Striatal dopamine D₂/₃ receptors in medication-naïve schizophrenia: an [¹²³I] IBZM SPECT study

BACKGROUND: The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels. METHODS: We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia. RESULT: The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI -0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = -0.01(binding ratio); 95% CI -0.01 to -0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores. CONCLUSIONS: Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release

Sprint interval and sprint continuous training increases circulating CD34+ cells and cardio-respiratory fitness in young healthy women

The improvement of vascular health in the exercising limb can be attained by sprint interval training (SIT). However, the effects on systemic vascular function and on circulating angiogenic cells (CACs) which may contribute to endothelial repair have not been investigated. Additionally, a comparison between SIT and sprint continuous training (SCT) which is less time committing has not been made

Clinical practice: Protein-losing enteropathy in children

Protein-losing enteropathy (PLE) is a rare complication of a variety of intestinal disorders characterized by an excessive loss of proteins into the gastrointestinal tract due to impaired integrity of the mucosa. The clinical presentation of patients with PLE is highly variable, depending upon the underlying cause, but mainly consists of edema due to hypoproteinemia. While considering PLE, other causes of hypoproteinemia such as malnutrition, impaired synthesis, or protein loss through other organs like the kidney, liver, or skin, have to be excluded. The disorders causing PLE can be divided into those due to protein loss from intestinal lymphatics, like primary intestinal lymphangiectasia or congenital heart disease and those with protein loss due to an inflamed or abnormal mucosal surface. The diagnosis is confirmed by increased fecal concentrations of alpha-1-antitrypsin. After PLE is diagnosed, the underlying cause should be identified by stool cultures, serologic evaluation, cardiac screening, or radiographic imaging. Treatment of PLE consists of nutrition state maintenance by using a high protein diet with supplement of fat-soluble vitamins. In patients with lymphangiectasia, a low fat with medium chain triglycerides (MCT) diet should be prescribed. Besides dietary adjustments, appropriate treatment for the underlying etiology is necessary and supportive care to avoid complications of edema. PLE is a rare complication of various diseases, mostly gastrointestinal or cardiac conditions that result into loss of proteins in the gastrointestinal tract. Prognosis depends upon the severity and treatment options of the underlying disease

BLAST Ring Image Generator (BRIG): simple prokaryote genome comparisons

<p>Abstract</p> <p>Background</p> <p>Visualisation of genome comparisons is invaluable for helping to determine genotypic differences between closely related prokaryotes. New visualisation and abstraction methods are required in order to improve the validation, interpretation and communication of genome sequence information; especially with the increasing amount of data arising from next-generation sequencing projects. Visualising a prokaryote genome as a circular image has become a powerful means of displaying informative comparisons of one genome to a number of others. Several programs, imaging libraries and internet resources already exist for this purpose, however, most are either limited in the number of comparisons they can show, are unable to adequately utilise draft genome sequence data, or require a knowledge of command-line scripting for implementation. Currently, there is no freely available desktop application that enables users to rapidly visualise comparisons between hundreds of draft or complete genomes in a single image.</p> <p>Results</p> <p>BLAST Ring Image Generator (BRIG) can generate images that show multiple prokaryote genome comparisons, without an arbitrary limit on the number of genomes compared. The output image shows similarity between a central reference sequence and other sequences as a set of concentric rings, where BLAST matches are coloured on a sliding scale indicating a defined percentage identity. Images can also include draft genome assembly information to show read coverage, assembly breakpoints and collapsed repeats. In addition, BRIG supports the mapping of unassembled sequencing reads against one or more central reference sequences. Many types of custom data and annotations can be shown using BRIG, making it a versatile approach for visualising a range of genomic comparison data. BRIG is readily accessible to any user, as it assumes no specialist computational knowledge and will perform all required file parsing and BLAST comparisons automatically.</p> <p>Conclusions</p> <p>There is a clear need for a user-friendly program that can produce genome comparisons for a large number of prokaryote genomes with an emphasis on rapidly utilising unfinished or unassembled genome data. Here we present BRIG, a cross-platform application that enables the interactive generation of comparative genomic images via a simple graphical-user interface. BRIG is freely available for all operating systems at <url>http://sourceforge.net/projects/brig/</url>.</p

FRET-Based Identification of mRNAs Undergoing Translation

We present proof-of-concept in vitro results demonstrating the feasibility of using single molecule fluorescence resonance energy transfer (smFRET) measurements to distinguish, in real time, between individual ribosomes programmed with several different, short mRNAs. For these measurements we use either the FRET signal generated between two tRNAs labeled with different fluorophores bound simultaneously in adjacent sites to the ribosome (tRNA-tRNA FRET) or the FRET signal generated between a labeled tRNA bound to the ribosome and a fluorescent derivative of ribosomal protein L1 (L1-tRNA FRET). With either technique, criteria were developed to identify the mRNAs, taking into account the relative activity of the mRNAs. These criteria enabled identification of the mRNA being translated by a given ribosome to within 95% confidence intervals based on the number of identified FRET traces. To upgrade the approach for natural mRNAs or more complex mixtures, the stoichiometry of labeling should be enhanced and photobleaching reduced. The potential for porting these methods into living cells is discussed

Synthesis and Enhanced Field-Emission of Thin-Walled, Open-Ended, and Well-Aligned N-Doped Carbon Nanotubes

Thin-walled, open-ended, and well-aligned N-doped carbon nanotubes (CNTs) on the quartz slides were synthesized by using acetonitrile as carbon sources. As-obtained products possess large thin-walled index (TWI, defined as the ratio of inner diameter and wall thickness of a CNT). The effect of temperature on the growth of CNTs using acetonitrile as the carbon source was also investigated. It is found that the diameter, the TWI of CNTs increase and the Fe encapsulation in CNTs decreases as the growth temperature rises in the range of 780–860°C. When the growth temperature is kept at 860°C, CNTs with TWI = 6.2 can be obtained. It was found that the filed-emission properties became better as CNT growth temperatures increased from 780 to 860°C. The lowest turn-on and threshold field was 0.27 and 0.49 V/μm, respectively. And the best field-enhancement factors reached 1.09 × 105, which is significantly improved about an order of magnitude compared with previous reports. In this study, about 30 × 50 mm2 free-standing film of thin-walled open-ended well-aligned N-doped carbon nanotubes was also prepared. The free-standing film can be transferred easily to other substrates, which would promote their applications in different fields

A Qualitative View of Drug Use Behaviors of Mexican Male Injection Drug Users Deported from the United States

Deportees are a hidden yet highly vulnerable and numerous population. Significantly, little data exists about the substance use and deportation experiences of Mexicans deported from the United States. This pilot qualitative study describes illicit drug use behaviors among 24 Mexico-born male injection drug users (IDUs), ≥18 years old, residing in Tijuana, Mexico who self-identified as deportees from the United States. In-person interviews were conducted in Tijuana, Mexico in 2008. Content analysis of interview transcripts identified major themes in participants’ experiences. Few participants had personal or family exposures to illicit drugs prior to their first U.S. migration. Participants reported numerous deportations. Social (i.e., friends/family, post-migration stressors) and environmental factors (e.g., drug availability) were perceived to contribute to substance use initiation in the U.S. Drugs consumed in the United States included marijuana, heroin, cocaine, methamphetamine, and crack. More than half of men were IDUs prior to deportation. Addiction and justice system experiences reportedly contributed to deportation. After deportation, several men injected new drugs, primarily heroin or methamphetamine, or a combination of both drugs. Many men perceived an increase in their substance use after deportation and reported shame and loss of familial social and economic support. Early intervention is needed to stem illicit drug use in Mexican migrant youths. Binational cooperation around migrant health issues is warranted. Migrant-oriented programs may expand components that address mental health and drug use behaviors in an effort to reduce transmission of blood-borne infections. Special considerations are merited for substance users in correctional systems in the United States and Mexico, as well as substance users in United States immigration detention centers. The health status and health behaviors of deportees are likely to impact receiving Mexican communities. Programs that address health, social, and economic issues may aid deportees in resettling in Mexico

External ballistics of Pleistocene hand-thrown spears: experimental performance data and implications for human evolution

The appearance of weaponry - technology designed to kill - is a critical but poorly established threshold in human evolution. It is an important behavioural marker representing evolutionary changes in ecology, cognition, language and social behaviours. While the earliest weapons are often considered to be hand-held and consequently short-ranged, the subsequent appearance of distance weapons is a crucial development. Projectiles are seen as an improvement over contact weapons, and are considered by some to have originated only with our own species in the Middle Stone Age and Upper Palaeolithic. Despite the importance of distance weapons in the emergence of full behavioral modernity, systematic experimentation using trained throwers to evaluate the ballistics of thrown spears during fight and at impact is lacking. This paper addresses this by presenting results from a trial of trained javelin athletes, providing new estimates for key performance parameters. Overlaps in distances and impact energies between hand-thrown spears and spearthrowers are evidenced, and skill emerges as a signifcant factor in successful use. The results show that distance hunting was likely within the repertoire of hunting strategies of Neanderthals, and the resulting behavioural flexibility closely mirrors that of our own specie

Genome-wide essential gene identification in Streptococcus sanguinis

A clear perception of gene essentiality in bacterial pathogens is pivotal for identifying drug targets to combat emergence of new pathogens and antibiotic-resistant bacteria, for synthetic biology, and for understanding the origins of life. We have constructed a comprehensive set of deletion mutants and systematically identified a clearly defined set of essential genes for Streptococcus sanguinis. Our results were confirmed by growing S. sanguinis in minimal medium and by double-knockout of paralogous or isozyme genes. Careful examination revealed that these essential genes were associated with only three basic categories of biological functions: maintenance of the cell envelope, energy production, and processing of genetic information. Our finding was subsequently validated in two other pathogenic streptococcal species, Streptococcus pneumoniae and Streptococcus mutans and in two other gram-positive pathogens, Bacillus subtilis and Staphylococcus aureus. Our analysis has thus led to a simplified model that permits reliable prediction of gene essentiality