating the adolescent idiopathic scoliosis patients. However, no studies reported on the analysis of interface pressure in double-curve adolescent idiopathic scoliosis patients. In this study, we evaluated the interface pressure of the Chêneau brace action in double-curve adolescent idiopathic scoliosis patient treatment. A total of 72 (60 girls and 12 boys) patients aged 10 years and above participated in the study. The F-Socket transducers (9811E) were used to evaluate the pressure on the right thoracic and left thoracolumbar curves between normal and maximum strap tension and variation in these interface pressures with other tasks. Each patient was asked to do nine different tasks corresponding to daily activities, and the interface pressures for each activity were recorded for both normal and maximum tension. The resultant mean peak pressure in double-curve adolescent idiopathic scoliosis was higher for right thoracic curves than left thoracolumbar curves in all tasks. The pressure significantly increased at the task of maximal inspiration (p < 0.0001) for both types of curves for normal and maximum tension. The degrees of correction for the thoracic and thoracolumbar curves were 23.2% and 34.5%, respectively, after 6 months of brace use (23 h per day). Hence, we could not find any substantial correlation between mean peak pressure in the standing position and degree of scoliosis correction for two curves having r = 0.158, p = 0.356 and r = -0.024, p = 0.889 values.


Inhibition of RNA and protein synthesis by ethanol in regenerating rat liver: evidence for transcriptional inhibition of protein synthesis.
The effect of ethanol on RNA and protein synthesis was studied in regenerating rat liver. Partial hepatectomy stimulated the activity of ornithine decaroxylase (ODC) and that of tyrosine aminotransferase (TAT) as well as the synthesis of RNA. The intubation of ethanol (3g/kg) 1 hr before the operation inhibited the stimulation of ODC and TAT when measured 4 hrs after the operation. Ethanol administration also inhibited RNA synthesis. By using inhibitors of alcohol dehydrogenase and aldehyde dehydrogenase it was shown that the inhibition of RNA synthesis (and also that of protein synthesis) was most probably a direct effect of ethanol itself. When RNA synthesis was measured in vivo in purified nuclei, ethanol inhibited the incorporation of nucleotides to RNA. It is suggested that ethanol inhibits protein synthesis in regenerating rat liver at the transcriptional level by interfering in nuclei with the synthesis of RNA.


The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin.
Coumarin antibiotics, such as clorobiocin, novobiocin, and coumermycin A1, inhibit the supercoiling activity of gyrase by binding to the gyrase B (GyrB) subunit. Previous crystallographic studies of a 24-kDa N-terminal domain of GyrB from E. coli complexed with novobiocin and a cyclothialidine analogue have shown that both ligands act by binding at the ATP-binding site. Clorobiocin is a natural antibiotic isolated from several Streptomyces strains and differs from novobiocin in that the methyl group at the 8 position in the coumarin ring of novobiocin is replaced by a chlorine atom, and the carbamoyl at the 3' position of the noviose sugar is substituted by a 5-methyl-2-pyrrolylcarbonyl group. To understand the difference in affinity, in order that this information might be exploited in rational drug design, the crystal structure of the 24-kDa GyrB fragment in complex with clorobiocin was determined to high resolution. This structure was determined independently in two laboratories, which allowed the validation of equivalent interpretations. The clorobiocin complex structure is compared with the crystal structures of gyrase complexes with novobiocin and 5'-adenylyl-beta, gamma-imidodiphosphate, and with information on the bound conformation of novobiocin in the p24-novobiocin complex obtained by heteronuclear isotope-filtered NMR experiments in solution. Moreover, to understand the differences in energetics of binding of clorobiocin and novobiocin to the protein, the results from isothermal titration calorimetry are also presented.


Gut microbiota of Busseola fusca (Lepidoptera: Noctuidae).
Busseola fusca (Fuller) (Lepidoptera: Noctuidae) is a stemborer pest that attacks maize (Zea mays) throughout sub-Saharan Africa. Genetically modified maize has been shown to be effective against B. fusca. However, resistance of B. fusca against Bt-maize has developed and spread throughout South Africa. Previous studies suggested that gut microbiota contribute to mortality across a range of Lepidoptera. To fully assess the role of microbiota within the gut, it is essential to understand the microbiota harboured by natural B. fusca populations. This study aimed to identify the gut-associated bacteria by 16S rRNA gene sequencing. A total of 78 bacterial strains were characterised from the midgut of B. fusca larvae that were collected from 30 sites across the maize producing region of South Africa. Molecular phylogenetic analyses revealed bacteria affiliated to Proteobacteria, Actinobacteria, and Firmicutes. Taxonomic distribution placed these isolates into 15 different genera representing 20 species. The majority of bacteria identified belong to the genera Bacillus, Enterococcus, and Klebsiella. The B. fusca gut represents an intriguing and unexplored niche for analysing microbial ecology. The study could provide opportunities for developing new targets for pest management and contribute to understanding the phenomenon of resistance evolution of this species.


Correlation energies for He isoelectronic sequence with Z=2-116 from four-component relativistic configuration interactions.
The relativistic correlation energies (CEs) for the He isoelectronic sequence from 2He to 116Uuh were investigated using configuration-interaction (CI) calculations. We used a large universal-type Gaussian basis set, which gives accurate Dirac-Fock total energies for the ions under consideration. In contrast to nonrelativistic CEs, the relativistic CEs decrease monotonically with increasing nuclear charge, but the p-, d-, and f-partial CEs have a hump like the relativistic Hylleraas CI.


[The amyloidoses].
There are many clinical types of amyloidosis, as many as chemical types of amyloid substance would be its substratum. This clinic-chemical plurality permits us to talk about the amyloidosis. This article is specially guided to those amyloidosis that present cutaneous damages during its clinical course. They are the immunocytic amyloidosis and the keratinocytic amyloidosis.


Fungal Hydrophobin Proteins Produce Self-Assembling Protein Films with Diverse Structure and Chemical Stability.
Hydrophobins are small proteins secreted by fungi and which spontaneously assemble into amphipathic layers at hydrophilic-hydrophobic interfaces. We have examined the self-assembly of the Class I hydrophobins EAS∆15 and DewA, the Class II hydrophobin NC2 and an engineered chimeric hydrophobin. These Class I hydrophobins form layers composed of laterally associated fibrils with an underlying amyloid structure. These two Class I hydrophobins, despite showing significant conformational differences in solution, self-assemble to form fibrillar layers with very similar structures and require a hydrophilic-hydrophobic interface to trigger self-assembly. Addition of additives that influence surface tension can be used to manipulate the fine structure of the protein films. The Class II hydrophobin NC2 forms a mesh-like protein network and the engineered chimeric hydrophobin displays two multimeric forms, depending on assembly conditions. When formed on a graphite surface, the fibrillar EAS∆15 layers are resistant to alcohol, acid and basic washes. In contrast, the NC2 Class II monolayers are dissociated by alcohol treatment but are relatively stable towards acid and base washes. The engineered chimeric Class I/II hydrophobin shows increased stability towards alcohol and acid and base washes. Self-assembled hydrophobin films may have extensive applications in biotechnology where biocompatible; amphipathic coatings facilitate the functionalization of nanomaterials.


Unilateral False Cord Nodule Presenting As Hoarseness in a Young Patient.
Vocal cord nodules are benign laryngeal lesions seen in professional voice users. They are usually bilateral and are thought to occur due to submucosal edema and hemorrhage, with resultant fibrosis. False cord occurrences are very rare; hence we report a unique case of unilateral right false cord nodule. A healthy 16-year-old female student presented with persistent hoarseness for two years without any history of voice abuse, trauma, infection, or endotracheal intubation. Endoscopic examination showed a mass occupying the right false cord. Subsequent direct laryngoscopy revealed a friable mass on the right false cord without any true cord involvement. Complete excision was done. Post-operatively her symptoms completely resolved, and flexible endoscopic examination seven months post-op showed no recurrence. Histopathological examination revealed fragments of fibro collagenous tissue covered by benign respiratory epithelium, favoring the diagnosis of a benign nodule. False cord benign lesions are rare. In a symptomatic case, endolaryngeal microsurgery gives a good outcome.


Knowledge and Attitudes on Organ Donation From the Perspective of Liver Transplant Patients.
This study was performed to investigate the knowledge and attitudes about organ donation from the perspective of liver transplant patients. The study was conducted at the organ transplantation clinics. The data were collected by the researchers from 129 participants using in-person interviews. In this study, 83% of patients received the organ from live donors, 36% received liver transplants in the previous 1 year, more than 70% agreed to donate their organs, and 80% thought awareness should be raised in society about organ donation. It was found that the participants in the sample needed information on the issue, although the sample consisted of individuals who had experienced organ donation. It is important that nurses and nurse managers understand the level of knowledge and the attitudes of organ donation patients who have undergone liver transplantation. Worldwide, organ donation is not at the desired level. This study aims to enhance in nurses and nurse managers the foresight regarding and awareness about behaviors of transplantation patients.


[An overexpression of retinoic acid receptor alpha blocks myeloid cell differentiation at the promyelocyte stage].
Retinoic acid (RA), a vitamin A derivative, exerts a wide range of biological effects related to cell proliferation and differentiation. The pleiotropic effects of RA are thought to be mediated through specific nuclear RA receptors (RARs). RARs are members of the steroid/thyroid hormone receptor superfamily and exhibit a molecular structure that possess discrete DNA-binding and RA (ligand)-binding domains. In hematopoietic system, RA and RARs, predominantly RAR alpha may play key roles for the proliferation and differentiation of hematopoietic progenitors. However, it is currently unknown how RA and RARs are involved in regulating normal hematopoietic differentiation. To make clear the roles of RA and RAR alpha in the normal hematopoiesis, I have introduced the construct of human RAR alpha (hRAR alpha) into murine bone marrow cells with retroviral vector, and selected infected cells with drug resistant marker (Neo(r)) cultured on the stroma cell line (PA6-neo), and analyzed the behavior of infected cells. All of procedure were done in vitro. Most cells infected with hRAR alpha exhibited promyelocytic morphology and were thought to be blocked at the promyelocytic stage in their myeloid differentiation. Furthermore, these immature cells differentiated terminally into mature granulocytes by adding with RA (10(-6) M). RAR alpha infected cells were also able to differentiate into mature macrophages in the both of long term culture and IL3 colony. These observations suggest that an overexpression of RAR alpha alone is effective to suppress myeloid cell differentiation and RAR alpha plays a crucial role in the terminal differentiation of myeloid precursors. The system described here may serve as a model for studying the the essential genes for differentiation of normal bone marrow cells.


[Relationship of endometrial thickness and endometrial cancer risk in postmenopausal women].
Evaluation of the vaginal bleeding of postmenopausal women is crucial to diagnose endometrial lesions. Endometrial thickness measured by transvaginal ultrasonography provides an important reference for diagnosis. Currently, no specific cut-off value of endometrial thickness has been identified to predict the malignant risk for endometrial thickening and postmenopausal women without any symptoms. Most of resected endometrial specimens from postmenopausal women without any symptoms are diagnosed as benign or normal tissues. It seems that postmenopausal women without any symptoms have no need for general screen or intervention of endometrial cancer.


Curative Therapies for Hepatitis C Virus Infection in Patients with Kidney Disease.
Through the discovery of direct-acting antiviral therapies over the last decade, hepatitis C virus (HCV) has been transformed from a highly morbid and potentially fatal chronic viral infection to a curable illness. HCV is common in patients with kidney disease, is a risk factor for progression of CKD, is associated with higher morbidity and mortality in patients receiving dialysis, and leads to worse allograft and patient outcomes in recipients of kidney transplants. Clinical trial and real-world data of direct-acting antivirals in patients with kidney disease demonstrate extremely high cure rates and favorable adverse event profiles. This review covers the transformative effects of curative HCV therapies on patients with kidney disease, including patients with CKD, ESKD, and those who have received a kidney transplant.


Noise source identification with the lattice Boltzmann method.
In this paper the sound source identification problem is addressed with the use of the lattice Boltzmann method. To this aim, a time-reversed problem coupled to a complex differentiation method is used. In order to circumvent the inherent instability of the time-reversed lattice Boltzmann scheme, a method based on a split of the lattice Boltzmann equation into a mean and a perturbation component is used. Lattice Boltzmann method formulation around an arbitrary base flow is recalled and specific applications to acoustics are presented. The implementation of the noise source detection method for two-dimensional weakly compressible (low Mach number) flows is discussed, and the applicability of the method is demonstrated.


LINC01087 Promotes the Proliferation, Migration, and Invasion of Thyroid Cancer Cells by Upregulating PPM1E.
This study is aimed at investigating the effect and mechanism of LINC01087 on the malignant evolution of thyroid cancer cells. The expression levels of LINC01087, miR-135a-5p, and PPM1E in thyroid carcinoma tissues were detected by QRT-PCR. Cell viability was detected using the CCK-8 method. Transwell assay was used to assess the ability of cells to invade. The targeting relationship between LINC01087 and miR-135a-5p was detected by dual luciferase reporting assay. In comparison with normal thyroid tissues and cells, the expression level of LINC01087 in thyroid cancer tissues and TPC-1 and K1 cells increased, and the expression level of miR-135a-5p in thyroid cancer tissues and TPC-1 and K1 cells decreased. LINC01087 knockdown and the high expression of miR-143-3p inhibited the proliferation, invasion, and EMT processes of TPC-1 and K1 in thyroid cancer cells. LINC01087 negatively targeted miR-135a-5p. Has-miR-135a-5p inhibited the malignant evolution and EMT of thyroid cancer by targeting PPM1E. The PPM1E overexpression can reverse the inhibitory effect of LINC01087 gene knockdown on the proliferation, migration, and invasion of thyroid cancer cells. LINC01087 can promote the proliferation and apoptosis of thyroid cancer cells, and its mechanism may be related to the miR-135a-5p/PPM1E axis.


Clinicopathological significance of altered metallothionein 2A expression in gastric cancer according to Lauren's classification.
Dysregulated metallothionein 2A (MT2A) has been implicated in carcinogenesis. The purpose of this study was to investigate the expression of MT2A in gastric cancer (GC) and its correlation with prognosis. Reverse transcription-polymerase chain reaction and real-time polymerase chain reaction were used to detect the mRNA expression of MT2A in 12 GC cell lines, normal gastric epithelial GES-1 cells, and 36 GC and adjacent normal tissues. MT2A protein expression was determined in 258 GC tissues and 171 adjacent normal tissues by immunohistochemistry. MT2A mRNA expression was lower in GC cells and primary tumors than in GES-1 cells and adjacent normal tissues, respectively. High protein expression of MT2A was present in 130 of 171 normal tissues (76.0%) and in 56 of 258 GC tissues (21.7%; P < 0.001). MT2A protein expression was higher in well/moderately differentiated GC (22/54; 40.7%) than in poorly differentiated GC (34/204; 16.7%; P < 0.001). Moreover, the protein expression of MT2A was lower in diffuse-type GC (6/82; 7.3%) than in intestinal-type GC (50/176; 28.4%; P = 0.0001). Importantly, MT2A expression was an independent prognostic factor for GC, and decreased MT2A expression was associated with poor clinical outcome (P < 0.001). The expression status of MT2A could predict prognosis in intestinal and diffuse-type GCs. Expression status of MT2A might be a useful prognostic biomarker for GC, especially when used in combination with Lauren's classification.


Intracellular magnesium depletion relates to increased urinary magnesium loss in type I diabetes.
We investigated whether erythrocyte magnesium (Mg) depletion exists in subjects with Type I diabetes. To this end, Mg levels in plasma, erythrocytes and urine were determined in 12 patients with Type I diabetes and compared with 12 healthy control subjects. Mean plasma Mg concentrations were comparable between diabetic patients and control subjects (0.90 +/- 0.29 mmol/l vs 1.04 +/- 0.14 mmol/l, respectively; p = 0.16). Mean erythrocyte Mg concentration was significantly lower in the diabetic group compared with the control group (1.41 +/- 0.56 mmol/l vs. 2.94 +/- 1.13 mmol/l, respectively; p < 0.0001). Mean urine Mg excretion was significantly elevated in the diabetic group with respect to the controls (6.86 +/- 3.5 mmol/g creatinine/24 h vs. 4.03 +/- 1.65 mmol/g creatinine/24 h, respectively; p = 0.02). As to the diabetic group, erythrocyte Mg concentration showed a significant inverse correlation with urine Mg excretion (r = -0.58, p = 0.049). There was no correlation between urine Mg concentration and glycosylated hemoglobin or fasting plasma glucose level. The data suggest that intracellular Mg depletion without significant hypomagnesemia is related to increased urinary Mg loss in patients with Type I diabetes. The urinary Mg loss is not correlated with the degree of metabolic control.


Total and Sustainable Utilization of Biomass Resources: A Perspective.
Feedstock cost is a major variable cost component in conversion to biofuels and chemicals. Consistent feedstock quality is critically important to achieve high product yield and maximum onstream time. Traditionally, raw biomass materials are delivered directly to the biorefineries where they are preprocessed to feedstock prior to being converted to products. Since many types of biomass materials-including agricultural residues, energy crops, and logging residues-are harvested according to growth cycles and optimal harvesting time, just-in-time steady supply of raw biomass to the biorefineries is not possible. Instead, biomass materials are stored, then delivered to the biorefineries as needed. Experience to date indicates that this approach has caused many issues related to logistics, biomass losses due to microbial degradation and fire, and inconsistent feedstock quality due to variability in the properties of as-delivered biomass. These factors have led to high feedstock cost, low throughput, and low product yield for the biorefineries. Idaho National Laboratory has developed a new strategy to address the problems encountered in the traditional approach in biomass feedstock supply, storage, and preprocessing mentioned above. The key components of this strategy are (1) preservation and preconditioning of biomass during storage, (2) utilization of all the biomass, including minor components that are normally considered wastes or contaminants, and (3) maximization of the value of each component. This new approach can be accomplished using feedstock preprocessing depots located near the biomass-production sources.


Modulation of F1 hybrid stature without altering parent plants through trans-activated expression of a mutated rice GAI homologue.
Hybrid breeding, by taking advantage of heterosis, brings about many superior properties to the F1 progeny. However, some properties, such as increased plant height, are not desirable for agronomic purposes. To specifically counter the height increase associated with hybrid progeny, we employed an Arabidopsis model and tested a trans-activation system for specifically expressing a mutated GAI gene only in the F1 hybrid plants to reduce plant stature. A transcriptional activator, the Gal4 DNA-binding domain fused to the acidic activation domain of herpes simplex virus VP16 protein, driven by a maize ubiquitin promoter, was introduced in one parental line. A rice GAI homologue with an N-terminal deletion of the DELLA domain, driven by a promoter that is responsive to the transcriptional activator, was transferred into another parental line. After genetic crossing, trans-activation of the GAI mutant gene resulted in a dwarf phenotype. Over 50 pair-wise crosses between the parental lines were performed, and analyses suggested that the percentage of F1 progeny exhibiting dwarfism ranged from about 25% to 100%. Furthermore, the dwarfism trait introduced in F1 progeny did not seem to affect total seed yield. Our result suggests the feasibility of manipulating F1 hybrid progeny traits without affecting parent plants or the agronomic property of the progeny.


Bridging Trans-Scale Electrode Engineering for Mass CO2 Electrolysis.
Electrochemical CO2 upgrade offers an artificial route for carbon recycling and neutralization, while its widespread implementation relies heavily on the simultaneous enhancement of mass transfer and reaction kinetics to achieve industrial conversion rates. Nevertheless, such a multiscale challenge calls for trans-scale electrode engineering. Herein, three scales are highlighted to disclose the key factors of CO2 electrolysis, including triple-phase boundaries, reaction microenvironment, and catalytic surface coordination. Furthermore, the advanced types of electrolyzers with various electrode design strategies are surveyed and compared to guide the system architectures for continuous conversion. We further offer an outlook on challenges and opportunities for the grand-scale application of CO2 electrolysis. Hence, this comprehensive Perspective bridges the gaps between electrode research and CO2 electrolysis practices. It contributes to facilitating the mixed reaction and mass transfer process, ultimately enabling the on-site recycling of CO2 emissions from industrial plants and achieving net negative emissions.


Electrophoretically pure mouse interferon exerts multiple biological effects.
Electrophoretically pure (EP) mouse interferon (IF), was examined for a number of biological effects of previously ascribed to crude or partially purified interferon preparations. The following effects were observed: inhibition of antibody formation in vitro; inhibition or enhancement of sensitization to sheep erythrocytes in the mouse, depending on time of administration of IF, and dosage of antigen; inhibition of the expression of delayed type hypersensitivity in vivo; enhancement of natural killer cell activity in vitro and in vivo; inhibition of mouse tumor cells multiplication in vitro; inhibition of the growth of a transplantable tumor in mice. EP mouse IF had a very pronounced priming effect but had no blocking activity.


Loss of Imprinting of IGF2 Gene in the Chorionic Tissues of Spontaneously Eliminated Human Embryos.
Insulin-like growth factor-2 (IGF-2) is a mitogen, growth and differentiation modulator for many cell types. It is mainly expressed during the prenatal development, and its activity strongly depends on the genomic imprinting. Genomic imprinting in the chorionic tissues of spontaneously eliminated human embryos has been studied on the model of 820-AG (Apa1) of the IGF-2 gene locus. Molecular and genetic analysis was performed on the polymorphic 820-AG IGF2 locus in 107 samples of DNA extracted from the chorionic tissues of spontaneously eliminated human embryos within 5-10 weeks of gestation. Presence of AG genotype Apa1 single nucleotide polymorphisms of the IGF-2 was shown to cause more than a 7-fold increase in the risk of embryo elimination. Thus, the loss of genomic imprinting of the IGF-2 gene may be an important cause of the miscarriages in human.


Myogenesis in primary cell cultures from larvae of the abalone, Haliotis rufescens.
Myogenesis culminating in the differentiation of contracting myocytes occurs in primary cell cultures derived from premyogenic trochophore and early veliger larvae of Haliotis rufescens (red abalone, gastropod mollusc). No detectable muscle cells were present at the start of the primary cultures. Onset and organization of myofibrillogenesis in culture (revealed by histochemical and immunohistochemical detection of filamentous actin, myosin, and desmin) generally paralleled those of smooth muscle development in vivo, although development of cells with striated sarcomeres was occasionally observed in culture, but not in the intact larvae. Most of the muscle cells that developed in culture were mononucleate, although some multinucleate syncytia were observed. Dissociated larval cells remained viable up to 12 weeks, exhibiting an average of one to two divisions in the first six days, and attachment of approximately 6 to 8% of the original population. Cell culture and in vitro myogenesis of Haliotis myoblasts and myocytes will facilitate studies of the molecular mechanisms controlling early muscle development, and should provide a useful model system for biotechnological improvement of the abalone.


Can Functional Testing for Ischemia and Viability Guide Revascularization?
Cardiac imaging procedures are a cornerstone of the diagnosis and management of patients with cardiac disease. The optimal management of the patient with stable ischemic heart disease or ischemic heart failure often rests on the totality of symptom burden, patient risk, and disease severity, whether assessed anatomically or functionally. Recent trials have demonstrated the power of flow measurements to direct revascularization as well as the strengths and limitations of ischemia and viability/hibernation imaging as markers of risk to direct interventions. They have also highlighted the challenges in evaluating imaging or functional testing to direct therapies, because imaging does not directly affect outcome itself, rather it affects the management decisions that may result in a positive outcome. Ongoing studies with randomized designs, such as FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation), ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), and AIMI-HF (Alternative Imaging Modalities in Ischemic Heart Failure) (IMAGE-HF [Imaging Modalities to Assist with Guiding Therapy in The Evaluation of Patients with Heart Failure]), will provide the highest level of evidence to support practice changes that may further clarify the role of cardiac imaging in the evaluation of these patients and result in improved patient outcomes.


Gut dysbiosis and neuroimmune responses to brain infection with Theiler's murine encephalomyelitis virus.
Recent studies have begun to point out the contribution of microbiota to multiple sclerosis (MS) pathogenesis. Theiler's murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD) is a model of progressive MS. Here, we first analyze the effect of intracerebral infection with TMEV on commensal microbiota and secondly, whether the early microbiota depletion influences the immune responses to TMEV on the acute phase (14 dpi) and its impact on the chronic phase (85 dpi). The intracranial inoculation of TMEV was associated with a moderate dysbiosis. The oral administration of antibiotics (ABX) of broad spectrum modified neuroimmune responses to TMEV dampening brain CD4+ and CD8+ T infiltration during the acute phase. The expression of cytokines, chemokines and VP2 capsid protein was enhanced and accompanied by clusters of activated microglia disseminated throughout the brain. Furthermore, ABX treated mice displayed lower levels of CD4+ and CD8+T cells in cervical and mesenteric lymph nodes. Increased mortality to TMEV was observed after ABX cessation at day 28pi. On the chronic phase, mice that survived after ABX withdrawal and recovered microbiota diversity showed subtle changes in brain cell infiltrates, microglia and gene expression of cytokines. Accordingly, the surviving mice of the group ABX-TMEV displayed similar disease severity than TMEV mice.


PLASMA COLLOID OSMOTIC PRESSURE IN CHRONICALLY DEBILITATED LOGGERHEAD SEA TURTLES (CARETTA CARETTA).
Colloid osmotic pressure (COP) is an important component of the forces that manage capillary filtration and is determined by circulating plasma proteins. Patients affected by conditions resulting in hypoproteinemia often suffer severe hemodynamic derangements, including decreased COP. Because chronically debilitated sea turtles (CDT) present with severe hypoproteinemia, the objectives of this study were to 1) determine differences in plasma COP and blood analyte data (packed cell volume [PCV], sodium, chloride, plasma protein fractions) in CDT at admission compared with data from apparently healthy rehabilitated turtles at time of release (HRT) admitted from various stranding causes, and 2) to investigate correlations of COP with these selected blood analytes. COP, PCV, and most plasma protein fractions (excluding pre-albumin and γ-globulins) were significantly lower in CDT upon admission as compared with HRT. Sodium and chloride did not significantly differ between CDT and HRT. A significant increase was observed with PCV and all plasma protein fractions as COP increased. Of all protein fractions tested, albumin contributed the most toward COP (r2 = 0.88, P < 0.001). The results of this study suggest that COP is significantly lower in CDT as compared with HRT, providing insight into the complexity of this critical clinical condition and a small step in advancing the understanding of associated hemodynamic imbalances. Although COP analysis is not readily available as a diagnostic test, this preliminary baseline data suggests that additional research studies are warranted, given the potential for optimization of fluid therapy during rehabilitation of CDT.


Adrenal cortical response to stress at Three Mile Island.
The present study examined the relationship between biochemical, psychologic, and behavioral components of chronic stress associated with living near the damaged nuclear power plant at Three Mile Island (TMI). Relative to control subjects, TMI subjects had higher levels of urinary cortisol, which correlated significantly with urinary catecholamines, self-report of physical and mental symptoms, and decrements in task performance. Further, it was found that males had higher urinary cortisol levels than females at TMI, while at the control sites, levels of cortisol were comparable between males and females. Finally, no significant relationship between coping style and urinary cortisol was detected. Levels of stress response among TMI are residents, though significantly greater than control subjects, were within normal ranges and thus should be considered subclinical in intensity. Their persistence over 17 months, however, suggests some cause for concern.


Nano-patterning of a monolayer molybdenum disulfide with sub-nanometer helium ion beam: considering its shape, size and damage.
We have studied nano-patterning of a two-dimensional (2D) material with an ultrafine helium ion beam considering shape-, size- and damage-control. The study reveals that the crystalline structure plays an important role in shape-control. Instead of commonly circular-shaped nanopores, spot irradiation onto a single layer of molybdenum disulfide (MoS2) gives rise to a rhombus-shaped nanopore, which is well explained by the sub-rhombus crystalline structure of MoS2. Helium ion beams also show promising capability to precisely control size using a delivered dose. However, the size of the nanopores is not linear with the delivered dose, due to the Gaussian distributed intensity profile of the helium ion beam. The intensity profiles are further estimated by considering aperture size, those results could be taken as a significant reference for size-control. In addition, we clarify that most of the damage is a result of re-deposition, thus controlling re-deposition might be a useful way to alleviate the damage.


Spherical-supported membranes as platforms for screening against membrane protein targets.
Screening assays performed against membrane protein targets (e.g. phage display) are hampered by issues arising from protein expression and purification, protein stability in detergent solutions and epitope concealment by detergent micelles. Here, we have studied a fast and simple method to improve screening against membrane proteins: spherical-supported bilayer lipid membranes ("SSBLM"). SSBLMs can be quickly isolated via low-speed centrifugation and redispersed in liquid solutions while presenting the target protein in a native-like lipid environment. To provide proof-of-concept, SSBLMs embedding the polytopic bacterial nucleoside transporter NupC were assembled on 100- and 200 nm silica particles. To test specific binding of antibodies, NupC was tagged with a poly-histidine epitope in one of its central loops between two transmembrane helices. Fluorescent labelling, small angle X-ray scattering (SAXS) and cryo-electron microscopy (cryo-EM) were used to monitor formation of the SSBLMs. Specific binding of an anti-his antibody and a gold-nitrilotriacetic acid (NTA) conjugate probe was confirmed with ELISAs and cryo-EM. SSBLMs for screening could be made with purified and lipid reconstituted NupC, as well as crude bacterial membrane extracts. We conclude that SSBLMs are a promising new means of presenting membrane protein targets for (biomimetic) antibody screening in a native-like lipid environment.


Position dependence of non-polar amino acid intrinsic helical propensities.
Until now and based on the success of the helix/coil transition theory it has been assumed that the alpha-helical propensities of the amino acids are position independent. This has been critical to derive the set of theoretical parameters for the 20 natural amino acids. Here, we have analyzed the behavior of several non-polar residues, Val, Ile, Leu, Met and Gly at the N-cap, at each position of the first helical turn and at a central helical position of a 16-residue peptide model system that starts with eight consecutive alanine residues. We have interpreted the results from these experiments with the model of the helix/coil transition (AGADIR), that indicates that the intrinsic helical propensity is position dependent. Gly, Val and Ile are more favorable at the first turn than in the middle of the alpha-helix, while for Leu and Met we observe the opposite behavior. The differences between the observed helical propensities are as large as 1.0 kcal/mol in some cases. Molecular modeling calculations using the ECEPP/2 force-field equipped with a hydration potential show that this effect can be explained by the combination of three factors: (a) the side-chains in the first helix turn are more solvent-exposed; (b) they have fewer intramolecular van der Waals' contacts; and (c) they posses higher configurational entropy than that in the central position of an alpha-helix. The position-dependent results of the calculations are in reasonable agreement with the experimental estimates and with the intrinsic propensities of the amino acids derived from the statistical analysis of the protein structure database.


[Construction of a recombinant Escherichia coli BL21/ pET-28a-lpgad and the optimization of transformation conditions for the efficient production of gamma-aminobutyric acid].
In order to enhance gamma-aminobutyric acid production from L-glutamate efficiently, we amplified the key enzyme glutamate decarboxylase (GAD) encoding gene lpgad from the strain Lactobacillus plantarum GB 01-21 which was obtained by way of multi-mutagenesis and overexpressed it in E. coli BL21. Then we purified GAD by Ni-NTA affinity chromatography and characterized the enzyme to optimize the conditions of the whole-cell transformation. The results showed that the recombinant E. coli BL21 (pET-28a-lpgad) produced 8.53 U/mg GAD, which was increased by 3.24 fold compared with the GAD activity in L. plantarum. The optimum pH and temperature of the enzyme were pH 4.8 and 37 degrees C, respectively. At the same time, we found that Ca2+ and Mg2+ could increase the activity significantly. Based on this, we investigated gamma-aminobutyric acid transformation in 5 L fermentor under the optimum transformation conditions. Accordingly, the yield of gamma-aminobutyric acid was 204.5 g/L at 24 h when the 600 g L-glutamate was added and the mole conversion rate had reached 97.92%. The production of gamma-aminobutyric acid was improved by 42.5% compared with that under the unoptimized transformation conditions. This paved a way for the gamma-aminobutyric acid construction of the industrial applications.


Decomposition of aberrated or turbulent wavefronts into a spatial mode spectrum using optical cavities.
It is shown that an aberrated wavefront incident upon a Fabry-Perot optical cavity excites higher order spatial modes in the cavity and that the spectral width and distribution of these modes is indicative of the type and magnitude of the aberration. The cavities are purely passive, and therefore frequency content is limited to that provided by the original light source. To illustrate this concept, spatial mode decomposition and transmission spectrum calculation are simulated on an example cavity; the effects of various phase delays, in the form of two basic Seidel aberrations and a composite of Zernike polynomial terms, are shown using both Laguerre-Gaussian and plane wave incident beams. The aggregate spectral width of the cavity modes excited by the aberrations is seen to widen as the magnitude of the aberrations' phase delay increases.


Organization and nucleotide sequence of genes encoding core components of the phycobilisomes from Synechococcus 6301.
Cyanobacteria possess specialized organelles, called phycobilisomes, which collect and transfer light energy to the reaction centres of photosystem II, in the photosynthetic membrane. Phycobilisomes consist of a central core, mainly composed of allophycocyanin, from which six rods radiate. We report here the isolation, for the first time, of three genes that encode core components of cyanobacterial phycobilisomes. The genes coding for the alpha- and beta-subunit apoproteins of allophycocyanin (apcA and apcB) were cloned from Synechococcus PCC 6301 and subjected to nucleotide sequence analysis. Dowstream of apcB, we found a third open reading frame (apcC) which, by comparison with known amino acid sequences, was assigned to L7.8c, a linker polypeptide associated with phycobiliproteins within the core of the phycobilisomes. Homologies between amino acid sequences deduced from the nucleotide sequence of the Synechococcus PCC 6301 apc genes and the amino acid sequences published for corresponding proteins either from cyanobacteria or chloroplast-like organelles of eukaryotic organisms, are 75% or more. The genetic organization of this photosynthetic gene cluster relative to that observed in the cyanelle genome of the flagellate Cyanophora paradoxa is discussed.


Nodal modulation of the lunar semidiurnal tide in the bay of fundy and gulf of maine.
Observations, numerical modeling, and theoretical calculations show how the 18.6-year modulation of the main lunar semidiurnal tide in the Bay of Fundy and Gulf of Maine is reduced from its astronomical value of 3.7 percent to 2.4 percent by the effects of friction and resonance. The agreement of the three approaches increases confidence in model predictions of widespread changes in the tidal regime resulting from development of tidal power.


Stimulation of protein synthesis by hemin in extracts of Friend erythroleukemia cells.
Extracts prepared from Friend erythroleukemia cells were highly active in translating endogenous mRNA and a consistent 2-fold stimulation by hemin was observed. When extracts were treated with micrococcal nuclease and incorporation was dependent on exogenous globin mRNA, there was more significant stimulation by 37.5 micron hemin and greater than 10-fold stimulation by 75 or 150 micron hemin. The effects of hemin were not strikingly different in extracts of dimethyl-sulfoxide-induced or uninduced cells. The results could reflect an effect on initiation of protein synthesis analogous to that in rabbit reticulocytes.


Using thermo-optical nonlinearity to robustly separate absorption and radiation losses in nanophotonic resonators.
Key for optical microresonator engineering, the total intrinsic loss is easily determined by spectroscopy; however, quantitatively separating absorption and radiative losses is challenging, and there is not a general and robust method. Here, we propose and experimentally demonstrate a general all-optical characterization technique for separating the loss mechanisms with high confidence using only linear spectroscopic measurements and an optically measured resonator thermal time constant. We report the absorption, radiation, and coupling losses for ten whispering-gallery modes of three different radial orders on a Si microdisk. Although the total dissipation rates show order-of-magnitude differences, the small absorptive losses are successfully distinguished from the overwhelming radiation losses and show similar values for all the modes as expected for the bulk material absorption.


Establishing the Trifluoromethylthio Radical Donating Abilities of Electrophilic SCF3-Transfer Reagents.
The recent recognition of the novel application of a few traditional electrophilic trifluoromethylthiolating reagents as SCF3 radical sources offers a remarkable new opportunity for the development of radical trifluoromethylthiolation reactions. Herein, the first trifluoromethylthio radical donating ability (Tt•DA) scale of electrophilic SCF3-transfer reagents has been developed. This scale is based on Y-SCF3 bond dissociation energies, which were obtained by density functional calculations (M06-2X). Single electron transfer is revealed to exhibit a substantial Y-SCF3 bond-weakening effect, thus significantly facilitating the SCF3 radical (•SCF3) release. The results may aid in future novel radical SCF3-transfer reagent design and new reaction development.


Ethical Considerations for Healthcare Organizations.
Ethical misbehavior in the delivery of healthcare creates harm not only to individual therapists and administrators who might choose to overstep ethical boundaries but also, more broadly, causes harm to patients, to healthcare organizations, to professional organizations, and ultimately to society. Both corporate codes of conduct and professional codes of ethics are important, because they set standards of conduct and penalize noncompliant or unethical conduct. The purposes of this article are (1) to differentiate corporate compliance from ethics in a healthcare organization; (2) to explain the application of ethics principles to organizational and professional behaviors; (3) to discuss three important ethical issues (cultural competence, conflict of interest, and employer demands); and (4) to emphasize that, whether applying a corporate code of conduct or a professional code of ethics (or both), the integrity of each individual is essential to ethical behavior. To illustrate these concepts, ASHA's Code of Ethics is discussed in detail (including the ethics complaint adjudication process), and hypothetical case studies are presented under the macro headings of Cultural Competence, Conflict of Interest, and Employer Demands.


Trifluorothymidine induces cell death independently of p53.
Trifluorothymidine (TFT), a potent anticancer agent, inhibits thymidylate synthase (TS) and is incorporated into the DNA, both events resulting in cell death. Cell death induction related to DNA damage often involves activation of p53. We determined the role of p53 in TFT cytotoxicity and cell death induction, using, respectively, the sulforhodamine B-assay and FACS analysis, in a panel of cell lines with either wild type, inactive, or mutated p53. Neither TFT cytotoxicity nor cell death induction changed with TFT exposure in cell lines with wt, inactive or mutated p53. sensitivity to TFT is not dependent on the expression of wt p53.


The first Toll receptor from the triangle-shell pearl mussel Hyriopsis cumingii.
Toll receptor was first discovered in Drosophila and has an important function in the innate immunity of invertebrates. In this study, the Toll receptor HcToll1 from Hyriopsis cumingii with a full length of 3810 bp consisting of a 3687 bp ORF that encodes a total of 1228 amino acids protein was selected for further study. The HcToll1 protein consisted of a signal peptide, 17 LRR domains, 2 LRRCT domains, 1 LRRNT domain, 1 TM domain, and 1 TIR domain. Phylogenetic analysis results showed that HcToll1 was clustered in one group together with other mollusca tolls. RT-PCR analysis results showed that HcToll1 was expressed in all tested tissues such as hemocytes, hepatopancreas, gills, and mantle. qRT-PCR analysis results showed that HcToll1 expression was increased by the presence of Escherichia coli, Vibrio anguillarum, Staphyloccocus aureus, and White Spot Syndrome Virus (WSSV). Over-expression of HcTIR could up-regulate expression of drosomycin gene in Drosophila S2 cells. The results of our study indicated that HcToll1 is a functional Toll and it has an important function in the generation of innate immune responses of H. cumingii against microbial challenge.


Impact of HbA1c, followed from onset of type 1 diabetes, on the development of severe retinopathy and nephropathy: the VISS Study (Vascular Diabetic Complications in Southeast Sweden).
HbA1c is strongly related to the development of diabetes complications, but it is still controversial which HbA1c level to strive for in the treatment of type 1 diabetes. The aim of the current study was to evaluate HbA1c, followed from diagnosis, as a predictor of severe microvascular complications and to formulate HbA1c target levels for treatment. A longitudinal observation study followed an unselected population of 451 patients diagnosed with type 1 diabetes during 1983-1987 before the age of 35 years in a region of Southeast Sweden. Retinopathy was evaluated by fundus photography and nephropathy data collected from medical records. HbA1c was measured starting from diagnosis and during the whole follow-up period of 20-24 years. Long-term weighted mean HbA1c was then calculated. Complications were analyzed in relation to HbA1c levels. The incidence of proliferative retinopathy and persistent macroalbuminuria increased sharply and occurred earlier with increasing long-term mean HbA1c. None of the 451 patients developed proliferative retinopathy or persistent macroalbuminuria below long-term weighted mean HbA1c 7.6% (60 mmol/mol); 51% of the patients with long-term mean HbA1c above 9.5% (80 mmol/mol) developed proliferative retinopathy and 23% persistent macroalbuminuria. Long-term weighted mean HbA1c, measured from diagnosis, is closely associated with the development of severe complications in type 1 diabetes. Keeping HbA1c below 7.6% (60 mmol/mol) as a treatment target seems to prevent proliferative retinopathy and persistent macroalbuminuria for up to 20 years.


Trapidil derivatives as potential antiatherosclerotic drugs.
Trapidil, a triazolopyrimidine, and its derivatives are coronary vasodilating drugs. Trapidil reduces the serum level of low density lipoprotein- and very low density lipoprotein-cholesterol and increases the serum level of high density lipoprotein-cholesterol in hyperlipemic patients. The present study demonstrates that trapidil and five different trapidil derivatives inhibit the proliferation of cells cultured from grossly normal intima and fatty streaks of human aorta. The inhibiting effect of trapidil derivatives is about 60%, similar to the standard substance 3-isobutyl-1-methyl-xanthine (MIX). In cells cultured from atherosclerotic plaques trapidil and trapidil derivatives reduced the content of cholesteryl esters by 36% for trapidil and between 47% and 68% for 4 of 5 trapidil derivatives, respectively. The trapidil derivative AR 12463 (5-piperidino-7-[N-(n-amyl)-N-(beta-hydroxyethyl)amino]-s-triazolo[1,5- a]pyrimidine) reduces the free cholesterol content by 29%, but the other trapidil derivatives are without effect on this parameter. Four of five derivatives decrease the content of triglycerides by 53 to 70%. The synthesis of collagen is inhibited by the trapidil derivative AR 12463 (25%). Trapidil and other derivatives have a smaller or no effect on the synthesis of collagen. These effects of trapidil derivatives point to potential antiatherosclerotic properties. The possible mechanisms are discussed.


Constitutive expression of the poplar WRKY transcription factor PtoWRKY60 enhances resistance to Dothiorella gregaria Sacc. in transgenic plants.
WRKY proteins are involved in various physiological processes in plants, especially in coping with diverse biotic and abiotic stresses. However, limited information is available on the roles of specific WRKY transcription factors in poplar defense. In this study, we reported the characterization of PtoWRKY60, a Group IIa WRKY member, from Populus tomentosa Carr. The gene expression profile of PtoWRKY60 in various tissues showed that it significantly accumulated in old leaves. Phylogenetic analyses revealed that PtoWRKY60 had a close relationship with AtWRKY18, AtWRKY40 and AtWRKY60. PtoWRKY60 was induced mainly by salicylic acid (SA) and slightly by Dothiorella gregaria Sacc., jasmonic acid, wounding treatment, low temperature and salinity stresses. Overexpression of PtoWRKY60 in poplar resulted in increased resistance to D. gregaria. The defense-associated genes, such as PR5.1, PR5.2, PR5.4, PR5.5 and CPR5, were markedly up-regulated in transgenic plants overexpressing PtoWRKY60. These results indicate that PtoWRKY60 might be partly involved in the signal transduction pathway initiated by SA in Populus.


[Biography of Dr. Enrique Pérez Castro (1908-1980)].
With the occasion of the Centenary of Dr. Enrique Pérez Castro's birth, being a relevant figure in our speciality in the second half of the 20th century, we performed a study of the urological environment in which his life was developed and collect the main data about his life and works with the aim of paying tribute to his memory as a great personality in urology. We review the books of History of Urology, his writings and the journal Archivos Españoles de Urología during the period of his directorship and as many references related to him as we found. He had a brilliant academic curriculum; he trained urology in the best centres. He lived in Madrid, his birth place, were his entire professional career developed, in the Hospital Provincial, where he was the chairman of urology, and the Central University where he was associated professor. He liked to study, and had researcher spirit; his works, which had great quality--he received several prizes--are clearly exposed, with a fine style, always with an extensive bibliography We emphasize his main merit, the foundation of the journal Archivos Españoles de Urología, a fruit of his personality, his organizing capacity and scientific restlessness, of which he was editor and directed with eagerness and dedication during 36 years and, thanks to his tenacity, he consolidated it as the reference of the Spanish urology.


Spectroscopic and Crystal Field Consequences of Fluoride Binding by [Yb⋅DTMA]3+ in Aqueous Solution.
Yb⋅DTMA forms a ternary complex with fluoride in aqueous solution by displacement of a bound solvent molecule from the lanthanide ion. [Yb⋅DTMA⋅F]2+ and [Yb⋅DTMA⋅OH2]3+ are in slow exchange on the relevant NMR timescale (<2000 s-1), and profound differences are observed in their respective NMR and EPR spectra of these species. The observed differences can be explained by drastic modification of the ligand field states due to the fluoride binding. This changes the magnetic anisotropy of the YbIII ground state from easy-axis to easy-plane type, and this change is easily detected in the observed magnetic anisotropy despite thermal population of more than just the ground state. The spectroscopic consequences of such drastic changes to the ligand field represent important new opportunities in developing fluoride-responsive complexes and contrast agents.


Synthesis of new chiral phosphorous- and nitrogen-containing ligands from resin acids.
Starting from the phytogenic diterpenes, chiral phosphine, urea, and thiourea derivatives were synthesized. Using these new chiral ligands, Rh(I) and Ru(II) complexes were prepared and used as catalysts for the catalytic asymmetric hydrogenation of unsaturated carboxylic acids and asymmetric hydrogen-transfer reduction of carbonyl compounds. Although the enantiopurity of the products obtained was not high, it was demonstrated that chiral ligands derived from diterpenes could be used for asymmetric reduction.


Effects of Door-In to Door-Out Time on Mortality Among ST-Segment Elevation Myocardial Infarction Patients Transferred for Primary Percutaneous Coronary Intervention - Systematic Review and Meta-Analysis.
Background: Primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is now widely accepted. Recent guidelines have focused on total ischemic time, because shorter total ischemic time is associated with a more favorable prognosis. The door-in to door-out (DIDO) time, defined as time from arrival at a non-PCI-capable hospital to leaving for a PCI-capable hospital, may affect STEMI patient prognosis. However, a relevant meta-analysis is lacking. Methods and Results: We searched PubMed for clinical studies comparing short-term (30-day and in-hospital) mortality rates of STEMI patients undergoing primary PCI with DIDO times of ≤30 vs. >30 min. Two investigators independently screened the search results and extracted the data. Random effects estimators with weights calculated by the inverse variance method were used to determine pooled risk ratios. The search retrieved 1,260 studies; of these, 2 retrospective cohort studies (15,596 patients) were analyzed. In the DIDO time ≤30 and >30 min groups, the primary endpoint (i.e., in-hospital or 30-day mortality) occurred for 51 of 1,794 (2.8%) and 831 of 13,802 (6.0%) patients, respectively. The incidence of the primary endpoint was significantly lower in the DIDO time ≤30 min group (odds ratio 0.45; 95% confidence interval 0.34-0.60). Conclusions: Our findings suggest that a DIDO time ≤30 min is associated with a lower short-term mortality rate. However, further larger systematic reviews and meta-analyses are needed to validate our findings.


A novel application of modified bamboo charcoal to treat oil-containing wastewater and its modified mechanism.
Three conventional coalescence filters including walnut shells (WS), polystyrene resin particles (PR), and quartz sand (QS) were compared with bamboo charcoal (BC) to treat oily wastewater in a coalescence system process. The results showed the order of oil removal efficiency was QS>BC>WS>PR. To improve the oil removal efficiency of BC further, six types of modified BC were prepared. The results showed that the modified BC using silane coupling agent (SCA) significantly increased oil removal efficiency, but the other types (including the use of NaOH, HNO3, H2O2, FeCl3 and ultrasound) of modified BC exhibited nearly the same level of efficiency as that of pure BC. Infra-red, X-ray diffraction, scanning electron microscopy, and the contact angle for modified BC were measured to reveal the modified mechanism. It was found that the higher oil removal efficiency of the SCA-modified BC occurred due to the changed crystal structure of the BC and the increase in its surface hydrophobicity, which resulted in higher oil removal efficiency. Therefore, modified bamboo charcoal is an attractive filter candidate for oil removal in a coalescence system process.


Influence of salt on the aqueous lubrication properties of end-grafted, ethylene glycol-based self-assembled monolayers.
We have investigated the influence of a high-concentration salt solution (1 M NaCl) on the aqueous lubrication properties of ethylene glycol-based molecules, namely, alpha-methoxy-omega-mercaptopoly(ethylene glycol) (MW 5000 Da) and alpha-methoxy-omega-mercaptoheptakis(ethylene glycol) (MW 356 Da), which have been end-grafted onto polycrystalline gold surfaces at high surface density. Macroscopic-scale, yet nondestructive, pin-on-disk tribometry experiments revealed that a high concentration of sodium chloride is deleterious to the aqueous lubricating properties of both films under low-sliding-speed conditions. This behavior was observed to be closely associated with the more collapsed conformation of surface-grafted poly(ethylene glycol) polymer chains in concentrated salt solutions, as confirmed by quartz-crystal microbalance measurements.


Adsorption calorimetry during metal vapor deposition on single crystal surfaces: increased flux, reduced optical radiation, and real-time flux and reflectivity measurements.
Thin films of metals and other materials are often grown by physical vapor deposition. To understand such processes, it is desirable to measure the adsorption energy of the deposited species as the film grows, especially when grown on single crystal substrates where the structure of the adsorbed species, evolving interface, and thin film are more homogeneous and well-defined in structure. Our group previously described in this journal an adsorption calorimeter capable of such measurements on single-crystal surfaces under the clean conditions of ultrahigh vacuum [J. T. Stuckless, N. A. Frei, and C. T. Campbell, Rev. Sci. Instrum. 69, 2427 (1998)]. Here we describe several improvements to that original design that allow for heat measurements with ~18-fold smaller standard deviation, greater absolute accuracy in energy calibration, and, most importantly, measurements of the adsorption of lower vapor-pressure materials which would have previously been impossible. These improvements are accomplished by: (1) using an electron beam evaporator instead of a Knudsen cell to generate the metal vapor at the source of the pulsed atomic beam, (2) changing the atomic beam design to decrease the relative amount of optical radiation that accompanies evaporation, (3) adding an off-axis quartz crystal microbalance for real-time measurement of the flux of the atomic beam during calorimetry experiments, and (4) adding capabilities for in situ relative diffuse optical reflectivity determinations (necessary for heat signal calibration). These improvements are not limited to adsorption calorimetry during metal deposition, but also could be applied to better study film growth of other elements and even molecular adsorbates.


Phylogeny and taxonomy of the food-borne pathogen Clostridium botulinum and its neurotoxins.
Until recently, all clostridia producing neurotoxins able to cause paralysis symptomatic of botulism were deemed to be Clostridium botulinum. Defining Cl. botulinum on the basis of this single phenotypic trait has resulted in the species encompassing metabolically very diverse organisms, and four distinct phenotypic groups are recognized within this taxon (designated groups I-IV). Nucleic acid hybridization and 16S ribosomal RNA sequencing studies have revealed the presence of four phylogenetically distinct lineages within the species, which correlate with these phenotypic divisions. In addition to marked phenotypic and genotypic heterogeneity between groups, the taxonomy of the species is further complicated by the existence of strains which are closely related, if not genetically identifiable, to members of each Cl. botulinum group, but are non-toxigenic. Furthermore, strains of species other than Cl. botulinum (viz. Cl. baratii, Cl. butyricum) have been found which express botulinum neurotoxin (BoNT). Great advances have been made in recent years in elucidating the nucleotide sequences of genes encoding the various BoNT antigenic types (A through to G). Genealogical trees derived from BoNTs show marked discordance with those depicting 'natural' relationships inferred from 16S rRNA and phenotypic clusters, and strong evidence exists for BoNT gene transfer between some groups of Cl. botulinum (e.g. groups I and II), and with non-botulinum species. Botulinum neurotoxin is produced by Cl. botulinum as a non-covalently bound progenitor toxin complex of two or more protein components. Information on the evolutionary histories of the various non-toxic progenitor proteins is currently limited, although there is evidence of gene recombination. In particular, chimera-like or mosaic non-toxic-non-haemagglutinins (NTNH) genes in group I Cl. botulinum have been described, and it is now apparent that the phylogeny of the NTNHs is not going to 'mirror' that of botulinal neurotoxins, although their genes are physically contiguous. In this article, the current state of knowledge of the phylogenetics of the species Cl. botulinum and its neurotoxins is reviewed, and a view is presented that a nomenclature based rigidly on BoNT production is no longer tenable.


Sorption of silver nanoparticles to laboratory plastic during (eco)toxicological testing.
Here, we evaluate the extent of sorption of silver nanoparticles (AgNPs) with different primary sizes (30 and 70 nm) and surface properties (branched polyethylene imine, "bPEI" and citrate coating) to laboratory plastic during (eco)toxicological testing. Under conditions of algal growth inhibition assay, up to 97% of the added AgNPs were sorbed onto the test vessels whereas under conditions of in vitro toxicological assay with mammalian cells, the maximum loss of AgNPs was 15%. We propose that the high concentration of proteins and biomolecules in the in vitro toxicological assay originating from serum-containing cell culture medium prevented NP sorption due to steric stabilisation. The sorption of AgNPs to test vessels was clearly concentration dependent. In the conditions of algal growth inhibition assay at 10 ng AgNPs/mL, up to 97% of AgNPs were lost from the test while at higher concentrations (1000 ng AgNPs/mL), the loss of AgNPs was remarkably smaller, up to 64%. Sorption of positively charged bPEI-coated AgNPs was more extensive than the sorption of negatively charged citrate-coated AgNPs and, when calculated on a mass basis, more 70 nm-sized Ag than 30 nm Ag sorbed to plastic surfaces. In summary, this study demonstrates that the loss of AgNPs during (eco)toxicological tests due to sorption on test vessel surfaces is significant, especially in diluted media (e.g. in algal growth medium) and at low NP concentrations. Thus, to ensure the accurate interpretation of (eco)toxicological results, the loss of AgNPs due to adsorption to test vessels should not be overlooked and considered for each specific case.


OpenTIMS, TimsPy, and TimsR: Open and Easy Access to timsTOF Raw Data.
The Bruker timsTOF Pro is an instrument that couples trapped ion mobility spectrometry (TIMS) to high-resolution time-of-flight (TOF) mass spectrometry (MS). For proteomics, lipidomics, and metabolomics applications, the instrument is typically interfaced with a liquid chromatography (LC) system. The resulting LC-TIMS-MS data sets are, in general, several gigabytes in size and are stored in the proprietary Bruker Tims data format (TDF). The raw data can be accessed using proprietary binaries in C, C++, and Python on Windows and Linux operating systems. Here we introduce a suite of computer programs for data accession, including OpenTIMS, TimsR, and TimsPy. OpenTIMS is a C++ library capable of reading Bruker TDF files. It opens up Bruker's proprietary codebase. TimsPy and TimsR build on top of OpenTIMS, enabling swift and user-friendly data access to the raw data with Python and R. Both programs are available under a GPL3 license on all major platforms, extending the possibility to interact with timsTOF data to macOS. Additionally, OpenTIMS is capable of translating Bruker data into HDF5 files that can be easily analyzed from Python with the vaex module. OpenTIMS and TimsPy therefore provide easy and quick access to Bruker timsTOF raw data.


Impaired integration in psychopathy: A unified theory of psychopathic dysfunction.
This article introduces a novel theoretical framework for psychopathy that bridges dominant affective and cognitive models. According to the proposed impaired integration (II) framework of psychopathic dysfunction, topographical irregularities and abnormalities in neural connectivity in psychopathy hinder the complex process of information integration. Central to the II theory is the notion that psychopathic individuals are "'wired up' differently" (Hare, Williamson, & Harpur, 1988, p. 87). Specific theoretical assumptions include decreased functioning of the Salience and Default Mode Networks, normal functioning in executive control networks, and less coordination and flexible switching between networks. Following a review of dominant models of psychopathy, we introduce our II theory as a parsimonious account of behavioral and brain irregularities in psychopathy. The II theory provides a unified theoretical framework for understanding psychopathic dysfunction and integrates principle tenets of affective and cognitive perspectives. Moreover, it accommodates evidence regarding connectivity abnormalities in psychopathy through its network theoretical perspective. (PsycINFO Database Record


Delayed hemolytic transfusion reaction with four antibodies undetected by pretransfusion tests.
A case of delayed hemolytic transfusion reaction in a 43-year-old patient is presented. Pretransfusion tests revealed no antibody, but tests performed when the reaction occurred demonstrated four. Ten months and 15 months later, when the patient's serum was again tested, the antibodies were undetectable. The significance of such antibodies is discussed.


Seroprevalence of HIV in Manipal.
A total of 32,406 persons were screened for HIV 1 and 2 antibodies between 1991 to 1999 by Enzyme Linked Immuno Sorbent Assay at Dept. of Microbiology, KMC, Manipal which is a rural teaching hospital. There was steady increase in seropositivity from 0.38% (1991) to 9.31% (1995) and thereafter there is decrease in the seropositivity rate to 4.15% (1999); but the number of cases screened increased from 1995 onwards. The HIV seropositivity is more in males 7.49% than in females (2.52%). The male to female positivity ratio is 2.72:1, inspite of the total number of samples screened of either sexes being equal. The prevalence of HIV among STD Clinic attendants was 8.22%. The foci of infection can be traced to cities such as Mumbai and the main mode of transmission is through unprotected heterosexual contact. The decrease in the seropositivity rate from 1996 onwards could be due to the AIDS awareness among public due to the control programmes. More awareness and public education is needed towards healthy sexual practices to avoid fresh HIV cases.


A Reversible Cause of Cutaneous Rash in a Patient With Alcohol Consumption.
The most common cutaneous manifestations of alcoholism include urticarial reaction, flushing, porphyria cutanea tarda, psoriasis, rosacea, seborrheic dermatitis, and pruritus. Here, we present a case of a young male with a history of alcohol abuse who presented with non-blanching, petechial, and perifollicular macular rash secondary to vitamin C deficiency in view of poor oral intake. The rash improved significantly with vitamin C supplementation. Although rare in developed countries, clinicians should keep vitamin C deficiency as a differential diagnosis for skin rash in alcohol consumers.


[The research progress of circular RNAs in the development and progression of cervical cancer].
Cervical cancer is one of the most common gynecological malignancies, and its morbidity and mortality are among the highest. Persistent infection of high-risk types of HPV is the main reason for its onset, with types 16 and 18 being the most prevalent. Circular RNA (circRNA) is a single-stranded circular non-coding RNA formed by covalent end to end bonding of RNA precursors. It has functions such as miRNA sponge, binding RNA binding protein (RBP), and protein translation, and plays an important role in the occurrence and development of various diseases. At present, the research on circRNA in cervical cancer is still at an early stage. The latest progress of circRNA in high-risk HPV infection, occurrence and development of cervical cancer, and sensitivity to chemoradiotherapy is briefly reviewed.


The cis-Diammineplatinum(II) Complex of Curcumin: A Dual Action DNA Crosslinking and Photochemotherapeutic Agent.
[Pt(cur)(NH3)2](NO3) (1), a curcumin-bound cis-diammineplatinum(II) complex, nicknamed Platicur, as a novel photoactivated chemotherapeutic agent releases photoactive curcumin and an active platinum(II) species upon irradiation with visible light. The hydrolytic instability of free curcumin reduces upon binding to platinum(II). Interactions of 1 with 5'-GMP and ct-DNA indicated formation of platinum-bound DNA adducts upon exposure to visible light (λ=400-700 nm). It showed apoptotic photocytotoxicity in cancer cells (IC50 ≈ 15 μM), thus forming (⋅)OH, while remaining passive in the darkness (IC50 >200 μM). A comet assay and platinum estimation suggest Pt-DNA crosslink formation. The fluorescence microscopic images showed cytosolic localization of curcumin, thus implying possibility of dual action as a chemo- and phototherapeutic agent.


The importance of mini-puberty for fertility in cryptorchidism.
Mini-puberty is the hormonal surge of gonadotropins and testosterone which occurs in early infancy. It induces the development and transformation of gonocytes into Ad spermatogonia, which is impaired in many cryptorchid testes. We examine the role of testosterone in the transformation and development of Ad spermatogonia. A total of 32 patients 1 to 7 years old were treated with human chorionic gonadotropin (HCG) to achieve epididymo-testicular descent before orchiopexy (group 1), and 33 patients underwent orchiopexy without previous hormonal treatment (group 2). A testicular biopsy was obtained during surgery from all the patients. The number of Ad spermatogonia per tubular cross section (Ad/tbx) was assessed and compared between the 2 groups. The number of Ad spermatogonia per tubular cross section in group 1 was also correlated with the post-stimulatory testosterone plasma values. In group 1, 17 patients had greater than 0.1 Ad/tbx, and the remaining patients had 0.1 or less Ad/tbx. In group 2, 6 patients had greater than 0.1 Ad/tbx. Of the boys with cryptorchidism 35% responded inadequately to HCG stimulation, while 10% did not respond. Those patients with suboptimal Leydig cell capacity (and an inadequate response to HCG stimulation) had a defective Ad spermatogonia differentiation of 0.1 or less. Boys with cryptorchidism with an insufficient testosterone surge after HCG risk infertility despite early and successful surgery. The testicular biopsy assists in identifying those who might benefit from hormonal treatment following successful orchiopexy.