Protein cutoff scanning: A comparative analysis of cutoff dependent and cutoff free methods for prospecting contacts in proteins

In this study, we carried out a comparative analysis between two classical methodologies to prospect residue contacts in proteins: the traditional cutoff dependent (CD) approach and cutoff free Delaunay tessellation (DT). In addition, two alternative coarse-grained forms to represent residues were tested: using alpha carbon (CA) and side chain geometric center (GC). A database was built, comprising three top classes: all alpha, all beta, and alpha/beta. We found that the cutoff value at about 7.0 angstrom emerges as an important distance parameter. Up to 7.0 angstrom, CD and DT properties are unified, which implies that at this distance all contacts are complete and legitimate (not occluded). We also have shown that DT has an intrinsic missing edges problem when mapping the first layer of neighbors. In proteins, it may produce systematic errors affecting mainly the contact network in beta chains with CA. The almost-Delaunay (AD) approach has been proposed to solve this DT problem. We found that even AD may not be an advantageous solution. As a consequence, in the strict range up to 7.0 angstrom, the CD approach revealed to be a simpler, more complete, and reliable technique than DT or AD. Finally, we have shown that coarse-grained residue representations may introduce bias in the analysis of neighbors in cutoffs up to 6.8 angstrom, with CA favoring alpha proteins and GC favoring beta proteins. This provides an additional argument pointing to the value of 7.0 angstrom as an important lower bound cutoff to be used in contact analysis of proteins.74372774

Molecular studies of the Brazilian infectious bronchitis virus isolates

Avian infectious bronchitis virus (IBV) isolates have been widely characterized by reverse transcription followed by polymerase chain reaction and DNA sequencing. In present study, these techniques were applied to three viral genomic regions comprising the complete and/or a partial S1 segment, S2 and nucleocapsid genes. DNA sequences from viral isolates obtained from 1972 to 1989 and from 2006 to 2008 were compared. High similarity (>90%) was observed among some of the genomic segments, including S1 hypervariable region, which could suggest a common origin or ancestry. DNA sequences from S2 and N protein genes obtained from different infected tissues of the same flock were analyzed, and a clear segregation between respiratory and intestinal tract was observed. Therefore, these data suggest co-circulation of more than one viral strain in the same flock. 57.1% of DNA sequences from the S1 complete segment samples, 53.3% from the S2 fragment and 62.5% from the partial N gene were found to be different from analyzed sequences from reference strains leading to the conclusion that parte of viral isolates included in this study may be considered region specific. Considering the simultaneous analysis of the three genes, a large IBV genetic profile was observed in both old and recent isolates groups. However, most prominent diversity between viral isolates was obtained in the period from 1972 and 1989, showing the presence of a large number of variants in the state of Minas Gerais before the official approval of vaccination (1980)

Estimated GFR and the Effect of Intensive Blood Pressure Lowering after Acute Intracerebral Hemorrhage

Background: The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain. Study Design: Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP < 140 mm Hg) or contemporaneous guideline-based (target SBP < 180 mm Hg) BP management. Setting & Participants: 2,823 patients from 144 clinical hospitals in 21 countries. Predictors Admission estimated glomerular filtration rates (eGFRs) of patients were categorized into 3 groups based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation: normal or high, mildly decreased, and moderately to severely decreased (>90, 60-90, and <60 mL/min/1.73 m2, respectively). Outcomes: The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms. Results: Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P = 0.5 for homogeneity). Limitations: Generalizability issues arising from a clinical trial population. Conclusions: Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs