The relation between sex drive and sexual attraction to men and women: a cross-national study of heterosexual, bisexual, and homosexual men and women.
Recent research suggests that, for most women, high sex drive is associated with increased sexual attraction to both women and men. For men, however, high sex drive is associated with increased attraction to one sex or the other, but not to both, depending on men's sexual orientation (Lippa, R. A., 2006, Psychological Science, 17, 46-52). These findings were replicated in a very large BBC data set and were found to hold true in different nations, world regions, and age groups. Consistent with previous research, lesbians differed from other women in showing the male-typical pattern, that high sex drive is associated with attraction to one sex but not the other. Bisexual women and men were more similar to same-sex heterosexuals than to same-sex homosexuals in their pattern of results. The correlation between same-sex and other-sex attraction was consistently negative for men, was near zero for heterosexual and bisexual women, and negative for lesbians. Thus, same-sex and other-sex attractions were, in general, more bipolar and mutually exclusive for men than for women. The current findings add to evidence that sexual orientation is organized differently in women and men and suggest a biological component to this difference.


Pivotal role of O-antigenic polysaccharide display in the sensitivity against phage tail-like particles in environmental Pseudomonas kin competition.
Environmental pseudomonads colonize various niches including insect and plant environments. When invading these environments, bacteria are confronted with the resident microbiota. To oppose with closely related strains, they rely on narrow-spectrum weaponry such as tailocins, i.e., phage tail-like particles. Little is known about the receptors for these tailocins especially among phylogenetically closely related species. Here, we studied the interaction between an R-tailocin from Pseudomonas protegens CHA0 and a targeted kin, Pseudomonas protegens Pf-5. Using genome-wide transposon insertion sequencing, we identified that lipopolysaccharides are involved in the sensitivity of Pf-5 towards the tailocin of CHA0. By generating Pf-5 lipopolysaccharide mutants and exposing them to extracted tailocin, we specified the two O-antigenic polysaccharides (O-PS) targeted by the tailocin. We affirmed the role of these O-PS through competition assays in vitro as well as in insects. Further, we demonstrate that O-PS are double-edge swords that are responsible for the sensitivity of P. protegens towards tailocins and phages produced by their kin, but shield bacteria from the immune system of the insect. Our results shed light on the trade-off that bacteria are confronted with, where specific O-PS decorations can both be of benefit or disadvantage depending on the host environment and its bacterial inhabitants.


Caught Between a Well-Intentioned State and a Hostile Federal System: Local Implementation of Inclusive Immigrant Policies.
Policy Points Inclusive state immigrant policies that expand rights and resources for immigrants may improve population health, but little is known about their local-level implementation. Local actors that have anti-immigrant attitudes can hinder the implementation of state policies, whereas the persistent influence of anti-immigrant federal policies reinforces barriers to accessing health and other resources granted by state policies. Local actors that serve immigrants and support state policy implementation lack the resources to counter anti-immigrant climates and federal policy threats. In the United States, inclusive state-level policies can advance immigrant health and health care access by extending noncitizens' access to public benefits, workplace rights, and protections from immigration enforcement. Although state policies carry promise as structural population health interventions, there has been little examination of their implementation at the local level. Local jurisdictions play multiple roles in state policy implementation and possess distinct immigration climates. Examining the local implementation of state immigrant policy can address challenges and opportunities to ensure the health benefits of inclusive policies are realized equitably across states' regions. To examine the local implementation of state immigrant policies, we selected a purposive sample of California counties with large immigrant populations and distinct social and political dynamics and conducted and analyzed in-depth interviews with 20 community-based organizations that provided health, safety net, and other services. We found that there were tensions between the inclusionary goals of state immigrant policies and local anti-immigrant climates and federal policy changes. First, there were tensions between state policy goals and resistance from local law enforcement agencies and policymakers (e.g., Board of Supervisors). Second, because of the ongoing threats from federal immigration policies, there was a mismatch between the services and resources provided by state policies and local community needs. Finally, organizations that served immigrants were responsible for contributing to policy implementation but lacked resources to meet community needs while countering local resistance and federal policy threats. This study contributes knowledge regarding the challenges that emerge after state immigrant policies are enacted. The tensions among state immigrant policies, local immigration climates, and federal policy changes indicate that state immigrant policies are not implemented equally across state communities, resulting in challenges and limited benefits from policies for many immigrant communities.


[Implantology in the general practice; management and efficiency].
In order to get successful dental implants, knowledge and routine in this field are prerequisites. Moreover, the efficiency demands an adequate organization of the dental office with clear protocols. Success depends also upon hygienic measurements.


Pathophysiology of dystonia: a neuronal model.
Dystonia has commonly been thought to represent a disorder of basal ganglia function. Although long considered a hyperkinetic movement disorder, the evidence to support such a classification was based on the presence of excessive involuntary movement, not on physiological data. Only recently, with the return of surgical procedures using microelectrode guidance for the treatment of dystonia, has electrophysiological data demonstrated an alteration in mean discharge rate, somatosensory responsiveness and the pattern of neuronal activity in the basal ganglia thalamocortical motor circuit. Previous models of dystonia suggested that reduced mean discharge rates in the globus pallidus internus (GPi) led to unopposed increases in activity in the thalamocortical circuit that precipitated the development of involuntary movement associated with dystonia. This model has subsequently been modified given the clear improvement in dystonic symptoms following lesions in the GPi, a procedure that is associated with a further reduction in pallidal output. The improvement in dystonia following pallidal lesions is difficult to reconcile with the "rate" hypothesis for hypokinetic and hyperkinetic movement disorders and has led to the development of alternative models that, in addition to rate, incorporate changes in pattern, somatosensory responsiveness and degree of synchronization of neuronal activity. Present models of dystonia, however, must not only take these changes into account but must reconcile these changes with the reported changes in cortical excitability reported with transcranial magnetic stimulation, the changes in metabolic activity in cortical and subcortical structures documented by positron emission tomography (PET), and the alterations in spinal and brainstem reflexes. A model incorporating these changes together with the reported changes in neuronal activity in the basal ganglia and thalamus is presented.


Peptide electron transfer: more questions than answers.
Nature has specifically designed proteins, as opposed to DNA, for electron transfer. There is no doubt about the electron transfer within proteins compared with the uncertain and continuing debate about charge transfer through DNA. However, the exact mechanism of electron transfer within peptide systems has been a source of controversy. Two different mechanisms for electron transfer between a donor and an acceptor, electron hopping and bridge-assisted superexchange, have been proposed, and are supported by experimental evidence and theoretical calculations. Several factors were found to affect the kinetics of this process, including peptide chain length, secondary structure and hydrogen bonding. Electrochemical measurements of surface-supported peptides have contributed significantly to the debate. Here we summarize the current approaches to the study of electron transfer in peptides with a focus on surface measurements and comment on these results in light of the current and often controversial debate on electron transfer mechanisms in peptides.


Changes in nature and antibiotic resistance of bacteria causing peritonitis in cirrhotic patients over a 20 year period.
To assess all clinically and bacteriologically documented episodes of spontaneous bacterial peritonitis diagnosed in a single unit over a 20 year period, to identify changes in the nature and antibiotic resistance of the causative bacteria. A specialist liver disease unit in a tertiary care centre. Cultured ascitic fluid obtained in the course of 240 consecutive episodes of clinically and bacteriologically proven spontaneous bacterial peritonitis. Patient recruitment remained stable during the 20 year period in terms of the number of cirrhotic patients admitted and the severity of their condition. 78.7% of isolates were Enterobacteriaceae (Escherichia coli in 51%) and 19% were Gram positive cocci. Until 1979 all the Enterobacteriaceae had the wild phenotype, compared with only 50% at the end of the study period. Since 1993, 22% of Enterobacteriaceae have been resistant to third generation cephalosporins. Methicillin resistant staphylococci were only isolated after 1989. Changes in the epidemiology and antibiotic resistance of bacteria causing spontaneous bacterial peritonitis must be monitored for optimal treatment.


Role of Laksha Churna and Madhu Pratisarana after ultrasonic scaling in the management of Dantasharkara (dental calculus): An open-label, standard controlled randomized clinical trial.
Dental calculus is one of the major problems in dentistry, which is characterized by calcified mass that forms on and adheres to the surface of teeth resulting in bad breath, receding gums and chronically inflamed gingiva. It can be correlated with Dantasharkara (dental calculus), which is characterized by the collection of hardened accumulation of Mala (tartar) at the junction of teeth and gums. Ultrasonic scalars are used for the removal of dental calculus for convenience. In texts, Laksha Churna (powder of Laccifer lacca Kerr) has been mentioned as Vranaropaka (wound healing) and indicated for the eliminating plaque through cleaning and polishing tooth surfaces. This study was aimed to evaluate the clinical efficacy of local application of Laksha Churna and Madhu (honey) Pratisarana after Dantasharkara Nirharana (scaling of dental calculus) in the management of Dantasharkara (dental calculus). Patients having calculus deposition, fulfilling the inclusion criteria were selected. In group A, Pratisarana with Laksha Churna (powder) 1 g and Madhu as per requirement was given, whereas in group B, chlor-hexidine gluconate 0.2% for gargling was given for 2 weeks. Ultrasonic scaling was done in both groups before given trial drugs. The outcomes were calculated on the base on changes in score of the subjective parameters like pain, inflammation of gum, bleeding gums, halitosis as well as objective parameters like oral hygiene index, debris index, calculus index, gingival index, and periodontal index. For analysing the effect of the result, Wilcoxon signed-rank test for nonparametric paired data and paired t-test for quantitative parametric paired data was applied. After analysing the data, it was found that Ultrasonic scaling of dental calculus followed by Pratisaraņa of honey with Laksha Churna provided statistically significant improvement in calculus index (97.77%) in debris index (84.44%), in oral hygiene index(96.66%), in gingival index (83.33%)and showed 96.15% improvement in periodontal index, whereas Ultrasonic scaling of dental calculus followed by gargling with chlorhexidine gluconate 0.2% provided 80% improvement in calculus index, 70% in debris index, 90% in oral hygiene index, in gingival index by 73.06%, and 93.75% improvement periodontal index which was statistically significant. The present study indicates Dantasharkara Nirharana followed by Pratisarana of Laksha Churna and Madhu is comparatively more effective than conventional standard treatment protocol (ultrasonic scaling and chlorhexidine gluconate mouth wash) in the management of dental calculus.


[Resident physicians' participation to the activities of the hospital hygiene unit in a teaching hospital: a pilot study].
The Hospital Hygiene Unit ensures hospital patient safety, through surveillance and control of environmental conditions of risk. In this context, resident physicians in Hygiene and Preventive Medicine of the Catholic University of the Sacred Heart (UCSC) are required to attend the unit to acquire professional skills, for two months (four weeks in the first year of residency and four weeks in the second year). In the initial phase of the rotation, residents are acquainted with the organization and assigned activities. Ongoing meetings with the tutor take place to verify the progress of activities in which they are involved; verification of acquired skills is performed at the end of the period of attendance. The aim of the study was to evaluate resident doctors' opinions about their training experience, in order to assess the perceived quality and pursue continuous improvement of the training program. A questionnaire was administered to resident physicians attending the first three years of residency; the survey consisted of 11 multiple choice questions on organization, attendance, training and overall satisfaction and 3 open-ended questions on strengths, weaknesses and proposals for improvement. Fourteen of 15 residents (93.3%) completed the questionnaire: seven were male, five were first-year residents, five were second-year and four were third-year residents. Overall, 78% gave a positive assessment of the quality of training; in particular, 11 of 14 residents reported that the experience was very relevant to their training in Hygiene and Preventive Medicine. Responses regarding the training organization were also mostly positive (75%), as were those regarding attendance (57%) and overall satisfaction (67%). Fifty percent reported difficulties in combining this internship with the other activities planned with their tutor. Positive opinions prevail in all areas of assessment, although there are some aspects that can be improved, including the possibility to extend the period of attendance. Overall, training activities at the Operative Unit of Hospital Hygiene are appreciated by resident physicians, who consider them an important opportunity for professional growth.


Discrimination between modes of toxic action of phenols using rule based methods.
Rule-based ensemble modelling has been used to develop a model with high accuracy and predictive capabilities for distinguishing between four different modes of toxic action for a set of 220 phenols. The model not only predicts the majority class (polar narcotics) well but also the other three classes (weak acid respiratory uncouplers, pro-electrophiles and soft electrophiles) of toxic action despite the severely skewed distribution among the four investigated classes. Furthermore, the investigation also highlights the merits of using ensemble (or consensus) modelling as an alternative to the more traditional development of a single model in order to promote robustness and accuracy with respect to the predictive capability for the derived model.


Charge transfer versus molecular conductance: molecular orbital symmetry turns quantum interference rules upside down.
Destructive quantum interference has been shown to strongly reduce charge tunneling rates across molecular bridges. The current consensus is that destructive quantum interference occurs in cross-conjugated molecules, while linearly conjugated molecules exhibit constructive interference. Our experimental results on photoinduced charge transfer in donor-bridge-acceptor systems, however, show that hole transfer is ten times faster through a cross-conjugated biphenyl bridge than through a linearly conjugated biphenyl bridge. Electronic structure calculations reveal that the surprisingly low hole transfer rate across the linearly conjugated biphenyl bridge is caused by the presence of destructive instead of constructive interference. We find that the specific molecular orbital symmetry of the involved donor and acceptor states leads to interference conditions that are different from those valid in single molecule conduction experiments. Furthermore, the results indicate that by utilizing molecular orbital symmetry in a smart way new opportunities of engineering charge transfer emerge.


Fast detection of hydrogen with nano fiber tapers coated with ultra thin palladium layers.
We report a miniature hydrogen sensor that consists of a subwavelength diameter tapered optical fiber coated with an ultra thin palladium film. The optical properties of the palladium layer changes when the device is exposed to hydrogen. Consequently, the absorption of the evanescent waves also changes. The sensor was tested in a simple light transmission measurement setup that consisted of a 1550 nm laser diode and a photodetector. Our sensor is much smaller and faster than other optical hydrogen sensors reported so far. The sensor proposed here is suitable for detecting low concentrations of hydrogen at normal conditions.


Therapy with and mechanisms of nonsteroidal anti-inflammatory drugs.
Nonsteroidal anti-inflammatory drugs have anti-inflammatory, analgesic, and antipyretic properties. Although most nonsteroidal anti-inflammatory drugs inhibit prostaglandin synthesis, these agents also have important pharmacologic actions unrelated to their effects on prostaglandins. Among these properties is the ability to inhibit the release of mediators of inflammation from neutrophils and macrophages. These effects are due to the ability of nonsteroidal anti-inflammatory drugs to intercalate into the lipid bilayer of the plasma membrane and thereby disrupt protein-protein and protein-lipid interactions critical for cell responses (eg, calcium translocations, membrane phospholipid turnover). Our data, for example, indicate that nonsteroidal anti-inflammatory drugs exert direct inhibitory actions at the regulatory GTP protein (G protein) within the plasma membrane. This exhibit examines the evidence for diverse mechanisms of action of nonsteroidal anti-inflammatory drugs including effects directed at the G protein as well as new evidence that nonsteroidal anti-inflammatory drugs regulate the expression of the cyclooxygenase enzyme at the level of gene transcription.


The management of bipolar disorder in general practice.
General practitioners have a key role in managing patients with bipolar disorder, a condition which affects at least one in 200 Australians each year and is the sixth leading cause of disability in the population. Although diagnosis and treatment of the illness is complex, effective treatment can lead to good outcomes for many patients. GPs can contribute significantly to early recognition of bipolar disorder, avoiding the long delays in accurate diagnosis that have been reported. As in other complex recurrent or persistent illnesses, GPs are well placed to coordinate multidisciplinary "shared care" with specialists and other health care professionals. GPs also provide continuing general medical care for patients with bipolar disorder, and are in a unique position to understand patients' life circumstances and to monitor their progress over time. The last decade has seen many advances in medication for bipolar disorder, including the introduction of new therapies and the refinement of treatment protocols using older medications. There has also been increasing recognition of the contribution of psychological therapies to symptom relief, relapse prevention, optimal function, and quality of life.


Metabolic costs of amino acid and protein production in Escherichia coli.
Escherichia coli is the most popular microorganism for the production of recombinant proteins and is gaining increasing importance for the production of low-molecular weight compounds such as amino acids. The metabolic cost associated with the production of amino acids and (recombinant) proteins from glucose, glycerol and acetate was determined using three different computational techniques to identify those amino acids that put the highest burden on the biosynthetic machinery of E. coli. Comparing the costs of individual amino acids, we find that methionine is the most expensive amino acid in terms of consumed mol of ATP per molecule produced, while leucine is the most expensive amino acid when taking into account the cellular abundances of amino acids. Moreover, we show that the biosynthesis of a large number of amino acids from glucose and particularly from glycerol provides a surplus of energy, which can be used to balance the high energetic cost of amino acid polymerization.


Distinct and opposite profiles of connectivity during self-reference task and rest in youth at clinical high risk for psychosis.
Self-reference is impaired in psychotic disorders such as schizophrenia, associated with disability, and closely related to characteristic patterns of aberrant brain connectivity. However, at present, it is unclear whether self-reference is impacted in pathogenesis of the disorder. Alterations in connectivity during a self-reference task or resting-state in the psychosis risk (i.e., prodromal) period may yield important clues for biomarker development, as well as for novel treatment targets. This study examined a task-based and resting-state functional magnetic resonance imaging in individuals at clinical high risk (CHR) for psychosis (n = 22) and healthy control unaffected peers (n = 20). The self-reference task comprised three task conditions where subjects were asked if an adjective was relevant to themselves (self), a designated other individual (other), or to evaluate the word's spelling (letter). Connectivity analyses examined medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC), regions commonly found in conjunction analyses of self-reference, during both the self-reference task and rest. In task connectivity analyses, CHR individuals exhibited decreased mPFC-PCC connectivity when compared to controls. In resting-state analyses, CHR participants showed greater mPFC-PCC connectivity. Taken together, results suggest that psychosis-like alterations in mPFC-PCC connectivity is present prior to psychosis onset across both task and rest.


In vivo and in vitro validation of reference tissue models for the mGluR(5) ligand [(11)C]ABP688.
The primary objective of this study was to verify the suitability of reference tissue-based quantification methods of the metabotropic glutamate receptor type 5 (mGluR(5)) with [(11)C]ABP688. This study presents in vivo (Positron Emission Tomography (PET)) and in vitro (autoradiography) measurements of mGluR(5) densities in the same rats and evaluates both noninvasive and blood-dependent pharmacokinetic models for the quantification of [(11)C]ABP688 binding. Eleven rats underwent [(11)C]ABP688 PET scans. In five animals, baseline scans were compared with blockade experiments with the antagonist 1,2-methyl-6-(phenylethynyl)-pyridine (MPEP), and arterial blood samples were drawn and corrected for metabolites. Afterward, saturation-binding autoradiography was performed. Blocking with MPEP resulted in an average decrease of the total distribution volume (V(T)) between 43% and 58% (thalamus and caudate-putamen, respectively) but had no significant effect on cerebellar V(T) (mean reduction: -0.01%). Comparing binding potential (BP(ND)) based on the V(T) with noninvasively determined BP(ND) revealed an average negative bias of 0.7% in the caudate-putamen and an average positive bias of 3.1% in the low-binding regions. Scan duration of 50 minutes is required. The cerebellum is a suitable reference region for the quantification of mGluR(5) availability as measured with [(11)C]ABP688 PET in rats. Blood-based and reference region-based PET quantification shows a significant linear relationship to autoradiographic determinations.


Variation in the oncogenic potential of human adenoviruses carrying a defective SV40 genome (PARA).
The acquisition of the defective SV40 genome by a variety of human adenovirus serotypes by the process of transcapsidation has resulted in the addition of oncogenic potential for newborn hamsters to the previously nononcogenic adenovirus types 1, 2, 5, and 6. These serotypes have previously been grouped together by the high GC content of their DNA. Transcapsidation of the SV40 genome to weakly oncogenic adenovirus types 3, 14, 16, and 21 has failed to increase their oncogenic potential although the parent adenovirus type 7 carrying PARA is highly oncogenic. These serotypes belong to the group possessing a DNA of intermediate GC content. All the PARA-adenovirus populations, even those that were nononcogenic, were able to induce SV40 transplantation immunity and therefore carry the SV40 transplantation marker as well as the marker for synthesis of SV40 tumor or T antigen.


HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer.
The HLA-E class Ib molecule constitutes a major ligand for the lectin-like CD94/NKG2 natural killer (NK) cell receptors. Specific HLA class I leader sequence-derived nonapeptides bind to endogenous HLA-E molecules in the HLA-defective cell line 721.221, inducing HLA-E surface expression, and promote CD94/NKG2A-mediated recognition. We compared the ability of NK clones which expressed either inhibitory or activating CD94/NKG2 receptors to recognize HLA-E molecules on the surface of 721.221 cells loaded with a panel of synthetic nonamers derived from the leader sequences of most HLA class I molecules. Our results support the notion that the primary structure of the HLA-E-bound peptides influences CD94/ NKG2-mediated recognition, beyond their ability to stabilize surface HLA-E. Further, CD94/ NKG2A+ NK clones appeared more sensitive to the interaction with most HLA-E-peptide complexes than did effector cells expressing the activating CD94/NKG2C receptor. However, a significant exception to this pattern was HLA-E loaded with the HLA-G-derived nonamer. This complex triggered cytotoxicity very efficiently over a wide range of peptide concentrations, suggesting that the HLA-E/G-nonamer complex interacts with the CD94/NKG2 triggering receptor with a significantly higher affinity. These results raise the possibility that CD94/NKG2-mediated recognition of HLA-E expressed on extravillous cytotrophoblasts plays an important role in maternal-fetal cellular interactions.


Production of plasmid DNA in a simple, inexpensive and reusable fermentor.
Performance data for the production of plasmid DNA in bacterial cultures have been obtained using a new concept of simplified fermentor, the Lofstrand Bactolift. The unique design of this fermentor incorporates a standard 500-ml or 1-liter centrifuge bottle as the bacterial growth vessel, thus eliminating the necessity to transfer the cultures for subsequent processing. Bacterial and plasmid yields have been shown to be equal to or greater than those obtained using conventional shake flasks. Twelve 1-liter Bactolift fermentors can be operated in a standard laboratory water bath that occupies less than two square feet of bench space, as compared to a limit of six 2.8-liter Fernbach flasks containing one liter of culture held in an incubator shaker cabinet that occupies nine square feet of laboratory floor space.


RIFM fragrance ingredient safety assessment, 2-decanone, CAS Registry Number 693-54-9.
The existing information supports the use of this material as described in this safety assessment. 2-Decanone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog 2-heptanone (CAS # 110-43-0) show that 2-decanone is not expected to be genotoxic. Data on read-across analog 2-heptanone (CAS # 110-43-0) provide a calculated margin of exposure (MOE) > 100 for the repeated dose toxicity and reproductive toxicity endpoints. The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 2-decanone is not expected to be phototoxic/photoallergenic. For the local respiratory endpoint, a calculated MOE >100 was provided by the read-across analog 4-methyl-2-pentanone (CAS # 108-10-1). The environmental endpoints were evaluated; for the hazard assessment based on the screening data, 2-decanone is not persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards. For the risk assessment, 2-decanone was not able to be risk screened as there were no reported volumes of use for either North America or Europe in the 2015 IFRA Survey.


Privilege as a Social Determinant of Health in Medical Education: A Single Class Session Can Change Privilege Perspective.
Accredited medical schools are required to prepare students to recognize the social determinants of health, such as privilege, yet privilege education has been overlooked in medical school curricula. The purpose of this study is to determine whether a single class session on privilege, within a social justice elective offered to first and second year medical students, is sufficient to change the perspective of medical students concerning their own personal privilege. A pre-class survey, followed by a class session on privilege, and post-class survey were conducted. Thirteen of the 18 students enrolled in the elective completed the pre-class survey. Ten students completed the post-class survey, although only 9 completed both the pre- and post-class surveys. The demographic profile of the participants was 93% Asian and 7% White ethnicity, with 57% identifying as being culturally American. There was no significant difference between average male and female or between age groups' self-assessed privilege amounts. For all characteristics tested, except hair color, participants had an increased self-assessed privilege perspective following the class. Three participants had an overall positive difference in privilege perspective, three participants had an overall negative difference in privilege perspective, and three participants had only a minimal change in privilege perspective. The absolute total difference in privilege perspective was 25 units of change. The single class session on privilege was sufficient to change significantly the perspective of medical students on their own personal privilege; however, future studies with larger groups of medical students are needed to elucidate other findings suggested by this study.


Toxicity of the Alternaria metabolites alternariol, alternariol methyl ether, altenuene, and tenuazonic acid in the chicken embryo assay.
The effects in the chicken embryo assay of four Alternaria metabolites (alternariol [AOH], alternariol methyl ether [AME], altenuene [ALT], and tenuazonic acid [TA]) were investigated. Administered to 7-day-old chicken embryos by yolk sac injection, AOH, AME, and ALT caused no mortality or teratogenic effect at doses up to 1,000, 500, and 1,000 micrograms per egg, respectively. TA exhibited a calculated 50% lethal dose of 548 micrograms per egg, with no teratogenic effect observed at either lethal or sublethal doses.


[Successful treatment with L-asparaginase-based combination chemotherapy for refractory T-cell post-transplant lymphoproliferative disorder].
A 31-year-old man underwent kidney transplantation in 1996, and had been on immunosuppressants. In 2005, he presented with discomfort on swallowing. Swelling of the left tonsil and a mediastinal mass were observed. A biopsy of the left tonsil showed a monotonous proliferation of atypical lymphocytes suggesting post-transplant lymphoproliferative disorder (PTLD). The reduction of immunosuppressants did not result in any clinical improvements, and he developed bilateral cervical lymphadenopathy. A biopsy of the cervical lymph node also showed monotonous proliferation of TdT, CD3, CD5, CD7, CD10, and CD34-positive immature cells. T-cell receptor rearrangement, but not EBER, was detected. Based on these findings, monomorphic T-cell PTLD was diagnosed. He was treated with four different chemotherapeutic regimens without any clinical improvements, and the PTLD became leukemic. Chemotherapy consisting of L-asparaginase, vincristine, and dexamethasone (LVD) was then given, which resulted in massive tumor lysis. However, after two courses of LVD, complete remission was achieved. T-cell PTLD is a rare disorder, characterized by its refractoriness to chemotherapy as opposed to B-cell PTLD. Our experience suggests that L-asparaginase-based chemotherapy may improve the prognosis of T-cell PTLD.


Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells.
Formation of the atherosclerotic intima must involve altered metabolism of the elastin-rich arterial extracellular matrix. Proteases potentially involved in these processes remain unclear. This study examined the expression of the potent elastases cathepsins S and K in human atheroma. Normal arteries contained little or no cathepsin K or S. In contrast, macrophages in atheroma contained abundant immunoreactive cathepsins K and S. Intimal smooth muscle cells (SMC), especially cells appearing to traverse the internal elastic laminae, also contained these enzymes. Extracts of atheromatous tissues had approximately twofold greater elastase-specific activity than extracts of uninvolved arteries, mostly due to cysteine proteases. Cultured human SMC displayed no immunoreactive cathepsins K and S and exhibited little or no elastolytic activity when incubated with insoluble elastin. SMC stimulated with the atheroma-associated cytokines IL-1beta or IFN-gamma secreted active cathepsin S and degraded substantial insoluble elastin (15-20 microg/10(6) cells/24 h). A selective inhibitor of cathepsin S blocked > 80% of this elastolytic activity. The presence of cathepsins K and S at sites of vascular matrix remodeling and the ability of SMC and macrophages to use these enzymes to degrade elastin supports a role for elastolytic cathepsins in vessel wall remodeling and identifies novel therapeutic targets in regulating plaque stability.


Management of involuntary childlessness in general practice--patients' and doctors' views.
In order to determine whether general practitioners (GPs) are interested in infertility counselling and whether infertile patients seek help from their family doctor, we personally interviewed doctors and infertile patients. Almost all of the board-certified GPs in Göttingen, Germany, and two independent samples of infertile women and men attending the Göttingen University Hospital participated. The majority of the GPs did not routinely ask childless patients about their desire to have children, although half of the infertile men and one-quarter of the infertile women would prefer it if their doctor were to raise the subject. About half of these doctors emphasized their role as an important source of information and advice during assisted conception and almost half of the patients expected emotional support from their GP.


Transfected single-cell imaging by scanning electrochemical optical microscopy with shear force feedback regulation.
Gene-transfected single HeLa cells were characterized using a scanning electrochemical/optical microscope (SECM/OM) system with shear-force-based probe-sample distance regulation to simultaneously capture electrochemical, fluorescent, and topographic images. The outer and inner states of single living cells were obtained as electrochemical and fluorescent signals, respectively, by using an optical fiber-nanoelectrode probe. A focused ion beam (FIB) was used to mill the optical aperture and the ring electrode at the probe apex (the inner and outer radii of the ring electrode were 37 and 112 nm, respectively). To apply an appropriate shear force between the probe tip and the living cell surface, we optimized the amplitude of oscillation of the tuning fork to which the probe was attached. Field-programmable gate arrays (FPGA) were adopted to drastically increase the feedback speed of the tip-sample distance regulation, shorten the scanning time for imaging, and enhance the accuracy and quality of the living cell images. In employing these improvements, we simultaneously measured the cellular expression activity of both secreted alkaline phosphatase outside and GFP inside by using the SECM/OM with shear force distance regulation.


Gray Matter Morphometry Correlates with Attentional Efficiency in Young-Adult Multiple Sclerosis.
Slowed processing on the alerting, orienting and executive control components of attention measured using the Attention Network Test-Interactions (ANT-I) have been widely reported in multiple sclerosis (MS). Despite the assumption that these components correspond to specific neuroanatomical networks in the brain, little is known about gray matter changes that occur in MS and their association with ANT-I performance. We investigated vertex-wise cortical thickness changes and deep gray matter volumetric changes in young MS participants (N = 21, age range: 18-35) with pediatric or young-adult onset and mild disease severity. ANT-I scores and cortical thickness were not significantly different between MS participants and healthy volunteers (N = 19, age range: 18-35), but thalamic volumes were significantly lower in MS. Slowed reaction times on the alerting component in MS correlated significantly with reduced volume of the right pallidum in MS. Slowed reaction times on executive control component correlated significantly with reduced thickness in the frontal, parietal and visual cortical areas and with reduced volume of the left putamen in MS. These findings demonstrate associations between gray matter changes and attentional performance even in the absence of widespread atrophy or slowed attentional processes.


Hepatoprotective effects of crocin on biochemical and histopathological alterations following acrylamide-induced liver injury in Wistar rats.
The objective of the present study is the treatment of oxidative damage caused by acrylamide induced oxidative stress in rats with the administration of a strong antioxidant, namely crocin. High acrylamide (AA) levels have genotoxic, carcinogenic and neurotoxic effects on living organisms. In the present study, 40 Wistar rats were randomly divided into four equal groups. These groups were control, acrylamide (25mg/kg), crocin (50mg/kg), acrylamide+crocin (25mg/kg acrylamide and 50mg/kg crocin) groups. At the end of the application, biochemical and histological variations were examined in liver and blood samples. It was observed that acrylamide administration significantly decreased liver GSH and TAS levels when compared to the control group. On the contrary, it was also observed that AST, ALT, ALP, SOD and CAT activities and TOS and MDA levels increased as a result of acrylamide administration. Histopathological examinations demonstrated inflammatory cell infiltration, hepatocellular necrosis and hemorrhage areas in AA group liver sections. Furthermore, intracytoplasmic vacuolization was detected in hepatocytes. After crocin treatment, it was observed that GSH and TAS levels increased while AST, ALT, ALP, SOD and CAT activities and TOS and MDA levels decreased. Significant decreases were observed in inflammatory cell infiltration and vascular congestion in liver sections and intracytoplasmic vacuolization in hepatocytes after the crocin treatment, while no hepatocellular necrosis and hemorrhages were observed. In the present study, it was demonstrated that crocin treatment removed acrylamide induced liver damage due to the strong antioxidant properties of crocin.


Azygos Vein Aneurysm with Thrombosis and Aspergillus fumigatus Diagnosed Using Bronchoscopy: Case Report.
BACKGROUND The venous system of the posterior thoracic wall merges into a single trunk called the azygos vein, located in the posterior mediastinum, before draining into the superior vena cava. An aneurysm in the azygos vein is extremely rare. Such aneurysms are discovered as incidental radiology findings or while investigating a mediastinal mass. Visualization via bronchoscopy is atypical. CASE REPORT An 86-year-old female patient presented to the Emergency Department with a 5-day complaint of dyspnea and chest pain. She was admitted because of worsening condition leading to respiratory failure and paresthesias. She underwent endotracheal intubation and invasive mechanical ventilatory support. A chest X-ray showed a thickened mediastinum, tortuous thoracic aorta, and bilateral perihilar infiltrate with right predominance. Bronchoscopy revealed bleeding along the right bronchus and a blue protrusion coated with white material at the entrance of the main right bronchus. A pulmonary computed tomography angiography confirmed the presence of an azygos vein dilatation. Culture of bronchoalveolar lavage revealed Aspergillus fumigatus. CONCLUSIONS Bronchoscopy as a diagnostic method allows clinicians to verify the state and permeability of the airways during investigation of azygos vein aneurysms, which are rare entities but should be considered in the differential diagnosis of mediastinal masses and may be complicated by fungal pathogens such as Aspergillus fumigatus mostly in immunocompromised patients.


Control of enhanced THz transmission through metallic hole arrays using nematic liquid crystal.
We demonstrate frequency tuning of enhanced THz radiation transmitted through a two-dimensional metallic hole array (2D-MHA) by controlling the index of refraction of the medium filling the holes and adjacent to the 2D-MHA on one side. The medium is a nematic liquid crystal (NLC) and its index of refraction is varied using magnetically controlled birefringence of the NLC. With the NLC, the peak transmission frequency of the 2D-MHA shift to the red by 0.112 THz and can be tuned from 0.193 to 0.188 THz. The peak transmittance is as high as 70% or an enhancement of 2.42 times, considering the porosity of the 2D-MHA. As a tunable THz filter, this device exhibits a continuous tuning range of 4.7 GHz , a low insertion loss of 2.35 to 1.55 dB and a quality factor of ~ 4-5.


Acute severe cardiac failure in a myeloma patient due to proteasome inhibitor bortezomib.
We present here a case of severe congestive cardiac failure, in a 47-year-old patient with myeloma who had no prior cardiac history, after receiving bortezomib. Bortezomib is a boron-containing molecule, which reversibly inhibits the proteasome, an intracellular organelle, which is central to the breakdown of ubiquitinated proteins and consequently crucial for normal cellular homeostasis. Phase II clinical trials demonstrate that it is effective for the treatment of relapsed refractory myeloma. Acute development of congestive cardiac failure associated with bortezomib therapy occurs very rarely or may be underestimated. Inhibition of proteasome activity may impair cardiac function due to accumulation of unfolded, damaged and undegraded proteins in myocytes. Patients with or without cardiac disease or previously received anthracycline-containing regimes should be closely monitored when being subjected to treatment with bortezomib.


Neutral stability, drift, and the diversification of languages.
The diversification of languages is one of the most interesting facts about language that seek explanation from an evolutionary point of view. Conceptually the question is related to explaining mechanisms of speciation. An argument that prominently figures in evolutionary accounts of language diversification is that it serves the formation of group markers which help to enhance in-group cooperation. In this paper we use the theory of evolutionary games to show that language diversification on the level of the meaning of lexical items can come about in a perfectly cooperative world solely as a result of the effects of frequency-dependent selection. Importantly, our argument does not rely on some stipulated function of language diversification in some co-evolutionary process, but comes about as an endogenous feature of the model. The model that we propose is an evolutionary language game in the style of Nowak et al. (1999) [The evolutionary language game. J. Theor. Biol. 200, 147-162], which has been used to explain the rise of a signaling system or protolanguage from a prelinguistic environment. Our analysis focuses on the existence of neutrally stable polymorphisms in this model, where, on the level of the population, a signal can be used for more than one concept or a concept can be inferred by more than one signal. Specifically, such states cannot be invaded by a mutation for bidirectionality, that is, a mutation that tries to resolve the existing ambiguity by linking each concept to exactly one signal in a bijective way. However, such states are not resistant against drift between the selectively neutral variants that are present in such a state. Neutral drift can be a pathway for a mutation for bidirectionality that was blocked before but that finally will take over the population. Different directions of neutral drift open the door for a mutation for bidirectionality to appear on different resident types. This mechanism-which can be seen as a form of shifting balance-can explain why a word can acquire a different meaning in two languages that go back to the same common ancestral language, thereby contributing to the splitting of these two languages. Examples from currently spoken languages, for instance, English clean and its German cognate klein with the meaning of "small," are provided.


State of the psychometric methods: comments on the ISOQOL SIG psychometric papers.
Psychometric analyses of patient reported outcomes typically use either classical test theory (CTT), item response theory (IRT), or Rasch measurement theory (RTM). The three papers from the ISOQOL Psychometrics SIG examined the same data set using the tree different approaches. By comparing the results from these papers, the current paper aims to examine the extent to which conclusions about the validity and reliability of a PRO tool depends on the selected psychometric approach. Regarding the basic statistical model, IRT and RTM are relatively similar but differ notably from CTT. However, modern applications of CTT diminish these differences. In analyses of item discrimination, CTT and IRT gave very similar results, while RTM requires equal discrimination and therefore suggested exclusion of items deviating too much from this requirement. Thus, fewer items fitted the Rasch model. In analyses of item thresholds (difficulty), IRT and RMT provided fairly similar results. Item thresholds are typically not evaluated in CTT. Analyses of local dependence showed only moderate agreement between methods, partly due to different thresholds for important local dependence. Analyses of differential item function (DIF) showed good agreement between IRT and RMT. Agreement might be further improved by adjusting the thresholds for important DIF. Analyses of measurement precision across the score range showed high agreement between IRT and RMT methods. CTT assumes constant measurement precision throughout the score range and thus gave different results. Category orderings were examined in RMT analyses by checking for reversed thresholds. However, this approach is controversial within the RMT society. The same issue can be examined by the nominal categories IRT model. While there are well-known differences between CTT, IRT and RMT, the comparison between three actual analyses revealed a great deal of agreement between the results from the methods. If the undogmatic attitude of the three current papers is maintained, the field will be well served.


Multiple locus variable number tandem repeat analysis (MLVA) of the pathogenic intestinal spirochaete Brachyspira pilosicoli.
Brachyspira pilosicoli is an anaerobic intestinal spirochaete that colonizes the large intestine of various host species, in which it may induce diarrhoea, poor growth rates and a localized colitis known as intestinal (or colonic) spirochaetosis. The spirochaete is considered to be potentially zoonotic. The purpose of the current study was to develop a multiple-locus variable number tandem repeat analysis (MLVA) method as a simple and rapid tool to investigate the molecular epidemiology of B. pilosicoli. The genomic sequence of B. pilosicoli strain 95/1000 was analyzed for potential tandem repeats using the default parameters of the Tandem Repeat Finder program. A total of 22 repeat loci were identified and tested for their presence and variability on a set of 10 B. pilosicoli isolates. Five loci that were present in most isolates and that showed evidence of allelic variation were selected and used with a collection of 119 isolates from different host species and geographical locations. Not all the isolates amplified at all loci, but using the available data a total of 103 VNTR profiles were generated. The discriminatory power of this method was 0.976. A phylogenetic tree constructed from the allelic profiles confirmed the diversity of B. pilosicoli, and the general lack of clustering of strains based on species of origin or geographic origin. Some isolates with known epidemiological links were found to be identical or highly similar. The MLVA method was simple and easy to use, and could readily differentiate between strains of B. pilosicoli. MLVA should prove to be a useful tool for rapid identification of relationships between B. pilosicoli isolates in epidemiological investigations.


Substrate-induced enhancement of the chemical reactivity in metal-supported graphene.
Graphene is commonly regarded as an inert material. However, it is well known that the presence of defects or substitutional hetero-atoms confers graphene promising catalytic properties. In this work, we use first-principles calculations to show that it is also possible to enhance the chemical reactivity of a graphene layer by simply growing it on an appropriate substrate. Our comprehensive study demonstrates that, in strongly interacting substrates like Rh(111), graphene adopts highly rippled structures that exhibit areas with distinctive chemical behaviors. According to the local coupling with the substrate, we find areas with markedly different adsorption, dissociation and diffusion pathways for both molecular and atomic oxygen, including a significant change in the nature of the adsorbed molecular and dissociated states, and a dramatic reduction (∼60%) of the O2 dissociation energy barrier with respect to free-standing graphene. Our results show that the graphene-metal interaction represents an additional and powerful handle to tailor the graphene chemical properties with potential applications to nano patterning, graphene functionalization and sensing devices.


Conservative versus interventional management for primary spontaneous pneumothorax in adults.
Primary spontaneous pneumothorax is widely managed according to size with interventional techniques based on practice guidelines. Interventional management is not without complications and observational data suggest conservative management works. The current guidelines are based on expert consensus rather than evidence, and a systematic review may help in identifying evidence for this practice. The objective of the review is to compare conservative and interventional treatments of adult primary spontaneous pneumothorax for outcomes of clinical efficacy, tolerability and safety. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 6, 2014); MEDLINE via Ovid SP (1920 to 26th June 2014); EMBASE via Ovid SP (1947 to 26th June 2014); CINAHL via EBSCO host (1980 to 26th June 2014); and ISI Web of Science (1945 to 26th June 2014). We searched ongoing trials via the relevant databases and contacted authors. We also searched the 'grey literature'. We included randomized controlled trials (RCTs) and we accepted quasi-RCTs if a systematic method of allocation was used. Participants were limited to adults aged 18 to 50 years, with their first symptomatic primary spontaneous pneumothorax with radiological evidence and no underlying lung disease. Two of five authors independently reviewed all studies in the search criteria and made inclusions and exclusions according to the selection criteria. No statistical methods were necessary as there were no included trials. We identified 358 studies with duplicates removed. There were three potentially relevant studies that we excluded as they were not randomized controlled trials. There was one ongoing trial that was relevant and we contacted the authors and confirmed the study is ongoing at June 2014. We will update this review when this ongoing study is completed. There are no completed randomized controlled trials comparing conservative and interventional management for primary spontaneous pneumothorax in adults. There is a lack of high-quality evidence for current guidelines in management and a need for randomized controlled trials comparing conservative and interventional management for this condition.


Angiopoietin-1 enhances skeletal muscle regeneration in mice.
Activation of muscle progenitor cell myogenesis and endothelial cell angiogenesis is critical for the recovery of skeletal muscle from injury. Angiopoietin-1 (Ang-1), a ligand of Tie-2 receptors, enhances angiogenesis and skeletal muscle satellite cell survival; however, its role in skeletal muscle regeneration after injury is unknown. We assessed the effects of Ang-1 on fiber regeneration, myogenesis, and angiogenesis in injured skeletal muscle (tibialis anterior, TA) in mice. We also assessed endogenous Ang-1 levels and localization in intact and injured TA muscles. TA fiber injury was triggered by cardiotoxin injection. Endogenous Ang-1 mRNA levels immediately decreased in response to cardiotoxin then increased during the 2 wk. Ang-1 protein was expressed in satellite cells, both in noninjured and recovering TA muscles. Positive Ang-1 staining was present in blood vessels but not in nerve fibers. Four days after the initiation of injury, injection of adenoviral Ang-1 into injured muscles resulted in significant increases in in situ TA muscle contractility, muscle fiber regeneration, and capillary density. In cultured human skeletal myoblasts, recombinant Ang-1 protein increased survival, proliferation, migration, and differentiation into myotubes. The latter effect was associated with significant upregulation of the expression of the myogenic regulatory factors MyoD and Myogenin and certain genes involved in cell cycle regulation. We conclude that Ang-1 strongly enhances skeletal muscle regeneration in response to fiber injury and that this effect is mediated through induction of the myogenesis program in muscle progenitor cells and the angiogenesis program in endothelial cells.


Effect of Intermediate Agents and Preheated Composites on Repair Bond Strength of Silorane-Based Composites.
Repairing composite restorations is a challenging procedure especially when two different types of composites are used. This study aimed to compare the repair strength of silorane-based composite (SC) (Filtek P90) with that of preheated SC, methacrylate composite (MC)(Z250), flowable MC (Filtek Supreme Plus) and different adhesive/composite combinations. Eighty-four SC specimens were fabricated and randomly divided into seven groups (G). In the control group (G7), SC was bonded immediately to SC. The other specimens were water-aged for two months and were then roughened, etched and repaired with the following materials: G1) Silorane Adhesive Bond (SAB)/SC; G2) Preheated SC; G3) SAB/MC; G4) Adper Single Bond (SB)/MC; G5) Flowable MC/MC; G6) Preheated MC. After water storage and thermocycling, the repaired specimens were subjected to shear bond strength testing. The data were analyzed using ANOVA and Tukey's test. Preheated SC and MC, flowable MC and SAB/SC resulted in bond strength comparable to that of the control group. Preheated SC showed significantly higher bond strength when compared to SAB/MC (P=0.04) and SB/MC (P<0.001). Bond strength of SB/MC was significantly lower than that of the other groups (P<0.05), except for SAB/SC and SAB/MC. All repairing materials except for SB/MC resulted in bond strength values comparable to that of the control group. Repair with preheated SC yielded the highest bond strength.


Genetic variation in AKT1 is linked to dopamine-associated prefrontal cortical structure and function in humans.
AKT1-dependent molecular pathways control diverse aspects of cellular development and adaptation, including interactions with neuronal dopaminergic signaling. If AKT1 has an impact on dopaminergic signaling, then genetic variation in AKT1 would be associated with brain phenotypes related to cortical dopaminergic function. Here, we provide evidence that a coding variation in AKT1 that affects protein expression in human B lymphoblasts influenced several brain measures related to dopaminergic function. Cognitive performance linked to frontostriatal circuitry, prefrontal physiology during executive function, and frontostriatal gray-matter volume on MRI were altered in subjects with the AKT1 variation. Moreover, on neuroimaging measures with a main effect of the AKT1 genotype, there was significant epistasis with a functional polymorphism (Val158Met) in catechol-O-methyltransferase [COMT], a gene that indexes cortical synaptic dopamine. This genetic interaction was consistent with the putative role of AKT1 in dopaminergic signaling. Supportive of an earlier tentative association of AKT1 with schizophrenia, we also found that this AKT1 variant was associated with risk for schizophrenia. These data implicate AKT1 in modulating human prefrontal-striatal structure and function and suggest that the mechanism of this effect may be coupled to dopaminergic signaling and relevant to the expression of psychosis.


Amplification of screening sensitivity through selective destruction: theory and screening of a library of carbonic anhydrase inhibitors.
A new method for identifying enzyme inhibitors is to conduct their synthesis in the presence of the targeted enzyme. Good inhibitors form in larger amounts than poorer ones because the binding either speeds up synthesis (target-accelerated synthesis) or shifts the synthesis equilibrium (dynamic combinatorial libraries). Several groups have successfully demonstrated this approach with simple systems, but application to larger libraries is challenging because of the need to accurately measure the amount of each inhibitor. In this report, we dramatically simplify this analysis by adding a reaction that destroys the unbound inhibitors. This works similar to a kinetic resolution, with the best inhibitor being the last one remaining. We demonstrate this method for a static library of several sulfonamide inhibitors of carbonic anhydrase. Four sulfonamide-containing dipeptides, EtOC-Phe(sa)-Phe (4a), EtOC-Phe(sa)-Gly (4b), EtOC-Phe(sa)-Leu (4c) and EtOC-Phe(sa)-Pro (4d), were prepared and their inhibition constants measured. These inhibitors migrated to the carbonic anhydrase compartment of a two-compartment vessel. Although higher concentrations of the better inhibitors were observed in the carbonic anhydrase compartment, the concentration differences were small (1.83:1.71:1.54:1.46:1 for 4a:4b:4c:4d:5, where 5 is a noninhibiting dipeptide EtOC-Phe-Phe). Addition of a protease rapidly cleaved the weaker inhibitors (4d and 5). Intermediate inhibitor 4c was cleaved at a slower rate, and at the end of the reaction, only 4a and 4b remained. In a separate experiment, the ratio of 4a to 4b was found to increase over time to a final ratio of nearly 4:1. This is greater than the ratio of their inhibition constants (approximately 2:1). The theoretical model predicts that these ratios would increase even further as the destruction proceeds. This removal of poorer inhibitors simplifies identification of the best inhibitor in a complex mixture.


Enhancement of c-Myc degradation by BLM helicase leads to delayed tumor initiation.
The spectrum of tumors that arise owing to the overexpression of c-Myc and loss of BLM is very similar. Hence, it was hypothesized that the presence of BLM negatively regulates c-Myc functions. By using multiple isogenic cell lines, we observed that the decrease of endogenous c-Myc levels that occurs in the presence of BLM is reversed when the cells are treated with proteasome inhibitors, indicating that BLM enhances c-Myc turnover. Whereas the N-terminal region of BLM interacts with c-Myc, the rest of the helicase interacts with the c-Myc E3 ligase Fbw7. The two BLM domains act as 'clamp and/or adaptor', enhancing the binding of c-Myc to Fbw7. BLM promotes Fbw7-dependent K48-linked c-Myc ubiquitylation and its subsequent degradation in a helicase-independent manner. A subset of BLM-regulated genes that are also targets of c-Myc were determined and validated at both RNA and protein levels. To obtain an in vivo validation of the effect of BLM on c-Myc-mediated tumor initiation, isogenic cells from colon cancer cells that either do or do not express BLM had been manipulated to block c-Myc expression in a controlled manner. By using these cell lines, the metastatic potential and rate of initiation of tumors in nude mice were determined. The presence of BLM decreases c-Myc-mediated invasiveness and delays tumor initiation in a mouse xenograft model. Consequently, in tumors that express BLM but not c-Myc, we observed a decreased ratio of proliferation to apoptosis together with a suppressed expression of the angiogenesis marker CD31. Hence, partly owing to its regulation of c-Myc stability, BLM acts as a 'caretaker tumor suppressor'.


Molting layers--alternative methods and their effectiveness.
The molting of commercial layers has been under increased scrutiny by animal rights groups, who have said that this practice is highly stressful and one which negatively affects the welfare of the hen due to the initial period of fasting that has been used to stop egg production. In recent years, there has been a recognized need to develop practical alternatives to molting layers other than the use of fasting. Thus, the University of Illinois, University of Nebraska, North Carolina State University, and the University of California have all researched this area. In all of these studies, the methods involved comparing a normal fasting method (i.e., 5 to 13 d), to feeding low-energy and protein diets using ingredients such as wheat middlings, soybean hulls, and corn or diets with graded levels of added salt and without salt (University of Nebraska, University of California). The molt period (28 d) included full-feeding of these diets. In these studies, postmolt production performance for the nonfeed withdrawal techniques was comparable to the fasting method. Several researchers have also evaluated the behavioral repertoire of laying hens, which includes feeding, drinking, comfort, social, reproductive, and anti-predator behaviors. In addition, related behaviors such as aggression, escape-avoidance, and submission have been of particular interest as potential indicators of welfare during molting. In these studies, genetic selection, strain, density, or molt program do not appear to adversely influence the behavioral patterns during the molt. The behavior patterns displayed during a molt program appear consistent with the response to physiological changes that layers experience and do not appear to compromise the welfare status of the hens. Appetitive behaviors were not affected by strain but were affected by production phase and molting. Strain or production phase did not influence the frequency of aggressive and submissive acts. Thus, the use of alternative nonfeed withdrawal molting methods provide comparable laying hen well-being and may enhance the transition from a productive to a resting state.


Promoting prosocial pupil behaviour: 2-secondary school intervention and pupil effects.
In an earlier article (Mooij, 1999c) a theoretical multilevel model to promote prosocial pupil behaviour by stimulating specific educational conditions was developed. To carry out school interventions to check empirically whether pupil level effects occur because of educational changes at the classroom and school level. Seven secondary schools with relatively high degrees of pupil aggression were selected. Four schools took part as intervention schools, three schools served as control schools. In 1995 (pretest) and 1997 (post-test) pupils and form teachers of the first and third school years participated by completing questionnaires. Within the pupil cohorts, a longitudinal group of 352 pupils was included. Pretest questionnaires in 1995 were followed by intervention in the intervention schools. Teachers collaborated with staff and researchers to increase pupils' participation and responsibility in specifying and controlling behavioural and didactic rules, related to didactic differentiation during lessons. The validity of the intervention implementation was checked using qualitative information and quantitative data from both pre- and post-test. Longitudinal intervention effects were tested by applying two-level multiple regression analyses. After controlling for pretest and covariables in school year 1, school intervention effects were found in school year 3 with the prediction of being a perpetrator of aggressive behaviour at school, aggressive behaviour outside school, and criminal behaviour. Some small effects were found with respect to victim behaviour. Social-pedagogical and didactic class and school variables, but also home variables and support by peers without problematic behaviour, could be integrated more systematically to promote prosocial development of a pupil's behaviour from the beginning in school.


Serum dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) in Alzheimer's disease and in cerebrovascular dementia.
A decreased concentration of dehydroepiandrosterone sulfate (DHEA-S) in patients with Alzheimer's disease (AD) has been reported but is still controversial. In the present study, serum concentrations of DHEA and DHEA-S were determined in 19 patients with AD, 21 patients with cerebrovascular dementia (CVD) and 45 age- and gender matched elderly control individuals from the Japanese community at large. Serum concentration of DHEA among controls, patients with AD and patients with CVD did not significantly differ from one another. However, patients with AD and patients with CVD were found to have lower concentration of serum DHEA-S and a lower DHEA-S/DHEA ration compared to normal control individuals. No significant difference was observed in the concentration of serum DHEA-S or the DHEA-S/DHEA ratio between patients with AD and those with CVD. These results suggest that reduced concentrations of serum DHEA-S may not be unique to AD, but instead reflect a common phenomenon in dementing diseases. However, since serum concentration of DHEA in these patients remained unchanged, the significance of DHEA in dementia remains unclear.


Epigenetic signature: implications for mitochondrial quality control in human aging.
Maintenance of functional mitochondria is essential to prevent damage leading to aging and diseases. What is more, the research of biomarkers of aging is focusing on better predicting functional capability along the lifetime beyond chronological age. Aim of this study was to identify novel CpG sites the methylation of which might be correlated to the chronological and biological age. We performed methylation analyses of the CpG sites in candidate genes involved in mitochondrial biogenesis, mitophagy, fusion, and fission, all key quality control mechanisms to ensure maintenance of healthy mitochondria and homeostasis during aging, using DNA samples from two independent datasets composed by 381 and 468 differently-aged individuals, respectively. Twelve potential CpG predictors resulted associated with aging in the discovery dataset. Of these, two sites located within RAB32 and RHOT2 genes were replicated in the second dataset. What is more, individuals exhibiting methylation levels of the RAB32 CpG site higher than 10% were observed more prone to disability than people with lower levels.These results seem to provide the first evidence that epigenetic modifications of genes involved in mitochondrial quality control occur over time according to the aging decline, and may then represent potential biomarkers of both chronological and biological age.


The structure of an infectious P22 virion shows the signal for headful DNA packaging.
Bacteriophages, herpesviruses, and other large double-stranded DNA (dsDNA) viruses contain molecular machines that pump DNA into preassembled procapsids, generating internal capsid pressures exceeding, by 10-fold, that of bottled champagne. A 17 angstrom resolution asymmetric reconstruction of the infectious P22 virion reveals that tightly spooled DNA about the portal dodecamer forces a conformation that is significantly different from that observed in isolated portals assembled from ectopically expressed protein. We propose that the tight dsDNA spooling activates the switch that signals the headful chromosome packing density to the particle exterior.


Nanog Fluctuations in Embryonic Stem Cells Highlight the Problem of Measurement in Cell Biology.
A number of important pluripotency regulators, including the transcription factor Nanog, are observed to fluctuate stochastically in individual embryonic stem cells. By transiently priming cells for commitment to different lineages, these fluctuations are thought to be important to the maintenance of, and exit from, pluripotency. However, because temporal changes in intracellular protein abundances cannot be measured directly in live cells, fluctuations are typically assessed using genetically engineered reporter cell lines that produce a fluorescent signal as a proxy for protein expression. Here, using a combination of mathematical modeling and experiment, we show that there are unforeseen ways in which widely used reporter strategies can systematically disturb the dynamics they are intended to monitor, sometimes giving profoundly misleading results. In the case of Nanog, we show how genetic reporters can compromise the behavior of important pluripotency-sustaining positive feedback loops, and induce a bifurcation in the underlying dynamics that gives rise to heterogeneous Nanog expression patterns in reporter cell lines that are not representative of the wild-type. These findings help explain the range of published observations of Nanog variability and highlight the problem of measurement in live cells.


Parallel computational steering for HPC applications using HDF5 files in distributed shared memory.
Interfacing a GUI driven visualization/analysis package to an HPC application enables a supercomputer to be used as an interactive instrument. We achieve this by replacing the IO layer in the HDF5 library with a custom driver which transfers data in parallel between simulation and analysis. Our implementation using ParaView as the interface, allows a flexible combination of parallel simulation, concurrent parallel analysis, and GUI client, either on the same or separate machines. Each MPI job may use different core counts or hardware configurations, allowing fine tuning of the amount of resources dedicated to each part of the workload. By making use of a distributed shared memory file, one may read data from the simulation, modify it using ParaView pipelines, write it back, to be reused by the simulation (or vice versa). This allows not only simple parameter changes, but complete remeshing of grids, or operations involving regeneration of field values over the entire domain. To avoid the problem of manually customizing the GUI for each application that is to be steered, we make use of XML templates that describe outputs from the simulation (and inputs back to it) to automatically generate GUI controls for manipulation of the simulation.


A two-dimensional screen for AMPK substrates identifies tumor suppressor fumarate hydratase as a preferential AMPKα2 substrate.
AMP-activated protein kinase (AMPK) is emerging as a central cellular signaling hub involved in energy homeostasis and proliferation. The kinase is considered as a suitable target for pharmacological intervention in several energy-related pathologies like diabetes type II and cancer, although its signaling network is still incompletely understood. Here we apply an original two-dimensional in vitro screening approach for AMPK substrates that combines biophysical interaction based on surface plasmon resonance with in vitro phosphorylation. By enriching for proteins that interact with a specific AMPK isoform, we aimed to identify substrates that are also preferentially phosphorylated by this specific AMPK isoform. Application of this screen to full-length AMPK α2β2γ1 and soluble rat liver proteins identified the tumor suppressor fumarate hydratase (FH). FH was confirmed to interact with and to be preferentially phosphorylated by the AMPKα2 isoform by using yeast-two-hybrid and in vitro phosphorylation assays. AMPK-mediated phosphorylation of FH significantly increased enzyme activity in vitro and in vivo, suggesting that it is a bona fide AMPK substrate. In vivo, AMPKα2 is supposed to target the cytosolic/nuclear pools of FH, whose tumor suppressor function relies on DNA damage repair and inhibition of HIF-1α-signaling.


Size of sentinel-node metastasis and chances of non-sentinel-node involvement and survival in early stage vulvar cancer: results from GROINSS-V, a multicentre observational study.
Currently, all patients with vulvar cancer with a positive sentinel node undergo inguinofemoral lymphadenectomy, irrespective of the size of sentinel-node metastases. Our study aimed to assess the association between size of sentinel-node metastasis and risk of metastases in non-sentinel nodes, and risk of disease-specific survival in early stage vulvar cancer. In the GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V), sentinel-node detection was done in patients with T1-T2 (<4 cm) squamous-cell vulvar cancer, followed by inguinofemoral lymphadenectomy if metastatic disease was identified in the sentinel node, either by routine examination or pathological ultrastaging. For the present study, sentinel nodes were independently reviewed by two pathologists. Metastatic disease was identified in one or more sentinel nodes in 135 (33%) of 403 patients, and 115 (85%) of these patients had inguinofemoral lymphadenectomy. The risk of non-sentinel-node metastases was higher when the sentinel node was found to be positive with routine pathology than with ultrastaging (23 of 85 groins vs three of 56 groins, p=0.001). For this study, 723 sentinel nodes in 260 patients (2.8 sentinel nodes per patient) were reviewed. The proportion of patients with non-sentinel-node metastases increased with size of sentinel-node metastasis: one of 24 patients with individual tumour cells had a non-sentinel-node metastasis; two of 19 with metastases 2 mm or smaller; two of 15 with metastases larger than 2 mm to 5 mm; and ten of 21 with metastases larger than 5 mm. Disease-specific survival for patients with sentinel-node metastases larger than 2 mm was lower than for those with sentinel-node metastases 2 mm or smaller (69.5%vs 94.4%, p=0.001). Our data show that the risk of non-sentinel-node metastases increases with size of sentinel-node metastasis. No size cutoff seems to exist below which chances of non-sentinel-node metastases are close to zero. Therefore, all patients with sentinel-node metastases should have additional groin treatment. The prognosis for patients with sentinel-node metastasis larger than 2 mm is poor, and novel treatment regimens should be explored for these patients.


Efficacy of ocular vestibular-evoked myogenic potential in identifying posterior semicircular canal benign paroxysmal positional vertigo.
Benign paroxysmal positional vertigo (BPPV) is a unilateral peripheral vestibular pathology, mostly involving the semicircular canals and the otolith organs. Although equivocal findings exist on the utility of cervical vestibular-evoked myogenic potential in identifying BPPV-associated changes in saccule, ocular vestibular-evoked myogenic potential (oVEMP), which is primarily a utricular response, has sparingly been explored in this population. Hence, the present study aimed at examining oVEMP in individuals with BPPV and comparing them with healthy individuals to illustrate its efficacy in identifying BPPV-associated changes in the utricle. Using a case-control design, oVEMPs were elicited by 500 Hz tone bursts at 125 dB peak sound pressure level and recorded bilaterally from 30 individuals with unilateral posterior canal BPPV and 30 age- and gender-matched healthy controls. There were no inter- or intragroup differences in latency aspects (p > 0.05); however, amplitudes were significantly smaller in BPPV ears compared with the non-BPPV ears of individuals with BPPV as well as ears of healthy controls (p < 0.05). Exceptions to this were five participants with BPPV in whom the affected ears demonstrated larger response amplitude (augmentation) than the unaffected ears. Furthermore, there was significantly larger interaural amplitude ratio in individuals with BPPV compared with the healthy controls (p < 0.05). Interaural amplitude ratio produced the largest effect size among the oVEMP parameters for differentiating BPPV from healthy controls. Large asymmetry ratio of oVEMP, usually exceeding 26.8%, is the most potent characteristic of oVEMP in BPPV. Abnormal oVEMP results confirm utricular pathology in ears with BPPV, and therefore, oVEMP can be used as an objective tool with asymmetry ratio as the parameter of choice for the evaluation of utricular function in persons with posterior canal BPPV.


Acetylcholine Inhibits Monomeric C-Reactive Protein Induced Inflammation, Endothelial Cell Adhesion, and Platelet Aggregation; A Potential Therapeutic?
Objectives: In this study, we examined the possibility of using targeted antibodies and the potential of small molecular therapeutics (acetylcholine, nicotine and tacrine) to block the pro-inflammatory and adhesion-related properties of monomeric C-reactive protein (mCRP). Methods: We used three established models (platelet aggregation assay, endothelial leucocyte binding assay and monocyte inflammation via ELISA and Western blotting) to assess the potential of these therapeutics. Results: The results of this study showed that monocyte induced inflammation (raised tumor necrosis factor-alpha-TNF-α) induced by mCRP was significantly blocked in the presence of acetylcholine and nicotine, whilst tacrine and targeted antibodies (clones 8C10 and 3H12) had less of or no significant effects. Western blotting confirmed the ability of acetylcholine to inhibit mCRP-induced cell signaling phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2), p38 and nuclear factor-kappa B (NF-κB). There was no evidence of direct binding between small molecules and mCRP. mCRP also induced endothelial cell-monocyte adhesion in a dose dependent fashion, however, both acetylcholine and nicotine as well as targeting antibodies notably inhibited adhesion. Finally, we investigated their effects on mCRP-induced platelet aggregation. All three small molecules significantly attenuated platelet aggregation as did the antibody 8C10, although 3H12 had a weaker effect. Discussion: Acetylcholine and to a lesser extent nicotine show potential for therapeutic inhibition of mCRP-induced inflammation and cell and platelet adhesion. These results highlight the potential of targeted antibodies and small molecule therapeutics to inhibit the binding of mCRP by prevention of membrane interaction and subsequent activation of cellular cascade systems, which produce the pro-inflammatory effects associated with mCRP.


Shrinkage of the brain during histological procedures with fixation in formaldehyde solutions of different concentrations.
The purpose of this study was to measure the shrinkage of the brain during fixation and the subsequent histological procedures. In neuropathology formaldehyde solutions are the most common fixative, but different concentrations are used. This may lead to uncertainty in connection with quantitative comparative studies, because of the possibility of different degrees of shrinkage. Three groups of five brains each were fixed in three different formaldehyde solutions containing 4% buffered solution, 10% and 12% solutions without additives, respectively. The further procedure to the final histological preparation was the same in all groups. The total shrinkage in volume was 48%, with no significant difference between the three groups. A significant difference appears in relation to the duration of fixation in the most concentrated formaldehyde solution. In all three groups the shrinkage due to the fixation was more than half of the total shrinkage. Finally, it is concluded that comparative quantitative studies on brains can be performed without regard to the technique after fixation in any of the concentrations of formaldehyde investigated.


Computational model of rabbit SA node pacemaker activity probed with action potential and calcium transient clamp.
In the past decades, various computational models of the pacemaker activity of single sinoatrial (SA) nodal cells have been developed, building on data obtained in patch-clamp experiments on isolated SA nodal myocytes. These models show widely different results regarding the contribution of individual ionic currents to diastolic depolarization and pacemaker activity of the SA nodal myocyte. Because several of these ionic currents are strongly dependent on time, voltage and/or intracellular free calcium concentration ([Ca(2+)](i), one may argue that the apparent differences in the contribution of a particular ionic current to pacemaker activity between SA nodal cell models reflect differences in action potential shape and calcium transient between models rather than intrinsic differences in the ionic current of interest. To better appreciate the contribution of individual ionic currents to pacemaker activity in a computational model of an SA nodal cell, we imposed a realistic action potential shape and calcium transient on the model cell. This was achieved by first simultaneously recording membrane potential and ([Ca(2+)](i) from single isolated SA nodal myocytes and then subjecting the model cell to a combined ;action potential clamp' and ;calcium transient clamp' using a data file with a train of experimentally recorded SA nodal action potentials and associated calcium transients. The thus computed individual ionic currents should then more closely resemble the ;true' ionic currents during pacemaker activity of an SA nodal myocyte. Also, differences between the recorded and the computed net membrane current may prove helpful in identifying shortcomings of the computational model.


Low temperature induced non-culturability and killing of Vibrio vulnificus.
Vibrio vulnificus cells progressively lose culturability during incubation at 5 degrees C. This process is accelerated by the addition of supernatants from non-culturable cells obtained by incubation at 5 degrees C for 17 days. Thus the organism apparently produces a factor upon cold incubation which is triggering or causing the decline in culturability. Reversing the temperature shift can restore a culturable population comparable in numbers to the original population, but this process is largely due to regrowth. A few cells retaining the ability to grow apparently utilize the substrates released by the moribund cells, thus mimicking resuscitation of the whole population.


PREP-Mt: predictive RNA editor for plant mitochondrial genes.
In plants, RNA editing is a process that converts specific cytidines to uridines and uridines to cytidines in transcripts from virtually all mitochondrial protein-coding genes. There are thousands of plant mitochondrial genes in the sequence databases, but sites of RNA editing have not been determined for most. Accurate methods of RNA editing site prediction will be important in filling in this information gap and could reduce or even eliminate the need for experimental determination of editing sites for many sequences. Because RNA editing tends to increase protein conservation across species by "correcting" codons that specify unconserved amino acids, this principle can be used to predict editing sites by identifying positions where an RNA editing event would increase the conservation of a protein to homologues from other plants. PREP-Mt takes this approach to predict editing sites for any protein-coding gene in plant mitochondria. To test the general applicability of the PREP-Mt methodology, RNA editing sites were predicted for 370 full-length or nearly full-length DNA sequences and then compared to the known sites of RNA editing for these sequences. Of 60,263 cytidines in this test set, PREP-Mt correctly classified 58,994 as either an edited or unedited site (accuracy = 97.9%). PREP-Mt properly identified 3,038 of the 3,698 known sites of RNA editing (sensitivity = 82.2%) and 55,956 of the 56,565 known unedited sites (specificity = 98.9%). Accuracy and sensitivity increased to 98.7% and 94.7%, respectively, after excluding the 489 silent editing sites (which have no effect on protein sequence or function) from the test set. These results indicate that PREP-Mt is effective at identifying C to U RNA editing sites in plant mitochondrial protein-coding genes. Thus, PREP-Mt should be useful in predicting protein sequences for use in molecular, biochemical, and phylogenetic analyses. In addition, PREP-Mt could be used to determine functionality of a mitochondrial gene or to identify particular sequences with unusual editing properties. The PREP-Mt methodology should be applicable to any system where RNA editing increases protein conservation across species.


Pharmacogenetic trial of a cannabinoid agonist shows reduced fasting colonic motility in patients with nonconstipated irritable bowel syndrome.
Cannabinoid receptors are located on cholinergic neurons. Genetic variants that affect endocannabinoid metabolism are associated with colonic transit in patients with irritable bowel syndrome (IBS) with diarrhea. We compared the effects of dronabinol, a nonselective agonist of the cannabinoid receptor, with those of placebo on colonic motility and sensation in patients with IBS, and examined the effects of IBS subtype and specific genetic variants in cannabinoid mechanisms. Seventy-five individuals with IBS (35 with IBS with constipation, 35 with IBS with diarrhea, and with 5 IBS alternating) were randomly assigned to groups that were given 1 dose of placebo or 2.5 mg or 5.0 mg dronabinol. We assessed left colonic compliance, motility index (MI), tone, and sensation during fasting and after a meal. We analyzed the single nucleotide polymorphisms CNR1 rs806378, fatty acid amide hydrolase (FAAH) rs324420, and MGLL rs4881. In all patients, dronabinol decreased fasting proximal left colonic MI compared with placebo (overall P = .05; for 5 mg dronabinol, P = .046), decreased fasting distal left colonic MI (overall P = .08; for 5 mg, P = .13), and increased colonic compliance (P = .058). The effects of dronabinol were greatest in patients with IBS with diarrhea or IBS alternating (proximal colonic MI, overall P = .022; compliance, overall P = .03). Dronabinol did not alter sensation or tone. CNR1 rs806378 (CC vs CT/TT) appeared to affect fasting proximal MI in all patients with IBS (P = .075). Dronabinol affected fasting distal MI in patients, regardless of FAAH rs324420 variant (CA/AA vs CC) (P = .046); the greatest effects were observed among IBS with constipation patients with the FAAH CC variant (P = .045). Dronabinol affected fasting proximal MI in patients with IBS with diarrhea or alternating with the variant FAAH CA/AA (P = .013). In patients with IBS with diarrhea or alternating, dronabinol reduces fasting colonic motility; FAAH and CNR1 variants could influence the effects of this drug on colonic motility.


Chlamydia pneumoniae infection in patients with chronic obstructive pulmonary disease.
The prevalence of chronic Chlamydia pneumoniae infection was assessed in 54 patients with established chronic obstructive pulmonary disease (COPD), 41 of these with severe COPD (group I), 13 with mild to moderate COPD (group II), and in 23 patients with community-acquired pneumonia (controls, group III). Specific IgG and IgA antibody levels and circulating immune complexes (ICs) were measured in paired sera, and specific secretory IgA (sIgA) levels in sputum specimens. A polymerase chain reaction (PCR) test was used for the detection of C. pneumoniae in sputum. According to our definite diagnosis criterion, 65% of the COPD patients showed evidence of suspected chronic C. pneumoniae infection and the prevalence was still higher (71%) in patients with severe disease. The occurrence of specific markers of infection was invariably highest in patients with severe COPD, next-highest in patients with mild to moderate COPD and lowest in pneumonia patients. The association between COPD and C. pneumoniae infection persisted after controlling for the potential confounding factors.


Chinchaysuyoa, a new genus of the fish family Ariidae (Siluriformes), with a redescription of Chinchaysuyoa labiata from Ecuador and a new species description from Peru.
In recent years, morphological and molecular studies have improved our understanding about the relationships and classification schemes of the marine catfishes of the family Ariidae. A taxonomic issue that is still contentious concerns the limits and status of the freshwater Neotropical ariid diversity, in particular the species in the genus Potamarius. The delimitation of Potamarius is currently uncertain given the disjunct distribution of the species in Mesoamerica (Potamarius izabalensis, P. nelsoni and P. usumacintae, from Lake Izabal and Usumacinta River basins in Mexico to Guatemala) and Brazil (P. grandoculis, from coastal lakes in southeastern Brazil). The freshwater Arius labiatus and Hexanematichthys henni from the Peripa and Daule rivers in Ecuador that drain to the Eastern Pacific (EP), have also at times been listed as species inquirenda in Potamarius. Here, we redescribe Arius labiatus, redefine the taxonomic status of Hexanematichthys henni, as junior synonym of Arius labiatus, and describe a new species from Peru that is closely related to Arius labiatus. Based on morphological and molecular phylogenetic evidence, we also describe a new genus (Chinchaysuyoa) for the two South American species.


Haloperidol: effect of long-term treatment on rat striatal dopamine synthesis and turnover.
The short- and long-term effects of neuroleptic drugs differ both clinically and biochemically. Short-term treatment with such a drug causes a kinetic activation of striatal tyrosine hydroxylase. Long-term treatment causes a prompt activation of the enzyme which is followed by a delayed, compensatory deactivation below control levels. Tolerance also develops to the stimulating effect of haloperidol on striatal dopamine turnover.


Test of the multifactorial aging method using skeletons with known ages-at-death from the Grant Collection.
The multifactorial aging method has been shown to be a highly reliable method of skeletal aging because it incorporates age information from as many age indicators as are available for each skeleton (Lovejoy et al.; Am. J. Phys. Anthropol. 68:1-14, 1985). The present study was a blind test to assess its accuracy on a skeletal sample composed of 55 individuals with verified death certificates (Grant Collection, University of Toronto). Three authors (C.O.L., M.E.B., and K.F.R.), with no access to the death certificate ages, independently seriated and aged the sample using three to four criteria: auricular surface, pubic symphysis, and radiographs of the proximal femur and clavicle. Summary ages were then calculated for each individual in the sample. The authors' independent summary age estimates showed strong correlations with one another (r = 0.84-0.89). Multifactorial age estimates correlated better with real age than did those from any single indicator used. The mean error (averaging 8.7 years) for summary age was at least 1 year less than that for any single indicator. Average bias ranged from -0.7 (underage) to 1.4 (overage) years. These results indicate that utilization of several age indicators, weighted according to their reliability, helps control for variation in the changes that occur with age in any single morphological indicator. This method may therefore be considered one of the most accurate available for the determination of skeletal age-at-death, particularly for paleodemographic analysis.


Force barriers for membrane tube formation.
We used optical tweezers to measure the force-extension curve for the formation of tubes from giant vesicles. We show that a significant force barrier exists for the formation of tubes, which increases linearly with the radius of the area on which the pulling force is exerted. The tubes form through a first-order transition with accompanying hysteresis. We confirm these results with Monte Carlo simulations and theoretical calculations. Whether membrane tubes can be formed in, for example, biological cells, thus depends on the details of how forces are applied.


Analysis of functional domains of Rts1 RepA by means of a series of hybrid proteins with P1 RepA.
The RepA protein of the plasmid Rts1, consisting of 288 amino acids, is a trans-acting protein essential for initiation of plasmid replication. To study the functional domains of RepA, hybrid proteins of Rts1 RepA with the RepA initiator protein of plasmid P1 were constructed such that the N-terminal portion was from Rts1 RepA and the C-terminal portion was from P1 RepA. Six hybrid proteins were examined for function. The N-terminal region of Rts1 RepA between amino acid residues 113 and 129 was found to be important for Rts1 ori binding in vitro. For activation of the origin in vivo, an Rts1 RepA subregion between residues 177 and 206 as well as the DNA binding domain was required. None of the hybrid initiator proteins activated the P1 origin. Both in vivo and in vitro studies showed, in addition, that a C-terminal portion of Rts1 RepA was required along with the DNA binding and ori activating domains to achieve autorepression, suggesting that the C-terminal region of Rts1 RepA is involved in dimer formation. A hybrid protein consisting of the N-terminal 145 amino acids of Rts1 and the C-terminal 142 amino acids from P1 showed strong interference with both Rts1 and P1 replication, whereas other hybrid proteins showed no or little effect on P1 replication.


Effect of an isolated active compound (Cg-1) of Cassia glauca leaf on blood glucose, lipid profile, and atherogenic index in diabetic rats.
The objective of present study was to evaluate the effect of active principle (Cg-1) from Cassia glauca leaf on serum glucose and lipid profile in normal and diabetic rats. Diabetes was induced by streptozotocin in neonates. Oral administration of petroleum ether, chloroform, acetone, and methanol of C. glauca leaf (100 mg/kg, p.o.) for 21 days caused a decrease in fasting blood glucose (FBG) in diabetic rats. Among all the extracts, acetone extract was found to lower the FBG level significantly in diabetic rats. Glibenclamide was used as standard antidiabetic drug (5 mg/kg, p.o). Acetone extract was subjected to column chromatography that led to isolation of an active principle, which was given trivial name Cg-1. Cg-1 (50 mg/kg, p.o.) was studied for its hypoglycemic and hypolipidemic potential. The unpaired t-test and analysis of variance (ANOVA) followed by post hoc test was used for statistical analysis. Cg-1 caused a significant reduction in FBG level. It also caused reduction in cholesterol, triglycerides, and LDL levels and improvement in the atherogenic index and HDL level in diabetic rats. Improvement in the FBG and the atherogenic index by Cg-1 indicates that Cg-1 has cardioprotective potential along with antidiabetic activity and provides a scientific rationale for the use as an antidiabetic agent.