Highly similar structural frames link the template tunnel and NTP entry tunnel to the exterior surface in RNA-dependent RNA polymerases.

RNA-dependent RNA polymerase (RdRp) is essential to viral replication and is therefore one of the primary targets of countermeasures against these dangerous infectious agents. Development of broad-spectrum therapeutics targeting polymerases has been hampered by the extreme sequence variability of these sequences. RdRps range in length from 400-800 residues, yet contain only ∼20 residues that are conserved in most species.

A randomized controlled trial of prophylactic intra-aortic balloon counterpulsation in high-risk aneurysmal subarachnoid hemorrhage.

Background And Purpose: To assess whether prophylactic postoperative intraaortic balloon counterpulsation (IABC) reduces the risk of poor outcome because of vasospasm following aneurysmal subarachnoid haemorrhage relative to conventional hypervolemic therapy (HT).

Methods: This was a single-center, parallel group randomized controlled trial. Patients suffering a subarachnoid hemorrhage at high risk of vasospasm were eligible.

Fibrin Sealant Injection: An Aid to Reduce Venous Bleeding during Jugular Bulb and Sigmoid Sinus Dissection in Glomus Jugulare (Jugulotympanic Paraganglioma) Surgery.

Glomus jugulare (jugulotympanic paraganglioma) surgery requires tumor dissection in the region of the jugular bulb, upper internal jugular vein, and sigmoid sinus. Despite ligation or external compression of the sigmoid sinus proximally and ligation of the internal jugular vein distally, troublesome venous bleeding can arise from the inferior petrosal sinus or condylar veins at the medial wall of the jugular bulb. Excessive packing in this area can place the integrity of the lower cranial nerves at risk.

Genome of Ochrobactrum anthropi ATCC 49188 T, a versatile opportunistic pathogen and symbiont of several eukaryotic hosts.

Ochrobactrum anthropi is a common soil alphaproteobacterium that colonizes a wide spectrum of organisms and is being increasingly recognized as an opportunistic human pathogen. Potentially life-threatening infections, such as endocarditis, are included in the list of reported O. anthropi infections.

StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase.

Background: Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory--still, they cannot provide reliable results at low levels of sequence identity.

Visual recovery following optic nerve decompression for chronic compressive neuropathy.

Purpose: Visual failure due to optic nerve compression is a common indication for decompressive surgery. Most data only refer to the odds of improvement, deterioration or remaining the same. However, patients frequently wish to know more detail about the outcomes of surgery.

Transition from long-term nonprogression to HIV-1 disease associated with escape from cellular immune control.

Transition from long-term nonprogressive infection to progressive HIV-1 disease presents an opportunity to investigate pathogenesis in a defined immunogenetic background. We studied a male long-term nonprogressor (LTNP) who remained asymptomatic and viremic and had normal CD4 T-cell counts without antiretroviral therapy for >18 years and then experienced a transition to disease progression. We analyzed the complete HIV-1 genomic RNA sequence from plasma and cellular immune responses to predefined human leukocyte antigen-matched autologous viral peptides spanning the viral genome, before and after progression.

Circuit assemblages derived from net dinucleotide values provide a succinct identity for the HIV-1 genome and each of its genes.

Dinucleotide composition has been recognized as a species-specific characteristic of organisms for more than 20 years. Lang (2000, Bioinformatics, 16, 212-221), found that in Monilinia rRNA a species-specific identity is conserved when dinucleotide counts are compressed into net dinucleotide counts (e.g.

Pestoides F, an atypical Yersinia pestis strain from the former Soviet Union.

Unlike the classical Yersinia pestis strains, members of an atypical group of Y. pestis from Central Asia, denominated Y. pestis subspecies caucasica (also known as one of several pestoides types), are distinguished by a number of characteristics including their ability to ferment rhamnose and melibiose, their lack of the small plasmid encoding the plasminogen activator (pla) and pesticin, and their exceptionally large variants of the virulence plasmid pMT (encoding murine toxin and capsular antigen).

Imperfect DNA mirror repeats in the gag gene of HIV-1 (HXB2) identify key functional domains and coincide with protein structural elements in each of the mature proteins.

Background: A DNA mirror repeat is a sequence segment delimited on the basis of its containing a center of symmetry on a single strand, e.g. 5'-GCATGGTACG-3'.

Genomic analysis of HIV type 1 strains derived from a mother and child pair of long-term nonprogressors.

To investigate the viral features of long-term nonprogressive HIV-1 infection and the selection of viral genomes, we studied serial complete HIV-1 sequences obtained from a mother-child pair, both long-term nonprogressors. Analysis of four genomic sequences demonstrated that all viral genes were intact, lacking major deletions or premature stop codons to easily explain the slow disease progression. These data suggest that viral attenuation, if present, was caused by subtle sequence variations or virus-host interactions.

Clade-specific differences between human immunodeficiency virus type 1 clades B and C: diversity and correlations in C3-V4 regions of gp120.

Current knowledge of human immunodeficiency virus type 1 envelope (Env) glycoprotein structure and function is based on studies of clade B viruses. We present evidence of sequence and structural differences in viral glycoprotein gp120 between clades B and C. In clade C, the C3 region alpha2-helix exhibits high sequence entropy at the polar face but maintains its amphipathicity, whereas in clade B it accommodates hydrophobic residues.

Imperfect DNA mirror repeats in E. coli TnsA and other protein-coding DNA.

DNA imperfect mirror repeats (DNA-IMRs) are ubiquitous in protein-coding DNA. However, they overlap and often have different centers of symmetry, making it difficult to evaluate their relationship to each other and to specific DNA and protein motifs and structures. This paper describes a systematic method of determining a hierarchy for DNA-IMRs and evaluates their relationship to protein structural elements (PSEs)--helices, turns and beta-sheets.

Selection for human immunodeficiency virus type 1 envelope glycosylation variants with shorter V1-V2 loop sequences occurs during transmission of certain genetic subtypes and may impact viral RNA levels.

Designing an effective human immunodeficiency virus type 1 (HIV-1) vaccine will rely on understanding which variants, from among the myriad of circulating HIV-1 strains, are most commonly transmitted and determining whether such variants have an Achilles heel. Here we show that heterosexually acquired subtype A HIV-1 envelopes have signature sequences that include shorter V1-V2 loop sequences and fewer predicted N-linked glycosylation sites relative to the overall population of circulating variants. In contrast, recently transmitted subtype B variants did not, and this was true for cases where the major risk factor was homosexual contact, as well as for cases where it was heterosexual contact.

Long-term survivors in Nairobi: complete HIV-1 RNA sequences and immunogenetic associations.

To investigate African long-term survivors (LTSs) infected with non-subtype B human immunodeficiency virus type 1 (HIV-1), we obtained full-length HIV-1 RNA sequences and immunogenetic profiles from 6 untreated women enrolled in the Pumwani Sex Worker Cohort in Nairobi, Kenya. There were no discernible sequence changes likely to cause attenuation. CCR2-V64I, an immunogenetic polymorphism linked to LTSs, was detected in 4 women, all of whom carried the HLA B58 allele.

Cost-benefit analysis of an integrated approach to reduce psychosocial trauma following neurosurgery compared with standard care: two-year prospective comparative study of enhanced specialist liaison nurse service for aneurysmal subarachnoid hemorrhage (ASAH) patients and carers.

Background: Dysfunctional psychosocial stress often follows standard treatment for aneurysmal subarachnoid hemorrhage (ASAH). An enhanced Specialist Liaison Nurse (SLN) service sought to reduce this stress in a 2-year comparative prospective study, and was designed to determine if such a service would be cost-effective?

Method: Clinical data based on consultant notes, included Glasgow Coma Scale (GCS) and high-risk bleed score. Psychosocial outcomes used a standardized patient/carer designed questionnaire to compare outcomes of the SLN cohort (n = 184) with retrospective 18/12 control ASAH cohort (n = 142).

Comparison of cohorts of elective and emergency neurosurgical patients: psychosocial outcomes of acoustic neuroma and aneurysmal sub arachnoid hemorrhage patients and carers.

Objectives: To compare the psychosocial outcomes of cohorts of elective [Acoustic Neuroma (AN)] and emergency [Aneu-rysmal Sub Arachnoid Hemorrhage (ASAH)] Neurosurgical patients and carers.

Methods: The standardized Wessex Patient Carer Questionnaire was designed with patients and carers and provided psychosocial and economic outcome data following elective or emergency surgery. Clinical data on size of tumor and size of bleed, respectively, were extracted from Consultant notes.

Liver transplantation with hepatitis C virus-infected graft: interaction between donor and recipient viral strains.

Superinfection of different viral strains within a single host provides an opportunity for studying host-virus and virus-virus interactions, including viral interference and genetic recombination, which cannot be studied in infections with single viral strains. Hepatitis C virus (HCV) is a positive single-strand RNA virus that establishes persistent infection in as many as 85% of infected individuals. However, there are few reports regarding coinfection or superinfection of HCV.

Evolution of hepatitis C viral quasispecies after liver transplantation.

Background & Aims: To determine whether HCV quasispecies diversity correlated positively with liver disease progression after orthotopic liver transplantation (OLT).

Methods: We studied 11 patients undergoing OLT for HCV-related cirrhosis with recurrent hepatitis C in 2 groups according to the stage of hepatic fibrosis on follow-up. The mild group had stage 1 or 2 fibrosis; the severe group, stage 3 or 4 fibrosis.

Diversity considerations in HIV-1 vaccine selection.

Globally, human immunodeficiency virus-type 1 (HIV-1) is extraordinarily variable, and this diversity poses a major obstacle to AIDS vaccine development. Currently, candidate vaccines are derived from isolates, with the hope that they will be sufficiently cross-reactive to protect against circulating viruses. This may be overly optimistic, however, given that HIV-1 envelope proteins can differ in more than 30% of their amino acids.

Mother-to-child transmission in the United States of subtypes D and A/G human immunodeficiency virus type 1.

In the United States and Western Europe, most human immunodeficiency virus type 1 (HIV-1) infections are caused by subtype B. We analyzed the nucleotide sequence of HIV-1 RNA in plasma samples from 141 children enrolled into PACTG 377, a comparative study of several antiretroviral therapy regimens. Phylogenetic analysis revealed that two children, both born in the United States, were infected with non-B subtypes that are most commonly found in Africa: one with subtype D and the other with circulating recombinant form CRF02, an A/G recombinant lineage.