Type VI Collagen Deficiency Causes Enhanced Periodontal Tissue Destruction.

The periodontal ligament (PDL) is a fibrillar connective tissue that lies between the alveolar bone and the tooth and is composed of highly specialized extracellular matrix (ECM) molecules and a heterogeneous population of cells that are responsible for collagen formation, immune response, bone formation, and chewing force sensation. Type VI collagen (COL6), a widely distributed ECM molecule, plays a critical role in the structural integrity and mechanical properties of various tissues including muscle, tendon, bone, cartilage, and skin. However, its role in the PDL remains largely unknown. Our study shows that deficiency of COL6 impairs PDL fibrillogenesis and exacerbates tissue destruction in ligature-induced periodontitis (LIP). We found that COL6-deficient mice exhibited increased bone loss and degraded PDL in LIP and that fibroblasts expressing high levels of Col6α2 are pivotal in ECM organization and cell-ECM interactions. Moreover, COL6 deficiency in the PDL led to an increased number of fibroblasts geared toward the inflammatory response. We also observed that cultured COL6-deficient fibroblasts from the PDL exhibited decreased expression of genes related to collagen fiber turnover and ECM organization as well as migration and proliferation. Our findings suggest that COL6 plays a crucial role in the PDL, influencing fibroblast function in fibrillogenesis and affecting the immune response in periodontitis. These insights advance our understanding of the molecular mechanisms underlying PDL maturation and periodontal disease.

Characteristics of depressive disorders in patients with rheumatoid arthritis and some related factors.

OBJECTIVE: Rheumatoid arthritis (RA), a type of chronic arthritis, is common in Vietnam. It has severe consequences for patients, both physically and psychologically, including depressive disorders. Therefore, early detection of depressive disorders is of high importance to help provide comprehensive treatment and improve RA patients' quality of life. This cross-sectional study explored the prevalence of depressive disorders and their salient characteristics and related factors in RA patients in Vietnam. PATIENTS AND METHODS: We enrolled 156 patients diagnosed with RA using the ACR-1987 criteria. The Patient Health Questionnaire-9 (PHQ-9) was used to screen for depressive disorders. Patients' demographic characteristics and clinical and laboratory investigation results, such as the visual analog score, complete blood count, erythrocyte sedimentation rate, Disease Activity Score 28 for RA with C-reactive protein (DAS28-CRP), and quality-of-life score (based on the SF-36 test) were analyzed. Depressive disorders assessed on the first day of admission were reevaluated by a psychiatrist if the PHQ-9 score was ≥ 5. RESULTS: According to the PHQ-9 results, depression prevalence among RA patients was 76.3%. The majority of patients (49.4%) had moderate-to-severe depression and 91% experienced sleep disorder symptoms. Negative thoughts -- suicidal ideation or self-injury - were reported by 21.8% of patients. Depression severity had a moderately positive relationship with disease activity level and a moderately negative relationship with quality of life. CONCLUSIONS: Depression prevalence was high among RA patients. Depression severity increased with disease activity and decreased quality of life.

Safety and immunogenicity of the epicutaneous reactivation of pertussis toxin immunity in healthy adults: a phase I, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Protection induced by acellular vaccines can be short, requiring novel immunization strategies. Objectives of this study were to evaluate safety and capacity of a recombinant pertussis toxin (PTgen) -coated Viaskin® epicutaneous patch to recall memory responses in healthy adults. METHODS: This double-blind, placebo-controlled randomized trial (Phase I) assessed the safety and immunogenicity of PTgen administered on days 0 and 14 to healthy adults using Viaskin® patches applied directly or after epidermal laser-based skin preparation. Patch administration was followed by Boostrix®dTpa on day 42. Antibodies were assessed at days 0, 14, 28, 42 and 70. RESULTS: Among 102 volunteers enrolled, 80 received Viaskin-PT (Viaskin-PT 25 µg (n = 25), Viaskin-PT 50 µg (n = 25), laser + Viaskin-PT 25 µg (n = 5), laser + Viaskin-PT 50 µg (n = 25)), Viaskin-placebo (n = 10) or laser + Viaskin-placebo (n = 2). Incidence of adverse events was similar across groups (any local event: 21/25 (84.0%), 24/25 (96.0%), 4/5 (80.0%), 24/25 (96.0%), 8/10 (80.0%), 10/12 (83.0%), respectively). Direct application induced no detectable response. On day 42, PT-IgG geometric mean concentrations were significantly higher following laser + Viaskin-PT 25 µg and 50 µg (139.87 (95% CI 87.30-224.10) and 121.76 (95% CI 95.04-156.00), respectively), than laser + Viaskin-placebo (59.49, 95% CI 39.37-89.90). Seroresponse rates were higher following laser + Viaskin-PT 25 µg (4/5 (80.0%), 95% CI 28.4-99.5) and 50 µg (22/25 (88.0%), 95% CI 68.8-97.5) than laser + Viaskin-placebo (0/12 (0.0%), 95% CI 0.0-26.5). CONCLUSIONS: Viaskin-PT applied after laser-based epidermal skin preparation showed encouraging safety and immunogenicity results: anti-PT booster responses were not inferior to those elicited by Boostrix®dTpa. This study is registered at ClinicalTrials.gov (NCT03035370) and was funded by DBV Technologies.

Rapid and sensitive diagnostic procedure for multiple detection of pandemic Coronaviridae family members SARS-CoV-2, SARS-CoV, MERS-CoV and HCoV: a translational research and cooperation between the Phan Chau Trinh University in Vietnam and University of Bari "Aldo Moro" in Italy.

OBJECTIVE: A new pandemic coronavirus causing coronavirus disease-2019 (COVID-19), initially called 2019-nCoV and successively named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The COVID-19 refers to the disease while the SARS-CoV-2 refers to the virus and is characterized by a rapid contagious capacity able to spread worldwide in a very short time. The rise in the number of infected patients and deaths is of great concern especially because symptoms are vague and similar to other forms of flu infection and corona syndrome infections characterized by fever, fatigue, dry cough, and dyspnea. According to the latest guidelines published by the World Health Organization (WHO), the diagnosis of COVID-19 must be confirmed by quantitative reverse transcription polymerase chain reaction (rRT-PCR) or gene sequencing of specimen obtained from throat, sputum and blood samples. However, the limitations due to logistics, as well as low sensitivity and specificity diagnostic tools currently available have been reported as the main cause of high incidence of either false-negative or positive results. PATIENTS AND METHODS: The purpose of the present translational research protocol is to discuss and present the original findings from our research team on new diagnostic technique to detect four Coronaviridae family members (SARS-CoV-2, SARS-CoV, HCoV and MERS-CoV), highlighting the methodology, the procedure and the possible advantages. Moreover, the authors review the current epidemiology, precautions and safety measures for health personnel to manage patients with known or suspected COVID-19 infection. RESULTS: Implementation of an effective and rapid plan of diagnosing, screening and checking is a key factor to reduce and prevent further transmission. This procedure based on rRT-PCR could be of great help to decisively validate the results obtained from more conventional diagnostic procedures such as chest computed tomography (CT) imaging and chest ultrasound. CONCLUSIONS: This translational diagnostic tool will assist emergency and primary care clinicians, as well as out-of-hospital providers, in effectively managing people with suspected or confirmed SARS-CoV-2.

Cooperative improvement in growth rate, red-colour score and astaxanthin level of white-leg shrimp by Bacillus strains originating from shrimp gut.

AIMS: We investigated the potential cooperative effects of carotenoid-producing Bacillus aquimaris SH6 and nonpigmented Bacillus subtilis SH23 on white-leg shrimp growth and health. METHODS AND RESULTS: SH6, SH23 and a combination of both spores (1 × 106  CFU per g pellet) were administered in shrimp. The growth rate (2·36% day-1 ), red-colour score (25) and astaxanthin concentration (3·5 µg g-1 shrimp) were maximum in two-spore-administered shrimp. Immune-related Rho mRNA expression level and phenoloxidase and superoxidase dismutase activities were higher in two-spore-administered shrimp than in control shrimp, with Rho mRNA expression level being 55-fold higher in two-spore-administered shrimp than in SH6-administered shrimp and phenoloxidase activity being 1·2-fold higher in two-spore-administered shrimp than in SH23-administered shrimp. Although live SH6 count was 2·7-fold lower, SH6 germination level was 3·5-fold higher in the combination group than in SH6 group. CONCLUSIONS: When both SH6 and SH23 spores were administered, SH6 spore germination was enhanced and cooperative improvement was seen in growth, astaxanthin level and red-colour score of white-leg shrimp; however, immune-related parameters were induced in a noncooperative manner. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report showing the cooperative probiotic activities of Bacillus strains and their possible mechanisms in a shrimp model.

O-GlcNAcylation of STAT5 controls tyrosine phosphorylation and oncogenic transcription in STAT5-dependent malignancies.

The signal transducer and activator of transcription 5 (STAT5) regulates differentiation, survival, proliferation and transformation of hematopoietic cells. Upon cytokine stimulation, STAT5 tyrosine phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. Post-translational modifications might contribute to enhanced STAT5 activation in the context of transformation, but the strength and duration of pYSTAT5 are incompletely understood. We found that O-GlcNAcylation and tyrosine phosphorylation act together to trigger pYSTAT5 levels and oncogenic transcription in neoplastic cells. The expression of a mutated hyperactive gain-of-function (GOF) STAT5 without O-GlcNAcylation resulted in decreased tyrosine phosphorylation, oligomerization and transactivation potential and complete loss of oncogenic transformation capacity. The lack of O-GlcNAcylation diminished phospho-ERK and phospho-AKT levels. Our data show that O-GlcNAcylation of STAT5 is an important process that contributes to oncogenic transcription through enhanced STAT5 tyrosine phosphorylation and oligomerization driving myeloid transformation. O-GlcNAcylation of STAT5 could be required for nutrient sensing and metabolism of cancer cells.

Financial Impacts of Priority Swine Diseases to Pig Farmers in Red River and Mekong River Delta, Vietnam.

A study was conducted between May 2013 and August 2014 in three provinces of Vietnam to investigate financial impacts of swine diseases in pig holdings in 2010-2013. The aim of the study was to quantify the costs of swine diseases at producer level in order to understand swine disease priority for monitoring at local level. Financial impacts of porcine reproductive and respiratory syndrome (PRRS), foot and mouth disease (FMD), and epidemic diarrhoea were assessed for 162 pig holders in two Red River Delta provinces and in one Mekong River Delta province, using data on pig production and swine disease outbreaks at farms. Losses incurred by swine diseases were estimated, including direct losses due to mortality (100% market value of pig before disease onset) and morbidity (abortion, delay of finishing stage), and indirect losses due to control costs (treatment, improving biosecurity and emergency vaccination) and revenue foregone (lower price in case of emergency selling). Financial impacts of swine diseases were expressed as percentage of gross margin of pig holding. The gross margin varied between pig farming groups (P < 0.0001) in the following order: large farm (USD 18 846), fattening farm (USD 7014) and smallholder (USD 2350). The losses per pig holding due to PRRS were the highest: 41% of gross margin for large farm, 38% for fattening farm and 63% for smallholder. Cost incurred by FMD was lower with 19%, 25% and 32% of gross margin of pig holding in large farm, fattening farm and smallholder, respectively. The cost of epidemic diarrhoea was the lowest compared to losses due to PRRS and FMD and accounted for around 10% of gross margin of pig holding in the three pig farming groups. These estimates provided critical elements on swine disease priorities to better inform surveillance and control at both national and local level.

A Matched Case-Control Study of Risk Factors for Breast Cancer Risk in Vietnam.

Background. Vietnam has a low age-standardized incidence of breast cancer, but the incidence is rising rapidly with economic development. We report data from a matched case-control study of risk factors for breast cancer in the largest cancer hospital in Vietnam. Methods. 492 incident breast cancer cases unselected for family history or age at diagnosis and 1306 control women age 25-75 were recruited from the National Cancer Hospital (BVK), Hanoi. Structured interviews were conducted and pathology data was centrally reported at the National Cancer Hospital of Vietnam, in Hanoi. Results. Our analysis included 294 matched pairs. Mean age at diagnosis was 46.7 years. Lower mean parity, older age at first parity, increasing weight and BMI at age 18, and increasing BMI at diagnosis were positively correlated with breast cancer cases compared to controls. Age at first menarche and duration of breastfeeding were not statistically different between cases and controls. Conclusions. In this study we demonstrate that breast cancer in Vietnam is associated with some but not all of the published risk factors from Western populations. Our data is consistent with other studies of breast cancer in Asian populations.

Vibrio cholerae O1 El Tor from southern Vietnam in 2010 was molecularly distinct from that present from 1999 to 2004.

The Vibrio cholerae O1 (VCO1) El Tor biotype appeared during the seventh cholera pandemic starting in 1961, and new variants of this biotype have been identified since the early 1990s. This pandemic has affected Vietnam, and a large outbreak was reported in southern Vietnam in 2010. Pulsed-field gel electrophoresis (PFGE) and multilocus variable-number tandem-repeat analyses (MLVA) were used to screen 34 VCO1 isolates from the southern Vietnam 2010 outbreak (23 patients, five contact persons, and six environmental isolates) to determine if it was genetically distinct from 18 isolates from outbreaks in southern Vietnam from 1999 to 2004, and two isolates from northern Vietnam (2008). Twenty-seven MLVA types and seven PFGE patterns were identified. Both analyses showed that the 2008 and 2010 isolates were distinctly clustered and separated from the 1999-2004 isolates.

Mesenchymal stem/progenitor cell isolation from tooth extraction sockets.

Bone marrow-derived mesenchymal stem/progenitor cells (BMSCs) are commonly used in regeneration therapy. The current primary source of BMSCs is the iliac crest; however, the procedure is associated with various burdens on the patient, including the risk of pain and infection. Hence, the possibility to collect BMSCs from other, more accessible, sources would be an attractive approach. It is well known that stem cells migrate from surrounding tissues and play important roles in wound healing. We thus hypothesized that stem/progenitor cells could be isolated from granulation tissue in the dental socket, and we subsequently collected granulation tissue from dog dental socket 3 d after tooth extraction. After enzyme digestion of the collected tissue, the cells forming colonies constituted the dental socket-derived stem/progenitor cells (dDSCs). Next, dDSCs were compared with dog BMSCs (dBMSCs) for phenotype characterization. A flow cytometric analysis showed that dDSCs were positive for CD44, CD90, and CD271 but negative for CD34 and CD45, similar to dBMSCs. dDSCs also exhibited osteogenic, adipogenic, and chondrogenic differentiation ability, similar to dBMSCs, with a higher capacity for colony formation, proliferation, and motility than dBMSCs. In addition, an in vivo ectopic bone formation assay showed that dDSCs and dBMSCs both induced hard tissue formation, although only dDSCs formed a fibrous tissue-like structure connected to the newly formed bone. Finally, we tested the ability of dDSCs to regenerate periodontal tissue in a one-wall defect model. The defects in the dDSC-transplanted group (ß-TCP/PGA/dDSCs) were regenerated with cementum-like and periodontal ligament-like tissues and alveolar bone, whereas only bony tissue was observed in the control group (ß-TCP/PGA). In conclusion, we identified and characterized a population of stem/progenitor cells in granulation tissue obtained from the dental socket that exhibited several characteristics similar to those of BMSCs. Dental sockets could therefore be a novel source for isolating stem/progenitor cells from bone.

Bacillus thaonhiensis sp. nov., a new species, was isolated from the forest soil of Kyonggi University by using a modified culture method.

Using a new culture method for unculturable soil bacteria, we discovered a novel species, NHI-38(T), from the forest soil of Kyonggi University campus, South Korea. It was a Gram-positive, rod-shaped, and endospore-forming bacterial strain. It grew over a wide pH range (6.5-9.5), with an optimum range of pH 7-9, and in a wide range of temperatures (15-60 °C), with an optimum range of 35-45 °C. Growth was possible at 0-2 % NaCl concentration, and the optimal range was between 0.5 and 1.5 % NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that this new species clustered within the genus Bacillus; it was closely related to "Bacillus abyssalis" SCSIO 15042(T) (98.86 %), B. methanolicus NCIMB 13113(T) (95.97 %), B. vietnamensis 15-1(T) (95.8 %), B. seohaeanensis BH724(T) (95.5 %), B. timonensis MM10403188(T) (95.33 %), and B. subtilis subsp. subtilis NCIB 3610(T) (94.87 %). The main fatty acid components of this bacterium were iso-C15:0 (35.92 %), summed feature 3 (C16:1ω7c/C16:1ω6c; 16.92 %), and anteiso-C15:0 (14.19 %). The predominant quinone in this bacterial strain was MK-7. The polar lipid profile primarily comprised phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol. The genomic DNA G+C composition of the isolate was 40.7 mol%. The DNA-DNA hybridization results indicated that this strain was distinct from other Bacillus species, the degree of similarity being 50 % with "B. abyssalis", 56 % with B. methanolicus, 47 % with B. vietnamensis, 43 % with B. seohaeanensis, 46 % with B. timonensis, and 32 % with B. subtilis. Based on our results, we regard strain NHI-38(T) as a novel member of the Bacillus genus, and we propose the name Bacillus thaonhiensis (=KACC 17216(T) = KEMB 9005-019(T) = JCM 18863(T)).

Female black flies of Simulium (Diptera: Simuliidae) collected on humans in Tam Dao National Park, Vietnam: description of a new species and notes on four species newly recorded from Vietnam.

A total of 29 female black flies were captured by a hand net as they swarmed around humans in Tam Dao National Park, Vinh Phuc Province, Vietnam. They included one species of the subgenus Gomphostilbia (Simulium (Gomphostilbia) asakoae Takaoka & Davies) and five species of the subgenus Simulium, of which one species is described as Simulium (Simulium) vietnamense sp. nov. and the other four species (S. (S.) chungi Takaoka & Huang, S. (S.) grossifilum Takaoka & Davies, S. (S.) maenoi Takaoka & Choochote, and S. (S.) rufibasis Brunetti) are newly recorded from Vietnam.

Clinical dyslipidaemia is associated with changes in the lipid composition and inflammatory properties of apolipoprotein-B-containing lipoproteins from women with type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to use lipidomics to determine if the lipid composition of apolipoprotein-B-containing lipoproteins is modified by dyslipidaemia in type 2 diabetes and if any of the identified changes potentially have biological relevance in the pathophysiology of type 2 diabetes. METHODS: VLDL and LDL from normolipidaemic and dyslipidaemic type 2 diabetic women and controls were isolated and quantified with HPLC and mass spectrometry. A detailed molecular characterisation of VLDL triacylglycerols (TAG) was also performed using the novel ozone-induced dissociation method, which allowed us to distinguish vaccenic acid (C18:1 n-7) from oleic acid (C18:1 n-9) in specific TAG species. RESULTS: Lipid class composition was very similar in VLDL and LDL from normolipidaemic type 2 diabetic and control participants. By contrast, dyslipidaemia was associated with significant changes in both lipid classes (e.g. increased diacylglycerols) and lipid species (e.g. increased C16:1 and C20:3 in phosphatidylcholine and cholesteryl ester and increased C16:0 [palmitic acid] and vaccenic acid in TAG). Levels of palmitic acid in VLDL and LDL TAG correlated with insulin resistance, and VLDL TAG enriched in palmitic acid promoted increased secretion of proinflammatory mediators from human smooth muscle cells. CONCLUSIONS: We showed that dyslipidaemia is associated with major changes in both lipid class and lipid species composition in VLDL and LDL from women with type 2 diabetes. In addition, we identified specific molecular lipid species that both correlate with clinical variables and are proinflammatory. Our study thus shows the potential of advanced lipidomic methods to further understand the pathophysiology of type 2 diabetes.

Design of a Bézier-profile horn for high displacement amplification.

A new horn for high displacement amplification is developed. The profile of the horn is a cubic Bézier curve. The ultrasonic actuation of the horn exploits the first longitudinal displacement mode of the horn. A design method of the horn using an optimization scheme and finite element analyses is developed. Prototypes of the horns are manufactured by a numerical control machining process. Performances of the proposed horn have been evaluated by experiments. Experimental results of the harmonic response of the fabricated horn confirm the effectiveness of the design method. The displacement amplification of the proposed horn is 71% higher than that of the traditional catenoidal horn with the same length and end surface diameters.

Mixed motion in deterministic ratchets due to anisotropic permeability.

Nowadays microfluidic devices are becoming popular for cell/DNA sorting and fractionation. One class of these devices, namely deterministic ratchets, seems most promising for continuous fractionation applications of suspensions (Kulrattanarak et al., 2008 [1]). Next to the two main types of particle behavior, zigzag and displacement motion as noted by the inventors (Huang et al., 2004 [2]) and (Inglis et al., 2006 [3]), we have shown recently the existence of a intermediate particle behavior, which we named 'mixed motion'. In this paper we formulate the hypothesis that the occurrence of mixed motion is correlated with anisotropy in the permeability of the obstacle array. This hypothesis we base on the comparison of experimental observations of mixed motion and the flow lane distribution as obtained from 2-D flow simulations.

Health-seeking behaviour for sexually transmitted infections and HIV testing among female sex workers in Vietnam.

This qualitative study was conducted to explore health-seeking behaviour for sexually transmitted infections (STIs) and HIV testing among female sex workers (FSWs) in the cities of Hanoi and Da Nang, Vietnam. Data were gathered from in-depth interviews, focus groups and participant observation. Results suggest that women's decision to seek STI treatment and HIV testing is influenced by the complex interplay of personal risk perceptions, social relationships and community discourse. The women exhibited adequate knowledge of HIV while their knowledge of STIs was limited. They demonstrated high-risk perceptions of HIV, but they showed little concern for STIs. Most women sought treatment at pharmacies when they noticed symptoms of the genital tract. Their decision to seek care in health facilities and HIV testing was hampered by the high costs of treatment, judgmental attitudes of service providers, and a lack of information on testing services. Future interventions need to focus on strengthening knowledge of STIs and the STI-HIV association, and increasing awareness of HIV counselling and testing services. Training for STI service providers including pharmacies and private practitioners on sex-worker friendly and non-judgmental services and counselling skills should be emphasized to provide timely diagnosis and treatment of STIs, and to refer women to HIV testing.

A prominent role for activator protein-1 in the transcription of the human 2B4 (CD244) gene in NK cells.

The cell surface glycoprotein 2B4 (CD244) of the Ig superfamily is involved in the regulation of NK and T lymphocyte functions. We have recently identified CD48 as the high affinity counterreceptor for 2B4 in both mice and humans. The cytoplasmic domain of 2B4 associates with src homology 2 domain-containing protein or signaling lymphocyte activation molecule-associated protein, whose mutation is the underlying genetic defect in the X-linked lymphoproliferative syndrome. In this study, we report the molecular cloning and characterization of the human 2B4 (h2B4) promoter. Through primer extension analysis, we found that the transcription of the h2B4 gene initiates at multiple start sites. We isolated h2B4 genomic clones and PCR amplified the 5' untranslated region containing the promoter elements. We have identified a functional AP-1 site that lies between (-106 to -100) through transient transfection analysis in YT cells, a human NK cell line. EMSAs with Abs specific for various protein factors of the AP-1 family revealed that multiple members of the Jun family are involved in the regulation of the h2B4 gene. Mutation of the AP-1 site not only abolishes protein/DNA interactions but also promoter activity. These results demonstrate a significant role for AP-1 in the transcriptional regulation of the h2B4 gene.

Alterations in protein phosphatase 2A subunit interaction in human carcinomas of the lung and colon with mutations in the A beta subunit gene.

Protein phosphatase 2A (PP2A) consists of three subunits, A, B and C. The A and B subunits have regulatory functions while C is the catalytic subunit. PP2A core enzyme is composed of subunits A and C, and the holoenzyme of subunits A, B and C. All subunits exist as multiple isoforms or splice variants. The A subunit exists as two isoforms, A alpha and A beta. Here we report about the properties of eight A beta mutants, which were found in human lung and colon cancer. These mutants were reconstructed by site-directed mutagenesis and assayed for their ability to bind B and C subunits. Two mutants showed decreased binding of PR72, a member of the B" family of B subunits, but normal C subunit binding; two mutants exhibited decreased binding of the C subunit and of B"/PR72; and one mutant showed increased binding of both the C subunit and B"/PR72. Of three mutants that behaved like the wild-type A beta subunit, one is a polymorphic variant and another one is altered outside the binding region for B and C subunits. Importantly, we also found that the wild-type A alpha and A beta isoforms, although 85% identical, are remarkably different in their ability to bind B and C subunits. Our findings may have important implications in regard to the role of PP2A as a tumor suppressor.

Disruption of protein phosphatase 2A subunit interaction in human cancers with mutations in the A alpha subunit gene.

The A subunit of protein phosphatase 2A (PP2A) consists of 15 nonidentical repeats. The catalytic C subunit binds to C-terminal repeats 11 - 15 and regulatory B subunits bind to N-terminal repeats 1 - 10. Recently, four cancer-associated mutants of the A-alpha subunit have been described: Glu64-->Asp in lung carcinoma, Glu64-->Gly in breast carcinoma, Arg418-->Trp in melanoma, and Delta171 - 589 in breast carcinoma. Based on our model of PP2A, we predicted that Glu64-->Asp and Glu64-->Gly might be defective in B subunit binding, whereas Arg418-->Trp and Delta171 - 589 might bind neither B nor C subunits. We generated these mutants by site-directed mutagenesis and assayed their ability to associate with different forms of B subunits (B, B', B") or with the catalytic C subunit. The results demonstrate that all mutants are defective in binding either B or B and C subunits. Specifically, the N-terminal mutants, Glu64-->Asp and Glu64-->Gly, are defective in B' but normal in B, B", and C subunit binding, whereas the C-terminal mutants Arg418-->Trp and Delta171 - 589 bind none of the B subunits nor the C subunit. The implications of these findings with regard to the potential role of PP2A as a tumor suppressor are discussed. Oncogene (2001) 20, 10 - 15.

Closely related HIV-1 CRF01_AE variant among injecting drug users in northern Vietnam: evidence of HIV spread across the Vietnam-China border.

To investigate the nature of recent HIV outbreaks among injecting drug users (IDUs) near the Vietnam-China border, we genetically analyzed 24 HIV-positive blood specimens from 2 northern provinces of Vietnam (Lang Son and quang Ninh) adjacent to the China border, where HIV outbreaks among IDUs were first detected in late 1996. Genetic subtyping based on gag (p17) and env (C2/V3) sequences revealed that CRF01_AE is a principal strain circulating throughout Vietnam, including the provinces near the China border. The majority of CRF01_AE sequences among IDUs in Quang Ninh and Lang Son showed significant clustering with those found in nearby Pingxiang City of China's Guangxi Province, sharing a unique valine substitution 12 amino acids downstream of the V3 loop. This particular subtype E variant, uniquely found among IDUs in northern Vietnam and southeastern China, is designated E(v). The genetic diversity of CRF01_AE distributed in Quang Ninh (1.5 +/- 0.6%) and Pingxiang City (1.9 +/- 1.2%) was remarkably low, indicating the emerging nature of HIV spread in these areas. It is also noted that the genetic diversity of CRF01_AE among IDUs was consistently lower than that in persons infected sexually, suggesting that fewer closely related CRF01_AE variants were introduced into IDUs and, conversely, that multiple strains of CRF01_AE had been introduced via the sexual route. The data in the present study provide additional evidence that HIV outbreaks among IDUs in northern Vietnam were caused by the recent introduction of a highly homogeneous CRF01_AE variant (E(v)) closely related to that prevailing in nearby southern China.