Know Thyself: Behavioral Evidence for a Structural Representation of the Human Body

Background

Representing one''s own body is often viewed as a basic form of self-awareness. However, little is known about structural representations of the body in the brain.

Methods and Findings

We developed an inter-manual version of the classical “in-between” finger gnosis task: participants judged whether the number of untouched fingers between two touched fingers was the same on both hands, or different. We thereby dissociated structural knowledge about fingers, specifying their order and relative position within a hand, from tactile sensory codes. Judgments following stimulation on homologous fingers were consistently more accurate than trials with no or partial homology. Further experiments showed that structural representations are more enduring than purely sensory codes, are used even when number of fingers is irrelevant to the task, and moreover involve an allocentric representation of finger order, independent of hand posture.

Conclusions

Our results suggest the existence of an allocentric representation of body structure at higher stages of the somatosensory processing pathway, in addition to primary sensory representation.     

Altered expression of T cell Immunoglobulin-Mucin (TIM) molecules in bronchoalveolar lavage CD4+ T cells in sarcoidosis

Background

Activated T helper (Th)-1 pulmonary CD4⁺ cells and their mediators are essential for the inflammation and granulomatous process in sarcoidosis. Recently, T-cell immunoglobulin and mucin domain (TIM) molecules were suggested to be important regulators of immune function. In this study, we wanted to investigate whether TIM molecules could play a role in sarcoidosis.

Methods

We used real-time polymerase chain reaction to investigate the differential gene expression of TIM-1 and TIM-3 as well as a few Th1 and Th2 cytokines (IL-2, IFN-γ, IL-4, IL-5 and IL-13) in CD4⁺ T cells isolated from bronchoalveolar lavage fluid (BALF) of patients (n = 28) and healthy controls (n = 8). Using flow cytometry, we were also able to analyse TIM-3 protein expression in 10 patients and 6 healthy controls.

Results

A decreased TIM-3 mRNA (p < 0.05) and protein (p < 0.05) expression was observed in patients, and the level of TIM-3 mRNA correlated negatively with the CD4/CD8 T cell ratio in BALF cells of patients. Compared to a distinct subgroup of patients i.e. those with Löfgren''s syndrome, BALF CD4⁺ T cells from non- Löfgren''s patients expressed decreased mRNA levels of TIM-1 (p < 0.05). mRNA expression of IL-2 was increased in patients (p < 0.01) and non-Löfgren''s patients expressed significantly higher levels of IFN-γ mRNA (p < 0.05) versus patients with Löfgren''s syndrome.

Conclusion

These findings are the first data on the expression of TIM-1 and TIM-3 molecules in sarcoidosis. The reduced TIM-3 expression in the lungs of patients may result in a defective T cell ability to control the Th1 immune response and could thus contribute to the pathogenesis of sarcoidosis. The down-regulated TIM-1 expression in non-Löfgren''spatients is in agreement with an exaggerated Th1 response in these patients.     

PROTEOMER: A workflow‐optimized laboratory information management system for 2‐D electrophoresis‐centered proteomics

In recent years proteomics became increasingly important to functional genomics. Although a large amount of data is generated by high throughput large‐scale techniques, a connection of these mostly heterogeneous data from different analytical platforms and of different experiments is limited. Data mining procedures and algorithms are often insufficient to extract meaningful results from large datasets and therefore limit the exploitation of the generated biological information. In our proteomic core facility, which almost exclusively focuses on 2‐DE/MS‐based proteomics, we developed a proteomic database custom tailored to our needs aiming at connecting MS protein identification information to 2‐DE derived protein expression profiles. The tools developed should not only enable an automatic evaluation of single experiments, but also link multiple 2‐DE experiments with MS‐data on different levels and thereby helping to create a comprehensive network of our proteomics data. Therefore the key feature of our “PROTEOMER” database is its high cross‐referencing capacity, enabling integration of a wide range of experimental data. To illustrate the workflow and utility of the system, two practical examples are provided to demonstrate that proper data cross‐referencing can transform information into biological knowledge.     

Staphylococcus aureus ClpC ATPase is a late growth phase effector of metabolism and persistence

Staphylococcus aureus Clp ATPases (molecular chaperones) alter normal physiological functions including an aconitase‐mediated effect on post‐stationary growth, acetate catabolism, and entry into death phase (Chatterjee et al., J. Bacteriol. 2005, 187, 4488–4496). In the present study, the global function of ClpC in physiology, metabolism, and late‐stationary phase survival was examined using DNA microarrays and 2‐D PAGE followed by MALDI‐TOF MS. The results suggest that ClpC is involved in regulating the expression of genes and/or proteins of gluconeogenesis, the pentose‐phosphate pathway, pyruvate metabolism, the electron transport chain, nucleotide metabolism, oxidative stress, metal ion homeostasis, stringent response, and programmed cell death. Thus, one major function of ClpC is balancing late growth phase carbon metabolism. Furthermore, these changes in carbon metabolism result in alterations of the intracellular concentration of free NADH, the amount of cell‐associated iron, and fatty acid metabolism. This study provides strong evidence for ClpC as a critical factor in staphylococcal energy metabolism, stress regulation, and late‐stationary phase survival; therefore, these data provide important insight into the adaptation of S. aureus toward a persister state in chronic infections.     

Islet Endothelial Activation and Oxidative Stress Gene Expression Is Reduced by IL-1Ra Treatment in the Type 2 Diabetic GK Rat

Background

Inflammation followed by fibrosis is a component of islet dysfunction in both rodent and human type 2 diabetes. Because islet inflammation may originate from endothelial cells, we assessed the expression of selected genes involved in endothelial cell activation in islets from a spontaneous model of type 2 diabetes, the Goto-Kakizaki (GK) rat. We also examined islet endotheliuml/oxidative stress (OS)/inflammation-related gene expression, islet vascularization and fibrosis after treatment with the interleukin-1 (IL-1) receptor antagonist (IL-1Ra).

Methodology/Principal Findings

Gene expression was analyzed by quantitative RT-PCR on islets isolated from 10-week-old diabetic GK and control Wistar rats. Furthermore, GK rats were treated s.c twice daily with IL-1Ra (Kineret, Amgen, 100 mg/kg/day) or saline, from 4 weeks of age onwards (onset of diabetes). Four weeks later, islet gene analysis and pancreas immunochemistry were performed. Thirty-two genes were selected encoding molecules involved in endothelial cell activation, particularly fibrinolysis, vascular tone, OS, angiogenesis and also inflammation. All genes except those encoding angiotensinogen and epoxide hydrolase (that were decreased), and 12-lipoxygenase and vascular endothelial growth factor (that showed no change), were significantly up-regulated in GK islets. After IL-1Ra treatment of GK rats in vivo, most selected genes implied in endothelium/OS/immune cells/fibrosis were significantly down-regulated. IL-1Ra also improved islet vascularization, reduced fibrosis and ameliorated glycemia.

Conclusions/Significance

GK rat islets have increased mRNA expression of markers of early islet endothelial cell activation, possibly triggered by several metabolic factors, and also some defense mechanisms. The beneficial effect of IL-1Ra on most islet endothelial/OS/immune cells/fibrosis parameters analyzed highlights a major endothelial-related role for IL-1 in GK islet alterations. Thus, metabolically-altered islet endothelium might affect the β-cell microenvironment and contribute to progressive type 2 diabetic β-cell dysfunction in GK rats. Counteracting islet endothelial cell inflammation might be one way to ameliorate/prevent β-cell dysfunction in type 2 diabetes.     

Viral Load Levels Measured at Set-Point Have Risen Over the Last Decade of the HIV Epidemic in the Netherlands

Background

HIV-1 RNA plasma concentration at viral set-point is associated not only with disease outcome but also with the transmission dynamics of HIV-1. We investigated whether plasma HIV-1 RNA concentration and CD4 cell count at viral set-point have changed over time in the HIV epidemic in the Netherlands.

Methodology/Principal Findings

We selected 906 therapy-naïve patients with at least one plasma HIV-1 RNA concentration measured 9 to 27 months after estimated seroconversion. Changes in HIV-1 RNA and CD4 cell count at viral set-point over time were analysed using linear regression models. The ATHENA national observational cohort contributed all patients who seroconverted in or after 1996; the Amsterdam Cohort Studies (ACS) contributed seroconverters before 1996. The mean of the first HIV-1 RNA concentration measured 9–27 months after seroconversion was 4.30 log₁₀ copies/ml (95% CI 4.17–4.42) for seroconverters from 1984 through 1995 (n = 163); 4.27 (4.16–4.37) for seroconverters 1996–2002 (n = 232), and 4.59 (4.52–4.66) for seroconverters 2003–2007 (n = 511). Compared to patients seroconverting between 2003–2007, the adjusted mean HIV-1 RNA concentration at set-point was 0.28 log₁₀ copies/ml (95% CI 0.16–0.40; p<0.0001) and 0.26 (0.11–0.41; p = 0.0006) lower for those seroconverting between 1996–2002 and 1984–1995, respectively. Results were robust regardless of type of HIV-1 RNA assay, HIV-1 subtype, and interval between measurement and seroconversion. CD4 cell count at viral set-point declined over calendar time at approximately 5 cells/mm³/year.

Conclusion

The HIV-1 RNA plasma concentration at viral set-point has increased over the last decade of the HIV epidemic in the Netherlands. This is accompanied by a decreasing CD4 cell count over the period 1984–2007 and may have implications for both the course of the HIV infection and the epidemic.     

MRI-based assessment of hip joint translations

To better understand movement limitations and, to some extent, the pathogenesis of osteoarthritis, it is important to quantitatively measure femoroacetabular translations to assess if any joint subluxation occurs. In this paper, we aim at measuring hip joint displacements from magnetic resonance images (MRI) based on a surface registration technique. Because this measurement is related to the location of the hip joint center (HJC), we investigate and compare different HJC estimation approaches based on patient-specific 3D bone models. We estimate the HJC based on a simulated circumduction while minimizing inter-articular distance changes. Measurements of femoroacetabular translations during low amplitude abductions ($80$ samples) and extreme flexions ($60$ samples) in female professional dancers, which is a population potentially exposed to femoroactebaluar impingements, do not show any significant subluxation.     

European map of alien plant invasions based on the quantitative assessment across habitats

Aim Recent studies using vegetation plots have demonstrated that habitat type is a good predictor of the level of plant invasion, expressed as the proportion of alien to all species. At local scale, habitat types explain the level of invasion much better than alien propagule pressure. Moreover, it has been shown that patterns of habitat invasion are consistent among European regions with contrasting climates, biogeography, history and socioeconomic background. Here we use these findings as a basis for mapping the level of plant invasion in Europe. Location European Union and some adjacent countries. Methods We used 52,480 vegetation plots from Catalonia (NE Spain), Czech Republic and Great Britain to quantify the levels of invasion by neophytes (alien plant species introduced after ad 1500) in 33 habitat types. Then we estimated the proportion of each of these habitat types in CORINE land‐cover classes and calculated the level of invasion for each class. We projected the levels of invasion on the CORINE land‐cover map of Europe, extrapolating Catalonian data to the Mediterranean bioregion, Czech data to the Continental bioregion, British data to the British Isles and combined Czech–British data to the Atlantic and Boreal bioregions. Results The highest levels of invasion were predicted for agricultural, urban and industrial land‐cover classes, low levels for natural and semi‐natural grasslands and most woodlands, and the lowest levels for sclerophyllous vegetation, heathlands and peatlands. The resulting map of the level of invasion reflected the distribution of these land‐cover classes across Europe. Main conclusions High level of invasion is predicted in lowland areas of the temperate zone of western and central Europe and low level in the boreal zone and mountain regions across the continent. Low level of invasion is also predicted in the Mediterranean region except its coastline, river corridors and areas with irrigated agricultural land.     

Benthic algae support zooplankton growth during winter in a clear-water lake

We used stable carbon (δ¹³C) and nitrogen (δ¹⁵N) isotopes to assess the importance of benthic algae for the zooplankton individual growth in winter in a shallow, clear subarctic lake. The δ¹³C values of calanoid ( Eudiaptomus graciloides ) and cyclopoid ( Cyclops scutifer ) zooplankton in autumn suggest a food resource of pelagic origin during the ice-free period. The zooplankton δ¹³C values were high in spring compared to autumn. E. graciloides did not grow over winter and the change in δ¹³C was attributed to a decrease in lipid content during the winter. In contrast, the increase in δ¹³C values of C. scutifer over the winter was explained by their growth on organic carbon generated by benthic algae. The δ¹⁵N of the C. scutifer food resource during winter was low compared to δ¹⁵N of the benthic community, suggesting that organic matter generated by benthic algae was mainly channelled to zooplankton via ¹⁵N-depleted heterotrophic bacteria. The results demonstrate that benthic algae can sustain zooplankton metabolic demands and growth during long winters, which, in turn, may promote zooplankton growth on pelagic resources during the summer. Such multi-chain omnivory challenges the view of zooplankton as mainly dependent on internal primary production and stresses the importance of benthic resources for the productivity of plankton food webs in shallow lakes.