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PubMed1993

Aging and body composition: possibilities for future studies.

Three approaches are being taken to the development of techniques for measuring body composition: 1) improving present methods, 2) formulating and devising new body composition measuring techniques and 3) focusing on specific problems of body composition changes in aging. The improvement of multi-frequency bioelectrical impedance, computerized tomography, magnetic resonance and dual-photon absorptiometry imaging belong under the first category. Recent developments in low radiation exposure measurement of body carbon and oxygen by neutron inelastic scattering and body protein by gamma-ray resonance are examples of new technology applied to the direct assessment of body composition of the elderly. The third category remains the most important one and should motivate the evolution of existing methods and the development of new. Current questions focus on distribution of regional body fat and its role in cardiovascular diseases and the depletion of lean body mass with age and its relation to functional capacity, quality of life and resistance to injury or disease. The relationship between the distribution of fat, the depletion of muscle tissue and changes in cellular function with age will become the focus of the future studies of body composition.

Aging↗

PubMed1999

Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose-binding protein chimera reveals structural evolution of retroviral transmembrane proteins.

Retroviral entry into cells depends on envelope glycoproteins, whereby receptor binding to the surface-exposed subunit triggers membrane fusion by the transmembrane protein (TM) subunit. We determined the crystal structure at 2.5-A resolution of the ectodomain of gp21, the TM from human T cell leukemia virus type 1. The gp21 fragment was crystallized as a maltose-binding protein chimera, and the maltose-binding protein domain was used to solve the initial phases by the method of molecular replacement. The structure of gp21 comprises an N-terminal trimeric coiled coil, an adjacent disulfide-bonded loop that stabilizes a chain reversal, and a C-terminal sequence structurally distinct from HIV type 1/simian immunodeficiency virus gp41 that packs against the coil in an extended antiparallel fashion. Comparison of the gp21 structure with the structures of other retroviral TMs contrasts the conserved nature of the coiled coil-forming region and adjacent disulfide-bonded loop with the variable nature of the C-terminal ectodomain segment. The structure points to these features having evolved to enable the dual roles of retroviral TMs: conserved fusion function and an ability to anchor diverse surface-exposed subunit structures to the virion envelope and infected cell surface. The structure of gp21 implies that the N-terminal fusion peptide is in close proximity to the C-terminal transmembrane domain and likely represents a postfusion conformation.

Amino Acid Sequence↗

PubMed2005

Dual renin angiotensin system blockade in patients with acute myocardial infarction and preserved left ventricular systolic function.

UNLABELLED: The activation of the renin-angiotensin system (RAS) is a major determinant of ventricular remodeling. We prospectively assessed whether the dual RAS blockade (angiotensin II AT 1-receptor blocker and angiotensin-converting enzyme inhibitor therapy) in patients with acute myocardial infarction (AMI) who were treated by primary percutaneous coronary intervention (PCI) and stenting provides benefit on the improvement of the left ventricle function. A secondary aim is to demonstrate that triple therapy with angiotensin-converting enzyme (ACE) inhibitors, angiotensin II AT 1-receptor blockers (ARBs) and beta blockers does not increase cardiovascular morbidity, cardiovascular mortality and all cause mortality. METHODS: We investigated 44 patients with AMI with ST elevation undergoing primary PCI and stenting. All patients received standard therapy including an ACE inhibitor and a beta blocker. We divided the patients into two groups, A and B. Valsartan was added to the standard therapy within the first 6 hours from the onset of AMI in group A. We assessed cardiovascular and all cause mortality, incidence of major acute coronary events (MACE), incidence of non-fatal AMI, the evolution of left ventricle ejection fraction (LVEF), wall motion score index (WMSI) and left ventricle end-systolic and end-diastolic diameters. The follow-up period was one year. RESULTS: There were no statistically significant differences between groups regarding cardiovascular and all cause mortality, incidence of MACE, incidence of non-fatal MI. LVEF significantly increased at 1 year in both groups. In both groups the reduction of end-systolic and end-diastolic diameters at 1 year was statistically significant. Echocardiographic findings demonstrated also a significant decrease of WMSI at 1 year in both groups. CONCLUSIONS: The dual renin-angiotensin system blockade (ARBs and ACE inhibitor) has proved its beneficial effect on the improvement of left ventricular function, without increasing cardiovascular mortality and incidence of non fatal myocardial infarction (MI) in patients with AMI treated by primary PCI and stenting within a 1 year follow-up period.

Acute Disease↗

PubMed2004

[Treatment of pulmonary arterial hypertension associated to systemic sclerosis].

PURPOSE: Pulmonary arterial hypertension (PAH) is one of the main causes of death in patients with systemic sclerosis (SSc), particularly in its limited forms. CURRENT KNOWLEDGE AND KEY POINTS: Survival with conventional treatment associated with Epoprostenol is two times less in SSc patients than in idiopathic PAH. WHO recommendations (annually heart echoscreening) must be applied in all patients with SSc. Conventional therapy associates anticoagulation, to avoid excessive exertion, pregnancy, warm baths, no pressurised flights. Calcium-channel blockers give long term survival in patients with positive acute vasodilatator test with nitric oxide (NO) but these patients are very rare in SSc. Diuretics are very useful in treating right heart insufficiency. Randomized control trials in PAH have demonstrated the short term efficacy of i.v. epoprostenol, nebulized iloprost, oral beraprost and oral bosentan, a dual endothelin-1 receptor antagonist. Results in SSc are very limited except for i.v. epoprostenol. Long-term efficacy in terms of survival has been demonstrated in non randomized studies for i.v. epoprostenol and oral bosentan in patients with idiopathic and familial PAH. Atrial septostomy and lung transplantation could be an alternative to treatment, even in SSc patients, in case of refractory evolution. FUTURE PROSPECTS AND PROJECTS: Randomized control trials with sildenafil and selective endothelin-1 receptor antagonists are ongoing.

Antihypertensive Agents↗

PubMed1990

Organization of the mitochondrial genome of Atlantic cod, Gadus morhua.

The mitochondrial DNA (mtDNA) from the Atlantic cod, Gadus morhua, was mapped using 11 different restriction enzymes and cloned into plasmid vectors. Sequence data obtained from more than 10 kilobases of cod mtDNA show that the genome organization, genetic code, and the overall codon usage have been conserved throughout the evolution of vertebrates. Comparison of the derived amino acid sequences of proteins encoded by cod mtDNA to the ones encoded by Xenopus laevis mtDNA revealed that the amino acid identity range from 46% to 93% for the different proteins. ND4L is most divergent while COI is most conserved. GUG was found as the translation initiation codon of the COI gene, indicating a dual coding function for this codon. The sequences of the 997 base pair displacement-loop (D-loop)-containing region and the origin of L-strand replication (oriL), are presented. Only few of the primary and secondary structure features found to be conserved among mammalian mitochondrial D-loops, can be identified in cod. Presence of CSB-2 in the D-loop-containing region and the conserved hairpin structure at oriL, indicates that replication of bony fish mtDNA may follow the same general scheme as described for higher vertebrates.

Amino Acid Sequence↗

PubMed1996

Dual energy X-ray absorptiometry in patients with lower limb reflex sympathetic dystrophy syndrome.

OBJECTIVE: To assess the difference in bone mineral density (BMD) between pathologic and healthy legs in reflex sympathetic dystrophy syndrome (RSDS) using a whole body BMD with dual energy X-ray absorptiometry (DEXA). METHODS: Cross sectional evaluation of BMD in 55 patients with RSDS compared BMD of the affected and the healthy limb with 121 controls. Followup was performed on 21 patients treated with intravenous pamidronate. RESULTS: In the cross sectional study, BMD was reduced in the dystrophic affected extremities and this reduction correlated with the duration of evolution of the disease. In the longitudinal study, BMD remained stable in patients treated with pamidronate. CONCLUSION: The cross sectional study confirms that DEXA is not a diagnostic tool. The longitudinal study confirms DEXA is accurate, nontraumatic, rapid, and safe for longterm quantitative assessment of unilateral bone loss caused by lower limb RSDS.

Absorptiometry, Photon↗

PubMed2006

Identification of a promoter element within the zebrafish colXalpha1 gene responsive to runx2 isoforms Osf2/Cbfa1 and til-1 but not to pebp2alphaA2.

Type X collagen is a short chain collagen specifically expressed by hypertrophic chondrocytes during endochondral ossification. We report here the functional analysis of the zebrafish (Danio rerio) collagen Xalpha1 gene (colXalpha1) promoter with the identification of a region responsive to two isoforms of the runt domain transcription factor runx2. Furthermore, we provide evidence for the presence of dual promoter usage in zebrafish, a finding that should be important to further understanding of the regulation of its restricted tissue distribution and spatial-temporal expression during early development. The zebrafish colXalpha1 gene structure is comparable to that recently identified by comparative genomics in takifugu and shows homology with corresponding mammalian genes, indicating that its general architecture has been maintained throughout vertebrate evolution. Our data suggest that, as in mammals, runx2 plays a role in the development of the osteogenic lineage, supporting zebrafish as a model for studies of bone and cartilage development.

Amino Acid Sequence↗

PubMed2001

Demonstration of reinfection and reactivation in HIV-negative autopsied cases of secondary tuberculosis: multilesional genotyping of Mycobacterium tuberculosis utilizing IS 6110 and other repetitive element-based DNA fingerprinting.

SETTING: Secondary tuberculosis may follow reinfection or endogenous reactivation. The design of effective preventive and treatment protocols requires knowledge about the relative importance of these mechanisms in specific communities. Molecular typing of Mycobacterium tuberculosis has permitted linkage of cases and demonstration of patterns of inter- or intrapatient strain diversity correlating with reinfection and reactivation. OBJECTIVE: The use of DNA fingerprinting to examine intrapatient strain diversity in autopsied, HIV-negative individuals resident in a high incidence community. DESIGN: Autopsy (12 cases) and pneumonectomy (one case) permitted multilesional sampling for bacterial culture and comparative genotyping. Mycobacterium tuberculosis strains were typed using probes directed against IS 6110, the direct repeat sequence (DR) and MTB484(1). RESULTS: In two patients, the demonstration of pulmonary infection by two distinct strains suggested dual infection of these individuals. In one other case, the strain isolated from a Ghon-focus was identical to that obtained from all secondary cavitating lesions, which suggested reactivation of the primary infection. In the remaining cases, all isolates were identical, but primary lesions could not be identified with certainty or were culture negative. One of these cases showed evidence of strain evolution. CONCLUSIONS: Multilesional strain genotyping suggested both reinfection and reactivation in a series of HIV-negative autopsied patients with secondary tuberculosis. In most (11/13) cases, the same strain (or clonal variant) was present in all lesions, pulmonary and extrapulmonary.

AIDS-Related Opportunistic Infections↗

PubMed1998

Magnetization transfer ratios in multiple sclerosis lesions enhancing after different doses of gadolinium.

We performed serial monthly magnetization transfer (MT) imaging to evaluate whether MS lesions that enhance only after the injection of a triple dose (TD) of gadolinium-DTPA (Gd) have different pathologic characteristics and evolution than those that enhance after the injection of a standard dose (SD). Every 4 weeks for 3 months and in two separate sessions, we obtained T1-weighted scans from 10 patients with relapsing-remitting MS, 5 minutes after SD (0.1 mmol/kg) or TD (0.3 mmol/kg) Gd injection. During each of the first monthly sessions, we obtained MT images and dual-echo scans before Gd injection. We measured the MT ratio (MTR) of newly enhancing lesions on co-registered quantitative MTR images. During the 3-month follow-up, 81 newly enhancing lesions were seen on SD scans. An additional 46 lesions enhanced only on TD scans. The mean (+/- standard deviation) MTR values were 31.4% +/- 8.4% for lesions enhancing after SD and 38.2% +/- 6.0% for lesions enhancing only after TD injection (p < 0.0001). The mean MTR values of lesions seen with both SD (p < 0.00001) and TD (p = 0.002) increased significantly during the follow-up. At each time point during the follow-up, the MTR values of TD lesions were significantly higher than the SD lesions. These results indicate that the enhancing lesion population in MS is heterogeneous and that the tissue damage occurring within lesions enhancing only after TD injection is less severe than in lesions enhancing after the injection of an SD.

Adult↗

PubMed1996

Antigen/antibody content of circulating immune complexes in HIV-infected patients.

Dual infection with HIV and hepatitis B virus (HBV) is not an uncommon feature. Immunity impairment due to HIV infection can be the cause of a higher rate of HBV replication with less intensive liver damage and less effective immune response to HBV. Many HIV-infected patients have an elevated level of circulating immune complexes (CIC) in serum, throughout all stages of illness evolution. The aim of our study was to estimate p24 and HBsAg content of CIC in dually infected patients, and the prevalence of major classes of complexed antibodies (IgM and IgG). We examined 146 samples of sera from 105 HIV positive patients of the Institute for Infectious and Tropical Diseases during 1992 and 1993. On those sera we performed p24Ag and HbsAg detection, with and without prior dissociation of CIC, we determined serum level of CIC and immunoglobulin classes IgM and IgG level in sera and in polyethilenglycol (PEG) precipitates of sera. Acid dissociation of immune complexes revealed a high proportion of HIV antigen positive sera in all stages of HIV disease progression. HbsAg in serum of HIV positive patients was also found coupled in immune complexes much more frequently than in the HIV negative control group. In many instances both antigens were simultaneously found coupled in CIC. Immune complexes detected have been shown to contain both IgM and IgG immunoglobulins, while IgM antibodies were associated to immune complexes in higher proportion than IgG, compared to total serum immunoglobulins.

AIDS-Related Complex↗

PubMed2003

The Mtr2-Mex67 NTF2-like domain complex. Structural insights into a dual role of Mtr2 for yeast nuclear export.

The formation of the Mtr2-Mex67 heterodimer is essential for yeast mRNA export as it constitutes a key nuclear component for shuttling mRNA between the nuclear and cytoplasm compartments through the nuclear pore complex. We report the crystal structures of apo-Mtr2 from the human pathogen Candida albicans and of its complex with the Mex67 NTF2-like domain. Compared with other members of the NTF2 fold family, Mtr2 displays novel structural features involved in the nuclear export of the large ribosomal subunit and consistent with a dual functional role of Mtr2 during yeast nuclear export events. The structure of the Mtr2-Mex67 NTF2-like domain complex, which overall is similar to those of the human and Saccharomyces cerevisiae homologs, unveils three putative Phe-Gly repeat binding sites, of which one contributes to the heterodimer interface. These structures exemplify an unrecognized adaptability of the NTF2 building block in evolution, identify novel structural determinants associated with key biological functions at the molecular surface of the yeast Mtr2-Mex67 complex, and suggest that the yeast and human mRNA export machineries may differ.

Active Transport, Cell Nucleus↗

PubMed2005

Seminal reservoirs during an HIV type 1 eradication trial.

Despite dramatic reduction of the levels of human immunodeficiency virus type I (HIV-1) virions in blood and seminal plasma of infected patients, highly active antiretroviral therapy (HAART) does not eradicate HIV-1. Three patients, with less than 50 copies/ml of plasma viral RNA, were enrolled in this eradication protocol. Didanosine (DDI) and hydroxyurea (HU) were added to their baseline HAART and after a month of therapy, low dose OKT3, followed by a 2-week course of interleukin 2 (IL-2), was administrated. All antiretroviral therapy was then interrupted and the three patients developed viral rebound in the peripheral blood. The V3 loop region of the HIV-1 gp120 from cell-free viral RNA and proviral DNA in blood and seminal compartments was sequenced in one patient. The two major viral isolates in semen cells were macrophage- tropic (R5) and dual-tropic (R5X4), and these isolates were also present in the PBMCs. Six months after the viral rebound, we demonstrated a shift toward dual tropism in semen cell-associated HIV-1 proviral DNA, with the first appearance of a T-lymphotropic (X4) provirus solely in this compartment. The virus responsible for the blood plasma viral rebound was never found in the semen microenvironment. This study suggests viral compartmentalization of the semen microenvironment after an intensification and stimulatory HIV-1 eradication protocol, with evidence of viral evolution.

Amino Acid Sequence↗

PubMed2005

Failed central nervous system regeneration: a downside of immune privilege?

Immunity is required to eliminate dangerous or degenerated material and to support regeneration, but also causes significant parenchymal damage. In the eye and the brain, in which cornea and lens poorly regenerate and neurons are hardly replaceable, early transplantation experiments demonstrated remarkable tolerance to various grafts. This "immunologically privileged status" (Billingham and Boswell, 1953) may reflect evolutionary pressure to downmodulate certain actions of immune cells within particularly vulnerable tissues. As an example, tolerating certain "neurotrophic" viruses may often be a more successful strategy for survival than the elimination of all infected neurons. While several constitutive and inducible signals maintaining or re-establishing immune tolerance within the brain have been identified, it has also become evident that the resulting anti-inflammatory environment limits certain beneficial effects of neuroinflammation such as neurotrophin secretion or glutamate buffering by T-cells and the clearance of growth-inhibiting myelin or amyloid. Following spinal cord injury, the costs and benefits of neuroinflammation seem to come close because enhancing as well as suppressing innate or adaptive immunity caused amelioration and aggravation of functional regeneration in similar experiments. Evaluating such balances has also begun in (animal models of) Alzheimer's disease, central nervous system trauma, and stroke, and the appreciation of the beneficial side of neuroinflammation has caused a rethinking of the ill-defined use of immune suppressants. As dual roles for individual molecules have been recognized (Merrill and Benveniste, 1996), we are uncovering an already fine-tuned system, but the challenge remains to further support beneficial immune cascades without causing additional damage, and vice versa.

Animals↗

PubMed2026

Advances in CRISPR Base Editing: From Molecular Evolution to Therapeutic Applications in Genomic Medicine.

CRISPR-Cas9 systems revolutionized gene editing, but inherent drawbacks, namely DNA double-strand breaks (DSBs) and the difficulty of achieving precise repairs (due to low HDR efficiency), led researchers to invent new, more accurate gene editing tools. Base editing represents a significant leap forward, enabling targeted single-nucleotide conversions directly on the DNA without DSBs or donor templates. The core technology involves fusing catalytically dead or nickase Cas proteins to DNA deaminase enzymes. Cytosine base editors (CBEs) convert C•G to T•A pairs, while adenine base editors (ABEs) change A•T to G•C. These editors exploit the deaminase function within the R-loop structure formed by Cas binding and co-opt endogenous DNA repair mechanisms for precision. While offering improved efficiency and editing precision, base editing faces persistent challenges, such as off-target effects, bystander edits, delivery and ethical concerns. Continuous engineering efforts have refined these tools, enhancing accuracy, expanding targetability and reducing unwanted edits. The base editing arsenal has also broadened to include C-to-G base editors (CGBEs), dual A&C editors and versions targeting organelles. Successful preclinical studies demonstrating the correction of mutations responsible for the disease have paved the way for clinical trials, which are now testing therapies for conditions like sickle cell disease, β-thalassaemia and hypercholesterolemia using various delivery systems. This review explores CRISPR base editing's origins, mechanisms of action, potential therapies and current restrictions, pointing to its broadening impact on medical genetics.

Humans↗

PubMed2002

Cardiomyoplasty: ventricular reconstruction after tumor resection.

OBJECTIVE: Although cardiac transplantation has been performed for complete removal of ventricular tumors, complete surgical resection with ventricular reconstruction is desirable. Thus patients with benign tumors would probably be cured, and those with malignant tumors would have a better prognosis. In this study extensive and complete surgical resection of ventricular tumors is followed by anatomic and functional ventricular reconstruction with a dynamic cardiomyoplasty procedure. METHODS: Seven patients (mean age, 32.7 years) underwent complete resection of ventricular tumors. Histologic types were distributed as follows: fibroma in 2 patients and sarcoma, lymphosarcoma, hemangioma, lipoma, and metastatic angiosarcoma, respectively, in the remaining 5 patients. Six of the patients were considered candidates for heart transplantation because of the extent of tumor invasion. Surgery consisted of 4 steps: (1) tumor resection; (2) coronary artery resection (when invaded by the tumor) and coronary artery bypass grafting; (3) valvular reconstruction (when possible) or replacement; and (4) ventricular wall reconstruction with a pericardial patch for closure of the ventricular defect (neoendocardium) covered by the electrostimulated latissimus dorsi muscle flap (neomyocardium). RESULTS: All patients survived surgical intervention, but 2 late postoperative deaths are reported. Among the surviving patients, early complications played a major role in their postoperative course and consisted of arrhythmias, atrioventricular block necessitating a dual-chamber pulse generator, respiratory insufficiency, and heart failure. Two patients were assisted postoperatively with an intra-aortic balloon pump. On postoperative follow-up (mean, 72.4 +/- 8.5 months), an improvement in the patients' functional status was observed. Patients moved from a mean New York Heart Association functional class of 2.8 to a mean functional class of 1.2. CONCLUSIONS: The excellent long-term evolution without recurrence, ventricular dysfunction, and/or thromboembolic complications implies that cardiomyoplasty could be recommended as an alternative to heart transplantation for the therapy of large ventricular tumors.

Adult↗

PubMed2026

The proteomic origin of the genetic code.

INTRODUCTION: The origin and evolution of the genetic code is a central problem in molecular biology. Classical models have emphasized stereochemistry, frozen accidents, or adaptive optimization, often treating proteins as passive products of preexisting codes. More recent views instead portray the code as a dynamic, coevolving system shaped by reciprocal interactions among amino acids, RNA, and early catalysts. AREAS COVERED: Here, I review efforts of phylogeny reconstruction of the history of tRNA, protein structural domains, and dipeptide sequences in proteomes. These complementary approaches allow exploration of the entry of amino acids and codons into the code, and the transition from an operational RNA code in the tRNA acceptor arm to the canonical code in the anticodon loop. Evidence for ancestral synthetase enzymes with dual functions in aminoacylation and peptide-bond formation, as well as early bidirectional (sense-antisense) coding reflected in dipeptide-antidipeptide emergence is also discussed. EXPERT OPINION: The genetic code is best viewed as a proteome-driven, evolvable system in which early peptides actively shaped coding rules by stabilizing structure, expanding chemical diversity, and enhancing catalysis. This perspective connects origin-of-life studies with modern efforts of code expansion, translational engineering, and peptide-based therapeutics, highlighting the impact of the code's proteomic origin.

Genetic Code↗

PubMed2001

Evolutionary analysis of vertebrate Notch genes.

We have conducted an evolutionary analysis of Notch genes of the vertebrates Danio rerio and Mus musculus to examine the expansion and diversification of the Notch family during vertebrate evolution. The existence of multiple Notch genes in vertebrate genomes suggests that the increase in Notch signaling pathways may be necessary for the additional complexity observed in the vertebrate body plan. However, orthology relationships within the vertebrate Notch family indicate that biological functions are not fixed within orthologous groups. Phylogenetic reconstruction of the vertebrate Notch family suggests that the zebrafish notch1a and 1b genes resulted from a duplication occurring around the time of the teleost/mammalian divergence. There is also evidence that the mouse Notch4 gene is the result of a rapid divergence from a Notch3-like gene. Investigation of the ankyrin repeat region sequences showed there to be little evidence for gene conversion events between repeat units. However, relationships between repeats 2-5 suggest that these repeats are the result of a tandem duplication of a dual repeat unit. Selective pressure on maintenance of ankyrin repeat sequences indicated by relationships between the repeats suggests that specific repeats are responsible for particular biological activities, a finding consistent with mutational studies of the Caenorhabditis elegans gene glp-1. Sequence similarities between the ankyrin repeats and the region immediately C-terminal of the repeats further suggests that this region may be involved in the modulation of ankyrin repeat function.

Amino Acid Sequence↗

PubMed2006

Viral evolution in macaques coinfected with CCR5- and CXCR4-tropic SHIVs in the presence or absence of vaccine-elicited anti-CCR5 SHIV neutralizing antibodies.

Macaques were immunized with SF162 Env-based gp140 immunogens and challenged simultaneously with the CCR5-tropic homologous SHIV(SF162P4) and the CXCR4-tropic heterologous SHIV(SF33A) viruses. Both mock-immunized and immunized animals became dually infected. Prior immunization preferentially reduced the viral replication of the homologous virus during primary infection but the relative replication of the two coinfecting viruses during chronic infection was unaffected by prior immunization, despite the fact that five of six immunized animals maintained a significantly lower overall viral replication that the control animals. Neutralizing antibodies participated in controlling the replication of SHIV(SF162P4), but not that of SHIV(SF33A). Dual infection resulted in the emergence and predominance within the circulating CCR5 virus pool, of a variant with a distinct neutralization phenotype. The signature of this variant was the presence of three amino acid changes in gp120, two of which were located in the receptor and coreceptor binding sites. Also, a significant fraction of the viruses circulating in the blood, as early as two weeks post-infection, was recombinants and prior immunization did not prevent their emergence. These findings provide new insights into the dynamic interaction of CCR5- and CXCR4-tropic HIV isolates that are potentially relevant in better understanding HIV-mediated pathogenesis.

AIDS Vaccines↗