Proportion Regulation in Globally Coupled Nonlinear Systems

As a model of proportion regulation in differentiation process of biological system, globally coupled activator-inhibitor systems are studied. Formation and destabilization of one and two cluster state are predicted analytically. Numerical simulations show that the proportion of units of clusters is chosen within a finite range and it is selected depend on the initial condition.Comment: 11 pages (revtex format) and 5 figures (PostScript)

Differences between <i>Trypanosoma brucei gambiense</i> groups 1 and 2 in their resistance to killing by Trypanolytic factor 1

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The three sub-species of &lt;i&gt;Trypanosoma brucei&lt;/i&gt; are important pathogens of sub-Saharan Africa. &lt;i&gt;T. b. brucei&lt;/i&gt; is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. &lt;i&gt;T. b. rhodesiense&lt;/i&gt; and &lt;i&gt;T. b. gambiense&lt;/i&gt; are able to resist lysis by TLF. There are two distinct sub-groups of &lt;i&gt;T. b. gambiense&lt;/i&gt; that differ genetically and by human serum resistance phenotypes. Group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (&lt;i&gt;HpHbR&lt;/i&gt;)) gene. Here we investigate if this is also true in group 2 parasites.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology:&lt;/b&gt; Isogenic resistant and sensitive group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the &lt;i&gt;HpHbR&lt;/i&gt; gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to &lt;i&gt;T. b. brucei&lt;/i&gt;. Both resistant and sensitive group 2, as well as group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt;, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data indicate that, despite group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of &lt;i&gt;HpHbR&lt;/i&gt;. Thus there are differences in the mechanism of human serum resistance between &lt;i&gt;T. b. gambiense&lt;/i&gt; groups 1 and 2.&lt;/p&gt

An expanded phylogeny of social amoebas (Dictyostelia) shows increasing diversity and new morphological patterns

<p>Abstract</p> <p>Background</p> <p>Social Amoebae or Dictyostelia are eukaryotic microbes with a unique life cycle consisting of both uni- and multicellular stages. They have long fascinated molecular, developmental and evolutionary biologists, and <it>Dictyostelium discoideum </it>is now one of the most widely studied eukaryotic microbial models. The first molecular phylogeny of Dictyostelia included most of the species known at the time and suggested an extremely deep taxon with a molecular depth roughly equivalent to Metazoa. The group was also shown to consist of four major clades, none of which correspond to traditional genera. Potential morphological justification was identified for three of the four major groups, on the basis of which tentative names were assigned.</p> <p>Results</p> <p>Over the past four years, the Mycetozoan Global Biodiversity Survey has identified many new isolates that appear to be new species of Dictyostelia, along with numerous isolates of previously described species. We have determined 18S ribosomal RNA gene sequences for all of these new isolates. Phylogenetic analyses of these data show at least 50 new species, and these arise from throughout the dictyostelid tree breaking up many previously isolated long branches. The resulting tree now shows eight well-supported major groups instead of the original four. The new species also expand the known morphological diversity of the previously established four major groups, violating nearly all previously suggested deep morphological patterns.</p> <p>Conclusions</p> <p>A greatly expanded phylogeny of Dictyostelia now shows even greater morphological plasticity at deep taxonomic levels. In fact, there now seem to be no obvious deep evolutionary trends across the group. However at a finer level, patterns in morphological character evolution are beginning to emerge. These results also suggest that there is a far greater diversity of Dictyostelia yet to be discovered, including novel morphologies.</p

Haemodynamic effects of plasma-expansion with hyperoncotic albumin in cirrhotic patients with renal failure: a prospective interventional study

<p>Abstract</p> <p>Background</p> <p>Patients with advanced cirrhosis of the liver typically display circulatory disturbance. Haemodynamic management may be critical for avoiding and treating functional renal failure in such patients. This study investigated the effects of plasma expansion with hyperoncotic albumin solution and the role of static haemodynamic parameters in predicting volume responsiveness in patients with advanced cirrhosis.</p> <p>Methods</p> <p>Patients with advanced cirrhosis (Child B and C) of the liver receiving albumin substitution because of renal compromise were studied using trans-pulmonary thermodilution. Paired measurements before and after two infusions of 200 ml of 20% albumin per patient were recorded and standard haemodynamic parameters such as central venous pressure (CVP), mean arterial pressure (MAP), systemic vascular resistance index (SVRI), cardiac index (CI) and derived variables were assessed, including global end-diastolic blood volume index (GEDVI), a parameter that reflects central blood volume</p> <p>Results</p> <p>100 measurements in 50 patients (33 m/17 w; age 56 years (± 8); Child-Pugh-score 12 (± 2), serum creatinine 256 μmol (± 150) were analyzed. Baseline values suggested decreased central blood volumes GEDVI = 675 ml/m²(± 138) despite CVP within the normal range (11 mmHg (± 5). After infusion, GEDVI, CI and CVP increased (682 ml/m²(± 128) vs. 744 ml/m²(± 171), p < 0.001; 4.3 L/min/m²(± 1.1) vs. 4.7 L/min/m²(± 1.1), p < 0.001; 12 mmHg (± 6) vs. 14 mmHg (± 6), p < 0.001 respectively) and systemic vascular resistance decreased (1760 dyn s/cm⁵/m²(± 1144) vs. 1490 dyn s/cm⁵/m²(± 837); p < 0.001). Changes in GEDVI, but not CVP, correlated with changes in CI (r²= 0.51; p < 0.001). To assess the value of static haemodynamic parameters at baseline in predicting an increase in CI of 10%, receiver-operating-characteristic curves were constructed. The areas under the curve were 0.766 (p < 0.001) for SVRI, 0.723 (p < 0.001) for CI, 0.652 (p = 0.010) for CVP and 0.616 (p = 0.050) for GEDVI.</p> <p>Conclusion</p> <p>In a substantial proportion of patients with advanced cirrhosis, plasma expansion results in an increase in central blood volume. GEDVI but not CVP behaves as an indicator of cardiac preload, whereas high baseline SVRI is predictive of fluid responsiveness.</p

Observation of electron-antineutrino disappearance at Daya Bay

The Daya Bay Reactor Neutrino Experiment has measured a non-zero value for the neutrino mixing angle $\theta_{13}$ with a significance of 5.2 standard deviations. Antineutrinos from six 2.9 GW$_{\rm th}$ reactors were detected in six antineutrino detectors deployed in two near (flux-weighted baseline 470 m and 576 m) and one far (1648 m) underground experimental halls. With a 43,000 ton-GW_{\rm th}-day livetime exposure in 55 days, 10416 (80376) electron antineutrino candidates were detected at the far hall (near halls). The ratio of the observed to expected number of antineutrinos at the far hall is $R=0.940\pm 0.011({\rm stat}) \pm 0.004({\rm syst})$. A rate-only analysis finds $\sin^22\theta_{13}=0.092\pm 0.016({\rm stat})\pm0.005({\rm syst})$ in a three-neutrino framework.Comment: 5 figures. Version to appear in Phys. Rev. Let

Trypanosoma brucei Glycogen Synthase Kinase-3, A Target for Anti-Trypanosomal Drug Development: A Public-Private Partnership to Identify Novel Leads

Over 60 million people in sub-Saharan Africa are at risk of infection with the parasite Trypanosoma brucei which causes Human African Trypanosomiasis (HAT), also known as sleeping sickness. The disease results in systemic and neurological disability to its victims. At present, only four drugs are available for treatment of HAT. However, these drugs are expensive, limited in efficacy and are severely toxic, hence the need to develop new therapies. Previously, the short TbruGSK-3 short has been validated as a potential target for developing new drugs against HAT. Because this enzyme has also been pursued as a drug target for other diseases, several inhibitors are available for screening against the parasite enzyme. Here we present the results of screening over 16,000 inhibitors of human GSK-3β (HsGSK-3) from the Pfizer compound collection against TbruGSK-3 short. The resulting active compounds were tested for selectivity versus HsGSK-3β and a panel of human kinases, as well as their ability to inhibit proliferation of the parasite in vitro. We have identified attractive compounds that now form potential starting points for drug discovery against HAT. This is an example of how a tripartite partnership involving pharmaceutical industries, academic institutions and non-government organisations such as WHO TDR, can stimulate research for neglected diseases

The Dictyostelium discoideum acaA Gene Is Transcribed from Alternative Promoters during Aggregation and Multicellular Development

Background: Extracellular cAMP is a key extracellular signaling molecule that regulates aggregation, cell differentiation and morphogenesis during multi-cellular development of the social amoeba Dictyostelium discoideum. This molecule is produced by three different adenylyl cyclases, encoded by the genes acaA, acrA and acgA, expressed at different stages of development and in different structures. Methodology/Principal Findings: This article describes the characterization of the promoter region of the acaA gene, showing that it is transcribed from three different alternative promoters. The distal promoter, promoter 1, is active during the aggregation process while the more proximal promoters are active in tip-organiser and posterior regions of the structures. A DNA fragment containing the three promoters drove expression to these same regions and similar results were obtained by in situ hybridization. Analyses of mRNA expression by quantitative RT-PCR with specific primers for each of the three transcripts also demonstrated their different temporal patterns of expression. Conclusions/Significance: The existence of an aggregation-specific promoter can be associated with the use of cAMP as chemo-attractant molecule, which is specific for some Dictyostelium species. Expression at late developmental stages indicates that adenylyl cyclase A might play a more important role in post-aggregative development than previously considered