Cliques and cavities in the human connectome

Encoding brain regions and their connections as a network of nodes and edges captures many of the possible paths along which information can be transmitted as humans process and perform complex behaviors. Because cognitive processes involve large, distributed networks of brain areas, principled examinations of multi-node routes within larger connection patterns can offer fundamental insights into the complexities of brain function. Here, we investigate both densely connected groups of nodes that could perform local computations as well as larger patterns of interactions that would allow for parallel processing. Finding such structures necessitates that we move from considering exclusively pairwise interactions to capturing higher order relations, concepts naturally expressed in the language of algebraic topology. These tools can be used to study mesoscale network structures that arise from the arrangement of densely connected substructures called cliques in otherwise sparsely connected brain networks. We detect cliques (all-to-all connected sets of brain regions) in the average structural connectomes of 8 healthy adults scanned in triplicate and discover the presence of more large cliques than expected in null networks constructed via wiring minimization, providing architecture through which brain network can perform rapid, local processing. We then locate topological cavities of different dimensions, around which information may flow in either diverging or converging patterns. These cavities exist consistently across subjects, differ from those observed in null model networks, and – importantly – link regions of early and late evolutionary origin in long loops, underscoring their unique role in controlling brain function. These results offer a first demonstration that techniques from algebraic topology offer a novel perspective on structural connectomics, highlighting loop-like paths as crucial features in the human brain’s structural architecture.     

Do nitroxides protect cardiomyocytes from hydrogen peroxide or superoxide?

The aim of the research was to study the role played by extracellular O ₂ ^.- radicals, which are implicated in cardiac cell damage and the protective effect by cell-permeable, nitroxide, superoxide dismutase-mimics. Cardiomyocytes cultures from 1-day-old rats served as the test-system. Experiments were performed since 5th day in culture when >80% of the cells were beating myocardial cells. Oxidative damage was induced by 0.5 mM hypoxanthine and 0.06 U/ml xanthine oxidase or by 10 mM glucose and 0.15 U/ml glucose oxidase. The parameters used to evaluate damages were spontaneous beating, lactate dehydrogenase release and ATP level. The rhythmic pulsation was followed microscopically. To determine the kinetics of cytosolic enzyme release from the cells, media samples were collected at various points of time and assayed for enzyme activity. To determine the cellular ATP, cells were washed with sodium phosphate buffer, scraped off and boiled for 3 min with sodium phosphate buffer. Following centrifugation the supernatant was collected and ATP was determined by the chemiluminogenic assay using firefly tails. The present results indicate that nitroxide stable free radicals, in the millimolar concentration range, provide full protection without toxic side-effect. Unlike exogenously added SOD that failed to protect, exogenous catalase provided almost full protection. In addition, the metal-chelating agent dipyridyl, but not diethylene-triamine-pentaacetate or desferrioxamine, protected the cultured cells. The present results suggest that H₂O₂ is the predominant toxic species mediating the oxidative damage whereas extracellular superoxide radical does not contribute to cultured cardiomyocyte damage. Since nitroxides do not remove H₂O₂ they can protect the cells possibly by oxidizing the metal ions and inhibiting the Fenton reaction. The superoxide dismutase-mimic activity of nitroxides does not seem to underlie their protective effect, however, the involvement of intracellular O ₂ ^.- cannot be excluded.Abbreviations CHDO 2-spirocyclohexane doxyl (2-cyclohexane-5,5-demethyl-3-oxazolidinoxyl) - DF desferrioxamine - DTPA diethylene-triamine-pentaacetate - EPR electron paramagnetic resonance - HX hypoxanthine - LDH lactate dehydrogenase - SOD superoxide dismutase - SEM standard error of mean: TEMPOL, 4-hydroxy-2,2,6,6-tetramethyl-piperidinoxyl - TEMPAMINE 4-amino-2,2,6,6-tetramethyl-piperidinoxyl - XO xanthine oxidase - CAT catalase     

Lack of detection of human papillomavirus DNA in prostate carcinomas in patients from northeastern Brazil

Prostate cancer is the second most common cancer among men in western populations, and despite its high mortality, its etiology remains unknown. Inflammatory processes are related to the etiology of various types of tumors, and prostate inflammation, in particular, has been associated with prostate cancer carcinogenesis and progression. Human papillomavirus (HPV) is associated with benign and malignant lesions in the anogenital tract of both females and males. The possible role of HPV in prostate carcinogenesis is a subject of great controversy. In this study, we aimed to examine the prevalence of HPV infections in prostate carcinomas of patients from northeastern Brazil. This study included 104 tissue samples from primary prostate carcinoma cases. HPV DNA was purified and then amplified using MY09/11 and GP5+/GP6+ degenerate primer sets that detect a wide range of HPV types, and with specific PCR primers sets for E6 and E7 HPV regions to detect HPV 16. None of the samples showed amplification products of HPV DNA for primer sets MY09/11 and GP5+/GP6+, or the specific primer set for the E6 and E7 HPV regions. HPV infection, thus, does not seem to be one of the causes of prostate cancer in the population studied.     

Effects of land use on taxonomic and functional diversity: a cross-taxon analysis in a Mediterranean landscape

Land-use change is the major driver of biodiversity loss. However, taxonomic diversity (TD) and functional diversity (FD) might respond differently to land-use change, and this response might also vary depending on the biotic group being analysed. In this study, we compare the TD and FD of four biotic groups (ants, birds, herbaceous, woody vegetation) among four land-use types that represent a gradient of land-use intensity in a Mediterranean landscape (Mediterranean shrublands, dehesas, mixed-pine forests, olive groves). Analyses were performed separately at two different spatial scales: the sampling unit scale and the site scale. Land-use intensity effects on TD and FD were quite different and highly varied among the four biotic groups, with no single clear pattern emerging that could be considered general for all organisms. Additive partitioning of species diversity revealed clear contrasting patterns between TD and FD in the percentage of variability observed at each spatial scale. While most variability in TD was found at the larger scales, irregardless of organism group and land-use type, most variability in FD was found at the smallest scale, indicating that species turnover among communities is much greater than functional trait turnover. Finally, we found that TD and FD did not vary consistently, but rather followed different trajectories that largely depended on the biotic group and the intensity of land-use transformation. Our results highlight that the relationship of land use with TD and FD is highly complex and context-dependent.     

Invasion of the Fungal Pathogen <Emphasis Type="Italic">Batrachochytrium dendrobatidis</Emphasis> on California Islands

Batrachochytrium dendrobatidis (Bd), an amphibian fungal pathogen, has infected >500 species and caused extinctions or declines in >200 species worldwide. Despite over a decade of research, little is known about its invasion biology. To better understand this, we conducted a museum specimen survey (1910–1997) of Bd in amphibians on 11 California islands and found a pattern consistent with the emergence of Bd epizootics on the mainland, suggesting that geographic isolation did not prevent Bd invasion. We propose that suitable habitat, host diversity, and human visitation overcome isolation from the mainland and play a role in Bd invasion.     

Association of Angiopoietin-2 and Ki-67 Expression with Vascular Density and Sunitinib Response in Metastatic Renal Cell Carcinoma

The Angiopoietin-2 (Ang2, Angpt2) growth factor is a context-dependent antagonist/agonist ligand of the endothelial Tie2 receptor tyrosine kinase and known to promote tumour angiogenesis and metastasis. Angiopoietin antagonists have been tested in clinical cancer trials in combination with VEGF-based anti-angiogenic therapy, including sunitinib, which is widely used as a first-line therapy for metastatic renal cell carcinoma (mRCC). However, little is known about Ang2 protein expression in human tumours and the correlation of tumour Ang2 expression with tumour vascularization, tumour cell proliferation and response to anti-angiogenic therapies. Here, we evaluated, using immunohistochemistry, the expression of Ang2, CD31 and the cell proliferation marker Ki-67 in the primary kidney cancer from 136 mRCC patients, who received first-line sunitinib after nephrectomy. Ang2 protein expression was restrained to RCC tumour vessels, and correlated with tumour vascularization and response to sunitinib. High pre-therapeutic Ang2 expression, and more strongly, combined high expression of both Ang2 and CD31, were associated with a high clinical benefit rate (CBR). Low cancer Ki-67 expression, but not Ang2 or CD31 expression, was associated with favourable progression-free (PFS) and overall survival (OS) as compared to patients with high Ki-67 expression (PFS 6.5 vs. 10.6 months, P = 0.009; OS, 15.7 vs. 28.5 months, P = 0.015). In summary, in this study to investigate endothelial Ang2 in mRCC patients treated with first-line sunitinib, high cancer Ang2 expression was associated with the CBR, but not PFS or OS, whereas low Ki-67 expression was significantly associated with long PFS and OS.     

A dnaB analog specified by bacteriophage P1

Bacteriophage P1 is shown to determine a product that can substitute in DNA replication for the protein specified by cistron dnaB of Escherichia coli. The viral dnaB analog (ban) is repressed in the wild-type P1 prophage and expressed constitutively in plaque-forming mutants, P1bac, described here. A particular P1bac prophage allows lysogens of dnaBts bacteria to survive as colony-formers at temperatures that arrest DNA synthesis in the non-lysogens. The P1bac prophage furthermore permits construction of an otherwise inviable strain bearing the unsuppressed amber mutation dnaB266.P1bac prophages also suppress the groP character which is associated with certain dnaB mutations. The subclass of dnaB mutations called groP are those which prevent the growth of bacteriophage λ⁺ at temperatures permissive for bacterial DNA synthesis, but allow the growth of certain λ mutants (λπ); π mutations have been mapped in gene P. Thus, λ⁺ is enabled to grow in groP hosts by the presence of P1bac-1 prophage. When dnaB protein is absent, however, as in the case of the unsuppressed amber mutant, the ban protein furnished by the P1bac prophage does not support λ growth. Therefore, in the groP(P1bac-1) lysogens both the dnaB and ban products are needed for λ growth, suggesting interactions between these E. coli and P1 proteins or their subunits.Mutations (termed ban) that prevent the expression of the dnaB analog determined by P1 have been obtained. P1bac-1ban-1, unlike P1bac-1, fails to replicate in dnaBts hosts at temperatures non-permissive for bacterial DNA synthesis. Thus, the dnaB protein and its P1-determined analog can interchangeably fulfill an essential role in the replication of both the E. coli and P1 replicons. At permissive temperatures the lysogenization of certain dnaBts strains by P1bac-1ban-1 is very inefficient, probably as a result of negative complementation.Mutations bac-1 and ban-1 are closely linked on the P1 chromosome and their order relative to several amber mutations has been determined. Dominance studies of the alleles in transient diploids show that the ban-1 mutation is recessive to ban⁺. The bac-1 mutation, on the other hand, behaves in dominance tests as a DNA site mutation that permits constitutive expression in cis of the operon to which the ban gene belongs.