Recovery of biological motion perception and network plasticity after cerebellar tumor removal.

Visual perception of body motion is vital for everyday activities such as social interaction, motor learning or car driving. Tumors to the left lateral cerebellum impair visual perception of body motion. However, compensatory potential after cerebellar damage and underlying neural mechanisms remain unknown. In the present study, visual sensitivity to point-light body motion was psychophysically assessed in patient SL with dysplastic gangliocytoma (Lhermitte-Duclos disease) to the left cerebellum before and after neurosurgery, and in a group of healthy matched controls. Brain activity during processing of body motion was assessed by functional magnetic resonance imaging (MRI). Alterations in underlying cerebro-cerebellar circuitry were studied by psychophysiological interaction (PPI) analysis. Visual sensitivity to body motion in patient SL before neurosurgery was substantially lower than in controls, with significant improvement after neurosurgery. Functional MRI in patient SL revealed a similar pattern of cerebellar activation during biological motion processing as in healthy participants, but located more medially, in the left cerebellar lobules III and IX. As in normalcy, PPI analysis showed cerebellar communication with a region in the superior temporal sulcus, but located more anteriorly. The findings demonstrate a potential for recovery of visual body motion processing after cerebellar damage, likely mediated by topographic shifts within the corresponding cerebro-cerebellar circuitry induced by cerebellar reorganization. The outcome is of importance for further understanding of cerebellar plasticity and neural circuits underpinning visual social cognition.

Ispol'zovanie metodov teorii vosstanovleniia v modeliakh optimal'nogo dobyvaniia pishchi [Restoration theory in models of optimal feeding behavior]

The method of stochastic dynamic programming is widely used in ecology of behavior, but has some imperfections because of use of temporal limits. The authors presented an alternative approach based on the methods of the theory of restoration. Suggested method uses cumulative energy reserves per time unit as a criterium, that leads to stationary cycles in the area of states. This approach allows to study the optimal feeding by analytic methods.

Are 10 min of seating enough to guarantee stable haemoglobin and haematocrit readings for the athlete's biological passport?

Haemoglobin (Hb) and haematocrit (Hct) are measured as indirect markers of doping in athletes. We studied the effect of posture on these parameters in a typical antidoping setting. Venous blood samples were obtained from nine endurance athletes (six males, three females) and nine control subjects (six males, three females) immediately and after 5, 10, 15, 20 and 30 min after having adopted a seated position from normal daily activity. Hb (CV 0.72%) and Hct (CV 0.87%) were determined using an automated cell counter, plasma volume changes were calculated. Differences between the time points, gender and groups were calculated using a mixed-model procedure. Significant changes were observed in the first 10 min after sitting down but no further changes were noted between 10 and 30 min. Mean directional change for Hb and Hct between 0 min and the average of the period from 10 to 30 min was -2.4% (-0.35 g/dl) for Hb and -2.7% (-1.2%) for Hct. Plasma volume increased accordingly. Neither group nor gender had significant effects. Under typical conditions encountered during blood testing in doping control, a period of 10 min in a seated position is sufficient for the vascular volumes to re-equilibrate and to adapt to the new posture.

Evidence of climatic niche shift during biological invasion

Niche-based models calibrated in the native range by relating species observations to climatic variables are commonly used to predict the potential spatial extent of species' invasion. This climate matching approach relies on the assumption that invasive species conserve their climatic niche in the invaded ranges. We test this assumption by analysing the climatic niche spaces of Spotted Knapweed in western North America and Europe. We show with robust cross-continental data that a shift of the observed climatic niche occurred between native and non-native ranges, providing the first empirical evidence that an invasive species can occupy climatically distinct niche spaces following its introduction into a new area. The models fail to predict the current invaded distribution, but correctly predict areas of introduction. Climate matching is thus a useful approach to identify areas at risk of introduction and establishment of newly or not-yet-introduced neophytes, but may not predict the full extent of invasions.

History of biological warfare and bioterrorism.

Bioterrorism literally means using microorganisms or infected samples to cause terror and panic in populations. Bioterrorism had already started 14 centuries before Christ, when the Hittites sent infected rams to their enemies. However, apart from some rare well-documented events, it is often very difficult for historians and microbiologists to differentiate natural epidemics from alleged biological attacks, because: (i) little information is available for times before the advent of modern microbiology; (ii) truth may be manipulated for political reasons, especially for a hot topic such as a biological attack; and (iii) the passage of time may also have distorted the reality of the past. Nevertheless, we have tried to provide to clinical microbiologists an overview of some likely biological warfare that occurred before the 18th century and that included the intentional spread of epidemic diseases such as tularaemia, plague, malaria, smallpox, yellow fever, and leprosy. We also summarize the main events that occurred during the modern microbiology era, from World War I to the recent 'anthrax letters' that followed the World Trade Center attack of September 2001. Again, the political polemic surrounding the use of infectious agents as a weapon may distort the truth. This is nicely exemplified by the Sverdlovsk accident, which was initially attributed by the authorities to a natural foodborne outbreak, and was officially recognized as having a military cause only 13 years later.

Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma

Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P = .01). High expression of cytotoxic gene-signature within the TBX21 subgroup also showed poor clinical outcome (P = .05). In AITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P = .004).

Unifying niche shift studies: insights from biological invasions.

Assessing whether the climatic niche of a species may change between different geographic areas or time periods has become increasingly important in the context of ongoing global change. However, approaches and findings have remained largely controversial so far, calling for a unification of methods. Here, we build on a review of empirical studies of invasion to formalize a unifying framework that decomposes niche change into unfilling, stability, and expansion situations, taking both a pooled range and range-specific perspective on the niche, while accounting for climatic availability and climatic analogy. This framework provides new insights into the nature of climate niche shifts and our ability to anticipate invasions, and may help in guiding the design of experiments for assessing causes of niche changes.

Sex differences in urinary levels of several biological indicators of exposure: a simulation study using a compartmental based toxicokinetic model

Toxicokinetic modeling is a useful tool to describe or predict the behavior of a chemical agent in the human or animal organism. A general model based on four compartments was developed in a previous study in order to quantify the effect of human variability on a wide range of biological exposure indicators. The aim of this study was to adapt this existing general toxicokinetic model to three organic solvents, which were methyl ethyl ketone, 1-methoxy-2-propanol and 1,1,1,-trichloroethane, and to take into account sex differences. We assessed in a previous human volunteer study the impact of sex on different biomarkers of exposure corresponding to the three organic solvents mentioned above. Results from that study suggested that not only physiological differences between men and women but also differences due to sex hormones levels could influence the toxicokinetics of the solvents. In fact the use of hormonal contraceptive had an effect on the urinary levels of several biomarkers, suggesting that exogenous sex hormones could influence CYP2E1 enzyme activity. These experimental data were used to calibrate the toxicokinetic models developed in this study. Our results showed that it was possible to use an existing general toxicokinetic model for other compounds. In fact, most of the simulation results showed good agreement with the experimental data obtained for the studied solvents, with a percentage of model predictions that lies within the 95% confidence interval varying from 44.4 to 90%. Results pointed out that for same exposure conditions, men and women can show important differences in urinary levels of biological indicators of exposure. Moreover, when running the models by simulating industrial working conditions, these differences could even be more pronounced. In conclusion, a general and simple toxicokinetic model, adapted for three well known organic solvents, allowed us to show that metabolic parameters can have an important impact on the urinary levels of the corresponding biomarkers. These observations give evidence of an interindividual variablity, an aspect that should have its place in the approaches for setting limits of occupational exposure.

Les biothérapies dans le lupus érythémateux disséminé et tes connectivites: nouvelles thérapeutiques [Treatment of connective tissue diseases with biological agents]

As B-cells are crucial for the production of antibodies and also in antigen presentation, they can play an important role in autoimmune connective tissue disease. B-cell surface antigens and receptors which are capable of activating B-cell function have been proposed as targets for therapy in these diseases. Anti-B cell treatments have been used recently in SLE and primary Sjogren's syndrome in a number of open studies, notably anti-CD20 (rituximab), with encouraging results. An anti-BAFF antibody (belimumab) has been tested in patients with SLE and also showed positive results in patients with increased levels of autoantibodies. In contrast, anti-TNF therapy in connective tissue disease and in RA can increase the levels of autoantibodies. Further studies are needed to define the place of these novel treatments in the management of autoimmune connective tissue diseases.

Marqueurs biologiques des statuts vitaminiques B12 et D: aspects analytiques d'importance clinique [Biological markers for the status of vitamins B12 and D: the importance of some analytical aspects in relation to clinical interpretation of results].

Biological markers for the status of vitamins B12 and D: the importance of some analytical aspects in relation to clinical interpretation of results When vitamin B12 deficiency is expressed clinically, the diagnostic performance of total cobalamin is identical to that of holotranscobalamin II. In subclinical B12 deficiency, the two aforementioned markers perform less well. Additional analysis of a second, functional marker (methylmalonate or homocysteine) is recommended. Different analytical approaches for 25-hydroxyvitamin D quantification, the marker of vitamin D deficiency, are not yet standardized. Measurement biases of up to +/- 20% compared with the original method used to establish threshold values are still observed.

Physicochemical and biological characterization of single-walled and double-walled carbon nanotubes in biological media

To study the toxicity of nanoparticles under relevant conditions, it is important to reproducibly disperse nanoparticles in biological media in in vitro and in vivo studies. Here, single-walled nanotubes (SWNTs) and double-walled nanotubes (DWNTs) were physicochemically and biologically characterized when dispersed in phosphate-buffered saline (PBS) and bovine serum albumin (BSA). BSA-SWNT/DWNT interaction resulted in a reduction of aggregation and an increase in particle stabilization. Based on the protein sequence coverage and protein binding results, DWNTs exhibited higher protein binding than SWNTs. SWNT and DWNT suspensions in the presence of BSA increased interleukin-6 (IL-6) levels and reduced tumor necrosis factor-alpha (TNF-α) levels in A549 cells as compared to corresponding samples in the absence of BSA. We next determined the effects of SWNTs and DWNTs on pulmonary protein modification using bronchoalveolar lavage fluid (BALF) as a surrogate collected form BALB/c mice. The BALF proteins bound to SWNTs (13 proteins) and DWNTs (11 proteins), suggesting that these proteins were associated with blood coagulation pathways. Lastly, we demonstrated the importance of physicochemical and biological alterations of SWNTs and DWNTs when dispersed in biological media, since protein binding may result in the misinterpretation of in vitro results and the activation of protein-regulated biological responses.

Biological, clinical and population relevance of 95 loci for blood lipids.

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.