Prenatal phthalate exposure and neurodevelopmental differences in twins at 2 years of age.

BACKGROUND: Previous studies of singletons evaluating prenatal phthalate exposure and early neurodevelopment reported mixed results and the associations could be biased by parental, obstetrical, and genetic factors. METHODS: A co-twin control design was employed to test whether prenatal phthalate exposure was associated with children's neurocognitive development. We collected information from 97 mother-twin pairs enrolled in the Wuhan Twin Birth Cohort between March 2016 and October 2018. Fourteen phthalate metabolites were measured in maternal urine collected at each trimester. Neurodevelopmental differences in twins at the age of two were examined as the outcome of interest. Multiple informant model was used to examine the covariate-adjusted associations of prenatal phthalate exposure with mental development index (MDI) and psychomotor development index (PDI) scores assessed at 2 years of age based on Bayley Scales of Infant Development (Second Edition). This model also helps to identify the exposure window of susceptibility. RESULTS: Maternal urinary levels of mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (ß = 1.91, 95% CI: 0.43, 3.39), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (ß = 1.56, 95% CI: 0.33, 2.79), and the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) (ß = 1.85, 95% CI: 0.39, 3.31) during the first trimester showed the strongest and significant positive associations with intra-twin MDI difference. When stratified with twin chorionicity, the positive associations of monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), individual DEHP metabolites, and ∑DEHP exposure during pregnancy with intra-twin neurodevelopmental differences were more significant in monochorionic diamniotic (MCDA) twins than those in dichorionic diamniotic (DCDA) twins. CONCLUSIONS: Neurodevelopmental differences in MCDA twins were strongly associated with prenatal phthalate exposure. Our findings warrant further confirmation in longitudinal studies with larger sample sizes.

Prenatal exposure to poly- and perfluoroalkyl substances and postpartum depression in women with twin pregnancies.

BACKGROUND: Women with multiple pregnancies are vulnerable to experience postpartum depression (PPD). Emerging evidence indicates an association between poly- and perfluoroalkyl substances (PFAS) exposure and PPD in women delivering singletons. The health risks of PFAS may also be present in women delivering twins. OBJECTIVE: To estimate the impacts of prenatal PFAS exposure on the risk of PPD in women with twin pregnancies. METHODS: Our study included 150 mothers who gave birth to twins and were enrolled in the Wuhan Twin Birth Cohort. The concentrations of maternal plasma PFAS were measured in each trimester and averaged. Eight individual PFAS were included in analyses. We used Edinburgh Postnatal Depression Scale to evaluate maternal depression at early pregnancy and 1 and 6 months after childbirth. The outcome was dichotomized using a cutoff value of ≥10 for main analyses. Associations were examined using multiple informant models and modified Poisson regressions. PFAS mixture effects were estimated using quantile g-computation. RESULTS: Using quantile g-computation models, a quartile increase in the PFAS mixture during the first, second, third, and average pregnancy was significantly associated with a relative risk (RR) of 1.73 (95% CI: 1.42, 2.12), 1.54 (95% CI: 1.27, 1.84), 1.75 (95% CI: 1.49, 2.08), and 1.63 (95% CI: 1.35, 1.97) for PPD at 6 months after childbirth, respectively. The results of the single-PFAS models also indicated significant positive associations between individual PFAS and PPD at both 1 and 6 months. CONCLUSIONS: The first study of women with twin pregnancies suggests that prenatal exposure to PFAS increases PPD risk up to 6 months postpartum. Twin pregnant women should receive long-term follow-up after delivery and extensive social support.

Toxicity of Polystyrene Nanoplastics in the Liver and Intestine of Normal and High-Fat-Diet Juvenile Zebrafish.

Nanoplastics (NPs) are widely found and threaten environmental and biological safety, because they do not degrade completely. We aimed to preliminarily explore the toxicity of NPs in obese children, because childhood obesity is a growing global health concern. We used zebrafish as a vertebrate toxicological model to examine the hepatic lipid metabolism and gut microbiota in juvenile zebrafish exposed to 1000 µg/L polystyrene NPs and a high-fat diet (HFD) using Raman spectroscopy, pathological examination, transcriptome analysis, and 16S sequencing techniques. Our study showed that polystyrene NPs perturb the lipid metabolism and gut microbiota stability in zebrafish. Furthermore, the combined effects of polystyrene NPs and HFD resulted in gastrointestinal injury. Our study is one of the first to investigate the toxicity of polystyrene NPs to normal-diet and HFD juvenile zebrafish using confocal Raman spectroscopy. Our results show the importance of a healthy diet and a reduction in the use of plasticware. Environ Toxicol Chem 2024;43:147-158. © 2023 SETAC.

A co-twin control study of in utero exposure to poly- and perfluoroalkyl substances and associations with neonatal thyroid-stimulating hormone.

Research quantifying associations between early-life exposure to poly- and perfluoroalkyl substances (PFAS) and neonatal thyroid hormone levels is limited and reports inconsistent results. This study aimed to examine the associations of in utero PFAS exposure with neonatal thyroid-stimulating hormone (TSH), and to verify whether genetic and familial factors contribute to these associations. Within Wuhan Twin Birth Cohort study, we included 148 mother-twin pairs recruited between March 2016 and January 2018. Maternal plasma PFAS concentrations were measured at three different trimesters and averaged. Additionally, we measured cord plasma PFAS concentrations for twin newborns and retrieved their TSH levels from the medical system. Multivariable linear regression, generalized estimation equation, and linear mixed models were used to examine the covariate-adjusted associations. For maternal PFAS analyses, a 2-fold increment of average maternal perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) concentrations was linked with a 15% (95% CI: 2.5%, 28%) and 14% (95% CI: 2.4%, 28%) increase in neonatal TSH, respectively. For twin newborns discordant for PFAS exposure, a 2-fold increment of cord plasma PFOA, PFDA, perfluoroundecanoic acid (PFUdA), and perfluorohexanesulfonic acid (PFHxS) concentrations was related to a 7.1% (95% CI: 0.31%, 14%), 12% (95% CI: 4.8%, 20%), 7.5% (95% CI: 0.30%, 15%), and 8.5% (95% CI: 3.0%, 14%) increase in TSH among twins as individuals, respectively. Although these associations were mainly observed between twin pairs, certain PFAS exposure might have an independent association with increased TSH. Our present study suggests that higher maternal and cord plasma PFAS concentrations are associated with increased neonatal TSH, and genetic and familial factors contribute to these associations.

Prenatal exposure to phthalates and child growth trajectories in the first 24 months of life.

BACKGROUND: Phthalates are a class of environmental chemicals with endocrine-disrupting properties. Prenatal phthalate exposure has been associated with adverse developmental outcomes in childhood. However, data assessing the effects of prenatal phthalate exposure on postnatal infant growth trajectories are sparse. OBJECTIVES: To evaluate the associations of prenatal phthalate exposure with child growth trajectories from birth to 24 months old. METHODS: Within a Chinese birth cohort study, 1051 mother-offspring pairs were included. Seven phthalate metabolites were quantified in maternal urine collected between weeks 33 and 39 of gestation. The trajectories for weight-for-age z-score (WAZ), length-for-age z-score (LAZ), weight-for-length z-score (WLZ) and head-circumference-for-age z-score (HCZ) were determined by group-based trajectory modeling (GBTM). Multinomial logistic regression and the weighted quantile sum approach (WQS) were used to investigate the association between individual and phthalate mixture exposure and the growth trajectories of four anthropometric metrics. RESULTS: Five trajectory groups were identified for each anthropometric measure using GBTM. Higher prenatal exposure to several phthalate metabolites (MEHP, MEHHP, MEOHP, MECCP, summed DEHP metabolites, as well as MBP) was associated with child growth trajectories, especially for WAZ and LAZ in the first 24 months of life. The associations were further confirmed by a mixture analysis of phthalate metabolites and a sex-specific effect was observed in the WAZ and LAZ trajectories. CONCLUSION: Prenatal phthalate exposure had heterogeneous associations with postnatal growth trajectories. More studies are warranted to confirm and elucidate the meaning of our findings.

Combined effects of high-fat diet and polystyrene microplastic exposure on microplastic bioaccumulation and lipid metabolism in zebrafish.

Extensive use of microplastics (MPs) threatens the safety of aquatic environments and hydrobionts. Increasing the weight of economic fish through high-fat diet (HFD) to increase production is common in aquaculture. However, little is known about the combined effects of MPs and HFD in fish. The aim of this study was to investigate the relationship between adiposity and MP bioaccumulation in fish. Using zebrafish as a vertebrate model, the content of polystyrene (PS) MPs in zebrafish tissues exposed to 5 and 50 µm of 1000 µg/L PS MPs was detected via confocal Raman spectroscopy in normal diet (ND) and HFD. The content of PS MPs in HFD group was significantly higher than that in ND group. The levels of hepatic lipids were significantly elevated in zebrafish subjected to HFD treatment, and this effect was aggravated by exposure to 5 µm PS MPs, and even caused liver injury. Transcriptomic analysis revealed that exposure to PS MPs interferes with hepatic lipid metabolism and energy homeostasis in zebrafish. These results suggests that in addition to controlling the use and performing proper recycling of plastic products in our daily life, we should not blindly increase the weight of fish through HFD. This aids protect the quality of economic fish and prevent MPs from being consumed by humans through the food chain. This study explored the interaction between fish feed culture and environmental pollutants to provide important reference for fish culture.

Exposure to bisphenols, parabens and phthalates during pregnancy and postpartum anxiety and depression symptoms: Evidence from women with twin pregnancies.

BACKGROUND: Women are vulnerable to suffer from the common mental disorders like anxiety and depression during the postpartum period. Exposure to bisphenols, parabens, and phthalates has been linked to anxiety and depression symptoms in the general population. However, little is known about their impacts on postpartum women. OBJECTIVE: To evaluate the effects of individual and joint exposure to 11 nonpersistent chemicals during pregnancy on postpartum anxiety and depression. METHODS: Among 278 mothers from the Wuhan Twin Birth Cohort (WTBC), bisphenols, parabens, and phthalate metabolites were measured in maternal urine samples from each trimester. Self-rating Anxiety Scale (SAS) and Edinburgh Postnatal Depression Scale (EPDS) were administrated at early pregnancy and 1 month and 6 months postpartum to determine anxiety and depression symptoms, respectively. Associations between urinary chemical biomarkers (individual or mixtures) and anxiety and depression symptoms were estimated using multiple informant model and quantile-based g-computation. RESULTS: With adjustment for confounders, one quartile increase in the overall chemical mixture (bisphenols, parabens and phthalate metabolites) during the second trimester was associated with 1.03-point (95% CI: 0.07, 1.99, P = 0.036) higher EPDS score at 1 month postpartum, in which bisphenol A (BPA) and bisphenol F (BPF) contributed the most to the positive association. Consistent effects were also observed in the multiple informant models. We found that second-trimester BPA and BPF exposure individually showed the strongest and significant associations with anxiety and depression symptoms, and some of associations differed across trimesters (Ptrimester-int < 0.05). CONCLUSIONS: Second-trimester nonpersistent chemical exposure was associated with increased postpartum anxiety and depression symptoms.

Prenatal exposure to perfluorooctane sulfonate alternatives and associations with neonatal thyroid stimulating hormone concentration: A birth cohort study.

BACKGROUND: Chlorinated polyfluorinated ether sulfonic acids (Cl-PFESA) and perfluorobutane sulfonate (PFBS), used as perfluorooctanesulfonate (PFOS) alternatives, were indicated as thyroid hormone disruptive toxicants in experimental studies. However, it is unclear whether prenatal exposure to Cl-PFESA and PFBS affects neonatal thyroid stimulating hormone (TSH) in human. OBJECTIVE: To disclose the relationships between prenatal Cl-PFESAs and PFBS exposure and neonatal thyroid-stimulating hormone (TSH) levels based on a perspective cohort study. METHODS: A total of 1015 pairs of mother and newborn were included from an ongoing birth cohort study in Wuhan, China, between 2013 and 2014. Six PFASs in cord blood sera and TSH concentration in neonatal postpartum heel sticks blood were quantified. Mixed linear and weighted quantile sum (WQS) regression models were applied to assess the individual and combination effects of PFASs exposure on neonatal TSH levels with multiple covariates adjustments. RESULTS: After adjusting for potential confounders and other five PFASs, for each 1-ng/mL increase of PFBS or 8:2 Cl-PFESA, was negatively associated with 25.90% (95%CI: 37.37%, -12.32%; P < 0.001) and 27.19% (95%CI: 46.15%, -1.55%; P = 0.033) change in TSH in male but not female infants, respectively. No significant association was found between other PFASs exposure and neonatal TSH. Higher PFAS mixture in cord blood was significantly associated with decrease TSH concentration in all newborns (ß = -0.36; 95%CI: 0.58, -0.13; P = 0.001) identified by WQS regression model. PFBS, PFOS and 6:2 Cl-PFESA were the major contributors to the neonatal TSH decrement with the weights of 56.50%, 18.71%, 12.81% among PFAS mixture, respectively. CONCLUSIONS: our prospective cohort study suggested a negative association of cord serum PFBS and 8:2 CI-PFESA with TSH concentration in newborns, especially for boys. Additional studies are required to elaborate on the underlying biological mechanisms, especially for PFBS.

Development of the gut microbiota in healthy twins during the first 2 years of life and associations with body mass index z-score: Results from the Wuhan twin birth cohort study.

The gut microbiota undergoes rapid and vital changes to microbial community structure and the microbial-immune crosstalk during the first 3 years of life, which is thought to be involved in the pathobiology of later-life disease. Compared to single-born children, little is known about the gut microbiota of twins in early childhood. Based on the Wuhan Twin Birth Cohort study, 344 stool samples from 204 twin families were analyzed to investigate the difference in gut microbiota composition at 6, 12, and 24 months of age. Furthermore, this study evaluated the association between gut microbiota development curves and body mass index z-score (BMI_Z) curves at 6, 12, and 24 months of age. The predominant microbiota phyla identified in twins were Proteobacteria, Actinobacteriota, Firmicutes, Bacteroidota, and Verrucomicrobiota. The richness and diversity of gut microbiota increased from 6 to 24 months old (alpha diversity with p < 0.05). Beta diversity revealed 61 gut microbiota genera that were significantly different in relative abundance among the three age groups. Among the 61 gut microbiota genera, 30 distinct trajectory curves (DTCs) were generated by group-based trajectory models after log2 transformation of their relative abundance. Subsequently, Spearman correlation analysis revealed that only five gut microbiota DTC were correlated with the BMI_Z DTC. Therefore, we further examined the association between the five gut microbiota genera DTC and BMI_Z DTC using generalized estimation equation models. The results revealed a significant association between the DTC groups of Parabacteroides and that of BMI_Z (coefficient = 0.75, p = 0.04). The results of this study validated the hypothesis that the richness and diversity of gut microbiota developed with age in twins. Moreover, participants with a higher DTC of log2-transformed Parabacteroides had a higher BMI_Z DTC during the first 2 years of life. Further studies are needed to confirm the association between Parabacteroides and BMI_Z in other populations.

Global trends and age-specific incidence and mortality of cervical cancer from 1990 to 2019: an international comparative study based on the Global Burden of Disease.

OBJECTIVE: To describe the trends of incidence and mortality of cervical cancer in different age groups and regions from 1990 to 2019. DESIGN: An international comparative study based on the Global Burden of Disease (GBD) study estimates. PARTICIPANTS: Data were publicly available and individuals were not involved. METHODS: We collected detailed information on cervical cancer from the GBD study between 1990 and 2019. Average annual percentage changes (AAPCs) of age-standardised incidence and mortality rate (ASIR and ASMR) in cervical cancer, by age group and region, were calculated to quantify the temporal trends. RESULTS: Globally, the absolute numbers of incident cases and deaths were increasing, with the most cervical cancer cases and deaths being reported in China, India and Brazil. Although the ASIR and ASMR have declined overall from 1990 to 2019, an increasing or stable trend was also observed in East Asia and Southern sub-Saharan Africa. Particularly, we found that the age-specific AAPC of incidence showed an increasing trend in the age group of 15-49 years globally, and the high Sociodemographic Index region increased the most. CONCLUSIONS: Cervical cancer remains a concerning disease that affects women all over the world, although the ASIR and ASMR are decreasing. Efforts to control the younger trend and to reduce the disparity between regions are imminent.

HPV E7 affects the function of cervical cancer cells via the TAL1/lnc­EBIC/KLHDC7B axis.

High­risk human papillomavirus (HPV)16 and 18 are the primary cause of cervical cancer (CC) and long non­coding RNAs (lncRNAs/lncs) are often abnormally expressed in patients with CC. The authors' previous study indicated that oncogenic enhancer of zeste homolog 2 (EZH2)­binding lncRNA in cervical cancer (lnc­EBIC) serves a role in the tumorigenic activity of the HPV E6 protein in patients with CC. However, whether HPV E7 affects the development of CC through lnc­EBIC, and the potential mechanisms underlying this remains unclear. Therefore, the present study investigated the effects of lnc­EBIC and HPV E7 in cervical cancer cell lines HeLa, CaSki and C33A in vitro. CCK­8, EdU and DAPI staining assays, flow cytometry, RT­qPCR, western blotting and Transwell assay were performed on these cell lines. The results revealed that exogenous expression of HPV16/18 E7 significantly promoted lnc­EBIC expression, and conversely, lnc­EBIC was downregulated by silencing endogenous HPV16/18 E7 expression in corresponding CaSki and HeLa cells. Overexpression of lnc­EBIC significantly increased cellular proliferation, migration and invasion, and inhibited apoptosis in HPV­ C33A cells. The tumorigenic effects of HPV16/18 E7 in corresponding CaSki and HeLa cells were significantly blocked by the silencing of lnc­EBIC expression. Molecular analysis revealed that HPV16/18 E7 depended on TAL BHLH transcription factor 1, erythroid differentiation factor inhibition to promote lnc­EBIC expression, which also resulted in the upregulation of oncogenic Kelch domain­containing 7B (KLHDC7B) in corresponding CaSki and HeLa cells. Additionally, KLHDC7B knockdown blocked the tumor­promotive effects of lnc­EBIC in HPV­ C33A cells. Collectively, the results of the present study indicated that lnc­EBIC acts as an oncogenic lncRNA by enhancing KLHDC7B expression in HPV+ and HPV­ CC cells, and can be exploited by HPV16/18 E7 to accelerate tumorigenic activity in CC. These results further revealed that the lnc­EBIC/KLHDC7B axis represents a novel molecular mechanism and potential therapeutic target for CC.

Association between vaccinations and clinical manifestations in children with COVID-19.

BACKGROUND: The infection rate of Coronavirus Disease 2019 (COVID-19) in children was less than that in adults. However, the underlining reason is not well known. METHODS: Children with COVID-19 were recruited from two Children's Hospitals in Wuhan and Shanghai in this case-control study. The associations of initial symptoms with age, vaccinations of Bacillus Calmette Guerin (BCG), and influenza and pathogens were determined by Chi-square t-test. RESULTS: We evaluated 248 confirmed cases, and 56 suspected cases with COVID-19. The median age was 6.82 years old, and 118 cases (38.82%) were girls. Furthermore, 30.26% of all patients were asymptomatic cases. The percentage of asymptomatic cases vaccinated with BCG was not significantly higher than that without BCG vaccination [86/280 (30.71%) vs. 6/13 (46.15%), P=0.203], and initial symptoms were not related with immunized influenza vaccine (P=0.267). Compared to parameters in pediatric patients with normal body temperatures, patients with fever had higher C reactive protein (CRP) (P<0.001). CONCLUSIONS: Pediatric COVID-19 patients with BCG vaccinations exhibit similar clinical manifestations compared to those without BCG vaccinations, and the severity of symptoms in pediatric patients may be related to the maturity of immune function.

Viral loads in throat and anal swabs in children infected with SARS-CoV-2.

Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay on anal swabs was recently reported to be persistently positive even after throat testing was negative during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, data about the consistent performance of RT-PCR assay on throat and anal swabs remain limited in paediatric patients. Here, we retrospectively reviewed RT-PCR-testing results of 212 paediatric patients with suspected SARS-CoV-2 infection at Wuhan Children's Hospital. The diagnostic potential of these two types of specimens showed significant difference (positive rate: 78.2% on throat swabs vs. 52.6% on anal swabs, McNemar Test P = 0.0091) and exhibited a weak positive consistency (Kappa value was 0.311, P < 0.0001) in paediatric patients. Furthermore, viral loads detected on both throat and anal swabs also showed no significant difference (P = 0.9511) and correlation (Pearson r = 0.0434, P = 0.8406), and exhibited an inconsistent kinetic change through the course of SARS-CoV-2 infection. Besides, viral loads in the throat and anal swabs were correlated with different types of immune states, immune-reactive phase, and the resolution phase/immunologic tolerance, respectively. These findings revealed that RT-PCR-testing on throat and anal swabs showed significant difference for monitoring SARS-CoV-2 infection and correlated with different immune state in paediatric patients.

Secreted Rv1768 From RD14 of Mycobacterium tuberculosis Activates Macrophages and Induces a Strong IFN-γ-Releasing of CD4+ T Cells.

As the first line defensive mediators against Mycobacterium tuberculosis (M.tb) infection, macrophages can be modulated by M.tb to influence innate and adaptive immunity. Recently, we have identified several potential immunodominant T-cell antigens from the region of deletion (RD) of M.tb H37Rv, including Rv1768 from RD14. In this study, we further determined that Rv1768 was highly conserved among virulent M.tb strains and mainly distributed as a secreted protein. Exposure to recombinant purified Rv1768 (rRv1768) induced apoptosis of bone marrow derived macrophages (BMDMs) but showed no dose-dependent manner. Regarding macrophage activation, significant higher levels of iNOS and pro-inflammatory cytokines (like IL-6 and TNF-α) were detected in rRv1768-challenged BMDMs, whereas arginase 1 (Arg1) expression was markedly decreased. Meanwhile, MHC-II expression and antigen presentation activity of BMDMs were also enhanced by rRv1768 stimulation, leading to significantly increased IFN-γ expression of CD4+ T cells isolated from H37Rv-infected mice. It is worthy to note that Rv1768-induced IFN-γ production of peripheral blood mononuclear cells (PBMCs) and Rv1768-specific immunoglobulins was specifically observed in H37Rv-infected mice, but not BCG-infected or normal mice. Analysis of clinical blood samples further revealed that Rv1768 had a higher sensitivity and specificity (91.38 and 96.83%) for tuberculosis diagnosis than the results obtained from clinical CFP10 and ESAT6 peptides (CE)-based enzyme-linked immunospot (ELISPOT) assay. The area under ROC curve of Rv1768 was 0.9618 (95% CI: 0.919-1.000) when cutoff value set as 7 spots. In addition, Rv1768-specific IgG and IgM also exhibited moderate diagnostic performance for tuberculosis compared with CE specific antibodies. Our data suggest that Rv1768 is an antigen that strongly activates macrophages and has potential to serve as a novel ELISPOT-based TB diagnostic agent.

Distribution characteristics of different human papillomavirus genotypes in women in Wuhan, China.

BACKGROUND: Human papillomaviruses (HPVs) are strongly associated with the development of cervical carcinoma, and the distribution of HPV genotypes varies regionally. METHODS: To investigate the distribution characteristics of different genotypes of HPV infection in women in Wuhan, China, a total of 13 775 patients were enrolled over 2 years. RESULTS: Of these, 2436 patients were infected with HPVs, and the total infection rate was 17.68%. The infection rate of high-risk HPV (HR-HPV) was significantly higher (13.96%) than that of single low-risk HPV (LR-HPV; 3.72%). Among the HR-HPV infections, the most common genotype was HPV 52 with an infection rate of 4.23%, followed by HPVs 16, 58, 39, and 51. The most common LR-HPV genotype was HPV 81, followed by HPVs 6, 11, and 44. Patients under the age of 25 years were found to have the highest HPV infection rate (P < .05). After the age range of 51-55 years, a downward trend in total HPVs and HR-HPVs was observed. The HPV infection rate for a single genotype was higher than that for multiple HPVs (P < .01), and the detection rates in summer and winter were significantly higher than those in spring and autumn. CONCLUSIONS: The results demonstrate that the distribution characteristics of various HPV genotype infections are associated with region and age and may be related to season. These data could be the basis for further epidemiological analysis into the control and prevention of HPV infection in this region.

Characterization of a mutant R11H αB-crystallin associated with human inherited cataract.

αB-Crystallin plays an important part in cataract development. A novel mutation (R11H) was previously detected by our group. In the present study, we set out to investigate the possible molecular mechanism by which the R11H mutation causes cataract. We found that the mutant αB-crystallin exhibits folding defects, decreased surface hydrophobicity and enhanced chaperone-like activity compared with the wild-type αB-crystallin. The mutant protein shows nearly the same molecular mass and thermal stability as the wild-type form. Transfection studies revealed that the R11H mutant was remarkably similar to the wild-type protein in its subcellular distribution, but has an abnormal ability to induce cell apoptosis. These results suggest that the changes in hydrophobic exposure and the abnormal ability to induce programmed cell death of the mutant protein are likely to be responsible for the onset of cataract.