Amino Acid Metabolism of Lemna minor L. : IV. N-Labeling Kinetics of the Amide and Amino Groups of Glutamine and Asparagine.
A serious limitation to the use of N(O,S)-heptafluorobutyryl isobutyl amino acid derivatives in the analysis of (15)N-labeling kinetics of amino acids in plant tissues, is that the amides glutamine and asparagine undergo acid hydrolysis to glutamate and aspartate, respectively, during derivatization. This led us to consider an alternative procedure (G Fortier et al. [1986] J Chromatogr 361: 253-261) for derivatization of glutamine and asparagine with N-methyl-N-(tert-butyldimethylsilyl)-trifluoroacetamide in pyridine. Gas chromatography-mass spectrometry (electron ionization) yielded fragment ions (M-57) of mass 417 and 431 for the [(14)N]asparagine and [(14)N]glutamine derivatives, respectively, suitable for monitoring unlabeled, single-(15)N- and double-(15)N-labeled amide species from the ion clusters at mass to charge ratio (m/z) 415 to 423 for asparagine, and m/z 429 to 437 for glutamine. From separate analyses of the specific isotope abundance of the amino-N groups of asparagine and glutamine as their N-heptafluorobutyryl isobutyl derivatives, the specific amide-[(15)N] abundance of these amino acids was determined. We demonstrate that this approach to (15)N analysis of the amides can yield unique insights as to the compartmentation of asparagine and glutamine in vivo. The ratios of unlabeled:single-(15)N:double-(15)N-labeled species are highly diagnostic of the relative sizes and turnover of metabolically active and inactive pools of the amides and their precursors. Kinetic evidence is presented to indicate that a significant proportion (approximately 10%) of the free asparagine pool may be metabolically inactive (vacuolar). If the amide group of asparagine is derived exclusively from glutamine-amide, then asparagine must be synthesized in a compartment of the cell in which both glutamine-amide and aspartate are more heavily labeled with (15)N than the bulk pools of these amino acids. This compartment is presumably the chloroplast. The transaminase inhibitor aminooxyacetate is shown to markedly inhibit amino acid synthesis; several amino acid pools accumulated in the presence of aminooxyacetate and [(15)N]H(4) (+) are (14)N-enriched and must be derived primarily from protein turnover.


Understanding why smokers do not want to use nicotine dependence medications to stop smoking: qualitative and quantitative studies.
Smokers' expected outcomes of using nicotine dependence medications may act as barriers to their use. In Study 1, 27 smokers were interviewed. Framework analysis was used to identify key themes in smokers' expectations of using nicotine dependence medications. In Study 2, a convenience sample of 212 smokers completed a survey. Multiple regression and mediation analyses were used to examine relationships between self-efficacy, outcome expectations, and intentions to use nicotine dependence medications. In Study 1, three themes emerged as factors for smokers' decisions to use nicotine dependence medications: (a) their effectiveness, (b) their desirability, including adverse effects, and (c) access to nicotine dependence medications. In Study 2, outcome expectations explained large amounts of variance in models predicting intentions to use (a) nicotine replacement therapy (f (2) = .97), and (b) bupropion (f (2) = .73). Effectiveness outcome expectations were the principal predictors in both models. Mild adverse effects outcome expectations explained additional variance in model 1, and medication-aversion outcome expectations explained additional variance in model 2. The effect of craving control outcome expectations on intentions in models 1 and 2 were mediated by effectiveness outcome expectations. Effectiveness outcome expectations were strong predictors of intentions, whereas outcome expectations that these medications are desirable were additional predictors. Expectations of effectiveness appear to be influenced by the ability of the medications to control cravings to smoke. Interventions aimed at increasing the likelihood with which smokers use nicotine dependence medications may be more successful if they address these expectations.


Wave modes in shear-deformed two-dimensional plasma crystals.
A theory of wave modes in shear-deformed two-dimensional plasma crystals is presented. Modification of the dispersion relations upon the pure and simple shear, and the resulting effect on the onset of the mode-coupling instability, are studied. In particular, it is explained why the velocity fluctuation spectra measured in experiments with sheared crystals exhibit asymmetric "hot spots": It is shown that the coupling of the in-plane compressional and the out-of-plane modes, leading to the formation of an unstable hybrid mode and generation of the hot spots, is enhanced in a certain direction determined by deformation.


Evidence for extraintestinal growth of bacteroidales originating from poultry litter.
Water quality monitoring techniques that target microorganisms in the order Bacteroidales are potential alternatives to conventional methods for detection of fecal indicator bacteria. Bacteroidales and members of the genus Bacteroides have been the focus of microbial source tracking (MST) investigations for discriminating sources of fecal pollution (e.g., human or cattle feces) in environmental waters. For accurate source apportionment to occur, one needs to understand both the abundance of Bacteroides in host feces and the survival of these host-associated microbial markers after deposition in the environment. Studies were undertaken to evaluate the abundance, persistence, and potential for growth of Bacteroidales originating from poultry litter under oxic and anoxic environmental conditions. Bacteroidales abundance, as determined by quantitative PCR (qPCR) with GenBac primers and probe, increased 2 to 5 log gene copies ml(-1) and 2 log gene copies g litter(-1) under most conditions during incubation of poultry litter in a variety of laboratory microcosm and field mesocosm studies. DNA sequencing of the Bacteroidales organisms in the litter identified taxa with sequences corresponding exactly to the GenBac primer and probe sequences and that were closely related to Bacteroides uniformis, B. ovatus, and B. vulgatus. These results suggest that MST studies using qPCR methods targeting Bacteroidales in watersheds that are affected by poultry litter should be interpreted cautiously. Growth of Bacteroidales originating from poultry litter in environmental waters may occur while Bacteroidales growth from other fecal sources declines, thus confounding the interpretation of MST results.


Care and survival of Mexican American women with node negative breast cancer: historical cohort evidence of health insurance and barrio advantages.
We hypothesized 3-way ethnicity by barrio by health insurance interactions such that the advantages of having adequate health insurance were greatest among Mexican American (MA) women who lived in barrios. Barrios were neighborhoods with relatively high concentrations of MAs (60% or more). Data were analyzed for 194 MA and 2,846 non-Hispanic white women diagnosed with, very treatable, node negative breast cancer in California between 1996 and 2000 and followed until 2011. Significant interactions were observed such that the protective effects of Medicare or private health insurance on radiation therapy access and long term survival were largest for MA women who resided in MA barrios, neighborhoods that also tended to be extremely poor. These paradoxical findings are consistent with the theory that more facilitative social and economic capital available to MA women in barrios enables them to better absorb the indirect and direct, but uncovered, costs of breast cancer care.


Underestimation of adolescent obesity.
Previous studies assessing the validity of adolescent self-reported height and weight for estimating obesity prevalence have not accounted for, potential bias due to nonresponse in self-reports. The aim of this study was to assess the implications of selective nonresponse in self-reports of height and weight for estimates of adolescent obesity. The authors analyzed 613 adolescents ages 12-17 years from the 2006-2008 Los Angeles Family and Neighborhood Survey, a longitudinal study of Los Angeles County households with an oversample of poor neighborhoods. Obesity prevalence estimates were compared based on (a) self-report, (b) measured height and weight for those who did report, and (c) measured height and weight for those who did report. Among younger teens, measured obesity prevalence was higher for those who did not report height and weight compared with those who did (40% vs. 30%). Consequently, obesity prevalence based on self-reported height and weight underestimated measured prevalence by 12 percentage points (when accounting for nonresponse) versus 9 percentage points (when nonresponse was not accounted for). Results were robust to the choice of difference child growth references. Adolescent obesity surveillance and prevention efforts must take into account selective nonresponse for self-reported height and weight, particularly for younger teens. Results should be replicated in a nationally representative sample.


Co-benefits analysis of energy cascade utilization in an industrial park in China.
As an important role in economic development in China, industrial parks have consumed plenty of energy, while emitting enormous air pollutants and discharging large quantities of waste heat. Energy cascade utilization is an effective way to improve the energy efficiency of industrial parks. The objective of this study was to assess the co-benefits of energy cascade utilization, including the energy savings potential, reduction potential of air pollutants, and air quality improvements, in an industrial park in China. Through an energy flow analysis of steam at different pressures and residual gas among various enterprises, this study identified the existing energy cascade utilization network in a baseline scenario and proposed an enhanced scenario. To evaluate the co-benefits of these two scenarios, the CALPUFF model was used to integrate energy savings and air pollutant mitigation for the park in 2017. The results show that energy cascade utilization can result in considerable co-benefits related to energy conservation, air pollutant emission reductions, and air quality improvements. In the enhanced scenario, the total energy savings potential is 11,425 TJ, with emission reductions of 859 tons of SO2 and 910 tons of NOx. Based on the CALPUFF simulations of SO2 and NOx diffusion in the four seasons, the concentrations of SO2 and NOx in the study area considerably decreased in the enhanced scenario compared with those in the baseline scenario. This study demonstrates that the park should focus on the cascade utilization of waste heat and residual gas to improve the energy utilization efficiency and reduce atmospheric pollutant emissions.


Peroxisomes Are Critical for the Development and Maintenance of B1 and Marginal Zone B Cells but Dispensable for Follicular B Cells and T Cells.
Antioxidant systems maintain cellular redox (oxidation-reduction) homeostasis. In contrast with other key redox pathways, such as the thioredoxin system, glutathione, and NF-E2-related factor 2 (Nrf2), little is known about the function of the redox-sensitive organelle "peroxisome" in immune cells. In this study, we show that the absence of peroxisomes in conditional Pex5-deficient mice strikingly results in impaired homeostatic maintenance of innate-like B cells, namely, B1 and marginal zone B cells, which translates into a defective Ab response to Streptococcus pneumoniae Surprisingly, however, follicular B2 cell development, homeostatic maintenance, germinal center reactions, Ab production, class switching, and B cell memory formation were unaffected in Pex5-deficient animals. Similarly, T cell development and responses to viral infections also remained unaltered in the absence of Pex5 Thus, this study highlights the differential requirement of peroxisomes in distinct lymphocyte subtypes and may provide a rationale for specifically targeting peroxisomal metabolism in innate-like B cells in certain forms of B cell malignancies involving B1 cells.


Rapid Growth and Apparent Total Nitrogen Increases in Rice and Corn Plants following Applications of Triacontanol.
Triacontanol (TRIA) increased fresh and dry weight and total reducible nitrogen (total N) of rice (Oryza sativa L.) seedlings within 40 minutes. Increases in total N in the supernatants from homogenates of corn (Zea mays L.) and rice leaves treated with TRIA for one minute before grinding occurred within 30 and 80 minutes, respectively. The source for the increase was investigated utilizing atmospheric substitution and enrichment and depletion studies with (15)N. The increase in total N in seedlings was shown to be independent of method of N analysis and the presence of nitrate in the plants. Automated Kjeldahl determinations showing apparent increases in N composition due to TRIA were shown to be correlated with hand Kjeldahl, elemental analysis, and chemiluminescent analysis in three independent laboratories. TRIA did not alter the nitrate uptake or endogenous levels of nitrate in corn and rice seedlings. Enrichment experiments revealed that the total N increases in rice seedlings, in vivo, and in supernatants of corn leaf homogenates, in vitro, are not due to atmospheric N(2). TRIA increased the soluble N pools of the plants, specifically the free amino acid and soluble protein fractions. No differences in depletion or enrichment of (15)N incorporated into soluble and insoluble N fractions of rice seedlings could be detected on an atom per cent (15)N basis. The apparent short-term total N increases cannot be explained by current knowledge of major N assimilation pathways. TRIA may stimulate a change in the chemical composition of the seedlings, resulting in interference with standard methods of N analysis.


Stress priming affects fungal competition - evidence from a combined experimental and modelling study.
Priming, an inducible stress defence strategy that prepares an organism for an impending stress event, is common in microbes and has been studied mostly in isolated organisms or populations. How the benefits of priming change in the microbial community context and, vice versa, whether priming influences competition between organisms, remain largely unknown. In this study, we grew different isolates of soil fungi that experienced heat stress in isolation and pairwise competition experiments and assessed colony extension rate as a measure of fitness under priming and non-priming conditions. Based on this data, we developed a cellular automaton model simulating the growth of the ascomycete Chaetomium angustispirale competing against other fungi and systematically varied fungal response traits to explain similarities and differences observed in the experimental data. We showed that competition changes the priming benefit compared with isolated growth and that it can even be reversed depending on the competitor's traits such as growth rate, primeability and stress susceptibility. With this study, we transfer insights on priming from studies in isolation to competition between species. This is an important step towards understanding the role of inducible defences in microbial community assembly and composition.


Piliation control mechanisms in Neisseria gonorrhoeae.
Gonococci (Gc) undergo pilus+ to pilus- "phase transitions" readily in vitro. In the present study we sequenced pilin mRNA from reverting, pilus- Gc by oligonucleotide primer extension and compared these pilin mRNA sequences with those expressed by their pilus+ predecessors and pilus+ revertants. The results suggest that genetic rearrangement within the pilin structural gene can generate defective pilin gene products, resulting in a pilus- phenotype. These pilus- Gc give rise to pilus+ revertants upon reconstitution of their modified pilin gene.


Mobilization of endothelial progenitor cells by intravenous cyclophosphamide in patients with systemic sclerosis.
To evaluate the effects of i.v. CYC on the number of circulating endothelial progenitor cells (EPCs) in patients with SSc, and the potential association of the EPC response with CYC's effect for treating interstitial lung disease (ILD). This open-label, prospective study involved 12 patients with SSc and alveolitis (CYC group). All patients received six courses of i.v. CYC (0.5 g/m2) at 4-week intervals in combination with low-dose prednisolone. Ten patients were followed for 24 months. Seven SSc patients treated with low-dose prednisolone alone were used as a control for the EPC measurement (control group). Five patients with non-SSc CTD who received i.v. CYC and prednisolone also served as disease controls. EPCs were quantified by the partial enrichment of CD34+ cells followed by three-colour flow cytometry. The circulating levels of vascular injury markers were measured by immunoassay. The EPC count was significantly increased at 2 weeks after treatment in the CYC group (P=0.02), but not in the control group, while CYC increased EPC count in all disease controls. The SSc patients in the CYC group were divided into five EPC responders and seven EPC non-responders. Circulating vascular injury markers were reduced in the responders, but not in the non-responders. During the 24-month follow-up, 3 of 10 patients developed end-stage lung disease, and all of them were EPC non-responders. A low-dose i.v. CYC induces EPC mobilization, which may contribute to the efficacy for treating SSc-associated ILD.


An integrative perspective on psychotherapeutic treatments for borderline personality disorder.
Although there is an abundance of literature on the psychotherapeutic treatment of borderline pathology, little is known about differences and similarities between treatments of borderline personality disorder (BPD). Potential differences and similarities are especially important in the absence of evidence of the superiority of one treatment over the other (e.g., Livesley, 2004). This article offers an overview of the theory and practice of contemporary psychotherapeutic treatments of BPD, and delineates similarities and differences between the specific treatments. Results show that similarities concerning (1) the formal characteristics, and (2) the importance of therapeutic techniques in treatments for BPD, outnumber the differences. This article concludes by viewing the similarities and differences from an integrative perspective, and recommendations are given for future work in treating patients with and research on the effectiveness of treatments and treatment techniques for BPD.


Azolla-Anabaena azollae Relationship: IV. Photosynthetically Driven, Nitrogenase-catalyzed H(2) Production.
The water fern, Azolla caroliniana Willd., containing the symbiotic, heterocystous blue-green alga, Anabaena azollae, has been studied under various growth conditions to characterize its light-dependent production of H(2). The response of H(2) production to N(2) and C(2)H(2) and the absence of a differential effect of m-chlorocarbonyl cyanide phenylhydrazone on H(2) production and C(2)H(2) reduction, coupled with the parallel inhibition of both processes by DCMU imply that the production of H(2) is nitrogenase-catalyzed and ATP-dependent.H(2) was produced by fronds grown under air-CO(2) in the presence or absence of combined nitrogen. When cultured under argon-O(2)-CO(2), only those fronds provided with combined nitrogen remained viable and produced H(2). Fronds grown on nitrate under air plus 2% CO also produced H(2). In comparison to fronds grown on N(2) alone, fronds grown on nitrate had an increased rate of H(2) production relative to C(2)H(2) reduction, and the inhibition of H(2) production by air was less.CO in argon +/- CO(2) resulted in a partial inhibition of H(2) production, whereas CO in argon-CO(2)-C(2)H(2) enhanced H(2) production in fronds grown without combined nitrogen. Our studies strongly indicate that H(2) production is nitrogenase-catalyzed but the possibility that the symbiont contains a hydrogenase cannot be totally excluded.


The Prognostic Significance of the Geriatric Nutritional Risk Index in Colorectal Cancer Patients.
This study retrospectively investigated the prognostic impact of the geriatric nutritional risk index (GNRI) in colorectal cancer (CRC). This study reviewed the medical records of 329 CRC patients who underwent curative surgery. The GNRI was calculated from the serum albumin level and the body weight. The cutoff value for the GNRI was set at 98. One hundred ninety (57.8%) patients had a GNRI of ≥98, and 139 (42.9%) had a GNRI of <98. The patients with a lower GNRI had a significantly lower overall survival (OS) rate than those with a higher GNRI (p < 0.001). The multivariate analysis demonstrated that the GNRI was an independent predictor of the OS (p = 0.042). Non-cancer death was more frequent in the patients with a lower GNRI than in those with a higher GNRI (p = 0.003). The mean age was significantly higher in the patients with a lower GNRI (p < 0.001). The GNRI was significantly associated with tumor location (p = 0.048), tumor depth (p < 0.001) and carcinoembryonic antigen (CEA) level (p = 0.032). The GNRI is a simple and useful prognostic factor in CRC. The present study suggests that a low GNRI be associated with a higher risk of non-cancer death.


Sex-manipulated Ascaris suum infections in pigs: implications for reproduction.
In spite of the vast distribution and considerable impact on human and animal health of Ascaris suum and A. lumbricoides, little is known of the sexual biology and reproductive capacity of these intestinal nematodes. By oral transfer of adult female worms to previously parasite-naive pigs we show that in the absence of males the egg production ceases after 2-3 weeks. Such females readily resume egg production a few days after oral transfer of male worms. These observations throw light on an important aspect of Ascaris biology, but also pave the way for possible experimental interbreeding between the human and pig Ascaris species.


Estimation of survival and gonotrophic cycle length of Culicoides variipennis (Diptera: Ceratopogonidae) in California.
The use of a time series analysis to estimate the survival rate and gonotrophic cycle length of Culicoides variipennis at 2 California sites is described. Collections were made daily for 28 days in Yolo County (northern California) and for 25 days in Riverside County (southern California) in July and August of 1989, respectively, using CO2-baited suction traps. The time series analysis of these collections yielded a gonotrophic cycle length estimate of 3 days. Stage-specific and daily survivorship estimates 0.242 and 0.623, respectively, were determined for the northern California site. The time series method was found unsuitable for estimating the gonotrophic cycle length or daily survivorship at the southern California site.


A survey of the opinions and attitudes of general practitioners in Kaunas to the prevention of ischaemic heart disease.
Fifty-four general practitioners were sent questionnaires inquiring into their attitudes to various aspects of preventive medicine and to primary prevention of ischaemic heart disease (IHD). Besides, their opinions were questioned about three risk factors of IHD (arterial hypertension, hypercholesterolaemia, impaired glucose tolerance), and these factors' values above which drug therapy should be started. It was found that the physicians tended to start drug therapy already at fairly low values of the three risk factors. A survey repeated after extensive preventive study among the population revealed no marked changes in the opinions of the practitioners questioned.


Epithelioid sarcoma. Report of a case with fine needle aspiration diagnosis.
Epithelioid sarcoma is a rare type of soft tissue sarcoma affecting the extremities, particularly the hands and fingers. Though it is well described histopathologically, publications regarding its cytologic findings are limited. A 52-year-old woman presented with swelling of the left middle finger. Fine needle aspiration was performed. Smears showed oval to polygonal cells with epithelioid features. A diagnosis of soft tissue sarcoma with a possibility of epithelioid sarcoma was suggested. Histopathologic examination and immunohistochemistry confirmed the diagnosis. In the presence of classic cytologic findings, the diagnosis of epithelioid sarcoma can be suggested. Subsequent histologic examination and immunohistochemistry can confirm the diagnosis.


[Nursing care in situations of facial image alteration].
This research studies how patients, nursing undergraduate students, and professors perceive the care of patients with facial image alterations, and the implications of this care to the education process. It followed an exploratory qualitative approach, and it was carried out in an university hospital in Santa Maria, Rio Grande do Sul, Brazil, between July 2008 and April 2009. Six patients with facial image alteration, seven nursing undergraduate students and five professors participated. Semistructured interviews and a focal group were used. The data were organized and submitted to the content analysis technique. Two categories were found: meaning of the altered facial image, and nursing education and care. The care to these patients is perceived as a complex, hard and striking experience, that constitutes a unique opportunity for the development of skills necessary to the nurse's education. It was observed the need to insert themes during education that address issues relevant to the needs of undergraduates, and enable them to reflect on their training experiences.


Large congenital facial teratoma.
This case report discusses a presentation of a giant facial teratoma, a rare congenital neoplasm. Head and neck locations of the tumour uncommonly distort the face and may be associated with functional problems. We present a case of teratoma arising from the right parotid extending to the extracranial regions, successfully managed by surgical resection. Reviewing this case with the supporting body of literature anticipates further investigation to address patients' needs more thoroughly.


Localization of methyl-branched ceramide [EOS] species within the long-periodicity phase in stratum corneum lipid model membranes: A neutron diffraction study.
The outermost layer of the mammalian skin, the stratum corneum (SC), is a very thin structure and realizes simultaneously the main barrier properties. The penetration barrier for xenobiotica is mostly represented by a complex lipid matrix. There is great interest in the subject of getting information about the arrangement of the lipids, which are mainly ceramides (CER), free fatty acids (FFA) and cholesterol (CHOL). SC lipid model membranes containing synthetically derived lipids in a non-physiological ratio were investigated. To compare the study to a former experiment, a methyl-branched ceramide [EOS] species in presence of the ultra-long chain CER[AP], CHOL and behenic acid (23/10/33/33, wt%) was applied. The membrane structure was studied using the very versatile technique of neutron diffraction. We were able to identify a long-periodicity phase (LPP) with a size of 114Å or 118Å with CER[EOS]-br in a ratio of >60wt% of the ceramides. Furthermore, we figured out two additional coexisting short-periodicity phases (SPP) with repeat distances of 48Å and 45Å, respectively. Partial deuterations of CER[EOS]-br and CER[AP] enabled the localization of the molecules within the multiphase system. CER[EOS]-d3 was present in the LPP, but absent in both SPP. CER[AP]-d3 was determined in both short phases but not localized within the LPP. Besides, we revealed influences of humidity and time with respect to the long-periodicity phase.


Chondromyxoid fibroma in a carpal bone.
An unusual lesion developed in the trapezoid of a 25-year-old man. The tumor had histologic features most consistent with a diagnosis of chondromyxoid fibroma and had not recurred four years after curettage and bone grafting.


Hypertrophic cardiomyopathy in the elderly.
Hypertrophic cardiomyopathy (HCM) is a relatively common genetic cardiac disorder with heterogeneous morphological, functional and clinical features. Although the risk of sudden death and incapacitating symptoms in young patients has been focused upon, the disease has been found with increasing frequency in elderly patients. However, there have been few studies on clinical features of HCM in the elderly. We established a cardiomyopathy registration study in Kochi Prefecture, which is one of the most aged communities in Japan, to provide detailed descriptions of the clinical features of HCM in a community-based patient cohort. The unselected regional HCM population consisted largely of elderly patients (70% of the study cohort being >or=60 years of age at registration), although HCM has been regarded largely as a disease of the young. Cardiac hypertrophy that becomes clinically apparent late in life can be a genetic disorder, and mutations in the cardiac myosin-binding protein C gene are the most common cause of late-onset or elderly HCM. In the morphological features, sarcomere gene defects seem to have a predilection for a crescent-shaped left ventricular cavity with reversed septal curvature even in elderly patients, although an ovoid left ventricular shape was frequently seen in elderly patients in previous clinical studies on morphological characteristics of HCM. In middle-aged or elderly patients with HCM, heart failure and embolic events, which were strongly associated with atrial fibrillation, were very important. It is important to manage HCM patients from the standpoint of longitudinal evolution in order to prevent those clinical complications.


Correlated mutation analyses on very large sequence families.
The 'omics era' (the era of genomics, proteomics, and so forth) is marked by a flood of data that need to be interpreted to become useful information. Thanks to genome sequencing projects, large numbers of sequence families with more than a thousand members each are now available. Novel analytical techniques are needed to deal with this avalanche of sequence data. Sequence entropy is a measure of the information present in an alignment, whereas sequence variability represents the mutational flexibility at a particular position. Entropy versus variability plots can reveal the roles of groups of residues in the overall function of a protein. Such roles can be as part of the main active site, part of a modulator binding site, or transduction of a signal between those sites. Residues that are involved in a common function tend to stay conserved as a group, but when they mutate, they tend to mutate together. Correlated mutation analysis can detect groups of residue positions that show this behaviour. The combination of entropy, variability and correlation is a powerful tool to convert sequence data into useful information. This analysis can, for example, detect the key residues involved in cooperativity in globins, the switch regions in ras-like proteins and the calcium binding and signalling residues in serine proteases. We have extrapolated from these three classes of structurally and functionally well-described proteins to G-protein-coupled receptors (GPCRs). We can detect the residues in the main functional site in GPCRs that are responsible for G-protein coupling, the residues in the endogenous agonist binding site, and the residues in between that transduce the signal to and fro between these sites. The results are discussed in the light of a simple two-step evolutionary model for the development of functional proteins.


Brain MR findings in patients with systemic lupus erythematosus with and without antiphospholipid antibody syndrome.
Antiphospholipid syndrome may affect the incidence and pathogenesis of cerebrovascular diseases in patients with systemic lupus erythematosus. We compared the spectrum of MR findings in patients with systemic lupus erythematosus with and without antiphospholipid syndrome. We identified 256 patients with systemic lupus erythematosus (45 with, 211 without antiphospholipid syndrome) who underwent MR studies; in 145 (57%), we detected abnormalities. These were categorized as large territorial, lacunar, localized cortical, and borderzone infarctions and as microembolisms, basal ganglia lesions, callosal lesions, hemorrhages, and white matter hyperintensity on T2-weighted and/or FLAIR images, and as stenotic arterial lesions on MR angiograms. Logistic regression analysis was performed to compare the MR findings in patients with systemic lupus erythematosus with and without antiphospholipid syndrome, with patient age and antiphospholipid syndrome as the covariates. Abnormal MR findings were more common in patients with systemic lupus erythematosus with antiphospholipid syndrome (73% versus 53%). Large territorial (P = .01), lacunar (P = .01), localized cortical (P < .01), borderzone infarcts (P < .01), basal ganglia lesions (P = .03), stenotic arterial lesions (P = .04), and the rate of positive findings on MR imaging (P = .01) were significantly associated with antiphospholipid syndrome. Irrespective of age, significantly more patients with antiphospholipid syndrome manifested lacunar infarcts in the deep white matter (P < .01), localized cortical infarcts in the territory of the MCA (P < .01), bilateral borderzone infarcts (P < .01), and anterior basal ganglia lesions (P = .01). Abnormal MR findings were more common in patients with systemic lupus erythematosus with than in those without antiphospholipid syndrome. Large territorial infarctions, lacunar infarctions in the deep white matter, localized cortical infarctions in the MCA territory, bilateral borderzone infarctions, anterior basal ganglia lesions, and stenotic arterial lesions are common MR findings in patients with systemic lupus erythematosus with antiphospholipid syndrome.


Survey of anaphylaxis management by general practitioners in Scotland.
To obtain a snapshot of how patients with potentially life-threatening allergies are managed within a Primary Care setting. A questionnaire-based survey sent to all General Practitioners in Scotland. Six hundred and thirteen replies were suitable for analysis. Ninety percent of respondents had prescribed adrenaline auto-injector pens, almost exclusively the EpiPen device. Less than half were personally confident in their use and only 17% had access to a dummy trainer pen for demonstration purposes. Twenty seven percent would prescribe one auto-injector only. Six percent reported accidental mis-firing of adrenaline pens, although with no serious sequelae. Refusal of pens by patients was noted by 1%. In the event of an anaphylactic emergency, 90% of respondents would use adrenaline as first-line treatment, although only half would use the UK Resuscitation Council recommended adult dose of 0.5mg by the intramuscular route (or 0.3mg by auto-injector). Eleven percent would give adrenaline by the slower subcutaneous route and 3% by the intravenous route. Thirty six percent had themselves treated such a case outside of hospital. Sixty two percent of respondents would seek specialist investigation of anaphylaxis, although only 31% felt that ready access was available. Frequent concerns were raised about current provision of care for patients with allergic disease and their own ability to deal with this. Investment is required, both to provide basic training and ongoing support for Primary healthcare staff in the management of allergic disease, and also for necessary accompanying specialist support.


Dual mechanisms of action of interferon-gamma in potentiating responses to LPS in mice: IL1, TNFalpha and IL6 production in serum and hypothermia.
IFNgamma potentiates the production of serum cytokines and mortality induced by LPS, but these responses do not change in parallel, and the underlying mechanisms are not clear. Pretreatment of mice with 15 microg rrIFNgamma intraperitoneally (IP) resulted in potentiation of LPS-induced serum cytokine production and hypothermia, but these changes depended on the pretreatment time and did not occur in parallel. TNFalpha and IL1beta levels showed peak potentiation after 8-h-IFNgamma pretreatment which may result from a process of sensitization of mechanisms involved in LPS responses. IL6 levels were most markedly potentiated after 3- and 6-h-IFNgamma-pretreatment and hypothermia was markedly potentiated after 0-8 h pretreatments. These effects may result from an additional synergistic action of IFNgamma with other mediators when it is present at significant levels earlier after its injection, given that IFNgamma had little (hypothermia) or no effect (cytokines) alone. The degree of potentiation induced by 18-h-IFNgamma pretreatment was related to the dose of LPS, the maximum response having been increased. Two injections of IFNgamma at 42 and 18 h prior to LPS induced greater increases in TNFalpha and IL1beta production than 18-h pretreatment alone, but not in IL6 production or hypothermia. There may be a maximum level of IL6 production which was surpassed under these conditions. These findings suggest that a balance of sensitizing and synergistic actions of IFNgamma with other mediators such as IL1 and TNFalpha, are the major mechanisms underlying its potentiation of LPS responses in mice.


Improving gene delivery efficiency of bioreducible poly(amidoamine)s via grafting with dendritic poly(amidoamine)s.
Dendritic poly(amidoamine)s (PAMAM)s were introduced into the side chains of disulfide-containing poly(amidoamine)s via repetitive Michael addition and amidation. The bioreducible poly(amidoamine)s grafted with dendritic polyamidoamines showed high buffer capacity, low cytotoxicity and strong DNA binding ability at low N/P ratio. They were able to condense DNA into small sized polycation/DNA complexes, which degraded and released the incorporated DNA under reductive conditions. In comparison to the original disulfide-containing poly(amidoamine) with aminoethyl side chain, the grafting of the bioreducible poly(amidoamine) with dendrimer greatly improved the transfection efficiencies of 293T and HeLa cells with foreign DNA at various N/P ratios. The structure-gene delivery property relations of dendrimer-grafted polycations will provide valuable insight into the design of highly efficient and less toxic polycationic gene carriers.


Inducible nitric oxide synthase blockade with aminoguanidine, protects mice infected with Nocardia brasiliensis from actinomycetoma development.
Mycetoma is a chronic infectious disease that can be caused by fungi or bacteria, Madurella mycetomatis and Nocardia brasiliensis are frequent etiologic agents of this disease. Mycetoma produced by bacteria is known as actinomycetoma. In mycetoma produced by fungi (eumycetoma) and actinomycetoma, diagnosis of the disease is based on clinical findings: severe inflammation, with deformities of affected tissues, abscesses, fistulae, sinuses and discharge of purulent material that contains micro colonies of the etiologic agent. Microscopic examination of infected tissue is similar regardless of the offending microbe; hallmark of infected tissue is severe inflammation with abundant neutrophils around micro colonies and granuloma formation with macrophages, lymphocytes, dendritic and foamy cells. Even though medical treatment is available for mycetoma patients, amputation, or surgical intervention is frequently needed. The pathogenesis of actinomycetoma is little known, most information was obtained from experimental animal models infected with bacteria. In other experimental mice infections with different microbes, it was demonstrated that nitric oxide is responsible for the intracellular killing of Mycobacterium tuberculosis by activated macrophages. Nitric oxide is a free radical with potent stimulatory and suppressive effects in innate and adaptive immunity. The unstable nitric oxide molecule is produced by action of nitric oxide synthases on L-arginine. There are three nitric oxide synthases expressed in different cells and tissues, two are constitutively expressed one in neurons, and the other in endothelial cells and one that is inducible in macrophages. Aminoguanidine is a competitive inhibitor of inducible nitric oxide synthase. Its administration in experimental animals may favor or harm them. We used aminoguanidine in mice infected with Nocardia brasiliensis, and demonstrated that all treated animals were protected from actinomycetoma development. Anti N. brasiliensis antibodies and T cell proliferation were not affected, but inflammation was reduced.


Influence of Processing Parameters on Tensile Properties of SLS Polymer Product.
Polymer products manufactured by additive processes are today increasingly flooding the market. Given that they have broad application ranging from various consumer products to medicine and automotive industry, the products must satisfy certain mechanical properties. In the past studies of selective laser sintering (SLS) for polymer materials, the processing parameter of energy density has been confirmed which affects the tensile properties. Energy density depends on the laser beam speed, laser power and hatch distance; however, in this paper the existing mathematical model has been expanded by the overlay ratio and tests have been conducted how on the basis of the new mathematical model a product with good tensile properties (tensile strength, tensile strength at break, tensile modulus, tensile strain at break) can be manufactured. However, in parameter selection as well, the layer thickness and the manufacturing strategy also play a role, and they may shorten the time and reduce the cost necessary to manufacture a new product from the initial concept to production. The paper also provides a proposal of processing parameters (laser beam speed, laser power and energy density) depending on the manufacturing strategy and layer thickness.


Effects of supra- and sub-MIC benzylpenicillin concentrations on group A beta-haemolytic streptococci during the postantibiotic phase in vivo.
A postantibiotic effect (PAE) in vivo was induced in group A streptococci established in a tissue cage model in rabbits. The bacteria were exposed to 10 x MIC of benzylpenicillin in tissue cage fluid (TCF) for 2 h. TCF was then aspirated, penicillin was eliminated by washing and the bacteria were transferred to tissue cages in other rabbits in order to study the in-vivo killing kinetics of streptococci in the postantibiotic phase. In these latter rabbits the concentration of benzylpenicillin in TCF corresponded to 10 or 0.3 x MIC. Bacteria not previously exposed to penicillin were used as controls. Streptococci in postantibiotic phase were killed as effectively after re-exposure to 10 x MIC in vivo as the growing controls. Although the concentration of penicillin fell below the MIC after 12 h, no regrowth was seen during the following 12 h in either culture. When only subinhibitory concentrations in TCF were used in the second phase, a killing of approximately 1 log10 cfu/ml was noted both in the previously exposed cultures and in controls. Both cultures started to multiply first after 6-7 h.


Disability-Adjusted Life-Years Associated With Intracerebral Hemorrhage and Secondary Injury.
Intracerebral hemorrhage (ICH) contributes significantly to the global burden of disease. To examine the association of ICH and secondary injury with disability-adjusted life-years (DALYs) for the individual patient. This cohort study was conducted using data from the Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage study. Consecutive patients admitted to a single tertiary care center from January 1, 2006, to December 31, 2015, were included. The sample comprised patients with oral anticoagulation-associated ICH (OAC-ICH) or primary spontaneous ICH (non-OAC-ICH). Statistical analysis was conducted from October 1 to December 31, 2020. ICH occurrence and secondary injury. DALYs, years of life lost (YLL), and years lived with disability (YLD) were analyzed by hematoma location, ICH volume, and secondary injury (ie, hematoma expansion [HE], intraventricular hemorrhage [IVH], and perihemorrhagic edema [PHE]). Among 1322 patients with ICH, 615 (46.5%) were women and the mean (SD) age at hospital admission was 71 (13) years; ICH was associated with a mean (SD) of 9.46 (8.08) DALYs, 5.72 (8.29) YLL, and 3.74 (5.95) YLD. There were statistically significant differences in mean (SD) DALYs by extent of hematoma volume (< 10 mL ICH: 7.05 [6.79] DALYs; 10-30 mL ICH: 9.91 [8.35] DALYs; >30 mL ICH: 12.42 [8.47] DALYs; P < .001) and ICH location (deep location: 10.60 [8.35] DALYs; lobar location: 8.18 [7.63] DALYs; cerebellum: 8.14 [6.80] DALYs; brainstem: 12.63 [9.21] DALYs; P < .001). Regarding population-level disease burden of secondary injuries after ICH, there was a statistically significant difference in mean (SD) by injury type, with 0.94 (3.19) DALYs for HE, 2.45 (4.16) DALYs for IVH, and 1.96 (2.66) DALYs for PHE (P < .001) among the entire ICH cohort. Regarding individual-level exposure to secondary injuries after ICH, there were a mean (SD) 7.14 (6.62) DALYs for HE, 4.58 (4.75) DALYs for IVH, and 3.35 (3.28) DALYs for PHE among patients with ICH affected by secondary injuries. These findings suggest that there is a high burden of disability associated with ICH and secondary injuries, and the findings may guide public health strategies. The study findings further suggest that IVH and PHE may be relevant for the overall outcome of patients with ICH, that DALYs may represent a viable outcome parameter for studies to evaluate treatment outcomes in ICH research, and that IVH and PHE may represent potential treatment targets.


Intrauterine insemination versus fallopian tube sperm perfusion for non-tubal infertility.
Intrauterine insemination (IUI) is a common treatment for couples with subfertility that does not involve the fallopian tubes. It is used to bring the sperm close to the released oocyte. Another method of introducing sperm is fallopian tube sperm perfusion (FSP). Fallopian tube sperm perfusion ensures the presence of higher sperm densities in the fallopian tubes at the time of ovulation than does standard IUI. These treatments are often used in combination with ovarian hyperstimulation. To compare intrauterine insemination versus fallopian tube sperm perfusion in the treatment of non-tubal subfertility, for live birth and pregnancy outcomes. We searched the Menstrual Disorders and Subfertility Group Trials Register, MEDLINE, CINAHL and EMBASE from inception to September 2013. We also searched study reference lists and trial registers. Randomised controlled trials (RCTs) comparing IUI with FSP in couples with non-tubal subfertility were included. Two review authors independently selected studies for inclusion, assessed study quality and extracted the data. If studies were sufficiently similar, data were combined using a fixed-effect model to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). A random-effects model was used if substantial statistical heterogeneity was detected. Studies that included participants with unexplained or mixed (non-tubal) subfertility were analysed separately from studies restricted to participants with mild or moderate male factor subfertility. The overall quality of evidence for the main outcomes was summarised using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. The review included 16 RCTs. Fourteen RCTs (1745 women) were included in the meta-analysis. Only three studies reported live birth per couple. No evidence of a statistically significant difference was noted between IUI and FSP in live birth (OR 0.94, 95% CI 0.59 to 1.49, three RCTs, 633 women, I(2) = 0%, low-quality evidence) or clinical pregnancy (OR 0.75, 95% CI 0.49 to 1.12, 14 RCTs, 1745 women, I(2) = 52%, low-quality evidence). These findings suggest that for a couple with a 13% chance of live birth using FSP, the chance when using IUI will be between 8% and 19%; and that for a couple with a 19% chance of pregnancy using FSP, the chance of pregnancy when using IUI will be between 10% and 20%. Nor was evidence found of a statistically significant difference between IUI and FSP in per-pregnancy of multiple pregnancy (OR 0.96, 95% CI 0.44 to 2.07, eight RCTs, 197 women, I(2) = 0%, low-quality evidence), miscarriage (OR 1.23, 95% CI 0.60 to 2.53, seven RCTs, 199 women, I(2) = 0%, low-quality evidence) or ectopic pregnancy (OR 1.71, 95% CI 0.42 to 6.88, four RCTs, 111 women, I(2) = 0%, very low quality evidence). Substantial heterogeneity was noted for the outcome of clinical pregnancy (I(2) = 54%), for which no clear explanation was provided. Currently no clear evidence suggests any difference between IUI and FSP with respect to their effectiveness and safety for treating couples with non-tubal subfertility. However, a high level of uncertainty is evident in the findings, and additional research may be useful.


Monte Carlo Study of Real Time Dynamics on the Lattice.
Monte Carlo studies involving real time dynamics are severely restricted by the sign problem that emerges from a highly oscillatory phase of the path integral. In this Letter, we present a new method to compute real time quantities on the lattice using the Schwinger-Keldysh formalism via Monte Carlo simulations. The key idea is to deform the path integration domain to a complex manifold where the phase oscillations are mild and the sign problem is manageable. We use the previously introduced "contraction algorithm" to create a Markov chain on this alternative manifold. We substantiate our approach by analyzing the quantum mechanical anharmonic oscillator. Our results are in agreement with the exact ones obtained by diagonalization of the Hamiltonian. The method we introduce is generic and, in principle, applicable to quantum field theory albeit very slow. We discuss some possible improvements that should speed up the algorithm.


[The surgical treatment of vasorenal hypertension].
Reconstructive procedures of renal arteries are routinely advocated for patients presenting documented renovascular hypertension (RVH). It is the purpose of this study to analyze experience had to date, and the results of operative reconstruction of 52 arteries in forty-seven patients, covering a 10-year period. Twenty-seven patients are operated on for RVH. In fourteen patients simultaneous procedures are performed for occlusive disease of the abdominal aorta, three patients are operated simultaneously--ACB, and two--carotid arteries. Aorto-renal bypass is the procedure of choice. In 11 patients TEA is performed for renal artery stenosis. In 45 patients (95.7 per cent) there is a significant improvement of hypertension, and in none of them is renal function lost postoperatively. Hospitalization is prolonged because of postoperative bleeding--two cases, and diffuse peritonitis--one patient, dying in the early postoperative period. Experience with the operative management of RVH shows that operative reconstruction of renal arteries is a method of choice in selected patients, and its indications may be extended to patients undergoing vascular reconstruction of the abdominal aorta.


Progressive modulation of endothelial phenotype during in vitro blood vessel formation.
"Sprouting" vascular endothelial cells were used as an in vitro model system to study the progressive morphologic and biosynthetic changes associated with the formation of tubular structures. In vitro, sprouting endothelial cells formed spontaneously without the addition of any exogenous factors from cultures of cloned endothelium exhibiting a polygonal/cobblestone phenotype. These phenotypically variant endothelial cells differentiated to form associated cell networks or nodules which gradually reorganized into tubular structures. Concomitant with these morphologic changes, the biosynthesis of extracellular matrix proteins was modulated, as determined by Northern blot analysis, metabolic labeling, and immunocytochemistry. The initial sprouting phase was characterized by the induction of type I collagen synthesis and the appearance of fibronectin containing the ED-A domain, in comparison to their absence in cloned cultures displaying a stable polygonal/cobblestone phenotype. The organizational stage, where the sprouting endothelial cells assembled into tubular structures, was additionally characterized by the expression of type IV collagen. These studies demonstrate that the progression from polygonal/cobblestone to sprouting cultures, and subsequent tubular organization, involves major alterations in extracellular matrix protein expression. This developmental phenomenon, although not completely analogous to blood vessel formation in vivo, nevertheless may be helpful in understanding the role of matrix macromolecules in the angiogenic process.


Microwave Radiometer Instability Due to Infrequent Calibration.
We directly quantify the effect of infrequent calibration on the stability of microwave radiometer temperature measurements (where a power measurement for the unknown source is acquired at a fixed time, but calibration data are acquired at variable earlier times) with robust and nonrobust implementations of a new metric. Based on our new metric, we also determine a component of uncertainty in a single measurement due to infrequent calibration effects. We apply our metric to experimental data acquired from experimental ground-based calibration data acquired from a NASA millimeter-wave imaging radiometer and a NIST radiometer (Noise Figure Radiometer-NFRad). Based on a stochastic model for the NFRad, we determine the random uncertainty of an empirical prediction model of our stability metric by a Monte Carlo method. For comparison purposes, we also present a secondary metric that quantifies stability for the case where calibration data are acquired at a fixed time, but power measurements for the unknown source are acquired at variable later times.


Characterization of IL-17AA and IL-17FF in rheumatoid arthritis and multiple sclerosis.
IL-17 is thought to play a prominent role in immune disorders. Sensitive and specific IL-17AA and IL-17FF assays were developed and used to determine levels in serum and cerebrospinal fluid (CSF) from patients with rheumatoid arthritis and relapsing remitting multiple sclerosis (RRMS). Qualified assays detected IL-17AA and IL-17FF in healthy and disease samples. Serum IL-17AA was significantly higher in rheumatoid arthritis and RRMS as compared with normal healthy subjects. IL-17AA was also elevated in RRMS CSF as compared with normal healthy subjects; although correlation was observed between serum levels of the two isoforms, no correlation was detected between serum and CSF levels. Reliable determination of IL-17 isoforms in the systemic and CNS compartments sheds light on the involvement of IL-17AA and IL-17FF in autoimmunity.


The prediction of accurate contraceptive use from attitudes and knowledge.
A framework of the relationship between knowledge, attitudes, and behavior was described in the context of couple's use of birth control. It was hypothesized that when knowledge of behavioral enactment is present, attitudes and beliefs about susceptibility to pregnancy will be predictive of accurate use of the diaphragm. Respondents were 111 women who participated in a three-wave panel design focusing on diaphragm use. Analyses indicated that the level of knowledge about what a woman should do to use the diaphragm correctly was high. Correct knowledge, however, did not translate into accurate behavior. Motivational factors focusing on attitudes, perceived susceptibility to pregnancy, and normative factors were also relevant.


Zinc Induced Aβ16 Aggregation Modeled by Molecular Dynamics.
It is widely accepted that the addition of zinc leads to the formation of neurotoxic nonfibrillar aggregates of beta-amyloid peptides Aβ40 and Aβ42 and at the same time destabilizes amyloid fibrils. However, the mechanism of the effect of zinc on beta-amyloid is not fully understood. In this study, a fast zinc-induced aggregation of Aβ16 (as compared to a system without zinc) via the formation of Aβ16 dimers with one zinc ion coordinated in the metal-binding site 11EVHH14, followed by their polymerization, has been studied by molecular dynamics. The best aggregation was shown by the system composed of Aβ16 dimers bound by one zinc ion, with no additional zinc in solution. The presence of Aβ16 dimers was a major condition, sufficient for fast aggregation into larger complexes. It has been shown that the addition of zinc to a system with already formed dimers does not substantially affect the characteristics and rate of aggregation. At the same time, an excessive concentration of zinc at the early stages of the formation of conglomerates can negatively affect aggregation, since in systems where zinc ions occupied the 11EVHH14 coordination center and the His6 residue of every Aβ16 monomer, the aggregation proceeded more slowly and the resulting complexes were not as large as in the zinc-free Aβ system. Thus, this study has shown that the formation of Aβ16 dimers bound through zinc ions at the 11EVHH14 sites of the peptides plays an important role in the formation of neurotoxic non-fibrillar aggregates of beta-amyloid peptide Aβ16. The best energetically favorable structure has been obtained for the complex of two Aβ16 dimers with two zinc ions.


Most meal and snack patterns are stable over a 3-year period in schoolchildren in southern Brazil.
This study aimed to identify meal and snack patterns in Brazilian schoolchildren and assess their stability over 3 years. This is a repeated cross-sectional study carried out in 2013, 2014 and 2015 with 6353 schoolchildren aged 7-12 years from public schools in Florianópolis, Brazil. Previous-day food consumption data for six pre-defined meals (breakfast, mid-morning snack, lunch, mid-afternoon snack, dinner and evening snack) were collected using the validated Web-CAAFE (Food Consumption and Physical Activity of Schoolchildren) questionnaire. Latent class analysis was performed to derive meal and snack patterns. The stability of patterns was analysed using multinomial logistic regression, and the probability of belonging to a meal pattern was calculated for each year. Three patterns were identified for breakfast and four patterns for a mid-morning snack, lunch, mid-afternoon snack, dinner and evening snack. Most meal and snack patterns were stable over the 3-year evaluation period. In the total sample, for a mid-afternoon snack, there was an increase in the probability of the children belonging to the 'Fruits and porridge' pattern (14.5%, 95% CI 12%-17% in 2015 vs. 9.2%, 95% CI 6.8%-11.7% in 2013) and a reduction in the 'Ultra-processed' pattern (42.5%, 95% CI 39.4%-45.6% in 2015 vs. 51.3%, 95% CI 46.5%-56.1% in 2013). These results appear to be in line with the recommendations of the Brazilian Dietary Guidelines and regional policies to increase the intake of healthy foods and limit that of ultra-processed, high fat, sugar and salt foods.


The influence of attention on the auditory brain stem evoked responses. Preliminary report.
The purpose of this study was to investigate the effects of attention on the auditory brainstem evoked responses (ABER). This was performed by measuring and statistically evaluating the interpeak latency times of wave I to wave V in 100 test subjects. The subjects were tested in three conditions: 1) selective attention to auditory click stimulation, 2) distraction by auditory stimuli, and 3) reinforced distraction by reading a newspaper during the click stimulations. It was observed that selective attention to the auditory stimulation leads to a decrease in the interpeak latency time (I-V) of, on the average, 0.2 milliseconds (statistically significant, 1%) in comparison with conditions 2 and 3.


Story in a sample-the potential (and limitations) of cryo-electron microscopy applied to molecular machines.
This article addresses recent developments in cryo-electron microscopy and single-particle reconstruction of macromolecules. With the advent of powerful classification techniques, it is now possible to extract and visualize multiple conformers contained within the same dataset. It is discussed how and to what extent this technique can be used in the study of the dynamics of molecular machines.


Revealing Methodological Challenges in Chronic Obstructive Pulmonary Disease Studies Assessing Comorbidities: A Narrative Review.
Beyond respiratory impairment, patients with chronic obstructive pulmonary disease (COPD) often suffer from comorbidities which are associated with worse health status, higher health care costs and worse prognosis. Reported prevalences of comorbidities largely differ between studies which might be explained by different assessment methods (objective assessment, self-reported assessment, or assessment by medical records), heterogeneous study populations, inappropriate control groups, incomparable methodologies, etc. This narrative review demonstrates and further evaluates the variability in prevalence of several comorbidities in patients with COPD and control individuals and discusses several shortcomings and pitfalls which need to be considered when interpreting comorbidity data. Like in other chronic organ diseases, the accurate diagnosis and integrated management of comorbidities is a key for outcome in COPD. This review highlights that there is a need to move from the starting point of an established index disease towards the concept of the development of multimorbidity in the elderly including COPD as an important and highly prevalent pulmonary component.


Interatomic potential models for natural apatite crystals: incorporating strontium and the lanthanides.
A comprehensive set of interatomic potential parameters for modeling natural apatite crystals is presented. These potentials build on those previously used in research on apatites with new potentials fitted empirically to crystal structures and their properties using the GULP program. We demonstrate that the new potentials produce good models for the different compounds used for fitting, as well as for several natural apatites. Also presented are predicted enthalpies of mixing of strontium and calcium apatites and predicted cation site preferences in strontium calcium fluorapatite.


Aerobic production and utilization of lactate satisfy increased energy demands upon neuronal activation in hippocampal slices and provide neuroprotection against oxidative stress.
Ever since it was shown for the first time that lactate can support neuronal function in vitro as a sole oxidative energy substrate, investigators in the field of neuroenergetics have been debating the role, if any, of this glycolytic product in cerebral energy metabolism. Our experiments employed the rat hippocampal slice preparation with electrophysiological and biochemical methodologies. The data generated by these experiments (a) support the hypothesis that lactate, not pyruvate, is the end-product of cerebral aerobic glycolysis; (b) indicate that lactate plays a major and crucial role in affording neural tissue to respond adequately to glutamate excitation and to recover unscathed post-excitation; (c) suggest that neural tissue activation is accompanied by aerobic lactate and NADH production, the latter being produced when the former is converted to pyruvate by mitochondrial lactate dehydrogenase (mLDH); (d) imply that NADH can be utilized as an endogenous scavenger of reactive oxygen species (ROS) to provide neuroprotection against ROS-induced neuronal damage.


The acute muscular response following a novel form of pulsed direct current stimulation (Neubie) or traditional resistance exercise.
To examine changes in muscle thickness (MT), soreness (SOR), and isometric torque (ISO) following exercise with pulsed direct current (Neubie) or traditional high-load (TRAD) exercise. Thirty-two participants had SOR, MT, and ISO measured before, immediately after, and 24 and 48h following TRAD and Neubie. Rating of perceived exertion (RPE) and discomfort were also measured. Results are displayed as means(SD). For MT, there was a condition x time interaction (p<0.001). For Neubie, MT increased pre [3.7(0.7)cm] to post [3.9(0.8) cm, p<0.001] and remained elevated at 24h. For TRAD, MT increased pre [3.7(0.6)cm] to post [4.0 (0.7)cm, p<0.001] and remained up to 48h. Greater values were observed for TRAD post-exercise. For ISO, both conditions decreased up to 48h. TRAD demonstrated a greater change post exercise (p<0.001). For SOR, both conditions increased up to 48h. Neubie demonstrated greater SOR at 48h (p=0.007). RPE was higher for all sets in TRAD [Mean across sets=16.0(1.9) vs. 13.5(2), p<0.001]. Discomfort was higher in all sets for Neubie [Mean across sets=5.8(1.5)vs. 4.5(2.0), p<0.05]. Both conditions showed increased SOR, and decreased ISO for up to 48h, with MT increased for up to 24h. MT remained elevated in TRAD at 48h. Neubie training might be effective for individuals who are looking to experience lower RPE responses during exercise.


Risk factors and risk for mortality of mild hypoparathyroidism in hemodialysis patients.
Relative hypoparathyroidism (parathyroid hormone [PTH] < or = 200 pg/mL) is prevalent in hemodialysis (HD) patients, with unknown pathogenesis and prognosis. Thus, to clarify risk factors and prognosis of time-dependent relative hypoparathyroidism in HD patients, a retrospective cohort study was performed for 126 HD patients with four or more PTH determinations and no previous total or subtotal parathyroidectomy. Values for intact PTH, ionized calcium, phosphate, magnesium, albumin, creatinine, urea reduction ratio (URR), glucose, hemoglobin A1c (HbA1c), aluminum, and 1,25(OH)2D were obtained at enrollment and at some time during follow-up. The prevalence of relative hypoparathyroidism at entry was 76 of 126 patients (60.3%). Univariate analysis showed that patients with hypoparathyroidism were older, more likely to have diabetes, and had greater ionized calcium levels and lower phosphate, albumin, blood urea nitrogen (BUN), and creatinine levels. Patients with diabetes were older and had a shorter duration of dialysis therapy and lower PTH, phosphate, albumin, BUN, and creatinine levels and URRs. Conversely, multivariate analysis showed that PTH levels at entry were associated directly with creatinine levels and inversely with age and ionized calcium levels (but not diabetes). During follow-up, PTH levels fluctuated concomitantly with ionized calcium and phosphate levels over time in all patients. Time-dependent PTH levels were associated directly with duration of dialysis therapy and use of vitamin D and phosphate and albumin levels, but inversely with age and ionized calcium and magnesium levels (but not glucose or HbA1c levels). Interestingly, time-dependent PTH levels were independently associated with survival after adjusting for traditional risk factors (diabetes, age, albumin and creatinine levels, and URR) and duration of dialysis therapy. We conclude that in HD patients, relative hypoparathyroidism was not associated with diabetes per se. Time-dependent PTH levels were associated with age, duration of dialysis, and levels of ionized calcium, phosphate, albumin, and magnesium. Moreover, relative hypoparathyroidism at entry and lower time-dependent PTH levels predict mortality.


Mechanism of Yangxinshi Intervention on Cardiac Fibrosis in Diabetic Cardiomyopathy Based on Network Pharmacology.
Cardiac fibrosis (CF) is major myocardial change in diabetic cardiomyopathy (DCM). Yangxinshi as a Chinese medicine formula is used to treat cardiovascular diseases. However, the exact effective mechanism of Yangxinshi on CF is still uncertain. Hence, based on the pharmacological network, predicting the active components, potential targets and pathways of Yangxinshi on diabetic fibrosis require to be further studied. By using Cytoscape 3.6.0 Bisogenet plug-in, the active components of Yangxinshi were obtained and screened through TCMSP, and the PPI network of DCM-CF was constructed and then screened by CytoNCA plug-in. GO analysis and KEGG pathway enrichment analysis were carried out by Cluego plug-in. Combined with the results of network pharmacological analysis, cells in vitro were performed to verify the CF stimulated with high glucose or intervence with Yangxinshi, and the expressions of Cbl-b, p-smad2, and α-SMA were detected. Yangxinshi might play a key role in reversing cardiac fibrosis in individuals with DCM by regulating the signal pathway of CBL and promoted the expression of Cbl-b and inhibited the expression of p-smad2 and α-SMA, verifying some predictive work via network pharmacology. Based on network pharmacology, this study demonstrates that the beneficial effect of Yangxinshi on CF is related to the Cbl-b/smad2 pathway, providing an idea for the therapeutic effect of Yangxinshi on cardiac fibrosis in DCM.


Lead-Free Double Perovskite Cs2 AgInCl6.
Lead-free halide perovskites have drawn wide attention as alternatives to their toxic and poorly stable lead-based counterparts. Among them, double perovskites with Cs2 AgInCl6 composition, often doped with various elements, have been in the spotlight owing to their intriguing optical properties, namely, self-trapped exciton (STEs) emission and dopant-induced photoluminescence. This interest has sparked different synthesis approaches towards both crystals and nanocrystals, and the exploration of many alloy compositions with mono- and trivalent cations other than Ag+ and In3+ . In this Minireview we describe the recent developments on Cs2 AgInCl6 bulk crystals and nanocrystals, their synthesis strategies, intrinsic optical properties, and tunable photoluminescence originating from different alloying and doping effects. We also discuss progress on computational studies aimed at understanding the thermodynamic stability, the role of defects, and the origin of photoluminescence in relation to the STEs and the direct band gap character.


Sonar Objective Detection Based on Dilated Separable Densely Connected CNNs and Quantum-Behaved PSO Algorithm.
Underwater sonar objective detection plays an important role in the field of ocean exploration. In order to solve the problem of sonar objective detection under the complex environment, a sonar objective detection method is proposed based on dilated separable densely connected convolutional neural networks (DS-CNNs) and quantum-behaved particle swarm optimization (QPSO) algorithm. Firstly, the dilated separable convolution kernel is proposed to extend the local receptive field and enhance the feature extraction ability of the convolution layers. Secondly, based on the linear interpolation algorithm, a multisampling pooling (MS-pooling) operation is proposed to reduce the feature information loss and restore image resolution. At last, with contraction-expansion factor and difference variance in the traditional particle swarm optimization algorithm introduced, the QPSO algorithm is employed to optimize the weight parameters of the network model. The proposed method is validated on the sonar image dataset and is compared with other existing methods. Using DS-CNNs to detect different kinds of sonar objectives, the experiments shows that the detection accuracy of DS-CNNs reaches 96.98% and DS-CNNs have better detection effect and stronger robustness.


Design and modeling of a high resolution and high sensitivity PET brain scanner with double-ended readout.
In the wake of recent advancements in scintillator, photodetector, and low-noise fast electronics technologies, as well as in fast reconstruction software, positron emission tomography (PET) scanners have seen considerable improvements in spatial resolution, time resolution, and absolute sensitivity. To continue this trend, we present a helmet type PET brain scanner design that combines high solid angle coverage and double-ended readout of 30 mm-thick scintillator crystals to achieve excellent absolute sensitivity, depth of interaction resolution, and time resolution. This scanner comprises 598 detector arrays, each with 8 × 8 Lu1.8Y0.2SiO5:Ce (LYSO:Ce) crystals with dimensions 3.005 × 3.005 × 30 mm3one-to-one coupled on either end to silicon photomultipliers (SiPMs). Our Monte Carlo simulations based in the platform Geant4 predict that this scanner would attain an absolute sensitivity to a 35 cm line source placed at the center of the radial field of view of (17.1 ± 0.1)%, a depth of interaction resolution of (3.99 ± 0.05) mm, and a coincidence time resolution of (198 ± 5) ps. Our simulations also predict radial, tangential, and axial spatial resolutions at the center of the field of view of 3.3 mm, 3.1 mm, and 3.3 mm, respectively. As this set of simultaneous parameters compares favorably to today's most advanced clinical PET scanners and other proposed designs, this scanner has a good chance of becoming a preferred tool for high quality brain imaging.


Tyrosine-functionalized CuInS2 quantum dots as a fluorescence probe for the determination of biothiols, histidine and threonine.
A novel, rapid and highly sensitive fluorescence turn-on assay for the detection of biothiols (glutathione, and L-cysteine), histidine and threonine was developed. Water-soluble CuInS2 ternary quantum dots (QDs) capped by mercaptopropionic acid (MPA) were directly synthesized in aqueous solution, and then functionalized using tyrosine molecules to form tyrosine-functionalized CuInS2 QDs (T-CuInS2 QDs). The fluorescence of T-CuInS2 QDs would decrease in the presence of Cu(2+) due to the coordination effect of phenolic hydroxyls of the tyrosine molecules. Subsequently, the addition of biothiols (glutathione and L-cysteine), histidine or threonine could turn on the fluorescence of the T-CuInS2 QDs-Cu(2+) system due to their strong affinity for Cu(2+). The proposed method was simple in design and fast in operation, and it was applied for the detection of glutathione, L-cysteine, histidine, and threonine in human serum samples with satisfactory results.


[Hematopoietic potential of Flk-1(+) populations in mouse embryonic AGM region].
This study aimed to investigate the expression of Flk-1 on distinct hematopoietic precursor cells in E10.5 mouse AGM region. By flow cytometry, we found that < 10% of Flk-1(+) cells of E10.5 AGM region co-expressed CD41 and CD45/Ter119. Then, E10.5 AGM cells were fractionated into two subsets, the CD31(+)CD45(-)Ter119(-)Flk-1(+)CD41(+) cells (R1, putative immature hematopoietic cells) and the CD31(+)CD45(-)Ter119(-)Flk-1(+)CD41(-) cells (R2, putative endothelial cells), followed by methylcellulose-based CFU-C assay and OP9-based stromal co-culture to examine their myeloid or/and lymphoid potential in vitro. The results showed that only R1 cells could give rise to typical hematopoietic colonies in CFU-C assay. In contrast, after co-cultured with OP9 for 7-9 days, both subsets could generate abundant hematopoietic progenitor cells (CD45(+)c-Kit(+)), myeloid cells (Gr-1(+)/Mac-1(+)), erythroid cells (Ter119(+)), and B lymphocytes (CD19(+)). It is concluded that both maturing CD41(+)CD45(-) hematopoietic percursor cells and homogenic endothelial cells express Flk-1 in E10.5 AGM region. It requires further functional assay in vivo to clarify whether the hematopoietic stem cells (HSCs) and their precursors retain Flk-1 expression at this developmental stage.


Cardiac calcification in acute intermittent porphyria.
Aetiology of pericardial calcifications can be multifactorial. Tuberculosis has been reported as the most common cause. Other known causes include uraemia, asbestosis, post-traumatic or postoperative. We report a rare case of pericardial calcification seen in a patient with established acute intermittent porphyria. A direct causal relationship cannot be established between porphyria and pericardial calcification, but it may be due to deposition of the porphyrin in the pericardium.


Comparison of Six Lytic Polysaccharide Monooxygenases from Thermothielavioides terrestris Shows That Functional Variation Underlies the Multiplicity of LPMO Genes in Filamentous Fungi.
Lytic polysaccharide monooxygenases (LPMOs) are mono-copper enzymes that oxidatively degrade various polysaccharides. Genes encoding LPMOs in the AA9 family are abundant in filamentous fungi while their multiplicity remains elusive. We describe a detailed functional characterization of six AA9 LPMOs from the ascomycetous fungus Thermothielavioides terrestris LPH172 (syn. Thielavia terrestris). These six LPMOs were shown to be upregulated during growth on different lignocellulosic substrates in our previous study. Here, we produced them heterologously in Pichia pastoris and tested their activity on various model and native plant cell wall substrates. All six T. terrestris AA9 (TtAA9) LPMOs produced hydrogen peroxide in the absence of polysaccharide substrate and displayed peroxidase-like activity on a model substrate, yet only five of them were active on selected cellulosic substrates. TtLPMO9A and TtLPMO9E were also active on birch acetylated glucuronoxylan, but only when the xylan was combined with phosphoric acid-swollen cellulose (PASC). Another of the six AA9s, TtLPMO9G, was active on spruce arabinoglucuronoxylan mixed with PASC. TtLPMO9A, TtLPMO9E, TtLPMO9G, and TtLPMO9T could degrade tamarind xyloglucan and, with the exception of TtLPMO9T, beechwood xylan when combined with PASC. Interestingly, none of the tested enzymes were active on wheat arabinoxylan, konjac glucomannan, acetylated spruce galactoglucomannan, or cellopentaose. Overall, these functional analyses support the hypothesis that the multiplicity of the fungal LPMO genes assessed in this study relates to the complex and recalcitrant structure of lignocellulosic biomass. Our study also highlights the importance of using native substrates in functional characterization of LPMOs, as we were able to demonstrate distinct, previously unreported xylan-degrading activities of AA9 LPMOs using such substrates. IMPORTANCE The discovery of LPMOs in 2010 has revolutionized the industrial biotechnology field, mainly by increasing the efficiency of cellulolytic enzyme cocktails. Nonetheless, the biological purpose of the multiplicity of LPMO-encoding genes in filamentous fungi has remained an open question. Here, we address this point by showing that six AA9 LPMOs from a single fungal strain have various substrate preferences and activities on tested cellulosic and hemicellulosic substrates, including several native xylan substrates. Importantly, several of these activities could only be detected when using copolymeric substrates that likely resemble plant cell walls more than single fractionated polysaccharides do. Our results suggest that LPMOs have evolved to contribute to the degradation of different complex structures in plant cell walls where different biomass polymers are closely associated. This knowledge together with the elucidated novel xylanolytic activities could aid in further optimization of enzymatic cocktails for efficient degradation of lignocellulosic substrates and more.


Synergistic Effects of Heavy Metals and Pesticides in Living Systems.
There is a widespread repeated exposure of the population to the pesticides and heavy metals of occupational and environmental origin. Such population is forced to undergo continuous stress imposed by combined exposure of the heavy metals and different classes of the pesticides used in agricultural as well as health practices. The existing reports from several workers have indicated that heavy metals and pesticides in combination may lead more severe impact on the human health when compared to their individual effects. Such a combination of pesticides and heavy metals may also change or influence the detection of exposure. Several studies in past have shown the synergistic toxic effects of heavy metals and pesticides. Such evaluations have revealed the synergistic interactions of various heavy metals and pesticides in animals as well as humans. The aim of the present article is to provide a synthesis of existing knowledge on the synergistic effects of heavy metal and pesticides in living systems. The information included in this article may be useful for different environment protection agencies and policy makers to consider the combined effects of heavy metals and pesticides on humans while designing strategies toward environmental protection and safety regulations about human health.


Protein structure-function exploration initiative in undergraduate biochemistry and independent research courses.
Protein structure-function relationship serves as the primary learning outcome in any undergraduate biochemistry course. We expanded the protein structure-function exploration, PSFE initiative during COVID-19 to provide more effective and engaging experience to our undergraduates in biochemistry and independent research courses. Multiple alignments of protein sequences provided crucial insight into sequence conservation across many species and thus allow identification of those sections of the sequence most critical to protein function. We used Anabaena Sensory Rhodopsin, ASR its transducer, ASRT and downstream novel kinase gene products of Anabaena PCC 7120 to seek their alignment with homologs in available database. Pymol served an opportunity to achieve this goal (interactive learning during lab session and stimulation of course content discussion) in interesting ways. The PSFE initiative expansion continued during pandemic using online/hybrid modality. Initially model examples all helical ASR and beta-sheet ASRT were introduced to connect and integrate our ongoing research interest into classroom activities. Subsequently, undergraduates in biochemistry course were assigned a homolog of model proteins any particular protein of students choice to study and characterize using Pymol in semester. During first phase, each undergraduate worked independently using established guidelines. Student's exploration progress was periodically reviewed in pilot phase with majority of students who perceived it as challenging task successfully completed the assignment. Using the PyMol application to reinforce visual understanding of protein structure was highly satisfying experience that greatly enriched undergraduates understanding and appreciation. This article reports a session from the virtual international 2021 IUBMB/ASBMB workshop, "Teaching Science on BigData."


Gene alterations in the PI3K/PTEN/AKT pathway as a mechanism of drug-resistance (review).
The most common therapeutic approach for many cancers is chemotherapy. However, many patients relapse after treatment due to the development of chemoresistance. Recently, targeted therapies represent novel approaches to destroy cancer cells. The PI3K/PTEN/AKT pathway is a key signaling pathway involved in the regulation of cell growth. Dysregulated signaling of this pathway may be associated with activating mutations of PI3K-related genes. Analyses of these mutations reveal that they increase the PI3K signal, stimulate downstream Akt signaling, promote growth factor-independent growth and increase cell invasion and metastasis. In this review, we summarize the PI3K/PTEN/AKT pathway genetic alterations in cancer and their potential clinical applications.


LncRNA AWPPH participates in the metastasis of non-small cell lung cancer by upregulating TGF-β1 expression.
Long non-coding RNA (lncRNA) AWPPH is a characterized oncogenic lncRNA in hepatocellular carcinoma and bladder cancer. The aim of the present study was to investigate the potential involvement of AWPPH in non-small cell lung cancer (NSCLC). Expression of AWPPH in lung biopsy tissues and serum of both healthy controls and patients with NSCLC with different tumor sizes, and with and without distant tumor metastasis was detected by reverse transcription-quantitative PCR. AWPPH expression vector was constructed and transfected into cells of human NSCLC cell lines. Expression of TGF-β1 was detected by western blot analysis. Cell migration and invasion were detected by Transwell migration and invasion assay. It was observed that AWPPH was significantly upregulated in patients with NSCLC, while AWPPH expression level did not increase with the increase of tumor size. In contrast, AWPPH expression levels were significantly higher in patients with distant metastasis than in patients without tumor distant metastasis. AWPPH overexpression promoted TGF-β1 expression in NSCLC cells, while TGF-β1 treatment showed no significant effects on AWPPH expression. AWPPH overexpression promoted NSCLC cell migration and invasion, while TGF-β signaling inhibition reduced this enhancing effect. Therefore, AWPPH may promote the metastasis, but not the growth of NSCLC by upregulating TGF-β1 expression.


AcrHub: an integrative hub for investigating, predicting and mapping anti-CRISPR proteins.
Anti-CRISPR (Acr) proteins naturally inhibit CRISPR-Cas adaptive immune systems across bacterial and archaeal domains of life. This emerging field has caused a paradigm shift in the way we think about the CRISPR-Cas system, and promises a number of useful applications from gene editing to phage therapy. As the number of verified and predicted Acrs rapidly expands, few online resources have been developed to deal with this wealth of information. To overcome this shortcoming, we developed AcrHub, an integrative database to provide an all-in-one solution for investigating, predicting and mapping Acr proteins. AcrHub catalogs 339 non-redundant experimentally validated Acrs and over 70 000 predicted Acrs extracted from genome sequence data from a diverse range of prokaryotic organisms and their viruses. It integrates state-of-the-art predictors to predict potential Acrs, and incorporates three analytical modules: similarity analysis, phylogenetic analysis and homology network analysis, to analyze their relationships with known Acrs. By interconnecting all modules as a platform, AcrHub presents enriched and in-depth analysis of known and potential Acrs and therefore provides new and exciting insights into the future of Acr discovery and validation. AcrHub is freely available at http://pacrispr.erc.monash.edu/AcrHub/.


Fear of Crime among Female North Korean Defectors in South Korea.
Although some studies have focused on immigrants' fear of crime in the United States, it is important to point out that the number of North Korean defectors to South Korea has rapidly increased since the 1990s. Therefore, understanding factors associated with fear of crime for North Korean immigrants, especially female defectors, is important for ensuring their successful transitions into South Korean culture. The present study used existing survey data from a sample of female North Korean defectors to explore factors related to fear of crime. Results indicate that the number of North Korean friends, language proficiency, and patriarchal attitudes toward gender were significant predictors of fear of crime for the North Korean female defectors. Findings are described and discussed as a potential source for policymaking to reduce North Korean immigrants' acculturative stress and fear of crime and to encourage smooth transitions into new cultures.


Compartmentalization of aquaporins in the human intestine.
Improper localization of water channel proteins called aquaporins (AQP) induce mucosal injury which is implicated in Crohn's disease and ulcerative colitis. The amino acid sequences of AQP3 and AQP10 are 79% similar and belong to the mammalian aquaglyceroporin subfamily. AQP10 is localized on the apical compartment of the intestinal epithelium called the glycocalyx while AQP3 is selectively targeted to the basolateral membrane. Despite the high sequence similarity and evolutionary relatedness, the molecular mechanism involved in the polarity, selective targeting and function of AQP3 and AQP10 in the intestine is largely unknown. Our hypothesis is that the differential polarity and selective targeting of AQP3 and AQP10 in the intestinal epithelial cells is influenced by amino acid signal motifs. We performed sequence and structural alignments to determine differences in signals for localization and posttranslational glycosylation. The basolateral sorting motif "YRLL" is present in AQP3 but absent in AQP10; while Nglycosylation signals are present in AQP10 but absent in AQP3. Furthermore, the C-terminal region of AQP3 is longer compared to AQP10. The sequence and structural differences between AQP3 and AQP10 provide insights into the differential compartmentalization and function of these two aquaporins commonly expressed in human intestines.


Elusive trypanosomes.
Professor Kershaw's encouragement of the development of anion-exchange separation of African trypanosomes from blood led to two decades of activity when, for the first time, considerable progress was made in the intrinsic characterization of these parasites. Such characterization depended on establishing high infections in laboratory rodents. However, the collection of samples from the field was restricted by the failure of certain trypanosomes either to infect, or to multiply adequately in, rodents. More recently, in vitro culture has come to play an increasingly important role in producing material. By obtaining procyclic forms directly from wild tsetse flies, or by transforming low numbers of bloodstream forms in field samples to the procyclic phase in experimental tsetse, trypanosomes of poor or nil infectivity to rodents were readily cultured in the large amounts required for biochemical characterization. A number of specimens of a new kind of Nannomonas, of Trypanosoma simiae, of T. grayi, and of an antigenically distinct T. brucei gambiense were found. Evidence is presented that many other kinds of trypanosome may be eluding isolation by their inability to infect rodents.


Pet ownership among persons with AIDS in three Florida counties.
Interviews were conducted among 408 adults with acquired immunodeficiency syndrome at three local health departments to determine the proportion who owned pets, their perceived attachment to their pets, and the proportion who were informed about zoonoses. Nearly half (187, or 46%) were living with pets, most commonly dogs (64%), followed by cats (38%), fish (15%), birds (8%), reptiles (3%), and rodents (2%). Most pet owners (81%) reported an attachment to their pet. Only 10% were informed of zoonoses, albeit some incorrectly. Health care providers should recognize the high pet ownership rate among persons infected with human immunodeficiency virus and correctly inform their patients of strategies to sustain a low zoonotic disease incidence.


Expression and function of vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, and their receptors in the human adrenal gland.
VIP and pituitary adenylate cyclase-activating polypeptide (PACAP) are two regulatory peptides that possess remarkable amino acid sequence homology and act through common receptors, named PAC(1), VPAC(1), and VPAC(2). PAC(1) receptor is selective for PACAP, whereas VPAC(1) and VPAC(2) receptors bind both VIP and PACAP. We have investigated the expression and function of VIP, PACAP, and their receptors in the zona glomerulosa (ZG), zonae fasciculata and reticularis, and adrenal medulla (AM) of the human adrenal cortex. RT-PCR and RIA detected VIP and PACAP expression exclusively in AM cells. RT-PCR demonstrated the presence of PAC(1) mRNA only in AM and of VPAC(1) and VPAC(2) mRNAs in both ZG and AM cells. VIP and PACAP concentration-dependently increased aldosterone and catecholamine secretion from cultured ZG and AM cells. The catecholamine response to both peptides was higher than the aldosterone response, and the secretagogue action of PACAP was more intense than that of VIP. The aldosterone response of cultured ZG cells to VIP or PACAP was unaffected by the PAC(1) receptor antagonist PACAP-(6-38) (PAC(1)-A), but was significantly decreased by the VPAC(1) receptor antagonist [Ac-His(1),D-Phe(2),Lys(15),Arg(16)]VIP-(3-7),GH-releasing factor-(8-27)-NH(2) (VPAC(1)-A). The catecholamine response of cultured AM cells to VIP was lowered by VPAC(1)-A and unaffected by PAC(1)-A; conversely, the catecholamine response to PACAP was reduced by both PAC(1)-A and VPAC(1)-A. Simultaneous exposure to both antagonists did not abolish the catecholamine response to PACAP. Collectively, our findings allow us to conclude that in human adrenals 1) VIP and PACAP biosynthesis exclusively occurs in AM cells; 2) ZG cells are provided with functional VPAC(1) and VPAC(2) receptors, whose activation by VIP or PACAP elicits a moderate aldosterone response; 3) AM cells possess PAC(1), VPAC(1), and VPAC(2) receptors, whose activation evokes a marked catecholamine response; and 4) the catecholamine response to PACAP is more intense than that to VIP, because it is mediated by all subtypes of VIP/PACAP receptors.


Structure-based modeling of the functional HIV-1 intasome and its inhibition.
The intasome is the basic recombination unit of retroviral integration, comprising the integrase protein and the ends of the viral DNA made by reverse transcription. Clinical inhibitors preferentially target the DNA-bound form of integrase as compared with the free protein, highlighting the critical requirement for detailed understanding of HIV-1 intasome structure and function. Although previous biochemical studies identified integrase residues that contact the DNA, structural details of protein-protein and protein-DNA interactions within the functional intasome were lacking. The recent crystal structure of the prototype foamy virus (PFV) integrase-viral DNA complex revealed numerous details of this related integration machine. Structures of drug-bound PFV intasomes moreover elucidated the mechanism of inhibitor action. Herein we present a model for the HIV-1 intasome assembled using the PFV structure as template. Our results pinpoint previously identified protein-DNA contacts within the quaternary structure and reveal hitherto unknown roles for Arg20 and Lys266 in DNA binding and integrase function. Models for clinical inhibitors bound at the HIV-1 integrase active site were also constructed and compared with previous studies. Our findings highlight the structural basis for HIV-1 integration and define the mechanism of its inhibition, which should help in formulating new drugs to inhibit viruses resistant to first-in-class compounds.


The role of laser therapy in the palliative treatment of esophageal cancer.
Laser has become in the recent years an important therapeutic tool for treating esophageal cancer in a palliative setting aiming to reopen the tumor stenosis. The literature shows that the initial enthusiasm for laser, compared with other methods--especially endoprosthesis--has somewhat been tempered because the success rate in restoring a normal food intake was lower than expected (65-68%). Although the complication rate is low, repeated therapy sessions are needed to maintain the lumen open. This constitutes a major drawback in terms of patient acceptability. Variations in the therapeutical methods (contact laser, photodynamic therapy, ...) have not added up to now significant value to laser therapy. Specific indications for laser therapy versus endoprosthesis are discussed and should bring both therapeutic modalities to a more considered application.


Recent Progress in Three-Terminal Artificial Synapses: From Device to System.
Synapses are essential to the transmission of nervous signals. Synaptic plasticity allows changes in synaptic strength that make a brain capable of learning from experience. During development of neuromorphic electronics, great efforts have been made to design and fabricate electronic devices that emulate synapses. Three-terminal artificial synapses have the merits of concurrently transmitting signals and learning. Inorganic and organic electronic synapses have mimicked plasticity and learning. Optoelectronic synapses and photonic synapses have the prospective benefits of low electrical energy loss, high bandwidth, and mechanical robustness. These artificial synapses provide new opportunities for the development of neuromorphic systems that can use parallel processing to manipulate datasets in real time. Synaptic devices have also been used to build artificial sensory systems. Here, recent progress in the development and application of three-terminal artificial synapses and artificial sensory systems is reviewed.


Linking Crohn's disease health status measurements with International Classification of Functioning, Disability and Health and vocational rehabilitation outcomes.
The International Classification of Functioning, Disability and Health (ICF) serves as a unifying model for rehabilitation medicine. Variables of the health status measurements, the Crohn's Disease Activity Index and the Harvey-Bradshaw Index, have not been linked with the ICF categories and compared with other predictors of rehabilitation outcomes. Crohn's Disease Activity Index variables were linked with ICF categories using linking rules. A chart review included the patients of our in-patient rehabilitation centre during one year (n=355) with International Classification of Disease Codes for Crohn's disease (ICD K50). We identified variables linked with clinical improvement (decrease in the Harvey-Bradshaw Index of > or = 2 U) and rehabilitation success (conversion from unfit-to-work to fit-to-work) by multivariate logistic regression. The ICF component, activities and participation, was not represented in the Crohn's Disease Activity Index and the Harvey-Bradshaw Index. A Harvey-Bradshaw Index > or = 5 U was associated with clinical improvement during rehabilitation (odds ratio 5.65 (95% CI 3.41-9.35)). Normal C-reactive protein (odds ratio 2.8 (95% CI 1.1-7.0)) and higher body mass index (odds ratio (per 1 kg/m2 increase) 1.1 (95% CI 1.0-1.2)), but not Harvey-Bradshaw Index, were associated with vocational rehabilitation success in 124 patients who were initially unfit-to-work. Variables representing activities and participation as well as immune functions may improve Crohn's disease health status measurements on the basis of better prediction of vocational rehabilitation success.