Laboratory diagnosis of invasive candidiasis.
Severe infections due to Candida species have become more frequent during the past two decades because of the increasing numbers of immunosuppressed patients being treated in our hospitals. Distinguishing colonization from invasive disease requires knowledge of the pathogenetic mechanisms leading to invasion. To assist the clinician in therapeutic decisions, clinical microbiologists should identify to species Candida organisms isolated from immunosuppressed patients. Quantitative or semiquantitative cultures of urine, burn tissues, intravascular catheter tips, and bronchoalveolar lavage specimens may provide useful information. Immunofluorescent staining of certain specimens can enhance diagnostic yield. The lysis-centrifugation blood culture technique offers some advantages over traditional broth techniques in detecting Candida fungemia. Antibody testing is of limited diagnostic value in highly immunosuppressed patients. Developing simple and reliable tests for detecting antigens or metabolites of Candida spp. in the sera of infected patients has proven difficult. Methods for typing Candida albicans are evolving. Typing should prove useful for studying the epidemiology of candidiasis in hospitalized patients.


Estimation precision of the degree of linear polarization and of the angle of polarization in the presence of different sources of noise.
We consider imaging systems that measure the three first elements of the Stokes vector and deduce from them the degree of linear polarization and the angle of polarization. They require the acquisition of at least three intensity measurements, but performing more measurements is often thought to improve the estimation precision. We show that if the total acquisition time is fixed, the optimal number of measurements depends on the type of noise that affects the image: the estimation variance increases with the number of measurements N when the noise is additive; it is independent of N in the presence of Poisson shot noise and decreases with N when the angles of the analyzers fluctuate. In general, the optimal number of measurements results from a compromise on the robustness of these different types of perturbations.


Flow sorting and molecular cytogenetic identification of individual chromosomes of Dasypyrum villosum L. (H. villosa) by a single DNA probe.
Dasypyrum villosum (L.) Candargy (sin. Haynaldia villosa) is an annual wild diploid grass species (2n = 2x = 14; genome VV) belonging to the Poaceae family, which is considered to be an important source of biotic and abiotic stress resistance genes for wheat breeding. Enhanced characterization of D. villosum chromosomes can facilitate exploitation of its gene pool and its use in wheat breeding programs. Here we present the cytogenetic identification of D. villosum chromosomes on slide by fluorescent in situ hybridization (FISH), with the GAA simple sequence repeat (SSR) as a probe. We also describe the isolation and the flow cytometric analysis of D. villosum chromosomes in suspension, resulting in a distinguished flow karyotype. Chromosomes were flow sorted into three fractions, according their DNA content, one of which was composed of a single type of chromosome, namely 6 V, sorted with over 85% purity. Chromosome 6 V is known to carry genes to code for important resistance and seed storage characteristics, and its isolation represents a new source of genetic traits and specific markers useful for wheat improvement.


Postapproval trials versus patient registries: comparability of advanced melanoma patients with brain metastases.
Postapproval trials and patient registries have their pros and cons in the generation of postapproval data. No direct comparison between clinical outcomes of these data sources currently exists for advanced melanoma patients. We aimed to investigate whether a patient registry can complement or even replace postapproval trials. Postapproval single-arm clinical trial data from the Medicines Evaluation Board and real-world data from the Dutch Melanoma Treatment Registry were used. The study population consisted of advanced melanoma patients with brain metastases treated with targeted therapies (BRAF- or BRAF-MEK inhibitors) in the first line. A Cox hazard regression model and a propensity score matching (PSM) model were used to compare the two patient populations. Compared to patients treated in postapproval trials (n = 467), real-world patients (n = 602) had significantly higher age, higher ECOG performance status, more often ≥3 organ involvement and more symptomatic brain metastases. Lactate dehydrogenase levels were similar between both groups. The unadjusted median overall survival (mOS) in postapproval clinical trial patients was 8.7 (95% CI, 8.1-10.4) months compared to 7.2 (95% CI, 6.5-7.7) months (P < 0.01) in real-world patients. With the Cox hazard regression model, survival was adjusted for prognostic factors, which led to a statistically insignificant difference in mOS for trial and real-world patients of 8.7 (95% CI, 7.9-10.4) months compared to 7.3 (95% CI, 6.3-7.9) months, respectively. The PSM model resulted in 310 matched patients with similar survival (P = 0.9). Clinical outcomes of both data sources were similar. Registries could be a complementary data source to postapproval clinical trials to establish information on clinical outcomes in specific subpopulations.


MyCartis NV.
MyCartis NV, a new player on the clinical and translational research market, aims at revolutionizing current healthcare systems. These are mostly based on treating the diseased rather than on caring better and longer for the healthy. The 'one size fits all' model is no longer sufficient and is unsustainable in the long run. Although it comes very scattered, today's access to molecular information has the potential to make healthcare more personal and effective, shifting it from treating diseases to improving quality of life. MyCartis wants to contribute to this process by developing broadly available next generation multiplex biomarker analysis solutions both at the technical and content levels. The Evalution™ platform provides a 'one technology fits all' solution to enable researchers to validate their biomarkers and assay providers to utilize them, no matter their physical nature: multiplexing in its true sense. The ability to quantify different types of markers on a single platform will help produce more comprehensive and coherent multiplex datasets, which will facilitate the integration into syndromic assay formats.


The Long Pentraxin 3 Plays a Role in Bone Turnover and Repair.
Pentraxin 3 (PTX3) is an inflammatory mediator acting as a fluid-phase pattern recognition molecule and playing an essential role in innate immunity and matrix remodeling. Inflammatory mediators also contribute to skeletal homeostasis, operating at multiple levels in physiological and pathological conditions. This study was designed to investigate the role of PTX3 in physiological skeletal remodeling and bone healing. Micro-computed tomography (μCT) and bone histomorphometry of distal femur showed that PTX3 gene-targeted female and male mice (ptx3-/- ) had lower trabecular bone volume than their wild-type (ptx3+/+ ) littermates (BV/TV by μCT: 3.50 ± 1.31 vs 6.09 ± 1.17 for females, p < 0.0001; BV/TV 9.06 ± 1.89 vs 10.47 ± 1.97 for males, p = 0.0435). In addition, μCT revealed lower trabecular bone volume in second lumbar vertebra of ptx3-/- mice. PTX3 was increasingly expressed during osteoblast maturation in vitro and was able to reverse the negative effect of fibroblast growth factor 2 (FGF2) on osteoblast differentiation. This effect was specific for the N-terminal domain of PTX3 that contains the FGF2-binding site. By using the closed transversal tibial fracture model, we found that ptx3-/- female mice formed significantly less mineralized callus during the anabolic phase following fracture injury compared to ptx3+/+ mice (BV/TV 17.05 ± 4.59 vs 20.47 ± 3.32, p = 0.0195). Non-hematopoietic periosteal cells highly upregulated PTX3 expression during the initial phase of fracture healing, particularly CD51+ and αSma+ osteoprogenitor subsets, and callus tissue exhibited concomitant expression of PTX3 and FGF2 around the fracture site. Thus, PTX3 supports maintenance of the bone mass possibly by inhibiting FGF2 and its negative impact on bone formation. Moreover, PTX3 enables timely occurring sequence of callus mineralization after bone fracture injury. These results indicate that PTX3 plays an important role in bone homeostasis and in proper matrix mineralization during fracture repair, a reflection of the function of this molecule in tissue homeostasis and repair.


Brain-computer interface with language model-electroencephalography fusion for locked-in syndrome.
Some noninvasive brain-computer interface (BCI) systems are currently available for locked-in syndrome (LIS) but none have incorporated a statistical language model during text generation. To begin to address the communication needs of individuals with LIS using a noninvasive BCI that involves rapid serial visual presentation (RSVP) of symbols and a unique classifier with electroencephalography (EEG) and language model fusion. The RSVP Keyboard was developed with several unique features. Individual letters are presented at 2.5 per second. Computer classification of letters as targets or nontargets based on EEG is performed using machine learning that incorporates a language model for letter prediction via Bayesian fusion enabling targets to be presented only 1 to 4 times. Nine participants with LIS and 9 healthy controls were enrolled. After screening, subjects first calibrated the system, and then completed a series of balanced word generation mastery tasks that were designed with 5 incremental levels of difficulty, which increased by selecting phrases for which the utility of the language model decreased naturally. Six participants with LIS and 9 controls completed the experiment. All LIS participants successfully mastered spelling at level 1 and one subject achieved level 5. Six of 9 control participants achieved level 5. Individuals who have incomplete LIS may benefit from an EEG-based BCI system, which relies on EEG classification and a statistical language model. Steps to further improve the system are discussed.


Causal Inference in Latent Class Analysis.
The integration of modern methods for causal inference with latent class analysis (LCA) allows social, behavioral, and health researchers to address important questions about the determinants of latent class membership. In the present article, two propensity score techniques, matching and inverse propensity weighting, are demonstrated for conducting causal inference in LCA. The different causal questions that can be addressed with these techniques are carefully delineated. An empirical analysis based on data from the National Longitudinal Survey of Youth 1979 is presented, where college enrollment is examined as the exposure (i.e., treatment) variable and its causal effect on adult substance use latent class membership is estimated. A step-by-step procedure for conducting causal inference in LCA, including multiple imputation of missing data on the confounders, exposure variable, and multivariate outcome, is included. Sample syntax for carrying out the analysis using SAS and R is given in an appendix.


Developmental profiles in tick water balance with a focus on the new Rocky Mountain spotted fever vector, Rhipicephalus sanguineus.
Recent reports indicate that the common brown dog tick, or kennel tick, Rhipicephalus sanguineus (Latreille) (Acari: Ixodidae) is a competent vector of Rocky Mountain spotted fever in the U.S.A. This tick is of concern to public health because of its high frequency of contact, as it has a unique ability to thrive within human homes. To assess the moisture requirements necessary for survival, water balance characteristics were determined for each developmental stage, from egg to adult. This is the first time that water relations in ticks have been assessed throughout the complete lifecycle. Notably, R. sanguineus is differentially adapted for life in a dry environment, as characterized by a suppressed water loss rate distinctive for each stage that distinguishes it from other ticks. Analysis of its dehydration tolerance limit and percentage body water content provides no evidence to suggest that the various stages of this tick can function more effectively containing less water, indicating that this species is modified for water conservation, not desiccation hardiness. All stages, eggs excepted, absorb water vapour from the air and can drink free water to replenish water stores. Developmentally, a shift in water balance strategies occurs in the transition from the larva, where the emphasis is on water gain (water vapour absorption from drier air), to the adult, where the emphasis is on water retention (low water loss rate). These results on the xerophilic-nature of R. sanguineus identify overhydration as the primary water stress, indicating that this tick is less dependent upon a moisture-rich habitat for survival, which matches its preference for a dry environment. We suggest that the controlled, host-confined conditions of homes and kennels have played a key role in promoting the ubiquitous distribution of R. sanguineus by creating isolated arid environments that enable this tick to establish within regions that are unfavourable for maintaining water balance.


Exposure to styrene and mortality from nonmalignant diseases of the genitourinary system.
A historical cohort study was carried out to investigate mortality from nonmalignant diseases of the genitourinary system among workers in the reinforced plastics industry, where high workroom concentrations of styrene are encountered. The external comparisons in this report were based on an average of 12.6 years of retrospective follow-up of 35 443 workers who were first employed in the reinforced plastics industry during 1945-1991 and were known to have been exposed to styrene in their work. For the internal comparisons, 2641 subjects with incomplete occupational histories were excluded, leaving 32 802 subjects. Previous individual exposure histories to styrene were reconstructed through job histories and environmental and biological monitoring data. Mortality from nonmalignant diseases of the genitourinary system (N = 20) was associated with average exposure to styrene (P for trend 0.05). Weaker increasing trends in risk were seen for time since first exposure and cumulative exposure, while no increase was identified for duration of exposure. There was a significant increasing trend in mortality from nephritis and nephrosis (N = 5), associated with an increasing average level of exposure to styrene (P for trend 0.03). No clear trend was observed for time since first exposure, duration of exposure, or cumulative exposure. In this large cohort study of workers exposed to styrene, mortality from nonmalignant diseases of the genitourinary system increased as the average intensity of exposure increased. This finding indicates that other data should be scrutinized.


A low carbohydrate, high protein diet slows tumor growth and prevents cancer initiation.
Since cancer cells depend on glucose more than normal cells, we compared the effects of low carbohydrate (CHO) diets to a Western diet on the growth rate of tumors in mice. To avoid caloric restriction-induced effects, we designed the low CHO diets isocaloric with the Western diet by increasing protein rather than fat levels because of the reported tumor-promoting effects of high fat and the immune-stimulating effects of high protein. We found that both murine and human carcinomas grew slower in mice on diets containing low amylose CHO and high protein compared with a Western diet characterized by relatively high CHO and low protein. There was no weight difference between the tumor-bearing mice on the low CHO or Western diets. Additionally, the low CHO-fed mice exhibited lower blood glucose, insulin, and lactate levels. Additive antitumor effects with the low CHO diets were observed with the mTOR inhibitor CCI-779 and especially with the COX-2 inhibitor Celebrex, a potent anti-inflammatory drug. Strikingly, in a genetically engineered mouse model of HER-2/neu-induced mammary cancer, tumor penetrance in mice on a Western diet was nearly 50% by the age of 1 year whereas no tumors were detected in mice on the low CHO diet. This difference was associated with weight gains in mice on the Western diet not observed in mice on the low CHO diet. Moreover, whereas only 1 mouse on the Western diet achieved a normal life span, due to cancer-associated deaths, more than 50% of the mice on the low CHO diet reached or exceeded the normal life span. Taken together, our findings offer a compelling preclinical illustration of the ability of a low CHO diet in not only restricting weight gain but also cancer development and progression.


Bone canalicular network segmentation in 3D nano-CT images through geodesic voting and image tessellation.
Recent studies emphasized the role of the bone lacuno-canalicular network (LCN) in the understanding of bone diseases such as osteoporosis. However, suitable methods to investigate this structure are lacking. The aim of this paper is to introduce a methodology to segment the LCN from three-dimensional (3D) synchrotron radiation nano-CT images. Segmentation of such structures is challenging due to several factors such as limited contrast and signal-to-noise ratio, partial volume effects and huge number of data that needs to be processed, which restrains user interaction. We use an approach based on minimum-cost paths and geodesic voting, for which we propose a fully automatic initialization scheme based on a tessellation of the image domain. The centroids of pre-segmented lacunæ are used as Voronoi-tessellation seeds and as start-points of a fast-marching front propagation, whereas the end-points are distributed in the vicinity of each Voronoi-region boundary. This initialization scheme was devised to cope with complex biological structures involving cells interconnected by multiple thread-like, branching processes, while the seminal geodesic-voting method only copes with tree-like structures. Our method has been assessed quantitatively on phantom data and qualitatively on real datasets, demonstrating its feasibility. To the best of our knowledge, presented 3D renderings of lacunæ interconnected by their canaliculi were achieved for the first time.


Day-to-Day consistency of lower extremity kinematics during walking and running.
Before conclusions can be drawn with respect to the quality of adaptations in human gait, the day-to-day consistency of the variables of interest must be known. The present study estimated the day-to-day consistency of kinematic variables collected during barefoot walking and running. Sixteen healthy subjects performed two gait analysis sessions based on skin markers. Test sessions were at least 1 week apart. In total, 48 ranges of motion were monitored for the hip, knee, ankle, and midfoot joint. Based on differences between the repeated gait analysis sessions, the day-to-day consistency was estimated. It was found that the day-to-day consistency was of the magnitude of 3 to 4 degrees for almost all ranges of motion independently of the test condition, the investigated joints, or the cardinal body plane. It was concluded that future studies on effects of interventions or on the characterization of pathological versus normative gait should consider the provided values of day-to-day consistency to improve their interpretation and conclusions.


Inadvertent retrieval of a broken PTCA catheter from the aorta during off-pump coronary bypass.
To cut costs, many centres around the world utilise previously used, re-sterilized balloon catheters to perform coronary angioplasty. The fracture and lodging of an angioplasty device within the coronary arteries is a rare but increasingly noted complication. In this article, we report on the inadvertent retrieval of a coronary angioplasty catheter during off-pump coronary bypass. The accidental removal of the catheter, which extended to the descending aorta, has obviously been life saving. This experience has shown that a high degree of caution is required when planning an operation for the retrieval of PTCA hardware.


Domain-general Stroop Performance and Hemispheric Asymmetries: A Resting-state EEG Study.
The ability to suppress irrelevant information while executing a task, also known as interference resistance ability, is a function of pFC that is critical for successful goal-directed human behavior. In the study of interference resistance and, more generally, executive functions, two key questions are still open: Does pFC contribute to cognitive control abilities through lateralized but domain-general mechanisms or through hemispheric specialization of domain-specific processes? And what are the underlying causes of interindividual differences in executive control performance? To shed light on these issues, here we employed an interindividual difference approach to investigate whether participants' hemispheric asymmetry in resting-state electrophysiological brain dynamics may reflect their variability in domain-general interference resistance. We recorded participants' resting-state electroencephalographic activity and performed spectral power analyses on the estimated cortical source activity. To measure participants' lateralized brain dynamics at rest, we computed the right-left hemispheric asymmetry score for the β/α power ratio. To measure their domain-general interference resistance ability, verbal and spatial Stroop tasks were used. Robust correlations followed by intersection analyses showed that participants with stronger resting-state-related left-lateralized activity in different pFC regions, namely the mid-posterior superior frontal gyrus, middle and posterior middle frontal gyrus, and inferior frontal junction, were more able to inhibit irrelevant information in both domains. The present results confirm and extend previous findings showing that neurophysiological difference factors may explain interindividual differences in executive functioning. They also provide support for the hypothesis of a left pFC hemispheric specialization for domain-independent phasic cognitive control processes mediating Stroop performance.


A small molecule glycosaminoglycan mimetic blocks Plasmodium invasion of the mosquito midgut.
Malaria transmission-blocking (T-B) interventions are essential for malaria elimination. Small molecules that inhibit the Plasmodium ookinete-to-oocyst transition in the midgut of Anopheles mosquitoes, thereby blocking sporogony, represent one approach to achieving this goal. Chondroitin sulfate glycosaminoglycans (CS-GAGs) on the Anopheles gambiae midgut surface are putative ligands for Plasmodium falciparum ookinetes. We hypothesized that our synthetic polysulfonated polymer, VS1, acting as a decoy molecular mimetic of midgut CS-GAGs confers malaria T-B activity. In our study, VS1 repeatedly reduced midgut oocyst development by as much as 99% (P<0.0001) in mosquitoes fed with P. falciparum and Plasmodium berghei. Through direct-binding assays, we observed that VS1 bound to two critical ookinete micronemal proteins, each containing at least one von Willebrand factor A (vWA) domain: (i) circumsporozoite protein and thrombospondin-related anonymous protein-related protein (CTRP) and (ii) vWA domain-related protein (WARP). By immunofluorescence microscopy, we observed that VS1 stains permeabilized P. falciparum and P. berghei ookinetes but does not stain P. berghei CTRP knockouts or transgenic parasites lacking the vWA domains of CTRP while retaining the thrombospondin repeat region. We produced structural homology models of the first vWA domain of CTRP and identified, as expected, putative GAG-binding sites on CTRP that align closely with those predicted for the human vWA A1 domain and the Toxoplasma gondii MIC2 adhesin. Importantly, the models also identified patches of electropositive residues that may extend CTRP's GAG-binding motif and thus potentiate VS1 binding. Our molecule binds to a critical, conserved ookinete protein, CTRP, and exhibits potent malaria T-B activity. This study lays the framework for a high-throughput screen of existing libraries of safe compounds to identify those with potent T-B activity. We envision that such compounds when used as partner drugs with current antimalarial regimens and with RTS,S vaccine delivery could prevent the transmission of drug-resistant and vaccine-breakthrough strains.


Boosting Natural Killer Cell-Mediated Targeting of Sarcoma Through DNAM-1 and NKG2D.
Sarcomas are malignancies of mesenchymal origin that occur in bone and soft tissues. Many are chemo- and radiotherapy resistant, thus conventional treatments fail to increase overall survival. Natural Killer (NK) cells exert anti-tumor activity upon detection of a complex array of tumor ligands, but this has not been thoroughly explored in the context of sarcoma immunotherapy. In this study, we investigated the NK cell receptor/ligand immune profile of primary human sarcoma explants. Analysis of tumors from 32 sarcoma patients identified the proliferative marker PCNA and DNAM-1 ligands CD112 and/or CD155 as commonly expressed antigens that could be efficiently targeted by genetically modified (GM) NK cells. Despite the strong expression of CD112 and CD155 on sarcoma cells, characterization of freshly dissociated sarcomas revealed a general decrease in tumor-infiltrating NK cells compared to the periphery, suggesting a defect in the endogenous NK cell response. We also applied a functional screening approach to identify relevant NK cell receptor/ligand interactions that induce efficient anti-tumor responses using a panel NK-92 cell lines GM to over-express 12 different activating receptors. Using GM NK-92 cells against primary sarcoma explants (n = 12) revealed that DNAM-1 over-expression on NK-92 cells led to efficient degranulation against all tested explants (n = 12). Additionally, NKG2D over-expression showed enhanced responses against 10 out of 12 explants. These results show that DNAM-1+ or NKG2D+ GM NK-92 cells may be an efficient approach in targeting sarcomas. The degranulation capacity of GM NK-92 cell lines was also tested against various established tumor cell lines, including neuroblastoma, Schwannoma, melanoma, myeloma, leukemia, prostate, pancreatic, colon, and lung cancer. Enhanced degranulation of DNAM-1+ or NKG2D+ GM NK-92 cells was observed against the majority of tumor cell lines tested. In conclusion, DNAM-1 or NKG2D over-expression elicited a dynamic increase in NK cell degranulation against all sarcoma explants and cancer cell lines tested, including those that failed to induce a notable response in WT NK-92 cells. These results support the broad therapeutic potential of DNAM-1+ or NKG2D+ GM NK-92 cells and GM human NK cells for the treatment of sarcomas and other malignancies.


Active RNA polymerases: mobile or immobile molecular machines?
It is widely assumed that active RNA polymerases track along their templates to produce a transcript. We test this using chromosome conformation capture and human genes switched on rapidly and synchronously by tumour necrosis factor alpha (TNFalpha); one is 221 kbp SAMD4A, which a polymerase takes more than 1 h to transcribe. Ten minutes after stimulation, the SAMD4A promoter comes together with other TNFalpha-responsive promoters. Subsequently, these contacts are lost as new downstream ones appear; contacts are invariably between sequences being transcribed. Super-resolution microscopy confirms that nascent transcripts (detected by RNA fluorescence in situ hybridization) co-localize at relevant times. Results are consistent with an alternative view of transcription: polymerases fixed in factories reel in their respective templates, so different parts of the templates transiently lie together.


Comprehensive Characterization of HIV-1 Molecular Epidemiology and Demographic History in the Brazilian Region Most Heavily Affected by AIDS.
The high incidence of AIDS cases and the dominance of HIV-1 subtype C infections are two features that distinguish the HIV-1 epidemic in the two southernmost Brazilian states (Rio Grande do Sul [RS] and Santa Catarina [SC]) from the epidemic in other parts of the country. Nevertheless, previous studies on HIV molecular epidemiology were conducted mainly in capital cities, and a more comprehensive understanding of factors driving this unique epidemic in Brazil is necessary. Blood samples were collected from individuals in 13 municipalities in the Brazilian southern region. HIV-1 env and pol genes were submitted to phylogenetic analyses for assignment of subtype, and viral population phylodynamics were reconstructed by applying Skygrid and logistic coalescent models in a Bayesian analysis. A high prevalence of subtype C was observed in all sampled locations; however, an increased frequency of recombinant strains was found in RS, with evidence for new circulating forms (CRFs). In the SC state, subtype B and C epidemics were associated with distinct exposure groups. Although logistic models estimated similar growth rates for HIV-1 subtype C (HIV-1C) and HIV-1B, a Skygrid plot reveals that the former epidemic has been expanding for a longer time. Our results highlight a consistent expansion of HIV-1C in south Brazil, and we also discuss how heterosexual and men who have sex with men (MSM) transmission chains might have impacted the current prevalence of HIV-1 subtypes in this region. The AIDS epidemic in south Brazil is expanding rapidly, but the circumstances driving this condition are not well known. A high prevalence of HIV-1 subtype C was reported in the capital cities of this region, in contrast to the subtype B dominance in the rest of the country. This study sought to comparatively investigate the HIV-1 subtype B and C epidemics by sampling individuals from several cities in the two states with the highest AIDS incidences in Brazil. Our analyses showed distinct epidemic growth curves for the two epidemics, and we also found evidence suggesting that separate transmission chains may be impacting the viral phylodynamics and the emergence of new recombinant forms.


Imbalance between neutrophil elastase and its inhibitor α1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure.
The molecular mechanisms involved in the development of obesity and related complications remain unclear. Here, we report that obese mice and human subjects have increased activity of neutrophil elastase (NE) and decreased serum levels of the NE inhibitor α1-antitrypsin (A1AT, SerpinA1). NE null (Ela2(-/-)) mice and A1AT transgenic mice were resistant to high-fat diet (HFD)-induced body weight gain, insulin resistance, inflammation, and fatty liver. NE inhibitor GW311616A reversed insulin resistance and body weight gain in HFD-fed mice. Ela2(-/-) mice also augmented circulating high molecular weight (HMW) adiponectin levels, phosphorylation of AMP-activated protein kinase (AMPK), and fatty acid oxidation (FAO) in the liver and brown adipose tissue (BAT) and uncoupling protein (UCP1) levels in the BAT. These data suggest that the A1AT-NE system regulates AMPK signaling, FAO, and energy expenditure. The imbalance between A1AT and NE contributes to the development of obesity and related inflammation, insulin resistance, and liver steatosis.


Triglyceride and HDL-C Dyslipidemia and Risks of Coronary Heart Disease and Ischemic Stroke by Glycemic Dysregulation Status: The Strong Heart Study.
High triglyceride (TG) levels and low HDL cholesterol (HDL-C) levels are risk factors for cardiovascular disease. It is unclear whether this relationship depends on glycemic dysregulation, sex, or LDL cholesterol (LDL-C) level. We studied 3,216 participants (40% men, 41% with diabetes) who were free of cardiovascular disease at baseline in a community-based, prospective cohort of American Indians (median follow-up 17.7 years). Cox models estimated hazard ratios (HRs) and 95% CIs for incident ischemic stroke and coronary heart disease (CHD) in relation to combined TG and HDL-C status, where a fasting TG level ≥150 mg/dL was "high" and a fasting HDL-C level <40 mg/dL for men (<50 mg/dL for women) was "low." Models included age, sex, BMI, smoking, diabetes, fasting LDL-C level, antihypertensive medications, physical activity, estimated glomerular filtration rate, and urinary albumin-to-creatinine ratio. Participants with high TG and low HDL levels had a 1.32-fold greater HR (95% CI 1.06-1.64) for CHD than those with normal TG and normal HDL levels. It was observed in participants with diabetes, but not in those without diabetes, that high TG plus low HDL levels were associated with a 1.54-fold greater HR (95% CI 1.15-2.06) for CHD (P value for interaction = 0.003) and a 2.13-fold greater HR (95% CI 1.06-4.29) for stroke (P value for interaction = 0.060). High TG and low HDL level was associated with CHD risk in participants with an LDL-C level of ≥130 mg/dL, but this was not observed in those participants with lower LDL-C levels. Sex did not appear to modify these associations. Adults with both high TG and low HDL-C, particularly those with diabetes, have increased risks of incident CHD and stroke. In particular, those with an LDL-C level ≥130 mg/dL may have an increased risk of incident stroke.


Association of follow-up infarct volume with functional outcome in acute ischemic stroke: a pooled analysis of seven randomized trials.
Follow-up infarct volume (FIV) has been recommended as an early indicator of treatment efficacy in patients with acute ischemic stroke. Questions remain about the optimal imaging approach for FIV measurement. To examine the association of FIV with 90-day modified Rankin Scale (mRS) score and investigate its dependency on acquisition time and modality. Data of seven trials were pooled. FIV was assessed on follow-up (12 hours to 2 weeks) CT or MRI. Infarct location was defined as laterality and involvement of the Alberta Stroke Program Early CT Score regions. Relative quality and strength of multivariable regression models of the association between FIV and functional outcome were assessed. Dependency of imaging modality and acquisition time (≤48 hours vs >48 hours) was evaluated. Of 1665 included patients, 83% were imaged with CT. Median FIV was 41 mL (IQR 14-120). A large FIV was associated with worse functional outcome (OR=0.88(95% CI 0.87 to 0.89) per 10 mL) in adjusted analysis. A model including FIV, location, and hemorrhage type best predicted mRS score. FIV of ≥133 mL was highly specific for unfavorable outcome. FIV was equally strongly associated with mRS score for assessment on CT and MRI, even though large differences in volume were present (48 mL (IQR 15-131) vs 22 mL (IQR 8-71), respectively). Associations of both early and late FIV assessments with outcome were similar in strength (ρ=0.60(95% CI 0.56 to 0.64) and ρ=0.55(95% CI 0.50 to 0.60), respectively). In patients with an acute ischemic stroke due to a proximal intracranial occlusion of the anterior circulation, FIV is a strong independent predictor of functional outcome and can be assessed before 48 hours, oneither CT or MRI.


Impact of pocket gopher disturbance on plant species diversity in a shortgrass prairie community.
We examined the impact of pocket gopher disturbances on the dynamics of a shortgrass prairie community. Through their burrowing activity, pocket gophers (Thomomys bottae) cast up mounds of soil which both kill existing vegetation and create sites for colonization by competitively-inferior plant species. Three major patterns emerge from these disturbances: First, we show that 10 of the most common herbaceous perennial dicots benefit from pocket gopher disturbance; that is, a greater proportion of seedlings are found in the open space created by pocket gopher disturbance than would be expected based on the availability of disturbed habitat. Additionally, these seedlings exhibited higher growth rates than adjacent seedlings of the same species growing in undisturbed habitat. Second, we tested two predictions of the Intermediate Disturbance Hypothesis and found that species diversity was greatest for plots characterized by disturbances of intermediate age. However, we did not detect significant differences in diversity between plots characterized by intermediate and high levels of disturbance, indicating that many species are adapted to or at least tolerant of high levels of disturbance. Third, we noted that the abundance of grasses decreased with increasing disturbance, while the abundance of dicots increased with increasing disturbance.


Epidemiology of knife carrying among young British men.
Knife carrying has caused considerable public concern in the UK. But little is known of the epidemiology and characteristics of men who carry knives. We investigated associations with socioeconomic deprivation, area-level factors, and psychiatric morbidity. Cross-sectional surveys of 5005 British men, 18-34 years, oversampling Black and Minority Ethnic (BME) men, lower social grades, and in London Borough of Hackney and Glasgow East. Participants completed questionnaires covering violent behaviour and psychiatric morbidity using standardised self-report instruments. Socioeconomic deprivation measured at small area level. Prevalence of knife carrying was 5.5% (4.8-6.9) and similar among white and BME subgroups. However, prevalence was twice the national rate in Glasgow East, and four times higher among Black men in Hackney, both areas with high levels of background violence and gang activity. Knife carrying was associated with multiple social problems, attitudes encouraging violence, and psychiatric morbidity, including antisocial personality disorder (AOR 9.94 95% CI 7.28-13.56), drug dependence (AOR 2.96 95% CI 1.90-4.66), and paranoid ideation (AOR 6.05 95% CI 4.47-8.19). There was no evidence of a linear relationship with socioeconomic deprivation. Men who carry knives represent an important public health problem with high levels of health service use. It is not solely a criminal justice issue. Rates are increased in areas where street gangs are active. Contact with the criminal justice system provides opportunity for targeted violence prevention interventions involving engagement with integrated psychiatric, substance misuse, and criminal justice agencies.


FoxA4 favours notochord formation by inhibiting contiguous mesodermal fates and restricts anterior neural development in Xenopus embryos.
In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula -chordin and -noggin expressing centre (BCNE) and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain) is directly required to restrict anterior neural development.


Changes in the haemostatic system after thermoneutral and hyperthermic water immersion.
Warm water bathing is a popular recreational activity and is frequently used in rehabilitation medicine. Although well tolerated in most cases, there are reports indicating an increased risk of thrombotic events after hot tub bathing. The effects of a 45 min thermoneutral bath followed by a 50 min bath with increasing water temperature (maximum 41 degrees C) until reaching a body core temperature of 39 degrees C on factors of blood coagulation and fibrinolysis were studied in eight healthy male volunteers. Blood was obtained after a 45-min resting period as control and after the thermoneutral and hyperthermic bath as well as after another 45 min recovery period at the end of the study. Hyperthermic immersion (HI) lead to a shortening of activated partial thromboplastin time (aPTT) (P < 0.05). Fibrinogen concentration decreased immediately after HI (P < 0.05) but increased during recovery (P < 0.05). Plasminogen activator inhibitor (PAI) activity decreased during HI (P < 0.05), D-dimer concentration was not found to change. Thrombocyte count increased (P < 0.05) during HI. The increases in tissue-type plasminogen activator concentration as well as leucocyte count during HI were due to haemoconcentration. Prothrombin time, PAI-activity and granulocyte count decreased during thermoneutral immersion (P < 0.05). Warm water bathing leads to haemoconcentration and minimal activation of coagulation. The PAI-1 activity is decreased. A marked risk for thrombotic or bleeding complications during warm water bathing in healthy males could not be ascertained.


The decrease in phosphatidylinositol 4,5-bisphosphate in ADP-stimulated washed rabbit platelets is not primarily due to phospholipase C activation.
Addition of 10 micron-ADP to washed rabbit platelets caused platelet shape change and aggregation without release of the contents of the amine-storage granules, and caused a transient decrease (8.8% at 10 s) in the amount of phosphatidylinositol 4,5-bisphosphate (PIP2). By 20 s the decrease in PIP2 was no longer apparent, but by 60 s the amount of PIP2 was again decreased. Addition of thrombin (1 unit/ml), which causes platelet shape change, aggregation and the release of the contents of the amine-storage granules, caused a decrease in the amount of PIP2 (8.0% at 10 s); at 60 s the amount of PIP2 was not significantly different from that in controls. In platelets prelabelled with [3H]glycerol, the specific radioactivity of PIP2 was increased at 10 s in ADP-stimulated platelets, and unchanged in thrombin-stimulated platelets. In platelets prelabelled with [3H]inositol and incubated with 20 mM-Li+ to inhibit the degradation of the inositol phosphates to inositol, there was no increase in the labelling of inositol trisphosphate (IP3) upon stimulation with ADP. In contrast, stimulation with thrombin caused a significant increase in the labelling of IP3 at 10 s. These differences in the changes in polyphosphoinositide metabolism in ADP- and thrombin-stimulated platelets are consistent with the hypothesis that the decrease in PIP2 in ADP-stimulated platelets may be due not to degradation of PIP2 by phospholipase C, but rather to a shift in the equilibrium between PIP2 and phosphatidylinositol 4-phosphate (PIP). Increases in the labelling of phosphatidic acid at 10 s and of inositol bisphosphate and inositol phosphate after 20 s are consistent with phospholipase C being stimulated through some other mechanism that leads to the degradation of PIP and phosphatidylinositol; one possibility is that ADP causes an increase in cytoplasmic Ca2+.


Clinical factors that impair health-related quality of life in ulcerative colitis patients vary with the disease duration.
The health-related quality of life (HRQOL) of patients with ulcerative colitis (UC) can be impaired because of the chronic symptoms. Although UC patients suffer from such symptoms over the long term, there have been few reports on the changes of HRQOL with disease duration. The aim of this study was to clarify these changes. The HRQOL of 331 Japanese UC patients was examined using the validated Japanese version of the Inflammatory Bowel Disease Questionnaire (J-IBDQ). HRQOL and factors affecting HRQOL identified using multiple linear regression analysis were stratified by disease duration. Of the 15 clinical factors examined, the clinical activity index score was the strongest determinant (P<0.0001) of all the scores of IBDQ regardless of disease duration. HRQOL did not differ significantly among patients with different disease durations. The factors, however, that affected HRQOL varied according to disease duration. In patients with disease duration of less than 5 years, the clinical activity index score was the predominant factor affecting HRQOL. Being 'on sick leave or hospitalized' was a significant factor impairing HRQOL in patients with disease duration of 5-9 years. Moreover, complications due to corticosteroids significantly impaired all of the IBDQ scores in patients with disease duration of 10 years or more. Factors that affected the HRQOL of UC patients varied according to the patients' disease duration. Our findings should assist in the development of a long-term strategy for the treatment of UC patients.


Health and social care professionals' experiences of supporting parents and their dependent children during, and following, the death of a parent: A qualitative review and thematic synthesis.
Children need to be prepared for the death of a parent and supported afterwards. Parents seek support from health and social care professionals to prepare their children. Support is not always forthcoming. To systematically identify, analyse and synthesise literature reporting of the experiences of health and social care professionals when supporting parents and children during, and following, the death of a parent. A systematically constructed qualitative review and thematic synthesis. Registered on Prospero (CRD42017076345). MEDLINE, CINAHL, Embase, PsycINFO, PsycARTICLES and PROSPERO, searched from January 1996 to July 2018 for qualitative studies in English, containing verbatim reporting of health and social care professionals' experiences of supporting parents and children during, and following, the death of a parent. Qualitative data were appraised using a modified Critical Appraisal Skills Programme qualitative appraisal checklist. The search yielded 15,758 articles. Of which, 15 met the inclusion criteria. A total of 13 included professionals' experiences of supporting parents and children before parental death. Two included experiences of supporting surviving parents and children afterwards. Three analytical themes identified as follows: (1) aspiring to deliver family-focussed care, (2) health and social care professionals' behaviours and emotions and (3) improving connections with parents and children. Connecting empathically with parents and children to prepare and support children entails significant emotional labour. Professionals seek to enhance their confidence to connect. Professionals struggle to connect empathically with parents and their children to prepare and to support children when a parent is dying and afterwards. Awareness of professionals' needs would enable provision of appropriate support for parents and children.


A comprehensive review of sensors and instrumentation methods in devices for musical expression.
Digital Musical Instruments (DMIs) are musical instruments typically composed of a control surface where user interaction is measured by sensors whose values are mapped to sound synthesis algorithms. These instruments have gained interest among skilled musicians and performers in the last decades leading to artistic practices including musical performance, interactive installations and dance. The creation of DMIs typically involves several areas, among them: arts, design and engineering. The balance between these areas is an essential task in DMI design so that the resulting instruments are aesthetically appealing, robust, and allow responsive, accurate and repeatable sensing. In this paper, we review the use of sensors in the DMI community as manifested in the proceedings of the International Conference on New Interfaces for Musical Expression (NIME 2009-2013). Focusing on the sensor technologies and signal conditioning techniques used by the NIME community. Although it has been claimed that specifications for artistic tools are harder than those for military applications, this study raises a paradox showing that in most of the cases, DMIs are based on a few basic sensors types and unsophisticated engineering solutions, not taking advantage of more advanced sensing, instrumentation and signal processing techniques that could dramatically improve their response. We aim to raise awareness of limitations of any engineering solution and to assert the benefits of advanced electronics instrumentation design in DMIs. For this, we propose the use of specialized sensors such as strain gages, advanced conditioning circuits and signal processing tools such as sensor fusion. We believe that careful electronic instrumentation design may lead to more responsive instruments.


Intermittency of water vapor fluxes from vineyards during light wind and convective conditions.
Vineyards in many semi-arid regions globally face limited water resources. Monitoring évapotranspiration (ET) of vineyards is critical for water resource management, but remains difficult due to the complex biophysics of the surfaces. Both measurement and modeling approaches for estimating turbulent water vapor transport rely on implicit assumptions that exchanges occur in a reasonably regular fashion over the time scales generally used for averaging. However, heterogeneous vegetation in semi-arid climates, such as many vineyards, presents inherent factors, including canopy row/row space structure and frequent periods of light wind, unstable conditions, that can create episodic transport characteristics. Eddy covariance data were collected above and within the canopy of two vineyards in the Central Valley of California during the Grape Remote sensing Atmospheric Profile & Evapotranspiration experiment (GRAPEX). The goal was to document and quantify the existence of intermittent turbulence transport of water vapor, and associated episodic canopy venting. These effects were found to correlate with periods light winds and highly unstable/convective conditions. Power and cross-spectra for intermittent periods documented enhancement of low-frequency water vapor exchange events compared to more steady periods, and diminished time scale correlation between humidity within the canopy and above the canopy. Analyses show that intermittent cases can necessitate longer flux-averaging periods (up to 2 h) than more steady conditions. Episodic exchange events were isolated and summed to determine their relative contribution to the overall water vapor flux. Since light wind, unstable conditions are relatively common in many arid vineyard regions, these findings have implications for mechanistic ET models that rely on time-averaged vertical gradients, which implies reasonably steady transport.


Clinimetric and psychometric strategies for development of a health measurement scale.
Clinimetrics and psychometrics, two accepted methods for developing multiitem health measurement scales, have fundamentally different aims and methods that have seldom been compared and never prospectively. The purpose of this study was to determine whether these two methodologies provided comparable scales in the development of an upper extremity disability measure. Psychometric analysis involved field testing a 70-item questionnaire on 407 patients. Equidiscriminatory item total correlation (EITC) was used to select the top 30 items. Clinimetric testing used the mean importance and severity ratings of the 70 items by 76 patients to select the top 30 items. Clinimetric and psychometric analyses were performed independently. Cronbach's alpha was 0.97 for the top 30 items selected by EITC and 0.96 for the items selected based on patient's ratings. The two scales (after clinician modification to improve face validity) shared 16 items in common (P=0.10). The intraclass correlation coefficient of the patient scores on the two 30-item scales was 0.93 before clinician input and 0.97 after. The mean (and standard deviation) difference between scales was 9.1 (8.8) before and 1.7 (5.2) after clinician input. A scale developed with a clinimetric strategy can measure a complex (so-called heterogeneous) clinical phenomenon (thought to be composed of several patient attributes) but still fulfill psychometric criteria for "homogeneity." Thus, these strategies for the development of health measurement scales, which have been considered potentially opposite or conflicting, may be complementary.


Severe alpha1-antitrypsin deficiency and pregnancy.
This case study describes a successful pregnancy in a 27-yr-old patient with severe emphysema, secondary to alpha1-antitrypsin deficiency, genotype PiZZ. Despite significant respiratory compromise, more severe than previously reported, no complications ensued. Maternal pulmonary function did not deteriorate significantly until the 32nd week of pregnancy, with an elective Caesarean section being performed during the 37th week. This experience suggests that even severe maternal airflow obstruction is, in itself, not an absolute contra-indication to pregnancy. Pre-pregnancy multidisciplinary counselling is likely to be helpful in these patients, including frank discussion on the risks of pregnancy, the prospects of successful completion and the mother's future prognosis in relation to caring for the child.


Insight into Pre-Clinical Models of Traumatic Brain Injury Using Circulating Brain Damage Biomarkers: Operation Brain Trauma Therapy.
Operation Brain Trauma Therapy (OBTT) is a multicenter pre-clinical drug screening consortium testing promising therapies for traumatic brain injury (TBI) in three well-established models of TBI in rats--namely, parasagittal fluid percussion injury (FPI), controlled cortical impact (CCI), and penetrating ballistic-like brain injury (PBBI). This article presents unique characterization of these models using histological and behavioral outcomes and novel candidate biomarkers from the first three treatment trials of OBTT. Adult rats underwent CCI, FPI, or PBBI and were treated with vehicle (VEH). Shams underwent all manipulations except trauma. The glial marker glial fibrillary acidic protein (GFAP) and the neuronal marker ubiquitin C-terminal hydrolase (UCH-L1) were measured by enzyme-linked immunosorbent assay in blood at 4 and 24 h, and their delta 24-4 h was calculated for each marker. Comparing sham groups across experiments, no differences were found in the same model. Similarly, comparing TBI + VEH groups across experiments, no differences were found in the same model. GFAP was acutely increased in injured rats in each model, with significant differences in levels and temporal patterns mirrored by significant differences in delta 24-4 h GFAP levels and neuropathological and behavioral outcomes. Circulating GFAP levels at 4 and 24 h were powerful predictors of 21 day contusion volume and tissue loss. UCH-L1 showed similar tendencies, albeit with less robust differences between sham and injury groups. Significant differences were also found comparing shams across the models. Our findings (1) demonstrate that TBI models display specific biomarker profiles, functional deficits, and pathological consequence; (2) support the concept that there are different cellular, molecular, and pathophysiological responses to TBI in each model; and (3) advance our understanding of TBI, providing opportunities for a successful translation and holding promise for theranostic applications. Based on our findings, additional studies in pre-clinical models should pursue assessment of GFAP as a surrogate histological and/or theranostic end-point.


The myth of cognitive decline: non-linear dynamics of lifelong learning.
As adults age, their performance on many psychometric tests changes systematically, a finding that is widely taken to reveal that cognitive information-processing capacities decline across adulthood. Contrary to this, we suggest that older adults'; changing performance reflects memory search demands, which escalate as experience grows. A series of simulations show how the performance patterns observed across adulthood emerge naturally in learning models as they acquire knowledge. The simulations correctly identify greater variation in the cognitive performance of older adults, and successfully predict that older adults will show greater sensitivity to fine-grained differences in the properties of test stimuli than younger adults. Our results indicate that older adults'; performance on cognitive tests reflects the predictable consequences of learning on information-processing, and not cognitive decline. We consider the implications of this for our scientific and cultural understanding of aging.


Serum total sialic acid and Hanganutziu-Deicher antibody in normals and in cancer patients.
To determine the levels of both TSA and HD antibody in sera of patients with various malignancies and evaluate their potential role as diagnostic and/ or prognostic markers. Laboratory based analysis. Kenyatta National Hospital, Kenya Medical Research Institute and the Department of Biochemistry, University of Nairobi. A total of 909 serum samples, 420 from cancer patients recruited at Kenyatta National Hospital and 509 from normal blood donors recruited at Nairobi Hospital. The mean age for the patients and controls was 36 and 37 years respectively. Carcinoma patients constituted 54%, sarcoma 12.1%, lymphoma 16.4% and 17.4% had other types of tumours. The mean TSA in patients was 0.86 mg/ml +/- 0.026 compared to 0.82 mg/ml +/- 0.014 in controls. The TSA level was significantly higher in patients compared to controls (Student's t-test p = 0.031 at 0.05 confidence level). The TSA increased with age in both study groups. In patient sera, both gender gave the same mean of 0.83 mg/ml while it was 0.82 mg/ml and 0.83 mg/ml in control females and in males respectively. Sarcomas had the highest amount of 0.93 mg/ml but there was no significant statistical variation between tumour types (p = 0.076). The HD antibody mean readings were 0.004 in pathologic sera compared to 0.011 in controls. The values were significantly elevated in patients (p = 0.03) with females giving a higher value for both study groups (p = 0.628). HD antibody readings was significantly higher in carcinomas (p = 0.017) compared to those of sarcomas and lymphomas. There was no association between antibody readings and age of patient (p = 0.601). Both TSA and HD antibody values were significantly elevated in patients compared to clinically healthy controls and while TSA levels increased with age and was independent of gender, HD antibody levels were independent of age, gender and also tumour type. The study demonstrates that although TSA is normally elevated in malignancy, most of the sialic acid shed is of N-acetyl type as some patients do not express HD antibody directed to the N-glycolyl sialic acid. The reason why some tumours would express Neu5Gc at any one time needs further evaluation.


Optimisation of handling, activation and assessment procedures for Bufo marinus spermatozoa.
In the present study, we investigated handling, activation and assessment procedures for cane toad (Bufo marinus) spermatozoa. Optimisation of these techniques will facilitate the maintenance of sperm viability during cryopreservation and during in vitro fertilisation (IVF) techniques in reproduction technologies for endangered species. Spermatozoa were taken from testicular macerates and assessed using plasma membrane integrity assays (live/dead stains) and quantitative scores of motility parameters. In the assessment of sperm viability using live/dead stains, there were small but significant differences in the percentage of sperm from cryopreserved samples staining positive with propidium iodide, Hoechst H33258 and Trypan blue; these differences were not large and all stains performed acceptably. Spermatozoa were activated by dilution of testicular macerates in water at one of two dilution ratios (1 : 6 or 1 : 20) with or without 0.1-5.0 mM theophylline. Sperm plasma membrane integrity (unstained spermatozoa) was unaffected by either dilution ratio (osmolarity) or theophylline concentration. However, sperm motility was significantly affected by osmolarity and theophylline concentration. The stimulation of sperm motility increased with higher theophylline concentrations and these strongly interacted with lower osmolarities through a higher dilution ratio of sperm macerates with water. Spermatozoa were exposed to increasing centrifugation forces to determine tolerance to physical stresses encountered during washing procedures. Forces between 50 and 800 g were associated with a significant reduction in motility (mean 56 +/- 3% decreasing to 27 +/- 3%), but did not affect staining. In conclusion, centrifugation should be minimised in anuran sperm washing procedures; osmotic shock associated with higher dilution ratios reduces the capacity of anuran sperm to achieve high percentages of motile sperm, leading to a likely trade-off between dilution required for activation and sperm motility to optimise IVF fertilisation rates; and optimal conditions for sperm motility after activation occur at lower dilutions of suspensions with 5.0 mM theophylline. The present study has improved protocols for the handling of anuran sperm during pre- and post-cryopreservation procedures.


Icariin ameliorates the progression of experimental autoimmune encephalomyelitis by down-regulating the major inflammatory signal pathways in a mouse relapse-remission model of multiple sclerosis.
This study aimed at investigating whether treatment with icariin (ICA) could modulate the progression of experimental autoimmune encephalomyelitis (EAE) and its potential mechanisms in SJL/J mice. Female SJL/J mice were immunized with PLP139-151 peptide to induce relapse-remitting EAE and the immunized mice were treated with vehicle alone (EAE) or ICA (12.5 or 25 mg/body weights) by gavage daily for 42 days. Compared with the control, the EAE mice developed relapse-remitting EAE and reduced body weights (15.76 ± 0.61 vs. 17.60 ± 0.98 g on day 13; 17.35 ± 0.44 vs. 18.46 ± 0.66 g on day 26), accompanied by severe inflammation with many microglia infiltrates and obvious demyelination in the spinal cord tissues. Conversely, ICA treatment significantly reduced the clinical scores (on day 13, 1.00 ± 0.16 and 1.10 ± 0.33 for ICA 12.5 and 25 mg/kg group, respectively vs. 1.62 ± 0.41 in the EAE group; on day 26, 0.50 ± 0.23 and 0.40 ± 0.24 for ICA 12.5 and 25 mg/kg group, respectively, vs. 1.56 ± 0.29 in the EAE group), mitigated the body weight reduction, spinal cord inflammation and demyelination in EAE mice (pathological scores of 2.33 ± 0.82 and 1.11 ± 0.57 for ICA 12.5 and 25 mg/kg, respectively; vs. 4.78 ± 1.13, P < 0.0001). Furthermore, ICA treatment significantly mitigated the EAE-increased iNOS, TNF-α, CD206 and TGF-β1, but further reduced IL-10 mRNA transcripts in the brain mice. More importantly, ICA treatment significantly mitigated the inflammation-related NF-κB, AKT, ERK1/2, p38, c-Jun and MEK phosphorylation in the brain of EAE mice. ICA treatment ameliorates the progression of EAE by down-regulating the major inflammation-related signal pathways in mice.


Decreased phosphatidylcholine plasmalogens--A putative novel lipid signature in patients with stable coronary artery disease and acute myocardial infarction.
Glycerophospholipids and sphingolipids are structurally heterogeneous due to differences in the O- and N-linked fatty acids and head groups. Sphingolipids also show a heterogeneity in their sphingoid base composition which up to now has been little appreciated. The aim of this study was to investigate the association of certain glycerophospholipid and sphingolipid species with stable coronary artery disease (CAD) and acute myocardial infarction (AMI). The lipid profile in plasma from patients with stable CAD (n = 18) or AMI (n = 17) was compared to healthy subjects (n = 14). Sixty five glycerophospholipid and sphingolipid species were quantified by LC-MS. The relative distribution of these lipids into lipoprotein fractions was analyzed. In the CAD cohort, 45 glycerophospholipid and sphingolipid species were significantly lower compared to healthy controls. In the AMI group, 42 glycerophospholipid and sphingolipid species were reduced. Four PC plasmalogens (PC33:1, PC33:2, PC33:3 and PC35:3) showed the most significant difference. Out of eleven analyzed sphingoid bases, four were lower in the CAD and six in the AMI group. Sphingosine-1-phosphate (S1P) levels were reduced in the AMI group whereas an atypical C16:1 S1P was lower in both groups. Phosphatidylcholine and sphingomyelin species were exclusively present in lipoprotein particles, whereas lysophosphatidylcholines were mainly found in the lipoprotein-free fraction. The observed differences were not explained by the use of statins as confirmed in a second, independent cohort. Reduced levels of four PC plasmalogens (PC33:1, PC33:2, PC33:3 and PC35:3) were identified as a putatively novel lipid signature for CAD and AMI.


Effects of dietary fat and L-carnitine on plasma and whole blood taurine concentrations and cardiac function in healthy dogs fed protein-restricted diets.
To evaluate plasma taurine concentrations (PTC), whole blood taurine concentrations (WBTC), and echocardiographic findings in dogs fed 1 of 3 protein-restricted diets that varied in fat and L-carnitine content. 17 healthy Beagles. Baseline PTC and WBTC were determined, and echocardiography was performed in all dogs consuming a maintenance diet. Dogs were then fed 1 of 3 protein-restricted diets for 48 months: a low-fat (LF) diet, a high-fat and L-carnitine supplemented (HF + C) diet, or a high-fat (HF) diet. All diets contained methionine and cystine concentrations at or above recommended Association of American Feed Control Officials (AAFCO) minimum requirements. Echocardiographic findings, PTC, and WBTC were evaluated every 6 months. The PTC and WBTC were not significantly different among the 3 groups after 12 months. All groups had significant decreases in WBTC from baseline concentrations, and the HF group also had a significant decrease in PTC. One dog with PT and WBT deficiency developed dilated cardiomyopathy (DCM). Taurine supplementation resulted in significant improvement in cardiac function. Another dog with decreased WBTC developed changes compatible with early DCM. Results revealed that dogs fed protein-restricted diets can develop decreased taurine concentrations; therefore, protein-restricted diets should be supplemented with taurine. Dietary methionine and cystine concentrations at or above AAFCO recommended minimum requirements did not prevent decreased taurine concentrations. The possibility exists that AAFCO recommended minimum requirements are not adequate for dogs consuming protein-restricted diets. Our results also revealed that, similar to cats, dogs can develop DCM secondary to taurine deficiency, and taurine supplementation can result in substantial improvement in cardiac function.


Chemical properties, mode of action, and in vivo anti-herpes activities of a lignin-carbohydrate complex from Prunella vulgaris.
The chemical nature, the mode of action, and the in vitro and in vivo anti-HSV activities of the polysaccharide from Prunella vulgaris were characterized. The polysaccharide was isolated by ethanol precipitation, dialysis, CTAB precipitation, and gel exclusion chromatography. The isolated compound (PPS-2b) was a lignin-carbohydrate complex with a molecular weight of 8500. The carbohydrate moiety was composed of glucose, galactose, mannose, galacturonic acid, rhamnose, xylose, and arabinose with glucose as the major sugar. In plaque reduction assay, PPS-2b showed activities against HSV-1 and HSV-2. The anti-HSV activity could be abolished by periodate oxidation. Mechanism studies showed that PPS-2b inactivated HSV-1 directly, blocked HSV-1 binding to Vero cells, and inhibited HSV-1 penetration into Vero cells. A similar inhibition was observed with a gC-deficient strain of HSV-1. The in vivo activities of a Prunella cream formulated with a semi-purified fraction was assessed in a HSV-1 skin lesion model in guinea pigs and a HSV-2 genital infection model in BALB/c mice. Guinea pigs that received the Prunella cream treatment showed a significant reduction (P<0.01) in skin lesions. Mice that received the Prunella cream treatment showed a significant reduction (P<0.01) in mortality. In conclusion, the anti-HSV compound from P. vulgaris is a lignin-polysaccharide complex with potent activity against HSV-1 and HSV-2. Its mode of action appears to be inhibiting viral binding and penetration into host cells.


Asymmetries of cortical shape: Effects of handedness, sex and schizophrenia.
Some evidence suggests that sex, handedness and disease processes associated with schizophrenia affect the magnitude and/or direction of structural brain asymmetries. There are mixed findings, however, on how these factors influence cerebral torque, when torque is assessed with linear or volumetric measurements. We obtained MRI data from 67 healthy (30 males, 10 non-dextrals) and 84 schizophrenia subjects (60 males; 16 non-dextrals) and applied cortical pattern matching to spatially relate and compare differences in the surface morphology of the two cerebral hemispheres at high spatial resolution. Asymmetry indices, computed at thousands of matched hemispheric locations, were used to examine effects of sex, handedness and schizophrenia on hemispheric shape asymmetries while controlling for age and the other factors. Highly significant and discriminative right-frontal and left parietal-occipital surface expansions and protrusions (petalias) were mapped within groups. Although hemispheric shape asymmetries appeared less pronounced within female non-dextrals, asymmetry indices were not shown to differ significantly across sex, hand preference or diagnosis, or to reveal interactions of handedness with sex or diagnosis. Our 3D maps of spatially detailed anterior and posterior hemispheric shape asymmetries reflect subtle geometric distortions in hemispheric surface morphology that cannot be characterized with 2D or volumetric methods. Inter-individual variations in hemispheric torque appear minimally influenced by sex, dextrality or disease status. Biological factors driving language dominance or other lateralized brain functions dissociable from handedness, may more closely relate to hemispheric shape asymmetries, while the lateralization of other discrete brain regions may be more influenced by sexually dimorphic factors or by schizophrenia pathophysiology.


The Effects of Hopelessness on Chronic Disease Among African Americans and Caribbean Blacks: Findings from the National Survey of American Life (NSAL).
This paper examines the relationship between hopelessness on chronic disease in a national sample of African Americans (3570) and Caribbean Blacks (1438) Using the National Survey of American Life. A multivariate negative binomial regression examined whether chronic disease is associated with hopelessness, controlling for sociodemographic characteristics. Overall, 13.14% of the sample reported they were highly hopeless, and 31.5% indicated they were moderately hopeless. About 19% of respondents experienced chronic disease. Bivariate associations showed that those who have ever had chronic disease significantly differed from those who did not in regard to age, gender and spirituality. Multivariate results showed that respondents who ever have had chronic disease reported significantly higher hopelessness scores than those with no chronic disease. The study findings contribute to the current body of literature by supporting findings from smaller studies on the relationship between depression and hopelessness in African Americans and Caribbean Blacks.


Studying survivors of nearly lethal suicide attempts: an important strategy in suicide research.
The series of articles in this special issue of SLTB from the Centers for Disease Control and Prevention (CDC) study of nearly lethal suicide attempts represents an important contribution to research on suicidal behavior. The investigative approach used is attractive, yet also challenging in terms of research methodology. In this commentary I take the opportunity to highlight certain aspects of this line of research as well as to comment on the specific findings of the CDC study and their relationship to existing knowledge. I also discuss the future potential for this research approach and further questions that might be addressed by it.


A clinical tool to measure the components of health-care transition from pediatric care to adult care: the UNC TR(x)ANSITION scale.
To describe the development of the University of North Carolina (UNC) TR(x)ANSITION Scale that measures the health-care transition and self-management skills by youth with chronic health conditions. Item and scale development of the UNC TR(x)ANSITION Scale was informed by two theoretical models, available literature, and expert opinion interviews and feedback from youth with chronic conditions, their parents, and interdisciplinary collaboration. Through an iterative process, three versions of the scale were piloted on a total of 185 adolescents and emerging adults with different chronic illnesses. This clinically administered scale relies on a semi-structured interview format of the patient and does not rely solely on patient report, but is verified with information from the medical record to validate responses. Following the item development and the three iterations of the scale, version 3 was examined in a more intensive fashion. The current version of the UNC TR(x)ANSITION Scale comprises 33 items scattered across the following 10 domains: Type of illness, Rx=medications, Adherence, Nutrition, Self-management, Informed-reproduction, Trade/school, Insurance, Ongoing support, and New health providers. It requires approximately 7-8 min to administer. With a sample of 128 adolescents and young adults, ranging in age from 12 to 20, inter-rater reliability was strong (r = 0.71) and item-total correlation scores were moderate to high. Content and construct validity were satisfactory, and the overall score was sensitive to advancing age. The univariate linear regression yielded a beta coefficient of 1.08 (p < 0.0001), indicating that the total score increased with advancing age. Specifically, there was about a one point increase in the total score for each year of age. The UNC TR(x)ANSITION Scale is a disease-neutral tool that can be used in the clinical setting. Initial findings suggest that it is a reliable and valid tool that has the potential to measure health-care transition skill mastery and knowledge in a multidimensional fashion.


Molecular characterization and infectivity of a Tomato leaf curl New Delhi virus variant associated with newly emerging yellow mosaic disease of eggplant in India.
Begomoviruses have emerged as serious problem for vegetable and fiber crops in the recent past, frequently in tropical and subtropical region of the world. The association of begomovirus with eggplant yellow mosaic disease is hitherto unknown apart from one report from Thailand. A survey in Nagpur, Central India, in 2009-2010 showed severe incidence of eggplant yellow mosaic disease. Here, we have identified and characterized a begomovirus responsible for the newly emerging yellow mosaic disease of eggplant in India. The complete DNA-A and DNA-B genomic components of the causative virus were cloned and sequenced. Nucleotide sequence analysis of DNA-A showed that it shared highest 97.6% identity with Tomato leaf curl New Delhi virus-India[India:Udaipur:Okra:2007] and lowest 87.9% identity with Tomato leaf curl New Delhi virus-India[India:NewDelhi:Papaya:2005], while DNA-B showed highest 94.1% identity with ToLCNDV-IN[IN:UD:Ok:07] and lowest 76.2% identity with ToLCNDV-India[India:Lucknow]. Thus, it appears that this begomovirus is a variant of ubiquitous ToLCNDV and hence, we suggest the name ToLCNDV-India[India:Nagpur:Eggplant:2009] for this variant. The pathogenicity of ToLCNDV-IN[IN:Nag:Egg:09] isolate was confirmed by agroinfiltraion and dimeric clones of DNA-A and DNA-B induced characteristic yellow mosaic symptoms in eggplants and leaf curling in tomato plants. This is the first report of a ToLCNDV variant moving to a new agriculturally important host, eggplant and causing yellow mosaic disease. This is also a first experimental demonstration of Koch's postulate for a begomovirus associated with eggplant yellow mosaic disease.


Comparison of two surveys of head injured patients presenting during a calendar year to an urban medical centre 32 years apart.
To study the patients presenting with head injuries to a tertiary hospital in Karachi during the year 2003. During the calendar year 2003, a cross-sectional study was conducted of all patients presenting to the casualty department of Jinnah Postgraduate Medical Centre (JPMC) with head injury. Personal information was collected from the patient's attendants at presentation or later if the patient had been brought in by the emergency services as an unknown person. The circumstances of the injury were similarly established and the clinical features documented. During the year 2003, a total of 3008 patients reported to the emergency room of JPMC. Of these 67% were males and the majority of the reporting patients (48%) had suffered their head injury in falls from a height. However, when considering the seriously injured patients warranting admission to the neurosurgery unit, road traffic injuries predominated (54%) and the age distribution was weighed towards an older age group with 70% being above the age of 20 years and mainly in the economically active 4th decade of life. One hundred and fifty four patients died for a mortality rate of 5% in the entire series of 3008 patients and 25% of the 623 admitted patients. The experience of head injuries reporting to our centre in two calendar years, 33 years apart, suggests that this attention to the crisis of death and disability occurring on roads is necessary.


Histamine and histamine receptor regulation of gastrointestinal cancers.
Histamine is a neurotransmitter released throughout the body that regulates multiple physiological responses. Primarily histamine is acknowledged for its role in inflammatory reactions to foreign pathogens that enter the body. Aside from inflammatory responses, histamine expression and synthesis has been detected in various cancer cell lines and multiple malignancies. Through experimentation histamine has demonstrated its ability to manage proliferation and angiogenesis in these cancerous cells, in either a positive or inhibitory manner. Regulation of angiogenesis and proliferation have been proven to be carried out by the stimulation or inhibition of numerous pathways and secondary response elements, such as VEGFA/C, IP3/Ca2+, G-proteins, cAMP, and many more. The activation of these different response pathways is linked to the binding of ligands to the histamine receptors H1-H4HR. These receptors exhibit various effects dependent on whether it binds an agonist, antagonist, or its specific ligand, histamine. In cancer cell lines and different tumor cells the binding of these different compounds has shown to be one of the main components in exerting proliferative or antiproliferative changes in the microenvironment. It is also known that the histamine receptors have varying degrees of expression in different forms of cancer, and this expression can impact the tumor in various ways. This clearly indicates the significance of histamine receptors in cancer formation, and one of the aims of this review is to cover this topic concisely and in depth. Histamine is produced from numerous cells such as basophils and mast cells and is synthesized from the enzyme histidine decarboxylase (HDC). In this review we will prominently discuss the function of mast cells and HDC in histamine expression in various gastrointestinal carcinomas. We also briefly discuss current studies to support these claims. In this review we hope to give the reader a clear and comprehensible overview of histamine in various gastrointestinal cancers, and how its regulation can affect the cancer cells in varying ways.


Building 2D crystals from 5-fold-symmetric molecules.
Concepts of close packing in monolayers of 5-fold-symmetric buckybowls are discussed. When the symmetry of lattice and molecular building blocks are incompatible, new strategies evolve. Corannulene forms a hexagonal lattice on Cu(111) by tilting away from the C(5) symmetry and aligning one hexagonal ring parallel to the surface. The chiral 5-fold-substituted chloro and methyl derivatives do not show this tilt and maintain the 5-fold symmetry as adsorbates. Consequently, a nonperfect tiling is observed. Their lattices are quasi-hexagonal: one in an antiparallel fashion with almost pm symmetry and the other with azimuthal and positional disorder on the hexagonal grid. Our results are in remarkable agreement with computational and mechanical modeling experiments of close packing of hard pentagonal discs in macroscopic two-dimensional systems and prove the validity of such modeling strategies.


Functional analysis of Mycoplasma arthritidis-derived mitogen interactions with class II molecules.
The ability of superantigens (SAGs) to trigger various cellular events via major histocompatibility complex (MHC) class II molecules is largely mediated by their mode of interaction. Having two MHC class II binding sites, staphylococcal enterotoxin A (SEA) is able to dimerize MHC class II molecules on the cell surface and consequently induces cytokine gene expression in human monocytes. In contrast, cross-linking with specific monoclonal antibodies or T-cell receptor is required for staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin 1 (TSST-1) to induce similar responses. In the present study, we report how Mycoplasma arthritidis-derived mitogen (MAM) may interact with MHC class II molecules to induce cytokine gene expression in human monocytes. The data presented indicate that MAM-induced cytokine gene expression in human monocytes is Zn2+ dependent. The MAM-induced response is completely abolished by pretreatment with SEA mutants that have lost their capacity to bind either the MHC class II alpha or beta chain, with wild-type SEB, or with wild-type TSST-1, suggesting that MAM induces cytokine gene expression most probably by inducing dimerization of class II molecules. In addition, it seems that SEA and MAM interact with the same or overlapping binding sites on the MHC class II beta chain and, on the other hand, that they bind to the alpha chain most probably through the regions that are involved in SEB and TSST-1 binding.


Glycemic index in sport nutrition.
Carbohydrates (CHO) can be classified on the basis of their glycemic index (GI), and the use of this classification has been increasingly supported by science. Because of its impact on blood glucose and insulin responses following the ingestion of CHO foods, the GI has been studied in many fields of medicine, including sport nutrition. As a new tool in sport nutrition, glycemic index manipulation has been evaluated to improve the first and second phases of glycogen recovery, glycogen load, and exercise metabolism, including control of rebound hypoglycemia and, it is interesting to note, stimulation of lipid oxidation for longer availability of glucose sources during endurance exercise. Although attractive, the use of GI in sport nutrition has received only partial support from available experimental evidence. At the biochemical level, consistent evidence has been attained to suggest that GI manipulation can determine variations in adipocyte lipolysis, plasma free fatty acids levels, and lipid and CHO oxidation rates during exercise. However, when the effects of GI manipulation have been assessed at the functional level, the results have been inconsistent, with evidence of improved exercise performance in some studies, but not in many others. The purpose of the current article is to review the effects and limits of GI manipulation in sport nutrition, and to propose an overall strategy for its application.


Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies.
Changes in the pulmonary microbiota are associated with progressive respiratory diseases including chronic obstructive pulmonary disease (COPD). Whether there is a causal relationship between these changes and disease progression remains unknown. To investigate the link between an altered microbiota and disease, we used a murine model of chronic lung inflammation that is characterized by key pathological features found in COPD and compared responses in specific pathogen-free (SPF) mice and mice depleted of microbiota by antibiotic treatment or devoid of a microbiota (axenic). Mice were challenged with LPS/elastase intranasally over 4 weeks, resulting in a chronically inflamed and damaged lung. The ensuing cellular infiltration, histological damage, and decline in lung function were quantified. Similar to human disease, the composition of the pulmonary microbiota was altered in diseased animals. We found that the microbiota richness and diversity were decreased in LPS/elastase-treated mice, with an increased representation of the genera Pseudomonas and Lactobacillus and a reduction in Prevotella. Moreover, the microbiota was implicated in disease development as mice depleted, or devoid, of microbiota exhibited an improvement in lung function, reduced inflammation, and lymphoid neogenesis. The absence of microbial cues markedly decreased the production of IL-17A, whereas intranasal transfer of fluid enriched with the pulmonary microbiota isolated from diseased mice enhanced IL-17A production in the lungs of antibiotic-treated or axenic recipients. Finally, in mice harboring a microbiota, neutralizing IL-17A dampened inflammation and restored lung function. Collectively, our data indicate that host-microbial cross-talk promotes inflammation and could underlie the chronicity of inflammatory lung diseases.


The development of Alternaria alternata is prevented by chitinases and beta-1,3-glucanases from Citrus limon seedlings.
In addition to phytoalexin synthesis, the defense response of intact Citrus limon seedlings against Alternaria alternata involves both constitutive and induced enzyme activities such as chitinases (Ch) and beta-1,3-glucanases (Glu). A alternata conidial germination was prevented by protein extracts from inoculated lemon seedlings, but also by extracts from mock-inoculated specimens. On the other hand, degradation of mycelia was accomplished only by protein extracts from inoculated seedlings. The presence of six Ch isoenzymes and of four Glu isoenzymes was detected in protein extracts from mock-inoculated seedlings. As a result of fungal inoculation, the isoenzyme pattern of Ch and Glu changed, making possible the detection of a new Ch isoenzyme and of three new Glu. Also, some constitutive Ch and Glu increased their enzyme activity, and those Ch that increased their activity also showed a broadening of their substrate specificity. These changes were prevented by alpha-amanitin and cycloheximide, suggesting that the presence of new Ch and Glu isoenzymes was due to de novo synthesis of proteins. Results suggest that constitutive Ch and Glu could act as pre-formed defense molecules in Citrus limon preventing A. alternata germination, while those induced after fungal inoculation of lemon seedlings could act along with the former, to produce lysis of fungal mycelia, resulting in a more efficient control of A. alternata development.


Effects of cannabis and psychosis vulnerability in daily life: an experience sampling test study.
Epidemiological findings suggest that cannabis use is a risk factor for the emergence of psychosis, and that the induction of psychotic symptoms in the context of cannabis use may be associated with a pre-existing vulnerability for psychosis. This study investigated in a non-clinical population the interaction between cannabis use and psychosis vulnerability in their effects on psychotic experiences in daily life. Subjects (N = 79) with high or low levels of cannabis use were selected among a sample of 685 undergraduate university students. Experience sampling method (ESM) was used to collect information on substance use and psychotic experiences in daily life. Vulnerability to develop psychosis was measured using a clinical interview assessing the level of psychotic symptoms. Statistical analyses were performed using multilevel linear random regression models. The acute effects of cannabis are modified by the subject's level of vulnerability for psychosis. Subjects with high vulnerability for psychosis are more likely to report unusual perceptions as well as feelings of thought influence than subjects with low vulnerability for psychosis, and they are less likely to experience enhanced feelings of pleasure associated with cannabis. There is no evidence that use of cannabis is increased following occurrence of psychotic experiences as would be expected by the self-medication model. Cannabis use interacts with psychosis vulnerability in their effects on experience of psychosis in daily life. The public health impact of the widespread use of cannabis may be considerable.


Assessment of carbon storage under rainforests in Humic Hapludox along a climosequence extending from the Atlantic coast to the highlands of northeastern Brazil.
An understanding of the stock of soil organic carbon (SOC) in the umbric epipedon of Oxisols located in the tropical forests surrounded by a semi-arid region is limited but essential because of their importance in the global cycle of carbon (C). The purpose of this study was to assess the effects of climatic (temperature and rainfall), soil organic matter (SOM) composition and litter on the stability of C in surfaces and subsurfaces in five Humic Oxisols along a 475-km climosequence from 143 to 963ma.s.l. in a tropical environment in northeastern Brazil. We assessed vertical changes in SOC; soil total nitrogen (N); C from the microbial biomass; δ(13)C, δ(15)N and the humified composition of SOM; the composition of the humin (HUM) fraction by Fourier Transform Infrared (FTIR); and Thermogravimetry (TG) and Differential Scanning Calorimetry (DSC) at depth. The elemental and isotopic composition of the litter samples were analyzed in all areas studied. The results indicated that the current climate and recalcitrant organic compounds are not preponderant factors in the formation of the umbric epipedon, as suggested by the partial influence of temperature and rainfall on SOM. In addition, SOM was dominated by easily decomposable compounds, as indicated by the predominance of aliphatic C-H groups in the HUM fraction in the FTIR spectra; by the thermal oxidation through DSC-TG, which revealed that approximately 50% of the HUM was composed easily decomposable compounds; and by the high proportion of organic C present in the microbial biomass. Values of δ(13)C showed a predominance of C3 plant-C in SOM whereas δ(15)N patterns indicated that N dynamics differ among the profiles and drive the accumulation of C. These findings can help to characterize the susceptibility of these soils to changes in climate and land use and the implications for the sequestration of soil C.


Translating principles of neural plasticity into research on speech motor control recovery and rehabilitation.
To review the principles of neural plasticity and make recommendations for research on the neural bases for rehabilitation of neurogenic speech disorders. A working group in speech motor control and disorders developed this report, which examines the potential relevance of basic research on the brain mechanisms involved in neural plasticity and discusses possible similarities and differences for application to speech motor control disorders. The possible involvement of neural plasticity in changes in speech production in normalcy, development, aging, and neurological diseases and disorders was considered. This report focuses on the appropriate use of functional and structural neuroimaging and the design of feasibility studies aimed at understanding how brain mechanisms are altered by environmental manipulations such as training and stimulation and how these changes might enhance the future development of rehabilitative methods for persons with speech motor control disorders. Increased collaboration with neuroscientists working in clinical research centers addressing human communication disorders might foster research in this area. It is hoped that this article will encourage future research on speech motor control disorders to address the principles of neural plasticity and their application for rehabilitation.


Fluorescent natural products as probes and tracers in biology.
Covering: 1985 up to the end of 2016Fluorescence is a remarkable property of many natural products in addition to their medicinal and biological values. Herein, we provide a review on these peculiar secondary metabolites to stimulate prospecting of them as original fluorescent tracers, endowed with unique photophysical properties and with applications in most fields of biology. The compounds are spectrally categorized (i.e. fluorescing from violet to the near infra-red) and further structurally classified within each category. Natural products selected for their high impact in modern fluorescence-based biological studies are highlighted throughout the article. Finally, we discuss aspects of chemical ecology where fluorescent natural products might have key evolutionary roles and thus open new research directions in the field.


A phylogenetic revision of the Glaucopsyche section (Lepidoptera: Lycaenidae), with special focus on the Phengaris-Maculinea clade.
Despite much research on the socially parasitic large blue butterflies (genus Maculinea) in the past 40 years, their relationship to their closest relatives, Phengaris, is controversial and the relationships among the remaining genera in the Glaucopsyche section are largely unresolved. The evolutionary history of this butterfly section is particularly important to understand the evolution of life history diversity connected to food-plant and host-ant associations in the larval stage. In the present study, we use a combination of four nuclear and two mitochondrial genes to reconstruct the phylogeny of the Glaucopsyche section, and in particular, to study the relationships among and within the Phengaris-Maculinea species. We find a clear pattern between the clades recovered in the Glaucopsyche section phylogeny and their food-plant associations, with only the Phengaris-Maculinea clade utilising more than one plant family. Maculinea is, for the first time, recovered with strong support as a monophyletic group nested within Phengaris, with the closest relative being the rare genus Caerulea. The genus Glaucopsyche is polyphyletic, including the genera Sinia and Iolana. Interestingly, we find evidence for additional potential cryptic species within the highly endangered Maculinea, which has long been suspected from morphological, ecological and molecular studies.


Seasonal changes in phosphorus competition and allelopathy of a benthic microbial assembly facilitate prevention of cyanobacterial blooms.
Interactions among microbes determine the prevalence of harmful algal blooms that threaten water quality. These interactions can be indirectly mediated by shared resources or consumers, or through interference by the production of allelochemicals. Allelopathic interactions and resource competition have been shown to occur among algae and associated microbes. However, little work has considered seasonal influences on ecosystem structure and function. Here, we report results of our investigations on seasonal changes in the interactions between benthic microbial assemblies and the bloom forming cyanobacterium Microcystis aeruginosa. We show that phosphorus (P) competition and allelopathy by the microbial assembly vary seasonally and inhibit growth of M. aeruginosa. The interactions per unit biomass of the microbial assembly are stronger under winter than summer conditions and inhibit the recruitment of the cyanobacteria, thereby preventing the reoccurrence of cyanobacterial blooms in the following summer. The seasonality of these interactions correlates with changes in composition, metabolic activity and functional diversity of the microbial assembly. Our findings highlight the importance of competitive and allelopathic interactions in regulating the occurrence of harmful algal blooms. Our results also imply that seasonal variation of competition and allelopathy of the microbial assembly might be beneficial to adjust aquatic ecosystem structure and function.