Illness causal beliefs in Turkish immigrants.
People hold a wide variety of beliefs concerning the causes of illness. Such beliefs vary across cultures and, among immigrants, may be influenced by many factors, including level of acculturation, gender, level of education, and experience of illness and treatment. This study examines illness causal beliefs in Turkish-immigrants in Australia. Causal beliefs about somatic and mental illness were examined in a sample of 444 members of the Turkish population of Melbourne. The socio-demographic characteristics of the sample were broadly similar to those of the Melbourne Turkish community. Five issues were examined: the structure of causal beliefs; the relative frequency of natural, supernatural and metaphysical beliefs; ascription of somatic, mental, or both somatic and mental conditions to the various causes; the correlations of belief types with socio-demographic, modernizing and acculturation variables; and the relationship between causal beliefs and current illness. Principal components analysis revealed two broad factors, accounting for 58 percent of the variation in scores on illness belief scales, distinctly interpretable as natural and supernatural beliefs. Second, beliefs in natural causes were more frequent than beliefs in supernatural causes. Third, some causal beliefs were commonly linked to both somatic and mental conditions while others were regarded as more specific to either somatic or mental disorders. Last, there was a range of correlations between endorsement of belief types and factors defining heterogeneity within the community, including with demographic factors, indicators of modernizing and acculturative processes, and the current presence of illness. Results supported the classification of causal beliefs proposed by Murdock, Wilson & Frederick, with a division into natural and supernatural causes. While belief in natural causes is more common, belief in supernatural causes persists despite modernizing and acculturative influences. Different types of causal beliefs are held in relation to somatic or mental illness, and a variety of apparently logically incompatible beliefs may be concurrently held. Illness causal beliefs are dynamic and are related to demographic, modernizing, and acculturative factors, and to the current presence of illness. Any assumption of uniformity of illness causal beliefs within a community, even one that is relatively culturally homogeneous, is likely to be misleading. A better understanding of the diversity, and determinants, of illness causal beliefs can be of value in improving our understanding of illness experience, the clinical process, and in developing more effective health services and population health strategies.


Expression of the calmodulin-dependent protein phosphatase, calcineurin, in rat brain: developmental patterns and the role of nigrostriatal innervation.
The distribution of neurons expressing the calmodulin-dependent protein phosphatase, calcineurin (CN) was characterized in developing and adult rat brain using a combination of immunocytochemical, immunoblot and in situ hybridization approaches. Immunoblot analysis revealed a strong increase postnatally in CN protein expression. Four differently-charged isoforms of CN were observed in adult brain with apparent regional differences in isoform expression. Immunocytochemistry showed highest levels of CN in hippocampus, striatum, substantia nigra, amygdala and septal nuclei with immunoreactivity first appearing in striatum and septal nuclei, followed by hippocampus, neocortex and limbic structures. In situ hybridization demonstrated that mRNA for the catalytic subunit of CN was seen as early as postnatal day (PND) 1 in striatum, cortex and hippocampus. Since immunoreactivity was not detectable until day 4, this suggests that mRNA expression may precede that of protein by several days in these regions. Lesioning of developing and adult nigrostriatal dopamine neurons either with 6-hydroxydopamine or by surgical hemitransection had little effect on expression of CN, suggesting that CN expression is not influenced transsynaptically by dopamine. Collectively, these findings demonstrate that CN protein and mRNA expression are subject to regional and temporal control during brain development suggesting that specific synaptic connections may influence CN gene expression. However, in striatum, dopaminergic innervation does not appear to affect CN levels.


Synthesis of a spatial filter for the combined operations of subtraction and correlation.
As is known, a coherent optical data processing system can be used to perform convolution and correlation with ease. Recently it has been shown that the system with diffraction gratings in the spatial filtering plane can also add or subtract complex patterns displayed symmetrically in the input plane. A method is described here for synthesizing a spatial filter so that the coherent system can perform both correlation and subtraction simultaneously in real time. As a particular application of this technique, we present results of using such filters in optical feature extraction.


Cooperative regulation of calcitonin gene-related peptide levels in rat sensory neurons via their central and peripheral processes.
Calcitonin gene-related peptide (CGRP) is present in both motor and sensory neurons and transported in the somatofugal direction. CGRP levels in sensory neurons are assumed to be regulated by NGF supplied from their peripheral targets. In cultured sensory neurons, however, a basal level of CGRP persists even without NGF. This suggests that some additional factors may be involved in regulation of CGRP levels of sensory neurons. The present study shows that chronic section of the sciatic nerve in the rat reduces CGRP levels in the lumbar dorsal root ganglia (DRG), whereas section of dorsal roots increases CGRP levels in the DRG. This increased CGRP level by dorsal rhizotomy was associated with enhancement of the CGRP mRNA expression in the DRG. Thus, CGRP expression in DRG appears to be regulated reciprocally via their central and peripheral processes. When the sciatic nerve had been cut 1 week previously, however, dorsal rhizotomy no longer increased CGRP levels in the lumbar DRG. Therefore, stimulation of CGRP synthesis in the DRG by dorsal rhizotomy may require the integrity of the peripheral processes. When NGF had been infused into the central stump of the cut sciatic nerve, dorsal rhizotomy again increased CGRP levels in the DRG, despite prior section of the peripheral processes. We conclude that CGRP expression in sensory neurons may be regulated by cooperative action of some factors derived via their central processes and NGF supplied from the peripheral targets.


Beyond online participant crowdsourcing: The benefits and opportunities of big team addiction science.
Participant crowdsourcing platforms (e.g., MTurk, Prolific) offer numerous advantages to addiction science, permitting access to hard-to-reach populations and enhancing the feasibility of complex experimental, longitudinal, and intervention studies. Yet these are met with equal concerns about participant nonnaivety, motivation, and careless responding, which if not considered can greatly compromise data quality. In this article, we discuss an alternative crowdsourcing avenue that overcomes these issues whilst presenting its own unique advantages-crowdsourcing researchers through big team science. First, we review several contemporary efforts within psychology (e.g., ManyLabs, Psychological Science Accelerator) and the benefits these would yield if they were more widely implemented in addiction science. We then outline our own consortium-based approach to empirical dissertations: a grassroots initiative that trains students in reproducible big team addiction science. In doing so, we discuss potential challenges and their remedies, as well as providing resources to help addiction researchers develop these initiatives. Through researcher crowdsourcing, together we can answer fundamental scientific questions about substance use and addiction, build a literature that is representative of a diverse population of researchers and participants, and ultimately achieve our goal of promoting better global health. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Effects of internet-based cognitive behavioural therapy and physical exercise on sick leave and employment in primary care patients with depression: two subgroup analyses.
Depression can negatively impact work capacity, but treatment effects on sick leave and employment are unclear. This study evaluates if internet-based cognitive behavioural therapy (ICBT) or physical exercise (PE), with already reported positive effects on clinical outcome and short-term work ability, has better effects on employment, sick leave and long-term work ability compared with treatment as usual (TAU) for depressed primary care patients (German clinical trials: DRKS00008745). After randomisation and exclusion of patients not relevant for work-related analysis, patients were divided into two subgroups: initially unemployed (total n=118) evaluated on employment, and employed (total n=703) evaluated on long-term sick leave. Secondary outcomes were self-rated work ability and average number of sick days per month evaluated for both subgroups. Assessments (self-reports) were made at baseline and follow-up at 3 and 12 months. For the initially unemployed subgroup, 52.6% were employed after 1 year (response rate 82%). Both PE (risk ratio (RR)=0.44; 95% CI 0.23 to 0.87) and ICBT (RR=0.37; 95% CI 0.16 to 0.84) showed lower rates compared with TAU after 3 months, but no difference was found after 1 year (PE: RR=0.97; 95% CI 0.69 to 1.57; ICBT: RR=1.23; 95% CI 0.72 to 2.13). For those with initial employment, long-term sick leave (response rate 75%) decreased from 7.8% to 6.5%, but neither PE (RR=1.4; 95% CI 0.52 to 3.74) nor ICBT (RR=0.99; 95% CI 0.39 to 2.46) decreased more than TAU, although a temporary positive effect for PE was found. All groups increased self-rated work ability with no differences found. No long-term effects were found for the initially unemployed on employment status or for the initially employed on sick leave. New types of interventions need to be explored.


Introducing a multi-site program for early diagnosis of HIV infection among HIV-exposed infants in Tanzania.
In Tanzania, less than a third of HIV infected children estimated to be in need of antiretroviral therapy (ART) are receiving it. In this setting where other infections and malnutrition mimic signs and symptoms of AIDS, early diagnosis of HIV among HIV-exposed infants without specialized virologic testing can be a complex process. We aimed to introduce an Early Infant Diagnosis (EID) pilot program using HIV DNA Polymerase Chain Reaction (PCR) testing with the intent of making EID nationally available based on lessons learned in the first 6 months of implementation. In September 2006, a molecular biology laboratory at Bugando Medical Center was established in order to perform HIV DNA PCR testing using Dried Blood Spots (DBS). Ninety-six health workers from 4 health facilities were trained in the identification and care of HIV-exposed infants, HIV testing algorithms and collection of DBS samples. Paper-based tracking systems for monitoring the program that fed into a simple electronic database were introduced at the sites and in the laboratory. Time from birth to first HIV DNA PCR testing and to receipt of test results were assessed using Kaplan-Meier curves. From October 2006 to March 2007, 510 HIV-exposed infants were identified from the 4 health facilities. Of these, 441(87%) infants had an HIV DNA PCR test at a median age of 4 months (IQR 1 to 8 months) and 75(17%) were PCR positive. Parents/guardians for a total of 242(55%) HIV-exposed infants returned to receive PCR test results, including 51/75 (68%) of those PCR positive, 187/361 (52%) of the PCR negative, and 4/5 (80%) of those with indeterminate PCR results. The median time between blood draw for PCR testing and receipt of test results by the parent or guardian was 5 weeks (range <1 week to 14 weeks) among children who tested PCR positive and 10 weeks (range <1 week to 21 weeks) for those that tested PCR negative. The EID pilot program successfully introduced systems for identification of HIV-exposed infants. There was a high response as hundreds of HIV-exposed infants were registered and tested in a 6 month period. Challenges included the large proportion of parents not returning for PCR test results. Experience from the pilot phase has informed the national roll-out of the EID program currently underway in Tanzania.


[Effect of electron irradiation on the structure of microsomal membrane proteins].
Using tryptophan fluorescence quenching by iodide and acrylamide the effect of electrons with the energy 5 Mev on the structure of microsomal membrane proteins has been studied. Conformation of microsomal proteins were found to change upon irradiation.


The Association between leisure time physical activity and smoking in adolescence: an examination of potential mediating and moderating factors.
Although physical activity has been associated negatively with smoking in adolescence, the association is not well understood. This study examines the relationship between adolescents' leisure time physical activity and smoking behavior, while considering BMI, weight concern, sense of coherence, and physically active self-concept as potential mediating and moderating variables. Data were obtained through a postal survey among 3,940 Danes aged 16 to 20. Bivariate and multivariate logistic regressions were performed to identify significant associations as well as mediating and moderating effects. In the bivariate model, leisure time physical activity was negatively associated with smoking; adolescents who were active at least one hour per week were up to half as likely to smoke as inactive adolescents. In the adjusted model, however, the association disappeared. Further analyses revealed that physically active self-concept acted both as a mediator and as a moderator of the studied relationship. The data suggest that participation in leisure time physical activity is indeed inversely associated with adolescent smoking, but only when physical activity is perceived as an important part of the self. Hence, interventions designed to promote physical activity among youth may also aim to boost physically active self-concepts.


In situ thrombosis of small pulmonary arteries in pulmonary hypertension developing after chemotherapy for malignancy.
A few reports have provided histopathological insight into pulmonary hypertension developing after antitumor chemotherapy. In general, plexogenic pulmonary arteriopathy is a commonly observed finding in patients with severe pulmonary hypertension. We herein report a novel pathological finding that may characterize the histopathological change occurring in patients with pulmonary hypertension after chemotherapy for malignancy. Lung biopsy or autopsy was performed in 7 patients with pulmonary hypertension that developed during or after chemotherapy between 2006 and 2013 to examine the pulmonary vascular changes or to determine the cause of death. Pathological findings included in situ thrombosis in the small pulmonary arteries in 4 of 7 patients. In 2 of 4 patients, pulmonary hypertension was controlled by anticoagulants and antithrombotic agents. One patient who had organized thrombi attained spontaneous remission with oxygen therapy. The other patient died of sudden cardiopulmonary arrest during chemotherapy. Autopsy showed complete occlusion of the peripheral small pulmonary arteries and veins by thrombi. These results demonstrate that in situ thrombosis in the small pulmonary arteries could cause pulmonary hypertension after chemotherapy.


Late holocene tectonic activity along the margins of the sinai subplate.
Remarkable folding and uplifting movements were active along the western margin of the Sinai subplate (the Bardawil Lagoon and its periphery) during the Upper Holocene. The coasts of the eastern margin (Gulf of Elat) were also uplifted during the same tectonic phase. The nature of this activity is discussed in relation to the regional tectonic framework.


Nurse resilience for clinical practice: An integrative review.
To evaluate and synthesize research that has investigated nurse resilience, to develop an understanding of what nurses' feel affects their resilience, their experiences and how resilience can impact individual nurses, patients and employers. Integrative review. CINAHL, MEDLINE and PsycINFO, searched from the date each database was available to July 2019. Primary research studies explicitly investigating resilience in any type of licensed nurse were eligible for inclusion. Studies were critically appraised for methodological quality using the Joanna Briggs Institute Quality Appraisal Framework. Data from each study were abstracted, coded and themes were identified according to the review aims and key findings of each study. Twenty-seven studies met the inclusion criteria. Eight sub-themes and three main themes were identified: The Resilient Nurse, Nurses' Experiences of Resilience and Employment Conditions and Nurse Resilience. Nurse resilience is a complex and dynamic process, and high levels of resilience are associated with reduced psychological harm and increased well-being. Attempts to determine the characteristics of the resilient nurse have been inconclusive and research has predominately focussed on individual factors which could affect resilience, with minimal research exploring external factors which affect nurse resilience including work environment and conditions. Nursing work was characterized by adversity and nurses described the development and use of strategies to maintain their resilience. This review found that individual factors have received most attention in research investigating nurse resilience. Findings suggest that nurse resilience protects against negative psychological outcomes and nurses independently develop and use strategies to manage adversity. Factors in the workplace which affect resilience are under-researched, and addressing this gap could assist with the development of comprehensive interventions and policies to build and maintain nurse resilience.


Transgenic Archaerhodopsin-3 Expression in Hypocretin/Orexin Neurons Engenders Cellular Dysfunction and Features of Type 2 Narcolepsy.
Narcolepsy, characterized by excessive daytime sleepiness, is associated with dysfunction of the hypothalamic hypocretin/orexin (Hcrt) system, either due to extensive loss of Hcrt cells (Type 1, NT1) or hypothesized Hcrt signaling impairment (Type 2, NT2). Accordingly, efforts to recapitulate narcolepsy-like symptoms in mice have involved ablating these cells or interrupting Hcrt signaling. Here, we describe orexin/Arch mice, in which a modified archaerhodopsin-3 gene was inserted downstream of the prepro-orexin promoter, resulting in expression of the yellow light-sensitive Arch-3 proton pump specifically within Hcrt neurons. Histological examination along with ex vivo and in vivo electrophysiological recordings of male and female orexin/Arch mice demonstrated silencing of Hcrt neurons when these cells were photoilluminated. However, high expression of the Arch transgene affected cellular and physiological parameters independent of photoillumination. The excitability of Hcrt neurons was reduced, and both circadian and metabolic parameters were perturbed in a subset of orexin/Arch mice that exhibited high levels of Arch expression. Orexin/Arch mice also had increased REM sleep under baseline conditions but did not exhibit cataplexy, a sudden loss of muscle tone during wakefulness characteristic of NT1. These aberrations resembled some aspects of mouse models with Hcrt neuron ablation, yet the number of Hcrt neurons in orexin/Arch mice was not reduced. Thus, orexin/Arch mice may be useful to investigate Hcrt system dysfunction when these neurons are intact, as is thought to occur in narcolepsy without cataplexy (NT2). These results also demonstrate the utility of extended phenotypic screening of transgenic models when specific neural circuits have been manipulated.SIGNIFICANCE STATEMENT Optogenetics has become an invaluable tool for functional dissection of neural circuitry. While opsin expression is often achieved by viral injection, stably integrated transgenes offer some practical advantages. Here, we demonstrate successful transgenic expression of an inhibitory opsin in hypocretin/orexin neurons, which are thought to promote or maintain wakefulness. Both brief and prolonged illumination resulted in inhibition of these neurons and induced sleep. However, even in the absence of illumination, these cells exhibited altered electrical characteristics, particularly when transgene expression was high. These aberrant properties affected metabolism and sleep, resulting in a phenotype reminiscent of the narcolepsy Type 2, a sleep disorder for which no good animal model currently exists.


Genome report: chromosome-level draft assemblies of the snow leopard, African leopard, and tiger (Panthera uncia, Panthera pardus pardus, and Panthera tigris).
The big cats (genus Panthera) represent some of the most popular and charismatic species on the planet. Although some reference genomes are available for this clade, few are at the chromosome level, inhibiting high-resolution genomic studies. We assembled genomes from 3 members of the genus, the tiger (Panthera tigris), the snow leopard (Panthera uncia), and the African leopard (Panthera pardus pardus), at chromosome or near-chromosome level. We used a combination of short- and long-read technologies, as well as proximity ligation data from Hi-C technology, to achieve high continuity and contiguity for each individual. We hope that these genomes will aid in further evolutionary and conservation research of this iconic group of mammals.


Overlapping and distinct mechanisms of action of multiple sclerosis therapies.
In the last two decades MS has changed from an idiopathic condition with only symptomatic treatments to a disease with better characterized pathophysiologic underpinnings and several treatments that modify its long-term course based on specific mechanisms of action. There are now several FDA approved options for therapy at the onset of disease, and discussions have begun on choosing the best treatment in individual patients and what option to choose next in patients who are failing their current treatment. Numerous studies have begun to highlight that the underlying pathology of CNS damage may be different in subsets of patients, raising the possibility that some may respond to a treatment with a mechanism of action that is targeted to 'their' MS. Trials are ongoing of numerous new agents with different mechanisms of action and some combination therapies. A better understanding of how each therapy works may guide decisions on initiating, combining or changing therapy in a more rational way to improve patient outcomes. Further knowledge of underlying mechanisms of disease in different patients with 'the same' disease may lead to more targeted therapies, as will biomarkers that predict clinical response to therapy. Studies of the effects of various agents used in MS reveal both overlapping and distinct mechanisms of actions that may be relevant to their efficacy and side effects in individual patients. However, it is important to remember that most agents are approved based on their reduction of MRI lesions and relapse rates over a short time frame. These measures only partially correlate with long-term disability, which may be the most relevant clinical outcome for people with MS. Fixed disability requires years to become apparent, and there is a lack of large studies of biomarkers for chronic outcomes. In addition, few large studies correlate response to therapy with cognitive outcomes, which are a major cause of chronic disability. This review will attempt to summarize clinically relevant knowledge of the mechanisms of action of current FDA approved therapies for MS in the context of ongoing clinical trials of combination therapy and address rational approaches to changing therapy in a patient suspected to be 'unresponsive' to their current treatment.


[High mortality following psychosis: not only due to suicide].
In the 1980s about 8.5% of patients in northern Netherlands with a psychotic disorder died due to suicide within five years of follow-up. Liemburg, Castelein and colleagues investigated whether this percentage had recently decreased. They found suicide in 2.4% of patients with recent psychosis after an average follow-up of 5 years. Although causality cannot be inferred from a naturalistic study such as theirs, it is plausible that the decreased suicide rate is associated with improvements in the care for psychotic patients. Preventing suicide is invaluable. However, given the alarmingly high mortality due to somatic diseases in patients with schizophrenia, other measures to substantially decrease the high mortality associated with schizophrenia are also warranted.


Directly observed antiretroviral therapy: a systematic review and meta-analysis of randomised clinical trials.
Directly observed therapy has been recommended to improve adherence for patients with HIV infection who are on highly active antiretroviral therapy, but the benefit and cost-effectiveness of this approach has not been established conclusively. We did a systematic review and meta-analysis of randomised trials of directly observed versus self-administered antiretroviral treatment. We did duplicate searches of databases (from inception to July 27, 2009), searchable websites of major HIV conferences (up to July, 2009), and lay publications and websites (March-July, 2009) to identify randomised trials assessing directly observed therapy to promote adherence to antiretroviral therapy in adults. Our primary outcome was virological suppression at study completion. We calculated relative risks (95% CIs), and pooled estimates using a random-effects method. 12 studies met our inclusion criteria; four of these were done in groups that were judged to be at high risk of poor adherence (drug users and homeless people). Ten studies reported on the primary outcome (n=1862 participants); we calculated a pooled relative risk of 1.04 (95% CI 0.91-1.20, p=0.55), and noted moderate heterogeneity between the studies (I(2)= 53.8%, 95% CI 0-75.7, p=0.0247) for directly observed versus self-administered treatment. Directly observed antiretroviral therapy seems to offer no benefit over self-administered treatment, which calls into question the use of such an approach to support adherence in the general patient population. None.


Discriminatory inhibition of protein synthesis in cell-free systems by vaccinia virus transcripts.
The effect of vaccinia virus early transcripts on cellular (globin, HeLa, Chinese hamster ovary) and viral (vaccinia, encephalomyocarditis) mRNA function was studied in reticulocyte and wheat germ cell-free protein-synthesizing systems. Vaccinia virus transcripts of two size classes (8-10 S and 4-7 S), generated in vitro by viral cores, inhibited function of cellular and encephalomyocarditis virus mRNA but not that of vaccinia virus in reticulocyte lysate systems. Mild alkaline hydrolysis or micrococcal nuclease treatment of vaccinia virus in vitro transcripts resulted in a loss of their ability to inhibit protein synthesis directed by HeLa cell RNA. Vaccinia virus in vitro transcripts also selectively inhibited HeLa cell protein synthesis in wheat germ systems, suggesting that double-stranded RNA is not involved in this inhibition of protein synthesis. The addition, to the reticulocyte translating system, of cytoplasmic RNA obtained from infected cells in conjunction with cellular mRNA (globin, HeLa) resulted in the inhibition of synthesis of the globin or HeLa polypeptides with little or no effect on the translation of the vaccinia virus proteins. RNA extracted from vaccinia virions inhibited cellular but not vaccinia virus mRNA function when added to the reticulocyte lysate systems with uninfected or infected HeLa cell cytoplasmic RNA.


Information retrieval maps for biomedical research.
Integration of computer-based information sources should be useful for biomedical research. An information retrieval map is a graphical representation of a set of expert rules for integrating computer-based information sources based on the data connections among those information sources. The use and implementation of an information retrieval map for sequence alignment is described.


Lung clearance index predicts pulmonary exacerbations in individuals with primary ciliary dyskinesia: a multicentre cohort study.
Lung clearance index (LCI) is a promising lung function outcome in individuals with primary ciliary dyskinesia (PCD). The impact of events clinically important for individuals with PCD, such as pulmonary exacerbations, on LCI is unknown. We conducted an international, multicentre, observational cohort study to assess the association of LCI and risk of pulmonary exacerbation, specific changes in LCI during pulmonary exacerbation and global variability of LCI across four visits every 4 months. Ninety individuals with PCD, aged 3-41 years, underwent nitrogen multiple-breath washout (MBW) and spirometry measurements. The association of LCI and pulmonary exacerbations was assessed by Cox proportional hazards and random-effects regression models. We obtained 430 MBW and 427 spirometry measurements. In total, 379 person-years at risk contributed to the analysis. Per one unit increase (deterioration) in LCI, the risk of future pulmonary exacerbation increased by 13%: HR (95% CI), 1.13 (1.04 to 1.23). If LCI changed from a range of values considered normal to abnormal, the risk of future pulmonary exacerbations increased by 87%: 1.87 (1.08 to 3.23). During pulmonary exacerbations, LCI increased by 1.22 units (14.5%). After pulmonary exacerbations, LCI tended to decline. Estimates of variability in LCI suggested lower variation within individuals compared with variation between individuals. Findings were comparable for forced expiratory volume in 1 s. On a visit-to-visit basis, LCI measurement may add to the prediction of pulmonary exacerbations, the assessment of lung function decline and the potential lung function response to treatment of pulmonary exacerbations.


Additive gene-environment effects on hippocampal structure in healthy humans.
Hippocampal volume loss has been related to chronic stress as well as genetic factors. Although genetic and environmental variables affecting hippocampal volume have extensively been studied and related to mental illness, limited evidence is available with respect to G × E interactions on hippocampal volume. The present MRI study investigated interaction effects on hippocampal volume between three well-studied functional genetic variants (COMT Val158Met, BDNF Val66Met, 5-HTTLPR) associated with hippocampal volume and a measure of environmental adversity (life events questionnaire) in a large sample of healthy humans (n = 153). All three variants showed significant interactions with environmental adversity with respect to hippocampal volume. Observed effects were additive by nature and driven by both recent as well as early life events. A consecutive analysis of hippocampal subfields revealed a spatially distinct profile for each genetic variant suggesting a specific role of 5-HTTLPR for the subiculum, BDNF Val66Met for CA4/dentate gyrus, and COMT Val158Met for CA2/3 volume changes. The present study underscores the importance of G × E interactions as determinants of hippocampal volume, which is crucial for the neurobiological understanding of stress-related conditions, such as mood disorders or post-traumatic stress disorder (PTSD).


Viewpoints on Medical Image Processing: From Science to Application.
Medical image processing provides core innovation for medical imaging. This paper is focused on recent developments from science to applications analyzing the past fifteen years of history of the proceedings of the German annual meeting on medical image processing (BVM). Furthermore, some members of the program committee present their personal points of views: (i) multi-modality for imaging and diagnosis, (ii) analysis of diffusion-weighted imaging, (iii) model-based image analysis, (iv) registration of section images, (v) from images to information in digital endoscopy, and (vi) virtual reality and robotics. Medical imaging and medical image computing is seen as field of rapid development with clear trends to integrated applications in diagnostics, treatment planning and treatment.


Cytotoxicity evaluation of phytochemicals from stingless bee (Tetragonula biroi) propolis.
Three prenylated flavonoids (1-3) were isolated from Tetragonula biroi propolis. The structures of the isolated compounds were characterized by NMR, IR, and UV spectroscopic and mass spectrometric analyses. The cytotoxicity activity of the crude extracts, fractions and the isolated compounds were established against four cell lines such as Caco-2, HeLa, MCF-7, and OVK-18. Among the tested compounds, compound 1 showed cytotoxicity activity against MCF-7 cell lines, whereas compound 2 showed good activity against Caco-2 and OVK-18 cell lines with IC50 values of 14.73 and 14.44, respectively. Moreover, compound 3 exhibited strong activity against OVK-18 cell lines. These findings contribute to the phytochemical understanding of the T. biroi propolis, and their cytotoxicity effects for future pharmaceutical purposes.


Somatostatinoma syndrome: does a clinical entity exist?
We report here 2 patients with somatostatin-secreting tumours and hypersomatostatinaemia. One subject, a 36 year old woman with diabetes, flushing, labile blood pressure and diarrhea, had elevated basal plasma levels of somatostatin-like immunoreactivity (SLIR) and calcitonin. Plasma SLIR increased further following tolbutamide administration. Plasma levels of prostaglandin E2 (PGE2) and pancreatic polypeptide (PP), normal in the basal state, showed exaggerated responses to pentagastrin and secretin, respectively. Immunocytochemistry of the tumour tissue revealed cells containing somatostatin-, calcitonin-, PGE2- and PP-like immunoreactivity. The other patient, a 52 year old male, had an SLIR-secreting tumour of the proximal duodenum and elevated basal and post-tolbutamide SLIR levels but no signs or symptoms suggestive of increased SLIR production. Tumour tissue revealed cells containing somatostatin- and calcitonin-like immunoreactivity. We conclude that patients with somatostatinomas do not always exhibit a predictable syndrome. Patients with these tumours may exhibit a range of clinical, biochemical and immunocytochemical features typical of endocrine tumours of mixed-cell origin, such that the dominant signs and symptoms associated with these neoplasms cannot readily be ascribed to overproduction of any single hormone.


Cholinergic innervation of the amygdaloid complex in the human brain and its alterations in old age and Alzheimer's disease.
The cholinergic innervation of the human amygdaloid complex was studied immunohistochemically with a choline acetyltransferase (ChAT) antibody in eight brains: five control and three with Alzheimer's disease (AD). All amygdaloid nuclei displayed ChAT-immunopositive axons and varicosities. The density of these axons reached levels that were higher than in any other part of the forebrain except for the striatum. The highest level of ChAT-immunopositive profiles was seen in the basolateral nucleus and the second highest in the lateral part of the central nucleus. The basomedial, accessory basal, and cortical nuclei, the amygdalohippocampal and cortico-amygdaloid transition areas, as well as the anterior amygdaloid area, showed a moderate density of ChAT-positive varicosities and fibers. The lateral nucleus displayed a relatively low density of cholinergic innervation, and there were only rare ChAT-positive fibers in the medial nucleus. Although the level of cholinergic innervation in the lateral nucleus was relatively lower than in many of the other amygdaloid nuclei, it was approximately equivalent to that of entorhinal cortex, a region that receives one of the heaviest cholinergic inputs in the cerebral cortex. The distribution of the cholinergic fibers as studied by ChAT immunohistochemistry was nearly identical to that observed with AChE histochemistry. Quantitative densitometry in control specimens showed that there was no decline of amygdaloid cholinergic input when middle-aged subjects were compared with senescent subjects. In AD there was a severe and regionally selective depletion of this innervation in the amygdaloid complex. The cortical, accessory basal, and lateral nuclei displayed the most severe loss of ChAT-positive profiles, whereas the basolateral, and especially the central, nuclei displayed relatively little change. There was no consistent relationship between the loss of cholinergic fibers and the density of amyloid plaques and neurofibrillary tangles in amygdaloid nuclei.


Potential Physiological Parameters to Indicate Inner States in Dogs: The Analysis of ECG, and Respiratory Signal During Different Sleep Phases.
The sleeping activity of family dogs has been studied increasingly in the past years. Recently, a validated, non-invasive polysomnographic method has been developed for dogs, enabling the parallel recording of several neurophysiological signals on non-anesthetized family dogs, including brain activity (EEG), eye movements (EOG), cardiac (ECG), and respiratory activity (PNG). In this study, we examined the ECG (N = 30) and respiratory signals (N = 19) of dogs during a 3-h sleep period in the afternoon, under laboratory conditions. We calculated four time-domain heart rate variables [mean heart rate (HR), SDNN, RMSSD, and pNN50] from the ECG and the estimated average respiratory frequency from the respiratory signal. We analyzed how these variables are affected by the different sleep-wake phases (wakefulness, drowsiness, NREM, and REM) as well as the dogs' sex, age and weight. We have found that the sleep-wake phase had a significant effect on all measured cardiac parameters. In the wake phase, the mean HR was higher than in all other phases, while SDNN, RMSSD, and pNN50 were lower than in all other sleep phases. In drowsiness, mean HR was higher compared to NREM and REM phases, while SDNN and RMSSD was lower compared to NREM and REM phases. In REM, SDNN, and RMSSD was higher than in NREM. However, the sleep-wake phase had no effect on the estimated average respiratory frequency of dogs. The dogs' sex, age and weight had no effect on any of the investigated variables. This study represents a detailed analysis of the cardiac and respiratory activity of dogs during sleep. Since variations in these physiological signals reflect the dynamics of autonomic functions, a more detailed understanding of their changes may help us to gain a better understanding of the internal/emotional processes of dogs in response to different conditions of external stimuli. As such, our results are important since they are directly comparable to human findings and may also serve as a potential basis for future studies on dogs.


Growth patterns for three generations of an intercross between red junglefowl and chickens selected for low body weight.
Growth is a complex and dynamic process that may be measured at a specific point or over a period of time. Compared was the growth of male and female chickens over a three-generation period. Involved were red junglefowl (RJF; Gallus gallus), a line of White Plymouth Rock chickens (LWS; Gallus gallus domesticus) selected for low body weight, and their reciprocal F1 and F2 crosses. In both sexes, Gompertz's description of growth showed that RJF had significantly lower asymptotes, earlier inflection points, and faster growth rates than LWS. Heterosis for these measures was positive for asymptote and negative for growth rate and inflection point. The RJF commenced egg production at a significantly younger age and lower body weight than LWS. Although F1 and F2 reciprocal crosses were similar for body weight and for age at first egg, the F1 reciprocal crosses began lay at significantly younger ages than the F2 crosses and parental lines. When viewed on a physiological basis where age and body weight were simultaneously standardized, both parental lines and reciprocal F1 and F2 crosses had differing rapid and lag growth phases. Overall, sexual dimorphism increased in all populations from hatch to sexual maturity. The LWS males had a longer growth period consistent with their female counterparts who became sexually mature at older ages. Comprehensively, these results indicate additive and nonadditive genetic variation for distinct growth patterns and changes in resource allocation strategies over time.


Premature escape beats. A model for triggered activity in the intact heart?
In conscious dogs with complete atrioventricular block, overdrive pacing of the idioventricular rhythm normally results in overdrive suppression (OS). Frequently, however, we observed another response to overdrive, that is, QRS complex or complexes with unexpectedly short coupling intervals followed by normal OS. We have named such a QRS complex a "premature escape beat" (PEB). Based on the response of PEBs to electrical stimulation, we postulate that PEBs are based on triggered activity resulting from delayed afterdepolarizations. This hypothesis was tested in 82 experiments by 1) stimulation under control conditions and in combination with 2) subtoxic and toxic amounts of ouabain 20-50 micrograms/kg, 3) lidocaine 3 mg/kg, and 4) doxorubicin 16-24 mg/m2. The stimulation protocol, which was repeated at random five to 10 times, consisted of 10 and 50 stimuli using interstimulus intervals of 200, 400, 600, and 800 msec. This protocol was not only performed during spontaneous idioventricular rhythm but also during a continuously paced rhythm with interstimulus intervals of 800 msec. It was found that 1) the chance to induce a PEB or PEBs increased and 2) their first postpacing interval significantly decreased using short or fast drives, or both. Ouabain increased significantly and in a dose-dependent manner 1) the ability to induce PEBs and 2) the number of PEBs per stimulation-train, and also shortened their first postpacing interval. Opposite effects were seen after lidocaine, doxorubicin, and continuous pacing as follows: 1) a lower incidence of PEBs and 2) lengthening of their first postpacing interval. These results support our hypothesis that PEBs are based on triggered activity resulting from delayed afterdepolarizations.


IMIX: a multivariate mixture model approach to association analysis through multi-omics data integration.
Integrative genomic analysis is a powerful tool used to study the biological mechanisms underlying a complex disease or trait across multiplatform high-dimensional data, such as DNA methylation, copy number variation and gene expression. It is common to perform large-scale genome-wide association analysis of an outcome for each data type separately and combine the results ad hoc, leading to loss of statistical power and uncontrolled overall false discovery rate (FDR). We propose a multivariate mixture model (IMIX) framework that integrates multiple types of genomic data and allows modeling of inter-data-type correlations. We investigated the across-data-type FDR control in IMIX and demonstrated lower misclassification rates at controlled overall FDR than established individual data type analysis strategies, such as the Benjamini-Hochberg FDR control, the q-value and the local FDR control by extensive simulations. IMIX features statistically principled model selection, FDR control and computational efficiency. Applications to The Cancer Genome Atlas data provided novel multi-omics insights into the genes and mechanisms associated with the luminal and basal subtypes of bladder cancer and the prognosis of pancreatic cancer. We have implemented our method in R package 'IMIX' available at https://github.com/ziqiaow/IMIX, as well as CRAN soon. Supplementary data are available at Bioinformatics online.


Emerging biomedical applications of polyaspartic acid-derived biodegradable polyelectrolytes and polyelectrolyte complexes.
Polyelectrolytes (PELs) - polymers with charged repeat units - have emerged as a useful class of polymers for biomedical applications due to their high aqueous solubility, low aggregation propensity and the opportunity they afford for polyvalent interactions with surfaces. Biodegradability and biocompatibility of PELs are important prerequisites for their utilization in in vivo applications. PELs that can be chemically functionalized with ease prove advantageous for creating diverse biomaterials. Polyaspartic acid (PASA) is a modular and biocompatible synthetic PEL that has all these features. It also shows many positive biomedical attributes such as bone-tissue targeting, muco-adhesive behavior and extended blood circulation time. Cationic PELs derived from PASA are rapidly internalized by mammalian and bacterial cells, and hence have immense utility in therapeutic delivery applications. Polyelectrolyte complexes (PECs) and multilayers (PEMs) formed from PASA PELs have further expanded their biomedical utility. This mini-review highlights some recent literature examples of unique biomedical applications of PELs, PECs and PEMs prepared through the molecular engineering of PASA. It discusses biomineralization modulators, anti-mycobacterial agents, underwater adhesives, mucoadhesive drug and gene delivery agents, and cell encapsulants fabricated using PASA derived PELs.


Controlling the nanoscale friction by layered ionic liquid films.
The nanofriction coefficient of ionic liquids (ILs), 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) and 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]), on the surfaces of mica and graphite was investigated using atomic force microscopy (AFM). A pronounced layered spatial distribution was found in the IL film formed on the solid substrates and can be divided into 3 well distinguishable regions exhibiting different physical properties with increasing distance from the substrate. We found that the friction coefficient (μ) increases monotonically as the layering thickness decreases, no matter what the thickness of the bulk IL is. This suggests that the layering assembled IL at solid surfaces is more important than the bulk phase in determining the magnitude of the nanoscale friction. The increase in the friction coefficient as the layering thickness decreases is most likely attributed to the assembled ordered IL layers closer to the substrate surfaces having a greater activation barrier for unlocking the surfaces to allow shear.


Why some plant species are rare.
Biodiversity, including plant species diversity, is threatened worldwide as a result of anthropogenic pressures such as an increase of pollutants and climate change. Rare species in particular are on the verge of becoming extinct. It is still unclear as to why some plant species are rare and others are not. Are they rare due to: intrinsic reasons, dispersal capacity, the effects of management or abiotic circumstances? Habitat preference of rare plant species may play an important role in determining why some species are rare. Based on an extensive data set of soil parameters we investigated if rarity is due to a narrow habitat preference for abiotic soil parameters. For 23 different abiotic soil parameters, of which the most influential were groundwater-table, soil-pH and nutrient-contents, we estimated species responses for common and rare species. Based on the responses per species we calculated the range of occurrence, the range between the 5 and 95 percentile of the response curve giving the habitat preference. Subsequently, we calculated the average response range for common and rare species. In addition, we designed a new graphic in order to provide a better means for presentation of the results. The habitat preferences of rare species for abiotic soil conditions are significantly narrower than for common species. Twenty of the twenty-three abiotic parameters showed on average significantly narrower habitat preferences for rare species than for common species; none of the abiotic parameters showed on average a narrower habitat preference for common species. The results have major implications for the conservation of rare plant species; accordingly management and nature development should be focussed on the maintenance and creation of a broad range of environmental conditions, so that the requirements of rare species are met. The conservation of (abiotic) gradients within ecosystems is particularly important for preserving rare species.


Crucial role of heme oxygenase-1 in the sensitivity of acute myeloid leukemia cell line Kasumi-1 to ursolic acid.
Ursolic acid (UA), which has been used extensively as an antileukemic agent in traditional Chinese medicine, is safely edible if originating from food. We found that the apoptotic rate of acute myeloid leukemia (AML) subtype M2 (AML-M2) cell line Kasumi-1 treated by UA was higher than those of other leukemia cell lines, but was not as high as that treated by arabinofuranosyl cytidine (Ara-C), suggesting that UA is an important chemotherapeutic agent to treat AML-M2. Heme oxygenase-1 (HO-1) is a key enzyme exerting potent cytoprotection, cell proliferation, and drug resistance. HO-1 in Kasumi-1 cells was upregulated by being treated with low-dose rather than high-dose UA. Inhibition of HO-1 by zinc protoporphyrin (ZnPP) IX sensitized Kasumi-1 cells to UA, and the apoptotic rate was close to that induced by Ara-C (P<0.01). The sensitizing effect of ZnPP was associated with caspase activation, bcl-2 downregulation, and PARP activation. After silencing HO-1 by siRNA transfection with lentivirus, the cells' proliferation induced by UA was increased as it was by Ara-C. Furthermore, combining ZnPP with UA prolonged the survival of mice bearing the AML subtype M2 tumor with smaller volume of tumor and size of spleen. The results showed that the Kasumi-1 cell line was the most sensitive to UA, but the apoptotic effect was inferior to that treated by Ara-C because of HO-1 upregulation. AML-M2 can feasibly be treated by target-inhibiting HO-1 that enhances the antileukemia effects of UA in vitro and in vivo.


A novel insight into the role of entry tears in type B aortic dissection: pressure measurements in an in vitro model.
Predicting aortic growth in acute type B dissection is fundamental in planning interventions. Several factors are considered to be growth predictors in the literature and, among them, size and location of entry tears have been recognized to particularly influence the false lumen pressure. In this study, we develop an in vitro setting to analyze the actual impact of size and location of the entry tears on false lumen pressure, in the absence of other confounding factors such as the deformability of the aortic wall. We formalize some indexes that synthetically describe the false lumen pressure with respect to the true lumen pressure. Then, we experimentally derive their values in several configurations of the in vitro setting, and we look for trends in the indexes with respect to the size and location of entry tears. Results show that the tears have a relevant impact on the false lumen pressure, but that their size and location alone are not enough to explain the phenomena observed in vivo. To predict the behavior of acute type B dissection, we therefore recommend not limiting to size and location, as many effects may derive from the interactions between these parameters and other patient characteristics.


Intestinal phosphate transport and alkaline phosphatase activity in the chick.
The initial rates of phosphate accumulation by isolated chick intestinal epithelial cells have been examined. At high concentrations of phosphate (1.5 mM), phosphate uptake is relatively independent of sodium and demonstrates a pH optimum of 8.0. At pH 8.0, 56% of the uptake is dependent on the presence of Ca in the uptake medium compared to 28% at pH 6.8. Membranes prepared from these same intestinal epithelial cells contain a Ca-dependent phosphatase that can be distinguished from the more abundant Mg-dependent alkaline phosphatase. The Ca-dependent phosphatase has a pH optimum between 8.5 and 9.0 and, compared to the Mg-dependent activity, is more readily inactivated at 58 degrees C and is relatively resistant to L-phenylalanine inhibition but more sensitive to ethane-1-hydroxy-1,1-diphosphonate (EHDP). Both activities are distributed in a constant proportion between the brush border and basal lateral membranes and at various segments along the intestine. Vitamin D in vivo and 25-hydroxyvitamin D [25(OH)D] in vitro stimulated both activities. In vitro, utilizing the isolated intestinal cells, the stimulation of phosphate uptake paralleled the increase in Ca-dependent alkaline phosphatase activity. The role of alkaline phosphatase in intestinal phosphate transport is discussed.


Risks and benefits of hormone replacement therapy: the evidence speaks.
Until recently, observational studies suggested a decreased risk of cardiovascular disease, osteoporotic fractures, cognitive decline and colon cancer with the use of hormone replacement therapy (HRT). Recent randomized controlled trials have failed to show a protective effect of HRT in reducing the risk of coronary artery disease and instead have revealed an increased risk of heart disease, stroke, invasive breast cancer and venous thromboembolism, but a decreased risk of colorectal cancer and osteoporotic fractures. In this article we review the current evidence of the risks and benefits of HRT.


Mechanistic insights into the protective roles of polyphosphate against amyloid cytotoxicity.
The universally abundant polyphosphate (polyP) accelerates fibril formation of disease-related amyloids and protects against amyloid cytotoxicity. To gain insights into the mechanism(s) by which polyP exerts these effects, we focused on α-synuclein, a well-studied amyloid protein, which constitutes the major component of Lewy bodies found in Parkinson's disease. Here, we demonstrate that polyP is unable to accelerate the rate-limiting step of α-synuclein fibril formation but effectively nucleates fibril assembly once α-synuclein oligomers are formed. Binding of polyP to α-synuclein either during fibril formation or upon fibril maturation substantially alters fibril morphology and effectively reduces the ability of α-synuclein fibrils to interact with cell membranes. The effect of polyP appears to be α-synuclein fibril specific and successfully prevents the uptake of fibrils into neuronal cells. These results suggest that altering the polyP levels in the extracellular space might be a potential therapeutic strategy to prevent the spreading of the disease.


Interaction between the progression of Alzheimer's disease and fractal degradation.
Many outputs from healthy neurophysiological systems including motor activity display nonrandom fluctuations with fractal scaling behavior as characterized by similar temporal fluctuation patterns across a range of time scales. Degraded fractal regulation predicts adverse consequences including Alzheimer's dementia. We examined longitudinal changes in the scaling behavior of motor activity fluctuations during the progression of Alzheimer's disease (AD) in 1068 participants in the Rush Memory and Aging Project. Motor activity of up to 10 days was recorded annually for up to 13 years. Cognitive assessments and clinical diagnoses were administered annually in the same participants. We found that fractal regulation gradually degraded over time (p < 0.0001) even during the stage with no cognitive impairment. The degradation rate was more than doubled after the diagnosis of mild cognitive impairment and more than doubled further after the diagnosis of Alzheimer's dementia (p's ≤ 0.0005). Besides, the longitudinal degradation of fractal regulation significantly correlated with the decline in cognitive performance throughout the progression from no cognitive impairment to mild cognitive impairment, and to AD (p < 0.001). All effects remained the same in subsequent sensitivity analyses that included only 255 decedents with autopsy-confirmed Alzheimer's pathology. These results indicate that the progression of AD accelerates fractal degradation and that fractal degradation may be an integral part of the process of AD.


Quinazoline-Based Antivirulence Compounds Selectively Target Salmonella PhoP/PhoQ Signal Transduction System.
The rapid emergence of multidrug resistance among bacterial pathogens has become a significant challenge to human health in our century. Therefore, development of next-generation antibacterial compounds is an urgent need. Two-component signal transduction systems (TCS) are stimulus-response coupling devices that allow bacteria to sense and elaborate adaptive responses to changing environmental conditions, including the challenges that pathogenic bacteria face inside the host. The differential presence of TCS, present in bacteria but absent in the animal kingdom, makes them attractive targets in the search for new antibacterial compounds. In Salmonella enterica, the PhoP/PhoQ two-component system controls the expression of crucial phenotypes that define the ability of the pathogen to establish infection in the host. We now report the screening of 686 compounds from a GlaxoSmithKline published kinase inhibitor set in a high-throughput whole-cell assay that targets Salmonella enterica serovar Typhimurium PhoP/PhoQ. We identified a series of quinazoline compounds that showed selective and potent downregulation of PhoP/PhoQ-activated genes and define structural attributes required for their efficacy. We demonstrate that their bioactivity is due to repression of the PhoQ sensor autokinase activity mediated by interaction with its catalytic domain, acting as competitive inhibitors of ATP binding. While noncytotoxic, the hit molecules exhibit antivirulence effect by blockage of S Typhimurium intramacrophage replication. Together, these features make these quinazoline compounds stand out as exciting leads to develop a therapeutic intervention to fight salmonellosis.


Streptococci isolated from bovine intramammary infections.
Streptococcal isolates from 71 dairy herds considered free of Streptococcus agalactiae were compared with isolates from 1 herd used in bovine mastitis research over a 12-year period. The incidence of streptococci was as follows: Streptococcus uberis, 56.5%; enterococci, 24.2%; Streptococcus dysgalactiae, 9.0%; Streptococcus bovis, 5.1%; unclassified streptococci, 3.1%; Streptococcus agalactiae, 1.5%; and Lancefield group G streptococci, 0.7%. The incidence for these streptococci in the 2 groups was generally the same except for Str bovis and unclassified streptococci. A study of cultural responses in numerous mediums indicated that differentiation of streptococci recovered from the bovine udder may be obtained with esculin broth, CAMP test, sodium hippurate broth, 0.1% methylene blue milk, inulin, and raffinose broths.


[Aseptic loosening of a total hip prosthesis].
Detachment of a total hip prosthesis, whether or not it is cemented, presents as an abnormal mobility between the implant and the bone. Mechanical pain, which may be continuous from the time of the operation or which may appear after a variable pain free period, is the usual presenting symptom. Clinical examination may induce the pain by forced rotation, by a shaking maneuver or by traction-impaction of the lower limb. The most suggestive signs of detachment of the prosthesis are the inability to extend the limb and the instability of weight-bearing on one foot. At this stage, the findings of radiological and laboratory investigations are able to characterise the type of detachment and its septic or aseptic nature. Two clinical situations can be defined on the basis of this survey: the diagnosis of detachment is obvious due to rupture or fracture of the prosthesis, of the cement or of the bone, by displacement of the prosthetic elements or by the destruction of the bone in contact with the prosthetic elements; the diagnosis may be suspected and can be confirmed by careful comparative analysis with the initial films or by further investigations: dynamic tests, scintigraphy, arthrography under traction and possibly coxonar. There are a number of causes of detachment: poor positioning, incorrect conception or design of the prosthesis, poor bony support and host reaction to the implant.(ABSTRACT TRUNCATED AT 250 WORDS)


[The antibiotic sensitivity of microorganisms isolated from newborn infants].
Bacterial strains (219) isolated from newborn children were studied for their sensitivity to 17 antibiotics. In the case of the species studied the increase of resistance to cephalothin, cefazolin, cefotaxime, ceftriaxone, gentamicin, tobramycin, chloramphenicol by 5.7 to 43% was found. This evidenced for a necessity to revise the tactics of their further use for treatment and prophylaxis, while the identification of the strains resistant to ofloxacin and ciprofloxacin evidenced for the appearance of new resistance determinants. The high level of resistance to antibiotics and practically identical profile of antibiotics in the strains isolated from newborns and epidemiologically significant environmental objects in the examined hospitals do point to possible colonization of newborns by the hospital strains.


[CME-Laboratory 61: New European Consensus Recommendations on Dyslipidemia].
CME-Laboratory 61: New European Consensus Recommendations on Dyslipidemia Abstract. The lipid status primarily serves to estimate the risk of atherosclerotic cardiovascular diseases (ASCVD). LDL cholesterol (LDL-C) is the primary target of lipid-lowering therapies. NonHDL cholesterol and apolipoprotein B are secondary targets. The European Cardiology and Atherosclerosis Societies have lowered their treatment targets for all risk groups. Triglycerides and HDL cholesterol are also recommended for risk assessment, but are not therapeutic goals. Lipoprotein (a) is a strongly genetically determined ASCVD risk factor and contains a statin-resistant part of LDL-C. The quality of laboratory diagnostics for all lipid risk factors is in need of improvement due to the fact that it is too dependent on methods and in view of the indication of new and expensive lipid-modifying therapies.


Natural and radiation-induced cataracts in man and mouse, and natural macular degeneration in man: proposed mechanisms.
A unified theory of growth and age-dependent disorders is applied to the interpretation of epidemiological data for natural and radiation-induced cataracts and natural macular degeneration in man. Using the same unified theory, mechanisms are also proposed to explain the experimental evidence for natural and radiation-induced lenticular opacities in the lens of the mouse. Epidemiological and experimental data are strikingly consistent with the hypothesis that natural cataract formation is an autoaggressive process but the details of pathogenesis differ greatly between the two species. Radiation dose-response relations reflect these contrasts. Lenticular opacities in the nuclear-bomb survivors at Hiroshima and Nagasaki were probably induced by a 'single-track' mechanism. Radiation-induced generalised opacification in the lens of the mouse results from a 'multi-track' process. The pathogenesis of natural macular degeneration in man happens to have close parallels with that of natural opacification in the mouse. We discuss some implications of these inferences for the phenomenon of radiation-induced lethal disorders in man.


Collaborative Learning Tools To Foster Inclusive Participation and Sense of Belonging in a Microbiology Outreach Partnership.
For secondary outreach programs to meet the goals of enhancing science education and attracting future scientists from underrepresented populations, we need an inclusive approach that integrates students' knowledge and experiences in the process of doing science. I present three pedagogical tools designed by developing equitable, inclusive collaboration among microbiologist outreach mentors and high school biology students. These activities aim to foster a sense of belonging in a scientific community and serve as an entry point to the practice of inclusion. Over a one-semester course at an alternative high school, ten secondary students and their scientist mentors met weekly to design and conduct microbiology experiments together. This group of students and scientists participated in structured collaborative learning activities to: i) understand each other's ideas about science; ii) collectively analyze their research findings; and iii) offer peer feedback. I modified the following three learning tools for use in my secondary science classroom from protocols of the National School Reform Faculty: 1) the Quotes Introduction Activity set the stage for equitable discourse between high school students and scientist mentors, while initiating important conversations about the process of biological research; 2) the Data Analysis Protocol allowed both students and mentors to contribute to the scientific process; and 3) the Feedback Carousel Activity engaged students and scientists alike in reviewing and refining poster presentations. This inclusive engagement in the social aspects of learning science can help students feel a sense of belonging and imagine their futures in the scientific community, key steps towards inclusion. The supportive system of structured feedback in these collaborative learning activities created a safe, inclusive space for secondary students to try on the role of microbiology expert, and for scientist volunteers to practice inclusive mentorship. Drawing from inclusive pedagogical tools in secondary education will help expand our capacity for inclusive science outreach and bring us closer to the goals of improving biology education and attracting future biologists at the university level.


SWNT nano-engineered networks strongly increase charge transport in P3HT.
We demonstrate the formation of arrays of 3D nanosized networks of interconnected single-wall carbon nanotubes (SWNTs) with well defined dimensions in a poly-3-hexylthiophene (P3HT) thin film. These novel nanotube nano-networks produce efficient ohmic charge transport, even at very low nanotube loadings and low voltages. An increase in conductivity between one and two orders of magnitude is observed compared to a random network. The formation of these nano-engineered networks is compatible with large area imprinting and roll to roll processes, which makes it highly desirable for opto-electronic and energy conversion applications using carbon nanotubes.


Quantitative comparison of within-sample heterogeneity scores for DNA methylation data.
DNA methylation is an epigenetic mark with important regulatory roles in cellular identity and can be quantified at base resolution using bisulfite sequencing. Most studies are limited to the average DNA methylation levels of individual CpGs and thus neglect heterogeneity within the profiled cell populations. To assess this within-sample heterogeneity (WSH) several window-based scores that quantify variability in DNA methylation in sequencing reads have been proposed. We performed the first systematic comparison of four published WSH scores based on simulated and publicly available datasets. Moreover, we propose two new scores and provide guidelines for selecting appropriate scores to address cell-type heterogeneity, cellular contamination and allele-specific methylation. Most of the measures were sensitive in detecting DNA methylation heterogeneity in these scenarios, while we detected differences in susceptibility to technical bias. Using recently published DNA methylation profiles of Ewing sarcoma samples, we show that DNA methylation heterogeneity provides information complementary to the DNA methylation level. WSH scores are powerful tools for estimating variance in DNA methylation patterns and have the potential for detecting novel disease-associated genomic loci not captured by established statistics. We provide an R-package implementing the WSH scores for integration into analysis workflows.


Drymaria veliziae (Caryophyllaceae), a new species from the Andes of Cajamarca (North Peru).
A new species from the Northern Peruvian Andes (Cajamarca department), Drymaria veliziae sp. nov., is proposed in the present paper. It grows in the high-elevation montane grasslands and it is morphologically similar to D. auriculipetala from which it differs in having elliptic-ovate leaves, blade margin bases glandular, large number of stipules arranged in a pedicel form at the leaf axis and by the short and glandular pedicels. A detailed description, original photographs and a location map are provided, as well as an updated diagnostic key of Drymaria Ser. Frutescens. The IUCN status of the new species is assessed as Endangered (EN).


Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants.
To assess the reversibility of the elevation of serum creatinine levels in patients with diabetes after 5 years of continuous on-trial fenofibrate therapy. An on-drug/off-drug ancillary study to the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial to investigate posttrial changes in serum creatinine and cystatin C. Eligible participants were recruited into a prospective, nested, three-group study based on retrospective on-trial serum creatinine levels: fenofibrate case subjects (n = 321, ≥ 20% increase after 3 months of therapy); fenofibrate control subjects (n = 175, ≤ 2% increase); and placebo control subjects (n = 565). Serum creatinine and cystatin C were measured at trial end and 6-8 weeks after discontinuation of trial therapy. RESULTS At trial end, case subjects had the highest adjusted serum creatinine (± SE) mg/dL (1.11 ± 0.02) and the lowest adjusted estimated glomerular filtration rate (eGFR) (± SE) mL/min/1.73 m(2) (68.4 ± 1.0) versus control subjects (1.01 ± 0.02; 74.8 ± 1.3) and placebo subjects (0.98 ± 0.01; 77.8 ± 0.7). After 51 days off-drug, serum creatinine in case subjects was still higher (0.97 ± 0.02) and eGFR still lower (77.8 ± 1.0) than control subjects (0.90 ± 0.02; 81.8 ± 1.3) but not different from placebo subjects (0.99 ± 0.01; 76.6 ± 0.7). Changes in serum cystatin C recapitulated the serum creatinine changes. Participants with significant initial on-trial increases in serum creatinine (≥ 20%) returned to the same level of renal function as participants receiving placebo while participants who had ≤ 2% increase in serum creatinine had net preservation of renal function compared with the same unselected placebo reference group. The fenofibrate-associated on-trial increases in serum creatinine were reversible, and the reversal was complete after 51 days off-drug. The similarity of the cystatin C results suggests that the mechanism of this change is not specific for serum creatinine.


Relationship between coronary artery disease and pulmonary arterial pressure in patients with chronic obstructive pulmonary disease.
The aim of the present study was to determine whether there is a relationship between coronary artery disease and pulmonary hypertension and whether pulmonary hypertension is an additional risk factor for the presence and extent of coronary artery disease in patients with chronic obstructive pulmonary disease. Patients diagnosed with chronic obstructive pulmonary disease and pulmonary hypertension, and undergone diagnostic coronary angiography for evaluation of suspected coronary artery disease constituted the study group. Patients were divided into two groups according to the presence or absence of coronary artery disease and compared for age, gender, accompanying chronic disease, and pulmonary function tests. A total of 95 patients were recruited in the study. Comparison of the groups revealed that two groups were significantly different on gender (p=0.029), presence of hypertension (p=0.027), and biomass (p=0.040). Correlation analysis of variables revealed that male gender (rs=0.224, p=0.029), hypertension (rs=0.227, p=0.07) were positively correlated with the presence of coronary artery disease. FEV1/FVC ratio (rs=-0.253, p=0.013) and sPAP (rs=-0.215, p=0.037) were negatively correlated with the presence of coronary artery disease. High prevalence of coronary artery disease in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease was found. However, no correlation between the presence and severity of coronary artery disease and pulmonary hypertension was detected.


Aberrant striatal plasticity is specifically associated with dyskinesia following levodopa treatment.
Chronic levodopa treatment for Parkinson's disease often results in the development of abnormal involuntary movement, known as L-dopa-induced dyskinesia (LIDs). Studies suggest that LIDs may be associated with aberrant corticostriatal plasticity. Using in vivo extracellular recordings from identified Type I and Type II medium spiny striatal neurons, chronic L-dopa treatment was found to produce abnormal corticostriatal information processing. Specifically, after chronic L-dopa treatment in dopamine-depleted rats, there was a transition from a cortically evoked long-term depression (LTD) to a complementary but opposing form of plasticity, long-term potentiation, in Type II "indirect" pathway neurons. In contrast, LTD could still be induced in Type I neurons. Interestingly, the one parameter that correlated best with dyskinesias was the inability to de-depress established LTD in Type I medium spiny striatal neurons. Taken as a whole, we propose that the induction of LIDs is due, at least in part, to an aberrant induction of plasticity within the Type II indirect pathway neurons combined with an inability to de-depress established plastic responses in Type I neurons. Such information is critical for understanding the cellular mechanisms underlying one of the major caveats to L-dopa therapy.


Autophagy protects auditory hair cells against neomycin-induced damage.
Aminoglycosides are toxic to sensory hair cells (HCs). Macroautophagy/autophagy is an essential and highly conserved self-digestion pathway that plays important roles in the maintenance of cellular function and viability under stress. However, the role of autophagy in aminoglycoside-induced HC injury is unknown. Here, we first found that autophagy activity was significantly increased, including enhanced autophagosome-lysosome fusion, in both cochlear HCs and HEI-OC-1 cells after neomycin or gentamicin injury, suggesting that autophagy might be correlated with aminoglycoside-induced cell death. We then used rapamycin, an autophagy activator, to increase the autophagy activity and found that the ROS levels, apoptosis, and cell death were significantly decreased after neomycin or gentamicin injury. In contrast, treatment with the autophagy inhibitor 3-methyladenine (3-MA) or knockdown of autophagy-related (ATG) proteins resulted in reduced autophagy activity and significantly increased ROS levels, apoptosis, and cell death after neomycin or gentamicin injury. Finally, after neomycin injury, the antioxidant N-acetylcysteine could successfully prevent the increased apoptosis and HC loss induced by 3-MA treatment or ATG knockdown, suggesting that autophagy protects against neomycin-induced HC damage by inhibiting oxidative stress. We also found that the dysfunctional mitochondria were not eliminated by selective autophagy (mitophagy) in HEI-OC-1 cells after neomycin treatment, suggesting that autophagy might not directly target the damaged mitochondria for degradation. This study demonstrates that moderate ROS levels can promote autophagy to recycle damaged cellular constituents and maintain cellular homeostasis, while the induction of autophagy can inhibit apoptosis and protect the HCs by suppressing ROS accumulation after aminoglycoside injury.


Spatial transcriptomics uncover sucrose post-phloem transport during maize kernel development.
Maize kernels are complex biological systems composed of three genetic sources, namely maternal tissues, progeny embryos, and progeny endosperms. The lack of gene expression profiles with spatial information has limited the understanding of the specific functions of each cell population, and hindered the exploration of superior genes in kernels. In our study, we conduct microscopic sectioning and spatial transcriptomics analysis during the grain filling stage of maize kernels. This enables us to visualize the expression patterns of all genes through electronical RNA in situ hybridization, and identify 11 cell populations and 332 molecular marker genes. Furthermore, we systematically elucidate the spatial storage mechanisms of the three major substances in maize kernels: starch, protein, and oil. These findings provide valuable insights into the functional genes that control agronomic traits in maize kernels.


[Methods for determining matrix metalloproteinase activity].
The paper describes methods for determining the activity of matrix metalloproteinases (MMP), primarily collagenases and gelatinases, by applying natural protein substrates. Reconstructed fluorescein-labeled type I collagen fibrils were used to determine collagenases as a substrate. The zymographic technique in polyacrylamide gel with copolymerized gelatin was employed for the identification and assay of gellatinases. These methods are rather sensitive, reproducible and may be used for screening. Collagenases specifically trigger the hydrolysis of fibrillar collagens; gelatinases are responsible for the hydrolysis of type IV collagen, the basis of basement membranes. MMP activity characterizes the development of a destructive or invasive process in the connective tissue matrix; this indicator is borne in mind when choosing therapeutic agents, has a prognostic value, determines targets for the development of pharmacological agents, and is required to understand the mechanism responsible for the destruction of matrix and for the development of invasion processes.


Membrane anchored and lipid raft targeted β-secretase inhibitors for Alzheimer's disease therapy.
β-secretase, a key enzyme involved in amyloid-β generation, is an attractive candidate for Alzheimer's disease therapy. Transition-state inhibitors of β-secretase are designed to achieve specificity. However, these inhibitors bind only to the active conformation of the enzyme and as the active β-secretase is sequestered in subcellular compartments, new strategies have to be implemented. We propose that membrane-anchoring of β-secretase inhibitors would render them endocytosis-competent thereby enabling the inhibitors to reach these compartments that harbor active β-secretase. By choosing cholesterol as a membrane anchor, we also enrich the inhibitor in lipid rafts where much of the β-secretase is present. In addition, membrane-anchoring of soluble inhibitors reduces the dimensionality of the inhibitor and consequently increases the inhibitor concentration at the target membrane plane. Such inhibitors have great potential in terms of substrate selectivity and reduced side effects. Not only for β-secretase, this strategy could be applied for many membrane targets that are localized either at the plasma membrane or in the endocytic compartments.


Is higher ASA class associated with an increased incidence of adverse events during procedural sedation in a pediatric emergency department?
To prospectively investigate whether American Society of Anesthesiologists (ASA) class, as assigned by nonanesthesiologists, is associated with adverse events during procedural sedation in a pediatric emergency department. A prospectively collected database of children aged 0 to 21 years undergoing procedural sedation in the emergency department of an urban, tertiary care, children's hospital was retrospectively reviewed. This database included clinical and demographic characteristics, including assigned ASA class. It also included information relative to the procedure, the sedation, and any complications related to the sedation. Complications were defined a priori as persistent oxygen desaturation to less than 93% on pulse oximetry requiring supplemental oxygen, bronchospasm, dizziness, apnea, seizure, hiccoughs, laryngospasm, stridor, arrhythmia, hypotension, rash, vomiting, aspiration, or a disinhibition/agitation/dysphoria emergence reaction. Main outcome measure was the incidence of complications relative to ASA class. Procedural sedation was performed in the emergency department 1232 times during the study period; 30 sedations did not have either ASA class or occurrence of a complication recorded. Thus, 1202 sedations were included in the study. Nine hundred eighty-eight patients were classified as ASA class 1, whereas 214 were classified as ASA class 2 or greater. There were a total of 215 adverse events in the study population. Most of these were hypoxia (185 total) and were more likely to occur in patients with an ASA class 2 or greater (P = 0.021). Adverse events during procedural sedation are more common in patients with higher ASA class.


Contrast-response functions for multifocal visual evoked potentials: a test of a model relating V1 activity to multifocal visual evoked potentials activity.
The multifocal visual evoked potential (mfVEP) is largely generated in V1. To relate the electrical activity recorded from humans to recordings from single cells in nonhuman primate (V1) cortex, contrast-response functions for the human mfVEP were compared to predictions from a model of V1 activity (D. J. Heeger, A. C. Huk, W. S. Geisler, & D. G. Albrecht, 2000) based upon single-cell recordings from monkey V1 (e.g., D. G. Albrecht, 1995; D. G. Albrecht, W. S. Geisler, R. A. Frazor, & A. M. Crane, 2002; D. G. Albrecht & D. B. Hamilton, 1982; W. S. Geisler & D. G. Albrecht, 1997). A second purpose was to fully articulate the assumptions of this model to better understand the implications of this comparison. Finally, as the third purpose, one of these assumptions was tested. Monocular mfVEPs were obtained from normal subjects with a contrast-reversing dartboard pattern. The display contained 16 sectors each with a checkerboard. Both the sectors and the checks were scaled approximately for cortical magnification. In Experiment 1, there were 64 checks per sector. The contrast-response functions were fitted well up to 40% contrast by the theoretical population curve for V1 neurons; there was a systematic deviation for higher contrasts. The model, as articulated here, predicts that the contrast-response function should be the same and independent of the size of the elements in the display. Varying the size of the elements by varying the viewing distance in Experiment 2 produced similar results to those in Experiment 1. In Experiment 3, the viewing distance and sector size were held constant, but the size of the elements (and therefore the number of checks per sector) was varied. Changing check size by a factor of 16 had relatively little effect on the contrast-response function. In general, the mfVEP results were consistent with the model based upon the V1 neuron population. However, two aspects of the results require further exploration. First, there was a systematic deviation from the model's contrast-response function for higher contrasts. This deviation suggests that one or more of the model's assumptions may be violated. Second, the latency of the mfVEP changed far less than expected based upon single-cell data.


Flagellar roots, mating structure and gametic fusion in the green alga Ulva lactuca (Ulvales).
The slightly anisogamous gametes of Ulva lactuca exhibit a cruciate flagellar root system consisting of 4 microtubular roots (4-2-4-2 system) and an elaborate system of fibrous roots associated with the 2-stranded microtubular roots. Two fibres (32-nm striation periodicity; system I fibres) closely underlie each of the 2-stranded roots, while different fibres (150-nm striation periodicity; system II fibres) run parallel to the root microtubules, and are 150-200 nm more internally located. Female gametes have 4 system II fibres, 3 of which are combined into a compound fibre associated with one microtubular root, while the fourth fibre is associated with the opposite root. In male gametes only 2 system II fibres are present, each underlying one of the two 2-stranded roots. A special region of the plasmalemma of both gamete types about 0.5 mum away from the basal bodies and located between 2 adjacent microtubular roots is structurally specialized and acts as a mating structure in gametic fusion. The region is oval-shaped and up to I.I mum long with a maximum diameter of 0.7 mum. A continuous electron-dense boundary layer underlies the plasmalemma at the edges of the mating structure. In both gamete types the mating structure consists of a fuzzy layer of material underlying the plasmalemma and special granules (60 nm diameter) are associated with this layer on its cytoplasmic side. In addition diffuse material overlies the mating structure, especially in male gametes. The mating structure is connected to 3 different kinds of flagellar roots: the boundary layer is linked to a 2-stranded microtubular root and its associated system I fibre; the fuzzy layer of the mating structure is connected with a system II fibre; and in female gametes this is the compound system II fibre. The ultrastructural changes which occur after mixing the 2 gamete types have been followed. Mating structure activation involves contraction of system II fibres (change of striation periodicity to 100 nm), detachment of special granules from the fuzzy layer of the mating structure and their replacement by electron-transparent vesicles at the prospective cell fusion site. Furthermore, release of electron-dense contents from Golgi-derived vesicles in the anterior part of both gamete types precedes cell fusion. Cell fusion is exclusively initiated in a region delimited by the 2 mating structures. After partial dissolution the 2 plasma membranes unite within the mating structure regions. The ultrastructure of gametic fusion in Ulva lactuca is compared to that of other green algae and the significance of flagellar roots in the mating process of green algae is discussed.


Modernization, sexual risk-taking, and gynecological morbidity among Bolivian Forager-horticulturalists.
Sexual risk-taking and reproductive morbidity are common among rapidly modernizing populations with little material wealth, limited schooling, minimal access to modern contraception and healthcare, and gendered inequalities in resource access that limit female autonomy in cohabiting relationships. Few studies have examined how modernization influences sexual risk-taking and reproductive health early in demographic transition. Tsimane are a natural fertility population of Bolivian forager-farmers; they are not urbanized, reside in small-scale villages, and lack public health infrastructure. We test whether modernization is associated with greater sexual risk-taking, report prevalence of gynecological morbidity (GM), and test whether modernization, sexual risk-taking and parity are associated with greater risk of GM. Data were collected from 2002-2010 using interviews, clinical exams, and laboratory analysis of cervical cells. We find opposing effects of modernization on both sexual risk-taking and risk of GM. Residential proximity to town and Spanish fluency are associated with greater likelihood of men's infidelity, and with number of lifetime sexual partners for men and women. However, for women, literacy is associated with delayed sexual debut after controlling for town proximity. Fifty-five percent of women present at least one clinical indicator of GM (n = 377); 48% present inflammation of cervical cells, and in 11% the inflammation results from sexually transmitted infection (trichomoniasis). Despite having easier access to modern healthcare, women residing near town experience greater likelihood of cervical inflammation and trichomoniasis relative to women in remote villages; women who are fluent in Spanish are also more likely to present trichomoniasis relative to women with moderate or no fluency. However, literate women experience lower likelihood of trichomoniasis. Parity has no effect on risk of GM. Our results suggest a net increase in risk of reproductive morbidity among rapidly modernizing, resource-stressed populations.


Enhanced depth-independent chondrocyte proliferation and phenotype maintenance in an ultrasound bioreactor and an assessment of ultrasound dampening in the scaffold.
Chondrocyte-seeded scaffolds were cultured in an ultrasound (US)-assisted bioreactor, which supplied the cells with acoustic energy around resonance frequencies (~5.0 MHz). Polyurethane-polycarbonate (BM), chitosan (CS) and chitosan-n-butanol (CSB) based scaffolds with varying porosities were chosen and the following US regimen was employed: 15 kPa and 60 kPa, 5 min per application and 6 applications per day for 21 days. Non-stimulated scaffolds served as control. For BM scaffolds, US stimulation significantly impacted cell proliferation and depth-independent cell population density compared to controls. The highest COL2A1/COL1A1 ratios and ACAN mRNA were noted on US-treated BM scaffolds compared to controls. A similar trend was noted on US-treated cell-seeded CS and CSB scaffolds, though COL2A1/COL1A1 ratios were significantly lower compared to BM scaffolds. Expression of Sox-9 was also elevated under US and paralleled the COL2A1/COL1A1 ratio. As an original contribution, a simplified mathematical model based on Biot theory was developed to understand the propagation of the incident US wave through the scaffolds and the model analysis was connected to cellular responses. Scaffold architecture influenced the distribution of US field, with the US field being the least attenuated in BM scaffolds, thus coupling more mechanical energy into cells, and leading to increased cellular activity.


Planar coupling to high-Q lithium niobate disk resonators.
We demonstrate optical coupling to high-Q lithium niobate disks from an integrated lithium niobate waveguide. The waveguides are made by proton exchange in X-cut lithium niobate substrate. The disks with diameter of 4.7 mm and thickness of 1 mm are made from commercial Z-cut lithium niobate wafers by polishing the edges into a spheroidal profile. Both resonance linewidth and cavity ringdown measurements were performed to calculate the Q factor of the resonator, which is in excess of 10(8). Planar coupling represents the most promising technique for practical applications of whispering gallery mode resonators.


Mutual optical injection in coupled DBR laser pairs.
We report an experimental study of nonlinear effects, characteristic of mutual optical coupling, in an ultra-short coupling regime observed in a distributed Bragg reflector laser pair fabricated on the same chip. Optical feedback is amplified via a double pass through a common on-chip optical amplifier, which introduces further nonlinear phenomena. Optical coupling has been introduced via back reflection from a cleave-ended fibre. The coupling may be varied in strength by varying the distance of the fibre from the output of the chip, without significantly affecting the coupling time.


Quantitative region-of-interest tomography using variable field of view.
In X-ray computed tomography, the task of imaging only a local region of interest (ROI) inside a larger sample is very important. However, without a priori information, this ROI cannot be exactly reconstructed using only the image data limited to the ROI. We propose here an approach of region-of-interest tomography, which reconstructs a ROI within an object from projections of different fields of view acquired on a specific angular sampling scheme in the same tomographic experiment. We present a stable procedure that not only yields high-quality images of the ROI but keeps as well the quantitative contrast on the reconstructed images. In addition, we analyze the minimum number of projections required for ROI tomography from the point of view of the band region of the Radon transform, which confirms this number must be estimated based on the size of the entire object and not only on the size of the ROI.


Evaluation of telomerase in non-melanoma skin cancer.
Telomerase, a ribonucleoprotein, is capable of adding telomeric sequences (TTAGGG hexameric repeats) to the ends of chromosomes and, thereby, halting the erosion of chromosome at each cell division. Whereas most normal somatic cells contain minimal or no detectable telomerase activity, most immortal and tumour cells exhibit significant levels of telomerase activity and show no net loss of telomere length during proliferation. The evaluation of telomerase has been proposed for diagnostic and therapeutic purposes in human cancer. Skin cancer is the most common cancer in humans; the precise molecular events in skin carcinogenesis are numerous and complicated and not yet completely clarified. In this study, we evaluated telomerase in 35 basal cell carcinomas and in 14 squamous cell carcinomas in order to determine if activation of the telomerase enzyme was a pivotal step in the development of skin cancer and whether telomerase activity levels were different between the two histotypes. A higher enzymatic level was shown to be associated with squamous cell carcinomas, while low levels were mainly detected in the basal cell histotype (chi2 test; p=0.02). Telomerase complex activity is dependent on its catalytic subunit, telomerase reverse transcriptase hTERT. By reverse transcription-PCR, using primers within the reverse transcriptase domain of hTERT, we observed a significant correlation between hTERT expression and telomerase activity in our skin tumour samples (p=0.0003). We detected the presence of multiple, alternately spliced transcripts, corresponding to full-length messages as well as spliced messages with critical reverse transcriptase motifs deleted. A higher telomerase messenger level was shown to be associated with squamous cell carcinomas (chi2 test; p<0.0001), as for telomerase activity. Our results provide arguments supporting the role of telomerase in skin cancer and suggest RT-PCR of telomerase RNA as a tool easier and faster than TRAP assay to identify more aggressive malignancies among non-melanoma skin specimens.


CellSTAR: a comprehensive resource for single-cell transcriptomic annotation.
Large-scale studies of single-cell sequencing and biological experiments have successfully revealed expression patterns that distinguish different cell types in tissues, emphasizing the importance of studying cellular heterogeneity and accurately annotating cell types. Analysis of gene expression profiles in these experiments provides two essential types of data for cell type annotation: annotated references and canonical markers. In this study, the first comprehensive database of single-cell transcriptomic annotation resource (CellSTAR) was thus developed. It is unique in (a) offering the comprehensive expertly annotated reference data for annotating hundreds of cell types for the first time and (b) enabling the collective consideration of reference data and marker genes by incorporating tens of thousands of markers. Given its unique features, CellSTAR is expected to attract broad research interests from the technological innovations in single-cell transcriptomics, the studies of cellular heterogeneity & dynamics, and so on. It is now publicly accessible without any login requirement at: https://idrblab.org/cellstar.


Is dietary mercury of neurotoxicological concern to wild polar bears (Ursus maritimus)?
Polar bears (Ursus maritimus) are exposed to high concentrations of mercury because they are apex predators in the Arctic ecosystem. Although mercury is a potent neurotoxic heavy metal, it is not known whether current exposures are of neurotoxicological concern to polar bears. We tested the hypotheses that polar bears accumulate levels of mercury in their brains that exceed the estimated lowest observable adverse effect level (20 microg/g dry wt) for mammalian wildlife and that such exposures are associated with subtle neurological damage, as determined by measuring neurochemical biomarkers previously shown to be disrupted by mercury in other high-trophic wildlife. Brain stem (medulla oblongata) tissues from 82 polar bears subsistence hunted in East Greenland were studied. Despite surprisingly low levels of mercury in the brain stem region (total mercury = 0.36 +/- 0.12 microg/g dry wt), a significant negative correlation was measured between N-methyl-D-aspartate (NMDA) receptor levels and both total mercury (r = -0.34, p < 0.01) and methylmercury (r = -0.89, p < 0.05). No relationships were observed among mercury, selenium, and several other neurochemical biomarkers (dopamine-2, gamma-aminobutyric acid type A, muscarinic cholinergic, and nicotinic cholinergic receptors; cholinesterase and monoamine oxidase enzymes). These data show that East Greenland polar bears do not accumulate high levels of mercury in their brain stems. However, decreased levels of NMDA receptors could be one of the most sensitive indicators of mercury's subclinical and early effects.