Showing papers by "New York Blood Center published in 2009"
TL;DR: Recent advances in the development of vaccines and therapeutics based on the S protein are highlighted, which plays key parts in the induction of neutralizing-antibody and T-cell responses, as well as protective immunity, during infection with SARS-CoV.
Abstract: Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease caused by a novel coronavirus, SARS-coronavirus (SARS-CoV). The SARS-CoV spike (S) protein is composed of two subunits; the S1 subunit contains a receptor-binding domain that engages with the host cell receptor angiotensin-converting enzyme 2 and the S2 subunit mediates fusion between the viral and host cell membranes. The S protein plays key parts in the induction of neutralizing-antibody and T-cell responses, as well as protective immunity, during infection with SARS-CoV. In this Review, we highlight recent advances in the development of vaccines and therapeutics based on the S protein.
1,404 citations
TL;DR: It is found that the accumulation of all of the major transmembrane and all skeletal proteins of the mature red blood cell, except actin, accrued progressively during terminal erythroid differentiation, and accumulation of various adhesion molecules decreased.
Abstract: Erythropoiesis is the process by which nucleated erythroid progenitors proliferate and differentiate to generate, every second, millions of nonnucleated red cells with their unique discoid shape and membrane material properties. Here we examined the time course of appearance of individual membrane protein components during murine erythropoiesis to throw new light on our understanding of the evolution of the unique features of the red cell membrane. We found that the accumulation of all of the major transmembrane and all skeletal proteins of the mature red blood cell, except actin, accrued progressively during terminal erythroid differentiation. At the same time, and in marked contrast, accumulation of various adhesion molecules decreased. In particular, the adhesion molecule, CD44 exhibited a progressive and dramatic decrease from proerythroblast to reticulocyte; this enabled us to devise a new strategy for distinguishing unambiguously between erythroblasts at successive developmental stages. These findings provide unique insights into the genesis of red cell membrane function during erythroblast differentiation and also offer a means of defining stage-specific defects in erythroid maturation in inherited and acquired red cell disorders and in bone marrow failure syndromes.
452 citations
TL;DR: It is suggested that thrombopoietic agents in patients with ITP have profound effects to restore immune tolerance, either directly or indirectly by enhanced release of TGF-β1 as a result of greater platelet turnover.
259 citations
TL;DR: Findings indicate that HIV-uninfected MSM with CSA histories are at greater risk for HIV infection, report higher rates of HIV sexual risk behavior, and may derive less benefit from prevention programs.
Abstract: BACKGROUND:: Previous studies have found high rates of childhood sexual abuse (CSA) among US men who have sex with men (MSM). CSA history has been associated with a variety of negative effects later in life including behaviors that place MSM at greater risk for HIV acquisition and transmission. The present analysis is the first to examine the longitudinal association between CSA and HIV infection, unprotected anal sex, and serodiscordant unprotected anal sex, as well as mediators of these relationships among a large sample of HIV-uninfected MSM. METHODS:: The EXPLORE Study was a behavioral intervention trial conducted in 6 US cities over 48 months with HIV infection as the primary efficacy outcome. Behavioral assessments were done every 6 months via confidential computerized assessments. Longitudinal regression models were constructed, adjusting for randomization arm, geographical location of study site, age at enrollment, education, and race/ethnicity. RESULTS:: Of the 4295 participants enrolled, 39.7% had a history of CSA. Participants with a history of CSA [adjusted hazards ratio = 1.30, 95% confidence interval (CI): 1.02 to 1.69] were at increased risk for HIV infection over study follow-up. A significant association was seen between history of CSA and unprotected anal sex (adjusted odds ratio = 1.24, 95% CI: 1.12 to 1.36) and serodiscordant unprotected anal sex (adjusted odds ratio = 1.30, 95% CI: 1.18 to 1.43). Among participants reporting CSA, the EXPLORE intervention had no effect in reducing HIV infection rates. Participants reporting CSA were significantly more likely to have symptoms of depression and use nonprescription drugs. CONCLUSIONS:: A predictive relationship between a history of CSA and subsequent HIV infection was observed among this large sample of HIV-uninfected MSM. Findings indicate that HIV-uninfected MSM with CSA histories are at greater risk for HIV infection, report higher rates of HIV sexual risk behavior, and may derive less benefit from prevention programs. Future HIV prevention interventions should address the specific mental health concerns of MSM with a history of CSA. Language: en
237 citations
TL;DR: The required relocation of part of the band 3 population to the spectrin/actin junctional complex and its formation of a new bridge with adducin necessitates a significant revision of accepted models of the erythrocyte membrane.
138 citations
TL;DR: The EXPLORE study examined depressive symptoms, utilization of mental health care, substance use and HIV risk taking behaviors in YMSM aged 16–25 years compared with their older counterparts, suggesting the need for more appropriate and accessible mental health health care and substance use services for this population.
Abstract: The EXPLORE study evaluated a behavioral intervention to prevent HIV infection among MSM. We examined depressive symptoms, utilization of mental health care, substance use and HIV risk taking behaviors in YMSM aged 16–25 years compared with their older counterparts. YMSM were more likely to report depressive symptoms (OR = 1.55) and less likely to report use of counseling (OR = 0.39) or medication (OR = 0.20) for psychiatric conditions. YMSM were more likely to report heavy alcohol and drug use. YMSM more often reported engaging in unprotected insertive (OR = 1.60) and receptive (OR = 2.07) anal intercourse with presumed HIV-uninfected partners, and unprotected receptive (OR = 1.72) anal intercourse with partners of unknown-HIV status. These findings suggest the need for more appropriate and accessible mental health care and substance use services for YMSM. Additionally, HIV prevention work with this population should provide comprehensive education about HIV testing and risk reduction counseling that focuses on communication about serostatus and safety in sexual situations.
130 citations
TL;DR: It is suggested that all three rRBDs are effective in eliciting immune responses and protection against SARS-CoV and any of the above expression systems can be used for production of rR BD-based SARS subunit vaccines.
123 citations
TL;DR: Fifteen 2-aryl 5-(4-oxo-3-phenethyl-2-thioxothiazolidinylidenemethyl)furans were synthesized by Suzuki-Miyaura cross-coupling followed by a Knoevenagel condensation and tested for their anti-HIV-1 activity and cytotoxicity on MT-2 cells, suggesting that these compounds can serve as leads for development of novel small molecule HIV fusion inhibitors.
Abstract: We previously identified two small molecules targeting the HIV-1 gp41, N-(4-carboxy-3-hydroxy)phenyl-2,5-dimethylpyrrole 12 (NB-2) and N-(3-carboxy-4-chloro)phenylpyrrole 13 (NB-64), that inhibit HIV-1 infection at low micromolar levels. On the basis of molecular docking analysis, we designed a series of 2-aryl 5-(4-oxo-3-phenethyl-2-thioxothiazolidinylidenemethyl)furans. Compared with 12 and 13, these compounds have bigger molecular size (437-515 Da) and could occupy more space in the deep hydrophobic pocket on the gp41 NHR trimer. Fifteen 2-aryl 5-(4-oxo-3-phenethyl-2-thioxothiazolidinylidenemethyl)furans (11a-o) were synthesized by Suzuki-Miyaura cross-coupling followed by a Knoevenagel condensation and tested for their anti-HIV-1 activity and cytotoxicity on MT-2 cells. We found that all 15 compounds had improved anti-HIV-1 activity and 3 of them (11a, 11b, and 11d) exhibited inhibitory activity against replication of HIV-1(IIIB) and 94UG103 at <100 nM range, more than 20-fold more potent than 12 and 13, suggesting that these compounds can serve as leads for development of novel small molecule HIV fusion inhibitors.
100 citations
TL;DR: Genomes of the major helminth species that affect humans, and many others of agricultural and veterinary significance, are now the subject of intensive genome sequencing and annotation, and the potential impact and importance of these new findings are presented.
Abstract: More than two billion people (one-third of humanity) are infected with parasitic roundworms or flatworms, collectively known as helminth parasites. These infections cause diseases that are responsible for enormous levels of morbidity and mortality, delays in the physical development of children, loss of productivity among the workforce, and maintenance of poverty. Genomes of the major helminth species that affect humans, and many others of agricultural and veterinary significance, are now the subject of intensive genome sequencing and annotation. Draft genome sequences of the filarial worm Brugia malayi and two of the human schistosomes, Schistosoma japonicum and S. mansoni, are now available, among others. These genome data will provide the basis for a comprehensive understanding of the molecular mechanisms involved in helminth nutrition and metabolism, host-dependent development and maturation, immune evasion, and evolution. They are likely also to predict new potential vaccine candidates and drug targets. In this review, we present an overview of these efforts and emphasize the potential impact and importance of these new findings.
96 citations
TL;DR: There is a strong association between use of alcohol and noninjecting substances, including methamphetamines, amyl nitrates, cocaine, and other drugs, and HIV-infection risk, which underscores the need for a comprehensive HIV prevention strategy that addresses substance use, including screening and behavioral intervention, among those at risk.
Abstract: Purpose of review Alcohol and noninjection drug use has been shown to be associated with increased risk of HIV infection in select populations. In this review, we discuss recent data on the prevalence of alcohol and noninjection drug use and the relationship to HIV acquisition and transmission risk. Recent findings A strong association between alcohol use and HIV-infection risk has been demonstrated in multiple studies conducted in sub-Saharan Africa. Among men who have sex with men in the USA as well as other countries, substance use is highly prevalent and has been associated with high-risk sexual behavior. Substance use, mental health problems, and sexual risk behaviors conjoin in what is known as a syndemic to increase HIV risk among young men who have sex with men. Only a limited number of intervention studies provide promising results in reducing HIV-infection risk among substance users. Summary Alcohol and noninjection drug use is prevalent in certain populations. There is a strong association between use of alcohol and noninjecting substances, including methamphetamines, amyl nitrates, cocaine, and other drugs, and HIV-infection risk. This underscores the need for a comprehensive HIV prevention strategy that addresses substance use, including screening and behavioral intervention, among those at risk.
86 citations
TL;DR: The results suggest that Pf332 both modulates the level of increased RBC rigidity induced by P falciparum and plays a significant role in adhesion by assisting transport of PfEMP1 to the iRBC surface.
TL;DR: The committee met in Macao Special Administrative Region,China, during the 2008 International Society of Blood Trans-fusion (ISBT) Congress and agreed some changes to the classification documented in Blood Group Terminology 2004.
Abstract: The committee met in Macao Special Administrative Region,China, during the 2008 International Society of Blood Trans-fusion (ISBT) Congress. Some changes to the classificationdocumented in Blood Group Terminology 2004 [1] and updatedin 2007 [2] were agreed and are described below. The fullupdated classification can be found on the blood groupterminology website at http://www.blood.co.uk/ibgrl. A newblood group system, the RHAG system, was established andnew antigens were added to the Rh, Kell, and Dombrocksystems (Table 1). A total of 308 antigens are now recognized,270 of which are clustered in 30 blood group systems.
TL;DR: A brief look at public CB banking highlights aspects of its current status to suggest that accomplishing the currently required tasks, though no small undertaking, is not enough: much remains to be contributed.
Abstract: Cord blood (CB) stem and progenitor cells from related donors have been transplanted for past 20 years and from unrelated donors issued by public CB banks for 16 years. This brief look at public CB banking highlights aspects of its current status to suggest that accomplishing the currently required tasks, though no small undertaking, is not enough: much remains to be contributed. CB banking started in the 1930s, collecting blood for transfusion and showed that CB could be effectively collected, stored and administered intravenously without negative consequences. The realization that it contains hematopoietic 'stem' cells (actually, colony-forming units) followed discoveries elsewhere in hematopoiesis research, while HLA and unrelated BMT were being investigated. Progress in the exploration of ethnically stratified HLA allele frequencies, together with plausible neonatal (partial) immunological tolerance, seemed to predict initially frequent, unavoidable, but sufficiently tolerable HLA mismatching with CB grafts. Gluckman et al. and Boyse et al. proved that HLA-identical sibling CB grafts led to definitive engraftment. Technical developments in processing and freezing enabled public banks to accumulate large inventories and to supply grafts that could succeed despite major HLA incompatibility and low cell doses and provide hope for universal access to unrelated-donor transplantation. Public CB banking has thrived worldwide. Regulation and accreditation defined Good Tissue Practice in the CB banking environment and provided accepted do's, don't's and how to's. Startling advances continue to be made, not only technical, but including the description of molecular regulation in the function of natural killer and other cells involved in allogeneic recognition that will have dramatic effects and will permit further improvement in CB selection and use.
TL;DR: An overview of the most current information on the key regulatory components in fat biology is provided, synthesize the diverse literature, pose new questions, and propose a new model organism for understanding fat biology using KLFs as the central theme.
Abstract: In mammals, adipose tissue stores energy in the form of fat The ability to regulate fat storage is essential for the growth, development and reproduction of most animals, thus any abnormalities caused by excess fat accumulation can result in pathological conditions which are linked to several interrelated diseases, such as cardiovascular diseases, dia- betes, and obesity In recent years significant effort has been applied to understand basic mechanism of fat accumulation in mammalian system Work in mouse has shown that the family of Kruppel-like factors (KLFs), a conserved and important class of transcrip- tion factors, regulates adipocyte differentiation in mammals However, how fat storage is coordinated in response to positive and negative feedback signals is still poorly under- stood To address mechanisms underlying fat storage we have studied two Caenorhabdi- tis elegans KLFs and demonstrate that both worm klfs are key regulators of fat metabo- lism in C elegans These results provide the first in vivo evidence supporting essential regulatory roles for KLFs in fat metabolism in C elegans and shed light on the human counterpart in disease-gene association This finding allows us to pursue a more com- prehensive approach to understand fat biology and provides an opportunity to learn about the cascade of events that regulate KLF activation, repression and interaction with other factors in exerting its biological function at an organismal level In this review, we provide an overview of the most current information on the key regulatory components in fat biology, synthesize the diverse literature, pose new questions, and propose a new model organism for understanding fat biology using KLFs as the central theme
TL;DR: These studies suggest that these filarial cathepsin-like cysteine proteases are likely to be functional orthologs of the C. elegans genes, and functional conservation may allow for a more thorough investigation of their distinct functions and their development as potential drug targets.
Abstract: Background
Cathepsin-like enzymes have been identified as potential targets for drug or vaccine development in many parasites, as their functions appear to be essential in a variety of important biological processes within the host, such as molting, cuticle remodeling, embryogenesis, feeding and immune evasion. Functional analysis of Caenorhabditis elegans cathepsin L (Ce-cpl-1) and cathepsin Z (Ce-cpz-1) has established that both genes are required for early embryogenesis, with Ce-cpl-1 having a role in regulating in part the processing of yolk proteins. Ce-cpz-1 also has an important role during molting.
Methods and Findings
RNA interference assays have allowed us to verify whether the functions of the orthologous filarial genes in Brugia malayi adult female worms are similar. Treatment of B. malayi adult female worms with Bm-cpl-1, Bm-cpl-5, which belong to group Ia of the filarial cpl gene family, or Bm-cpz-1 dsRNA resulted in decreased numbers of secreted microfilariae in vitro. In addition, analysis of the intrauterine progeny of the Bm-cpl-5 or Bm- cpl Pro dsRNA- and siRNA treated worms revealed a clear disruption in the process of embryogenesis resulting in structural abnormalities in embryos and a varied differential development of embryonic stages.
Conclusions
Our studies suggest that these filarial cathepsin-like cysteine proteases are likely to be functional orthologs of the C. elegans genes. This functional conservation may thus allow for a more thorough investigation of their distinct functions and their development as potential drug targets.
TL;DR: Prevention interventions should focus on sexual assertiveness, especially for CSA and SV survivors, as well as targeting depression, especially among men.
Abstract: This study examined whether the Multifaceted Model of HIV Risk (MMOHR) would predict unprotected sex based on predictors including gender, childhood sexual abuse (CSA), sexual victimization (SV), depression, and sexual assertiveness for condom use. A community-based sample of 473 heterosexually active men and women, aged 18–46 years completed survey measures of model variables. Gender predicted several variables significantly. A separate model for women demonstrated excellent fit, while the model for men demonstrated reasonable fit. Multiple sample model testing supported the use of MMOHR in both men and women, while simultaneously highlighting areas of gender difference. Prevention interventions should focus on sexual assertiveness, especially for CSA and SV survivors, as well as targeting depression, especially among men.
TL;DR: Findings indicate that lung edema in SARS infection may be due at least in part to activation of PKC by SARS proteins, leading to decreasing levels and activity of ENaC at the apical surfaces of lung epithelial cells.
Abstract: Among the multiple organ disorders caused by the severe acute respiratory syndrome coronavirus (SARS-CoV), acute lung failure following atypical pneumonia is the most serious and often fatal event....
TL;DR: It is shown that modulation of medium tonicity in vitro regulates the secretion of AQP-1, thus showing that extracellular osmotic conditions can drive sorting of selected proteins by the exosomal pathway.
TL;DR: It is recommended that transplant centers give priority to GVH-O-mismatched units over other mismatches and avoid selecting R-O mismatches, if possible, and CB search algorithms should be modified to identify unidirectional mismatch.
TL;DR: HIV Combo detected nearly two thirds of acute HIV infections identified in this high-risk population by non-pooled HIV RNA assays, suggesting HIV Combo may be useful for high-throughput screening to identify individuals with acute HIV infection.
Abstract: Background:We evaluated use of the ARCHITECT HIV Ag/Ab Combo assay (HIV Combo; Abbott Diagnostics; available for sale outside the United States only) for detection of acute HIV infection.Methods:Samples were obtained from a behavioral intervention study (EXPLORE). HIV-uninfected men who have sex wit
TL;DR: The results of CB transplantation are comparable to those of bone marrow transplants with several important advantages: the graft is available ‘off the shelf’, thereby reducing the waiting time, and the requirements of human lecucoyte antigen (HLA) matching are less restrictive than those of adult sources.
Abstract: Summary
Transplantation of cord blood (CB) is increasingly used as therapy for patients whose own marrow is affected by genetic mutations that prevent the development of normal cells of the blood or immune tissues, or for patients whose marrow has been destroyed in the course of treatment for leukaemia and other malignancies. CB is a rich source of haematopoietic stem cells, can be easily harvested and stored in frozen aliquots in a CB bank. The first public CB bank was established in 1993 allowing unrelated CB transplantation to become an option for patients lacking a suitable adult donor. Today, the results of CB transplantation are comparable to those of bone marrow transplants with several important advantages: the graft is available ‘off the shelf’, thereby reducing the waiting time, and the requirements of human lecucoyte antigen (HLA) matching are less restrictive than those of adult sources. The reduced requirement for HLA matching allows transplants between incompletely matched donors and recipients, thus reducing the size of the inventory required at the national level. This also mitigates the disadvantage encountered by persons of rare HLA genotypes or those who do not belong to populations of North Western European descent. Finally, national CB programmes can easily make available for research individual surplus units not meeting minimal criteria for clinical use.
TL;DR: It is found that combinations of T20 with T1249 and/or T1144 resulted in exceptionally potent synergism against HIV-1-mediated membrane fusion by 2 to 3 orders of magnitude in dose reduction, suggesting a new therapeutic strategy for the treatment of HIV- 1 infection/AIDS.
Abstract: T20 (generic name, enfuvirtide; brand name, Fuzeon) is a first-generation human immunodeficiency virus (HIV) fusion inhibitor approved for salvage therapy of HIV-infected patients refractory to current antiretroviral drugs. However, its clinical use is limited because of rapid emergence of T20-resistant viruses in T20-treated patients. Therefore, T1249 and T1144 are being developed as the second- and third-generation HIV fusion inhibitors, respectively, with improved efficacy and drug resistance profiles. Here, we found that combinations of T20 with T1249 and/or T1144 resulted in exceptionally potent synergism (combination index, <0.01) against HIV-1-mediated membrane fusion by 2 to 3 orders of magnitude in dose reduction. Highly potent synergistic antiviral efficacy was also achieved against infection by laboratory-adapted and primary HIV-1 strains, including T20-resistant variants. The mechanism underlying the synergistic effect could be attributed to the fact that T20, T1249, and T1144 all contain different functional domains and have different primary binding sites in gp41. As such, they may work cooperatively to inhibit gp41 six-helix bundle core formation, thereby suppressing virus-cell fusion. Therefore, these findings strongly imply that, rather than replacing T20, combining it with HIV fusion inhibitors of different generations might produce synergistic activity against both T20-sensitive and -resistant HIV-1 strains, suggesting a new therapeutic strategy for the treatment of HIV-1 infection/AIDS.
TL;DR: Development and validation of culturally adapted measures of the transtheoretical model (TTM) constructs of Stage of Change, Decisional Balance, and Self-efficacy applied to blood donation in an African American sample provide support for use of the TTM applied toBlood donation.
Abstract: Despite a specific need for transfused blood among African Americans due to higher rates of sickle cell disease, African Americans donate blood significantly less frequently than their White counterparts. This study describes the development and validation of culturally adapted measures of the transtheoretical model (TTM) constructs of Stage of Change, Decisional Balance, and Self-efficacy applied to blood donation in an African American sample. Exploratory and confirmatory analyses produced one pros and two cons scales for the Decisional Balance Inventory, and one scale for the Situational Self-efficacy Measure. Expected patterns for the Decisional Balance and Self-efficacy Scales by Stage of Change were found, but only the pros and one cons scale varied significantly. Results provide support for use of the TTM applied to blood donation and have important implications for development of effective assessment and intervention tools to increase blood donation among the African American population.
TL;DR: It is suggested that the recombinant RBD produced in an established stable cell line maintains strong immunogenicity with high potential for use as an effective and economic subunit SARS vaccine.
TL;DR: Results suggest that ADS-J1 may bind to the viral gp41 NHR region through its hydrophobic and ionic interactions with the hydrophilic and positively charged resides located in the pocket region, subsequently blocking the association between the gp 41 NHR and CHR regions to form the fusion-active gp41 core, thereby inhibiting HIV-1-mediated membrane fusion and virus entry.
Abstract: We previously identified a small-molecule anti-human immunodeficiency virus type 1 (anti-HIV-1) compound, ADS-J1, using a computer-aided molecular docking technique for primary screening and a sandwich enzyme-linked immunosorbent assay (ELISA) as a secondary screening method. In the present study, we demonstrated that ADS-J1 is an HIV-1 entry inhibitor, as determined by a time-of-addition assay and an HIV-1-mediated cell fusion assay. Further mechanism studies confirmed that ADS-J1 does not block gp120-CD4 binding and exhibits a marginal interaction with the HIV-1 coreceptor CXCR4. However, ADS-J1 inhibited the fusion-active gp41 core formation mimicked by peptides derived from the viral gp41 N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR), as determined by ELISA, native polyacrylamide gel electrophoresis, and circular dichroism analysis. Moreover, using a surface plasmon resonance assay, we found that ADS-J1 could bind directly to IQN17, a trimeric peptide containing the gp41 pocket region, resulting in the conformational change of IQN17 and the blockage of its interaction with a short D peptide, PIE7. The positively charged residue (K574) located in the gp41 pocket region is critical for the binding of ADS-J1 to NHR. These results suggest that ADS-J1 may bind to the viral gp41 NHR region through its hydrophobic and ionic interactions with the hydrophobic and positively charged resides located in the pocket region, subsequently blocking the association between the gp41 NHR and CHR regions to form the fusion-active gp41 core, thereby inhibiting HIV-1-mediated membrane fusion and virus entry.
TL;DR: Red blood cell alloimmunization remains a major complication for transfusion-dependent patients, and the possibility that Treg activity may be used as a marker for identifying responder/nonresponder status in transfusion recipients is raised.
TL;DR: An important and previously unidentified role of 4.1R is demonstrated in linking the cadherin/ catenin complex to the cytoskeleton through its direct interaction with beta-catenin and in regulating the integrity of adherens junction.
TL;DR: Upregulation of protein translation and amino acid synthesis may indicate a generalized stress response induced in B. malayi due to a shortage of essential nutrients/factors that are otherwise supplied by Wolbachia.
Abstract: Background: Brugia malayi, like most human filarial parasite species, harbors an endosymbiotic bacterium of the genus Wolbachia. Elimination of the endosymbiont leads to sterilization of the adult female. Previous biochemical and genetic studies have established that communication with its endobacterium is essential for survival of the worm. Methodology/Principal findings: We used electron microscopy to examine the effects of antibiotic treatment on Wolbachia cell structure. We have also used microarray and quantitative RT-PCR analyses to examine the regulation of the B. malayi transcripts altered in response to the anti-Wolbachia treatment. Microscopy of worms taken from animals treated with tetracycline for 14 and 21 days (14 d and 21 d) demonstrated substantial morphologic effects on the Wolbachia endobacterium by 14 d and complete degeneration of the endobacterial structures by 21 d. We observed upregulation of transcripts primarily encoding proteins involved in amino acid synthesis and protein translation, and downregulation of transcripts involved in cuticle biosynthesis after both 7 d and 14 d of treatment. In worms exposed to tetracycline in culture, substantial effects on endobacteria morphology were evident by day 3, and extensive death of the endobacteria was observed by day 5. In a detailed examination of the expression kinetics of selected signaling genes carried out on such cultured worms, a bimodal pattern of regulation was observed. The selected genes were upregulated during the early phase of antibiotic treatment and quickly downregulated in the following days. These same genes were upregulated once more at 6 days post-treatment. Conclusions/Significance: Upregulation of protein translation and amino acid synthesis may indicate a generalized stress response induced in B. malayi due to a shortage of essential nutrients/factors that are otherwise supplied by Wolbachia. Downregulation of transcripts involved in cuticle biosynthesis perhaps reflects a disruption in the normal embryogenic program. This is confirmed by the expression pattern of transcripts that may be representative of the worms’ response to Wolbachia in different tissues; the early peak potentially reflects the effect of bacteria death on the embryogenic program while the second peak may be a manifestation of the adult worm response to the affected bacteria within the hypodermis. Citation: Ghedin E, Hailemariam T, DePasse JV, Zhang X, Oksov Y, et al. (2009) Brugia malayi Gene Expression in Response to the Targeting of the Wolbachia
TL;DR: A detailed characterization of a Babesia divergens homolog of AMA1 is presented, and it is shown that proteolytic products of native BdAMA1 bind to a trypsin- and chymotrypsIn-sensitive receptor on the red blood cell.
Abstract: Multiple parasite ligand-erythrocyte receptor interactions must occur for successful Babesia and Plasmodium invasion of the human red cell. One such parasite ligand is the apical membrane antigen 1 (AMA1) which is a conserved apicomplexan protein present in the micronemes and then secreted onto the surface of the merozoite. Much evidence exists for a vital role for AMA1 in host cell invasion; however, its interaction with the host erythrocyte has remained controversial. In this paper, we present a detailed characterization of a Babesia divergens homolog of AMA1 (BdAMA1), and taking advantage of the relatively high amounts of native BdAMA1 available from the parasite culture system, show that proteolytic products of native BdAMA1 bind to a trypsin- and chymotrypsin-sensitive receptor on the red blood cell. Moreover, immuno-electron microscopic images of the B. divergens merozoite captured during invasion offer additional evidence of the presence of BdAMA1 on the red cell membrane. Given the importance of AMA1 in invasion and the central role invasion plays in pathogenesis, these studies have implications both for novel drug design and for the development of new vaccine approaches aimed at interfering with AMA1 function.
TL;DR: This review will address efforts to optimize CBT from 3 different perspectives: that of the transplant center, the CBT registry, and the CB bank.