Qualities and Inequalities in Online Social Networks through the Lens of the Generalized Friendship Paradox

The friendship paradox is the phenomenon that in social networks, people on average have fewer friends than their friends do. The generalized friendship paradox is an extension to attributes other than the number of friends. The friendship paradox and its generalized version have gathered recent attention due to the information they provide about network structure and local inequalities. In this paper, we propose several measures of nodal qualities which capture different aspects of their activities and influence in online social networks. Using these measures we analyse the prevalence of the generalized friendship paradox over Twitter and we report high levels of prevalence (up to over 90% of nodes). We contend that this prevalence of the friendship paradox and its generalized version arise because of the hierarchical nature of the connections in the network. This hierarchy is nested as opposed to being star-like. We conclude that these paradoxes are collective phenomena not created merely by a minority of well-connected or high-attribute nodes. Moreover, our results show that a large fraction of individuals can experience the generalized friendship paradox even in the absence of a significant correlation between degrees and attributes.     

Brucellosis Causes Alteration in Trace Elements and Oxidative Stress Factors

Brucellosis is regarded as one of the most common diseases among humans and livestock. In the present study, we aimed to assess the effect of this disease on the level of various cations including copper (Cu), manganese (Mn), zinc (Zn), and magnesium (Mg) as well as oxidative stress status in the serum of people suffering from brucellosis. The present case-study was carried out on 40 patients with brucellosis (case) and 20 healthy people (control). Blood specimens were taken from all the people and the level of essential trace elements and oxidative stress status were measured. The serum level of copper in the case group (165.39 ± 43.19 μg/dl) was significantly higher compared with that in the control group (122.12 ± 28.88 μg/dl). Whereas the serum level of zinc was significantly lower in the case group compared with that in the control group (76.47 ± 28.88 vs. 92.85 ± 23.16 μg/dl). The manganese and magnesium serum levels did not differ significantly between the two groups. Furthermore, total antioxidant capacity level was significantly lower in the case group (122.12 ± 28.22 μmol/ml) than that in the control group (3.08 ± 0.12 μmol/ml) and the level of serum malondialdehyde was significantly higher in the case group (7.20 ± 0.23 mmol/ml) than that in the control group (4.0 ± 0.19 mmol/ml). Brucellosis can cause alteration in the serum level of essential trace elements. Moreover, the present study indicated that brucellosis produces oxidative stress in patients.     

Structural Basis of the Regulation of the CbpA Co-chaperone by its Specific Modulator CbpM

CbpA, one of the Escherichia coli DnaJ homologues, acts as a co-chaperone in the DnaK chaperone system. Despite its extensive similarity in domain structure and function to DnaJ, CbpA has a unique and specific regulatory mechanism mediated through the small protein CbpM. Both CbpA and CbpM are highly conserved in bacteria. Earlier studies showed that CbpM interacts with the N-terminal J-domain of CbpA inhibiting its co-chaperone activity but the structural basis of this interaction is not known. Here, we have combined NMR spectroscopy, site-directed mutagenesis and surface plasmon resonance to characterize the CbpA/CbpM interaction at the molecular level. We have determined the solution structure of the CbpA J-domain and mapped the residues that are perturbed upon CbpM binding. The NMR data defined a broad region on helices α2 and α3 as involved in the interactions. Site-directed mutagenesis has been used to further delineate the CbpA J-domain/CbpM interface. We show that the binding sites of CbpM and DnaK on CbpA J-domain overlap, which suggests a competition between DnaK and CbpM for binding to CbpA as a mechanism for CbpA regulation. This study also provides the explanation for the specificity of CbpM for CbpA versus DnaJ, by identifying the key residues for differential binding.     

Transient activation of tumor-associated T-effector/memory cells promotes tumor eradication via NK-cell recruitment: minimal role for long-term T-cell immunity in cure of metastatic disease

Local delivery of IL-12 and GM-CSF to advanced primary tumors results in T- and NK-cell-dependent cure of disseminated disease in a murine spontaneous lung metastasis model. Post-therapy functional dynamics of cytotoxic T- and NK-cells were analyzed in primary and metastatic tumors to determine the specific roles of each subset in tumor eradication. Time-dependent depletion of CD8+ T and NK-cells demonstrated that CD8+ T-cells were critical to eradication of metastatic tumors within 3 days of treatment, but not later. In contrast, NK-cells were found to be essential to tumor regression for at least 10 days after cytokine delivery. Analysis of tumor-infiltrating lymphocyte populations in post-therapy primary tumors demonstrated that treatment resulted in the activation of tumor-associated CD8+ T-cells within 24 h as determined by IFNγ and perforin production. T-cell activity peaked between days 1 and 3 and subsided rapidly thereafter. Activation was not accompanied with an increase in cell numbers suggesting that treatment mobilized pre-existing T-effector/memory cells without inducing proliferation. In contrast, therapy resulted in a ≥3-fold enhancement of both the quantity and the cytotoxic activity of NK-cells in primary and metastatic tumors on day 3 post-therapy. NK-cell activity was also transient and subsided to pre-therapy levels by day 5. Depletion of CD4+ and CD8+ T-cells prior to treatment completely abrogated NK-cell infiltration into primary and metastatic tumors demonstrating the strict dependence of NK-cell recruitment on pre-existing T-effector/memory cells. Treatment failed to induce significant NK-cell infiltration in IFNγ-knockout mice establishing the central role of IFNγ in NK-cell chemotaxis to tumors. These data show that transient activation of tumor-associated T-effector/memory and NK-cells, but not long-term CD8+ T-cell responses, are critical to suppression of metastatic disease in this model; and reveal a novel role for pre-existing adaptive T-cell immunity in the recruitment of innate effectors to tumors. This work was supported by NIH/NCI grant R01-CA100656-01A1 to N.K.E.     

Proinflammatory cytokine gene polymorphisms in Behçet's disease

Beh?et's disease (BD) is a chronic, systemic disease, characterized by oral and genital lesions, and ocular inflammation. There is evidence indicating altered levels of proinflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) in patients with BD. This study involved 150 patients with BD and 140 healthy controls, and investigated the role of proinflammatory cytokine gene polymorphisms in the disease. The frequency of the TNF-α (-238) G/G genotype was significantly higher in the patient group, compared to the controls (p < 0.001), whilst the G/A genotype was significantly lower in the patients with BD (p < 0.001). Patients with BD showed a significant increase in the TNF-α (- 308, - 238) GG haplotype (p < 0.001), whilst there was a significant decrease in the GA haplotype (p < 0.001). The heterozygous, IL-6 (- 174) C/G genotype (p = 0.005), and the IL-6 (- 174, nt565) haplotype CG (p < 0.001), were significantly decreased in the patient group. The increased production of proinflammatory cytokines in BD could be a consequence of specific, cytokine gene polymorphisms. Particular genotypes and haplotypes in TNF-α were over-represented in BD, which may, in turn, predispose individuals to this disease.     

Ras oncogene mutations in urine sediments of patients with bladder cancer

Early detection of bladder cancer is particularly important since it dramatically affects the survival rates. However, neither urinary cytology nor tumor markers that are currently used are sensitive enough for the early detection of bladder cancer or recurrent disease. The ras genes are frequently mutated in cancer. In this study, we investigated the diagnostic potential of ras mutation analysis in urinary sediments of patients with bladder cancer using a single-strand conformation polymorphism analysis and polymerase chain reaction. Mutation in codon 12 of the H-ras gene was observed in 39% of the patients. Our results indicate that this approach may significantly improve diagnostic sensitivity in detecting bladder tumors.     

Mechanisms underlying modulation of podocyte TRPC6 channels by suPAR: Role of NADPH oxidases and Src family tyrosine kinases

The soluble urokinase receptor (suPAR) has been implicated in the pathogenesis of chronic kidney diseases (CKD) and may function as a circulating “permeability factor” driving primary focal and segmental glomerulosclerosis (FSGS). Here we examined the mechanisms whereby suPAR causes mobilization and increased activation of Ca²⁺-permeable TRPC6 channels, which are also implicated in FSGS. Treatment of immortalized mouse podocytes with recombinant suPAR for 24?h caused a marked increase in cytosolic reactive oxygen species (ROS) that required signaling through integrins. This effect was associated with increased assembly of active cell surface NADPH oxidase 2 (Nox2) complexes and was blocked by the Nox2 inhibitor apoycynin. Treatment with suPAR also evoked a functionally measurable increase in TRPC6 channels that was blocked by concurrent treatment with the ROS-quencher TEMPOL as well as by inhibition of Rac1, an essential component of active Nox2 complexes. Elevated ROS evoked by exposing cells to suPAR or H₂O₂ caused a marked increase in the abundance of tyrosine-phosphorylated proteins including Src, and suPAR-evoked Src activation was blocked by TEMPOL. Moreover, mobilization and increased activation of TRPC6 by suPAR or H₂O₂ was blocked by concurrent exposure to PP2, an inhibitor of Src family tyrosine kinases. These data suggest that suPAR induces oxidative stress in podocytes that in turn drives signaling through Src family kinases to upregulate TRPC6 channels. The combination of oxidative stress and altered Ca²⁺ signaling may contribute to loss of podocytes and progression of various forms of CKD.     

Fine-scale population genetic structure of Endangered Caspian Sea trout,Salmo caspius: implications for conservation

Hydrobiologia - Many populations of Caspian Sea trout (Salmo caspius)—a nationally endangered species in Iran—have been extirpated or depleted due to anthropogenic impacts. The Lar...