Origin and differentiation of human memory CD8 T cells after vaccination.

The differentiation of human memory CD8 T cells is not well understood. Here we address this issue using the live yellow fever virus (YFV) vaccine, which induces long-term immunity in humans. We used in vivo deuterium labelling to mark CD8 T cells that proliferated in response to the virus and then assessed cellular turnover and longevity by quantifying deuterium dilution kinetics in YFV-specific CD8 T cells using mass spectrometry. This longitudinal analysis showed that the memory pool originates from CD8 T cells that divided extensively during the first two weeks after infection and is maintained by quiescent cells that divide less than once every year (doubling time of over 450 days). Although these long-lived YFV-specific memory CD8 T cells did not express effector molecules, their epigenetic landscape resembled that of effector CD8 T cells. This open chromatin profile at effector genes was maintained in memory CD8 T cells isolated even a decade after vaccination, indicating that these cells retain an epigenetic fingerprint of their effector history and remain poised to respond rapidly upon re-exposure to the pathogen.

Is There Any Association between Nutrition and Myopia? A Systematic Review.

SIGNIFICANCE: This systematic review highlights the possible role of nutrition in myopia based on qualitative analysis of vast and diverse literature that investigated this association. PURPOSE: We systematically reviewed the outcomes of the studies that previously investigated the association between nutrition and myopia. METHODS: EMBASE, MEDLINE, and PubMed were searched by two independent authors to identify cross-sectional, cohort, retrospective, or interventional studies that assessed the association of nutrition with myopia from inception to the year 2021. Furthermore, the reference list of the included articles was screened. The data from the included studies were extracted, and qualitative analysis was performed. Quality assessment for noninterventional studies and interventional trials was performed using the Newcastle-Ottawa Scale and Cochrane RoB 2, respectively. RESULTS: Twenty-seven articles were included in the review. Most of the nutrients and dietary elements investigated in noninterventional studies showed inconsistencies in their association with myopia, with the majority indicating no association. Nine studies showed a significant association of diverse nutrients and dietary elements with either an increase (odds ratio, 1.07) or a decrease (odds ratio, 0.5 to 0.96) in the risk of myopia development. However, a majority of these studies have minimal odds ratios with wider or overlapping confidence intervals, implicating weaker associations. All three nutrients and dietary elements assessed in the interventional trial had implications for myopia control, with two trials indicating a clinically minimal effect. CONCLUSIONS: This review implies that there is some evidence to indicate a potential influence of specific nutrients and dietary elements in myopia development, which are supported by several theories. However, given the vast, diverse, and complex nature of nutrition, more systematic investigation is warranted to comprehend the extent to which these specific nutrients and dietary elements are associated with myopia through longitudinal studies by subduing the limitations in the existing literature.

Association between relative peripheral refraction and corresponding electro-retinal signals.

PURPOSE: Considering the potential role of the peripheral retina in refractive development and given that peripheral refraction varies significantly with increasing eccentricity from the fovea, we investigated the association between relative peripheral refraction (RPR) and corresponding relative peripheral multifocal electroretinogram (mfERG) responses (electro-retinal signals) from the central to the peripheral retina in young adults. METHODS: Central and peripheral refraction using an open-field autorefractor and mfERG responses using an electrophysiology stimulator were recorded from the right eyes of 17 non-myopes and 24 myopes aged 20-27 years. The relative mfERG N1, P1 and N2 components (amplitude density and implicit time) of a mfERG waveform were compared with the corresponding RPR measurements at the best-matched eccentricities along the principal meridians, that is at the fovea (0°), horizontal (±5°, ±10° and ± 25°) and vertical meridians (±10° and ± 15°). RESULTS: The mean absolute mfERG N1, P1 and N2 amplitude densities (nV/deg2 ) were maximum at the fovea in both non-myopes (N1: 57.29 ± 14.70 nV/deg2 , P1: 106.29 ± 24.46 nV/deg2 , N2: 116.41 ± 27.96 nV/deg2 ) and myopes (N1: 56.25 ± 15.79 nV/deg2 , P1: 100.79 ± 30.81 nV/deg2 , N2: 105.75 ± 37.91 nV/deg2 ), which significantly reduced with increasing retinal eccentricity (p < 0.01). No significant association was reported between the RPR and corresponding relative mfERG amplitudes at each retinal eccentricity (overall Pearson's correlation, r = -0.25 to 0.26, p ≥ 0.09). In addition, the presence of relative peripheral myopia or hyperopia at extreme peripheral retinal eccentricities did not differentially influence the corresponding relative peripheral mfERG amplitudes (p ≥ 0.24). CONCLUSIONS: Relative peripheral mfERG signals are not associated with corresponding RPR in young adults. It is plausible that the electro-retinal signals may respond to the presence of absolute hyperopia (and not relative peripheral hyperopia), which requires further investigation.

Naringenin improves ovarian health by reducing the serum androgen and eliminating follicular cysts in letrozole-induced polycystic ovary syndrome in the Sprague Dawley rats.

Polycystic ovary syndrome (PCOS) is most common in women of reproductive age, giving rise to androgen excess and anovulation, leading to infertility and non-reproductive complications. We explored the ameliorating effect of naringenin in PCOS using the Sprague Dawley (SD) rat model and human granulosa cells. Letrozole-induced PCOS rats were given either naringenin (50 mg/kg/day) alone or in combination with metformin (300 mg/kg/day), followed by the estrous cycle, hormonal analysis, and glucose sensitivity test. To evaluate the effect of naringenin on granulosa cell (hGC) steroidogenesis, we treated cells with naringenin (2.5 µM) alone or in combination with metformin (1 mM) in the presence of forskolin (10 µM). To determine the steroidogenesis of CYP-17A1, -19A1, and 3ßHSD2, the protein expression levels were examined. Treatment with naringenin in the PCOS animal groups increased ovulation potential and decreased cystic follicles and levels of androgens. The expression levels of CYP-17A1, -19A1, and 3ßHSD2, were seen restored in the ovary of PCOS SD rats' model and in the human ovarian cells in response to the naringenin. We found an increased expression level of phosphorylated-AKT in the ovary and hGCs by naringenin. Naringenin improves ovulation and suppress androgens and cystic follicles, involving AKT activation.

Electroretinogram responses in myopia: a review.

The stretching of a myopic eye is associated with several structural and functional changes in the retina and posterior segment of the eye. Recent research highlights the role of retinal signaling in ocular growth. Evidence from studies conducted on animal models and humans suggests that visual mechanisms regulating refractive development are primarily localized at the retina and that the visual signals from the retinal periphery are also critical for visually guided eye growth. Therefore, it is important to study the structural and functional changes in the retina in relation to refractive errors. This review will specifically focus on electroretinogram (ERG) changes in myopia and their implications in understanding the nature of retinal functioning in myopic eyes. Based on the available literature, we will discuss the fundamentals of retinal neurophysiology in the regulation of vision-dependent ocular growth, findings from various studies that investigated global and localized retinal functions in myopia using various types of ERGs.

Helical nanofiber yarn enabling highly stretchable engineered microtissue.

Development of microtissues that possess mechanical properties mimicking those of native stretchable tissues, such as muscle and tendon, is in high demand for tissue engineering and regenerative medicine. However, regardless of the significant advances in synthetic biomaterials, it remains challenging to fabricate living microtissue with high stretchability because application of large strains to microtissues can damage the cells by rupturing their structures. Inspired by the hierarchical helical structure of native fibrous tissues and its behavior of nonaffine deformation, we develop a highly stretchable and tough microtissue fiber made up of a hierarchical helix yarn scaffold, scaling from nanometers to millimeters, that can overcome this limitation. This microtissue can be stretched up to 15 times its initial length and has a toughness of 57 GJ m-3 More importantly, cells grown on this scaffold maintain high viability, even under severe cyclic strains (up to 600%) that can be attributed to the nonaffine deformation under large strains, mimicking native biopolymer scaffolds. Furthermore, as proof of principle, we demonstrate that the nanotopography of the helical nanofiber yarn is able to induce cytoskeletal alignment and nuclear elongation, which promote myogenic differentiation of mesenchymal stem cells by triggering nuclear translocation of transcriptional coactivator with PDZ-binding motif (TAZ). The highly stretchable microtissues we develop here will facilitate a variety of tissue engineering applications and the development of engineered living systems.

High stretchability, strength, and toughness of living cells enabled by hyperelastic vimentin intermediate filaments.

In many developmental and pathological processes, including cellular migration during normal development and invasion in cancer metastasis, cells are required to withstand severe deformations. The structural integrity of eukaryotic cells under small deformations has been known to depend on the cytoskeleton including actin filaments (F-actin), microtubules (MT), and intermediate filaments (IFs). However, it remains unclear how cells resist severe deformations since both F-actin and microtubules yield or disassemble under moderate strains. Using vimentin containing IFs (VIFs) as a model for studying the large family of IF proteins, we demonstrate that they dominate cytoplasmic mechanics and maintain cell viability at large deformations. Our results show that cytoskeletal VIFs form a stretchable, hyperelastic network in living cells. This network works synergistically with other cytoplasmic components, substantially enhancing the strength, stretchability, resilience, and toughness of cells. Moreover, we find the hyperelastic VIF network, together with other quickly recoverable cytoskeletal components, forms a mechanically robust structure which can mechanically recover after damage.

Buckeye Rot of Tomato in India: Present Status, Challenges, and Future Research Perspectives.

Tomato in India is commonly exposed to various diseases of fungal, bacterial, and viral origin, resulting in substantial yield losses (≥50%). Buckeye rot (caused by Phytophthora nicotianae var. parasitica) is among the major constraints in the successful cultivation of tomato crops in various parts of the world, including the Solan district of Himachal Pradesh state, India. The fruit rot becomes more devastating under high humidity and wet soils. Symptoms generally appear on green fruit as alternate dark- and light-brown concentric rings. The genome size of P. nicotianae var. parasitica is 82 Mb with >23,000 predicted genes. High humidity (>60%) and optimal temperatures (20 to 25°C), along with rainfall (≥10 mm), help to disperse the pathogen because the inoculum reaches the fruit through splashing rain. Sporangia germinate indirectly by producing zoospores at 20 to 25°C or directly via germ tubes at >25°C. In the absence of suitable resistant varieties, no single management practice is sufficient to keep the disease below the economic threshold level; therefore, integration of cultural and chemical methods is preferable. This article aims to focus on the etiology and management challenges of buckeye rot. We recommend innovative disease management strategies such as identification and deployment of resistant cultivars as well as spraying of synthetic chemical fungicides, biocontrol agents, and use of abiotic chemicals that induce resistance for developing sustainable crop production practices.

Polymorphisms in MMP-1, MMP-2, MMP-7, MMP-13 and MT2A do not contribute to breast, lung and colon cancer risk in polish population.

BACKGROUND: Matrix metalloproteinases (MMPs) and metallothioneins (MTs) are Zinc-related proteins which are involved in processes crucial for carcinogenesis such as angiogenesis, proliferation and apoptosis. Several single nucleotide polymorphisms (SNPs) in MMPs and MTs that affect genes expression have been associated with cancer risk, including breast, lung and colon. METHODS: The study group consisted of 648 unselected patients (299 with breast cancer, 199 with lung cancer, 150 with colon cancer) and 648 unaffected individuals. Five SNPs, rs1799750 in MMP-1, rs243865 in MMP-2, rs11568818 in MMP-7, rs2252070 in MMP-13 and rs28366003 in MT2A were genotyped and serum zinc (Zn) level was measured. The cancer risk was calculated using multivariable logistic regression with respect to Zn. RESULTS: None of the 5 tested polymorphisms showed a correlation with cancer risk in studied groups, although for MMP-2, MMP-7 and MT2A non-significant differences in genotypes frequencies among cases and controls were observed. CONCLUSIONS: Analyses of polymorphisms, rs1799750 in MMP-1, rs243865 in MMP-2, rs11568818 in MMP-7, rs2252070 in MMP-13 and rs28366003 in MT2A in relation to serum Zn level did not show significant association with breast, lung and colon cancer risk among polish patients. Further studies are needed to verify this observation.

Role of STAT signaling and autocrine action of chemokines during H2 O 2 induced HTR-8/SVneo trophoblastic cells invasion.

During pregnancy, regulated generation of reactive oxygen species (ROS) is important for activation of signaling pathways and placentation. In the current study, the effect of H2 O2 on invasion of HTR-8/SVneo cells, a human extravillous trophoblast cell line, is investigated. Treatment of HTR-8/SVneo cells for 24 hr with H 2 O2 (25 µM) leads to a significant increase in invasion without affecting cell proliferation, viability, and apoptosis. Concomitantly, a significant increase in the matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinases-1 (TIMP-1) ratio is observed. Further, significant increase in phosphorylation of signal transducer and activator of transcription 1 (STAT-1) and STAT-3 (both at ser727 residue) is observed on treating HTR-8/SVneo cells with 25 µM of H2 O2 accompanied by an increase in the secretion of interleukin-8 (IL-8) and macrophage inflammatory protein-1ß (MIP-1ß). A significant decrease in H2 O2 -mediated invasion of HTR-8/SVneo cells and reduced expression of IL-8 and MIP-1ß accompanied by decrease in MMP-9/TIMP-1 ratio are observed on inhibiting STAT-1 and STAT-3 by small interfering RNA (siRNA). Inhibition of STAT-1 activity by fludarabine and STAT-3 activity by Stattic also leads to a decrease in H2 O2 -mediated increase in HTR-8/SVneo cell invasion. Inhibition of IL-8 and MIP-1ß by siRNA also leads to a significant decrease in both basal and H2 O2 -mediated invasion. Interestingly, inhibition of MIP-1ß by siRNA leads to a significant reduction in H2 O2 -mediated increase in IL-8. However, no significant effect of IL-8 silencing on H2 O2 -mediated MIP-1ß expression was observed. From the above results, it can be concluded that H2 O2 activates STAT signaling, MIP-1ß & IL-8 secretion and increases MMP-9/TIMP-1 ratio leading to an increased invasion of HTR-8/SVneo cells without affecting their viability.

HGF promotes HTR-8/SVneo cell migration through activation of MAPK/PKA signaling leading to up-regulation of WNT ligands and integrins that target ß-catenin.

Inadequate migration and invasion of the trophoblast cells during embryo implantation is one of the reasons for pregnancy-related complications such as intrauterine growth restriction and preeclampsia. In the present study, relevance of WNT ligands and integrins associated with hepatocyte growth factor (HGF)-mediated migration of HTR-8/SVneo trophoblastic cells has been investigated. Treatment of HTR-8/SVneo cells with HGF led to a dose-dependent increase in their migration. RT-PCR studies revealed a significant increase in the transcripts of WNT4, WNT11, ITGA2, and ITGAV, which was further confirmed at protein level by Western blotting. HGF treatment also led to increased expression of integrin α2ß1 and αVß5 in HTR-8/SVneo cells. Silencing of WNT4, WNT11, ITGA2, and ITGAV by siRNA led to a significant decrease in HGF-mediated migration of cells. Treatment of cells with HGF led to activation of mitogen-activated protein kinases (MAPK) and protein kinase A (PKA) signaling pathways. Inhibition of MAPK/PKA, by selective inhibitors, led to decrease in the expression of above WNT ligands and integrins. Silencing of WNT4/WNT11 led to concomitant decrease in the expression of ITGA2 and ITGAV and vice versa. HGF treatment also led to significant increase in ß-catenin expression, a downstream target of both WNT ligands and integrins. Silencing of ß-catenin led to decrease in HGF-mediated migration. ß-catenin expression was also down-regulated in WNT4/WNT11/ITGA2/ITGAV silenced cells suggesting a possible cross-communication of WNT ligands and integrins via ß-catenin. These studies have established the significance of WNT4/WNT11 as well as ITGA2/ITGAV during HGF-mediated migration of HTR-8/SVneo trophoblastic cells.

Anisotropic mechanics and dynamics of a living mammalian cytoplasm.

During physiological processes, cells can undergo morphological changes that can result in a significant redistribution of the cytoskeleton causing anisotropic behavior. Evidence of anisotropy in cells under mechanical stimuli exists; however, the role of cytoskeletal restructuring resulting from changes in cell shape in mechanical anisotropy and its effects remain unclear. In the present study, we examine the role of cell morphology in inducing anisotropy in both intracellular mechanics and dynamics. We change the aspect ratio of cells by confining the cell width and measuring the mechanical properties of the cytoplasm using optical tweezers in both the longitudinal and transverse directions to quantify the degree of mechanical anisotropy. These active microrheology measurements are then combined with intracellular movement to calculate the intracellular force spectrum using force spectrum microscopy (FSM), from which the degree of anisotropy in dynamics and force can be quantified. We find that unrestricted cells with aspect ratio (AR) ∼1 are isotropic; however, when cells break symmetry, they exhibit significant anisotropy in cytoplasmic mechanics and dynamics.

Measles-Rubella Supplementary Immunization Activity Readiness Assessment - India, 2017-2018.

In 2013, during the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR), the 11 SEAR countries* adopted goals to eliminate measles and control rubella and congenital rubella syndrome by 2020† (1). To accelerate progress in India (2,3), a phased§ nationwide supplementary immunization activity (SIA)¶ using measles-rubella vaccine and targeting approximately 410 million children aged 9 months-14 years commenced in 2017 and will be completed by first quarter of 2019. To ensure a high-quality SIA, planning and preparation were monitored using a readiness assessment tool adapted from the WHO global field guide** (4) by the India Ministry of Health and Family Welfare. This report describes the results and experience gained from conducting SIA readiness assessments in 24 districts of three Indian states (Andhra Pradesh, Kerala, and Telangana) during the second phase of the SIA. In each selected area, assessments were conducted 4-6 weeks and 1-2 weeks before the scheduled SIA. At the first assessment, none of the states and districts were on track with preparations for the SIA. However, at the second assessment, two (67%) states and 21 (88%) districts were on track. The SIA readiness assessment identified several preparedness gaps; early assessment results were immediately communicated to authorities and led to necessary corrective actions to ensure high-quality SIA implementation.

Prevalence and coexistence of KRAS, BRAF, PIK3CA, NRAS, TP53, and APC mutations in Indian colorectal cancer patients: Next-generation sequencing-based cohort study.

Colorectal cancer incidences are on a rise in India. In this study, we have analyzed the mutation frequencies of six potential biomarkers, their coexistence, association with clinicopathological characteristics, and tumor location in Indian colorectal cancer patients. Next-generation sequencing was performed to identify mutations in the six potential biomarker genes using formalin-fixed paraffin-embedded tissue blocks of 112 colorectal cancer patients. The mutation frequency observed in KRAS, BRAF, PIK3CA, NRAS, TP53, and APC was 35.7%, 7.1%, 16.1%, 6.3%, 39.3%, and 29.5%, respectively. The significant associations of mutations were KRAS with age less than 60 years (p = 0.041), PIK3CA with males (p = 0.032), tumor stage I-II (p = 0.013), lack of metastasis in lymph nodes (p = 0.040), NRAS with rectum (p = 0.002), and APC with T2 stage of tumor growth (p = 0.013). No single patient harbored mutations in these six genes or any five genes simultaneously. Significance was noted in coexistence of KRAS with APC (p = 0.024) and mutual exclusion of KRAS with BRAF (p = 0.029). PIK3CA exon 9 was observed to be more frequently associated with KRAS mutations than PIK3CA exon 20 (p = 0.072). NRAS mutations were mutually exclusive with BRAF and PIK3CA mutations. As per our knowledge, this is the first next-generation sequencing-based biomarker study in Indian colorectal cancer patients. Frequent coexistence of gene mutations in pairs and triplets suggests that synergistic effect of overlapping mutations might further trigger the disease. In addition, infrequent coexistence of multiple gene mutations hints toward different signaling pathways for colorectal cancer tumorigenesis.

Relevance of the NR4A sub-family of nuclear orphan receptors in trophoblastic BeWo cell differentiation.

Nur-77, a member of the NR4A sub-family of nuclear orphan receptors, is downregulated in the placentae of pre-eclamptic women. Here, we investigate the relevance of Nor-1, Nurr-1 and Nur-77 in trophoblastic cell differentiation. Their transcript levels were found to be significantly upregulated in BeWo cells treated with forskolin. The maximum increase was observed after 2 h, with a second peak in the expression levels after 48 h. The expression of NR4A sub-family members was also found to be upregulated in BeWo cells after treatment with hCG and GnRH. A similar significant increase was observed at the respective protein levels after 2 and 48 h of treatment with forskolin, hCG or GnRH. Silencing Nor-1, Nurr-1 or Nur-77 individually did not show any effect on forskolin-, hCG- and/or GnRH-mediated BeWo cell fusion and/or hCG secretion. After silencing any one member of the NR4A sub-family, an increase in the transcript levels of the other sub-family members was observed, indicating a compensatory effect due to their functional redundancy. Simultaneously silencing all three NR4A sub-family members significantly downregulated forskolin- and hCG-mediated BeWo cell fusion and/or hCG secretion. However, a considerable amount of cell death occurred after forskolin or hCG treatment as compared to the control siRNA-transfected cells. These results suggest that the NR4A sub-family of nuclear orphan receptors has a role in trophoblastic cell differentiation.

Anti-HSV-2 activity of Terminalia chebula Retz extract and its constituents, chebulagic and chebulinic acids.

BACKGROUND: Development of new and effective therapeutics for sexually transmitted herpes simplex virus-2 (HSV-2) infection is important from public health perspective. With an aim to identify natural products from medicinal plants, in the present study, the potential of Terminalia chebula Retz was investigated for its activity against HSV-2. METHODS: Fruits of Terminalia chebula Retz were used to prepare 50% ethanolic extract. In addition, chebulagic acid and chebulinic acid both purified from T. chebula were also used. The extract as well as purified compounds were first used to determine their in vitro cytotoxicity on Vero cells by MTT assay. T. chebula extract, chebulagic acid, chebulinic acid along with acyclovir were subsequently assessed for direct anti-viral activity, and their ability to inhibit attachment and penetration of HSV-2 to the Vero cells. In addition, their anti-HSV-2 activity was also determined by in vitro post-infection plaque reduction assay. RESULTS: Cytotoxicity assay using Vero cells revealed CC50 = 409.71 ± 47.70 µg/ml for the extract whereas chebulagic acid and chebulinic acid showed more than 95% cell viability up to 200 µg/ml. The extract from T. chebula (IC50 = 0.01 ± 0.0002 µg/ml), chebulagic (IC50 = 1.41 ± 0.51 µg/ml) and chebulinic acids (IC50 = 0.06 ± 0.002 µg/ml) showed dose dependent potent in vitro direct anti-viral activity against HSV-2. These also effectively prevented the attachment as well as penetration of the HSV-2 to Vero cells. In comparison, acyclovir showed poor direct anti-viral activity and failed to significantly (p > 0.05) prevent the attachment as well as penetration of HSV-2 to Vero cells when tested upto 50 µg/ml. However, in post-infection plaque reduction assay, T. chebula extract, chebulagic and chebulinic acids showed IC50 values of 50.06 ± 6.12, 31.84 ± 2.64, and 8.69 ± 2.09 µg/ml, respectively, which were much lower than acyclovir (71.80 ± 19.95 ng/ml). CONCLUSIONS: The results presented herein suggest that T. chebula extract, chebulagic and chebulinic acids have higher direct antiviral activity against HSV-2 and efficacy to inhibit virus attachment and penetration to the host cells as compared to acyclovir. However, acyclovir is more potent to inhibit post-infection virus replication. Hence, T. chebula may be a useful candidate for developing alternative therapy for prevention of sexually transmitted HSV-2 infection. ᅟ.

Novel Sperm and Gonadotropin-releasing Hormone-based Recombinant Fusion Protein: Achievement of 100% Contraceptive Efficacy by Co-immunization of Male and Female Mice.

Improvements in long-term female contraception can be achieved by vaccinating with sperm-derived proteins. Here, recombinant proteins comprising either (i) N- (amino acid residues 1-80) or C- (amino acid residues 76-126) terminal fragments of mouse sperm protein 17 (Sp17) fused to the promiscuous T non-B cell epitope of tetanus toxoid (TT), amino acid residues 830-844 followed by di-lysine linker (KK) (TT-KK-Sp17N or TT-KK-Sp17C , respectively) or (ii) mouse equatorin (amino acid residues 21-185) fused to the T non-B cell epitope of bovine RNase (amino acid residues 94-104) were expressed in Escherichia coli. Immunization of female FVB/J mice, using alum as an adjuvant, led to the generation of high antibody titers against the above proteins. Antibodies against both N- and C-terminal fragments of Sp17 reacted with the entire capacitated mouse spermatozoa, whereas those against equatorin reacted exclusively with the equatorial region. Despite the reactivity of all immune sera, only sera from mice immunized with TT-KK-Sp17N and TT-KK-Sp17C significantly reduced mouse in vitro fertilization. Mating studies of the immunized females with un-immunized male mice revealed the highest infertility in the TT-KK-Sp17C -immunized group. In an attempt to further boost the immune response, the C-terminal fragment of Sp17 was expressed as fusion protein with a tandem repeat of gonadotropin-releasing hormone (GnRH) (Sp17C -GnRH2 ). Immunization of both male and female mice with Sp17C -GnRH2 led to higher contraceptive efficacy compared to mice immunized with TT-KK-Sp17C . Interestingly, mating studies wherein partners were both immunized with Sp17C -GnRH2 showed a complete failure of female mice to conceive. Thus, immunization of both males and females with Sp17C -GnRH2 has the potential to increase contraceptive efficacy. Mol. Reprod. Dev. 83: 1048-1059, 2016. © 2016 Wiley Periodicals, Inc.

Estimation of child vaccination coverage at state and national levels in India.

OBJECTIVE: To review the data, for 1999-2013, on state-level child vaccination coverage in India and provide estimates of coverage at state and national levels. METHODS: We collated data from administrative reports, population-based surveys and other sources and used them to produce annual estimates of vaccination coverage. We investigated bacille Calmette-Guérin vaccine, the first and third doses of vaccine against diphtheria, tetanus and pertussis, the third dose of oral polio vaccine and the first dose of vaccine against measles. We obtained relevant data covering the period 1999-2013 for each of 16 states and territories and the period 2001-2013 for the state of Jharkhand - which was only created in 2000. We aggregated the resultant state-level estimates, using a population-weighted approach, to give national values. FINDINGS: For each of the vaccinations we investigated, about half of the 253 estimates of annual coverage at state level that we produced were based on survey results. The rest were based on interpolation between - or extrapolation from - so-called anchor points or, more rarely, on administrative data. Our national estimates indicated that, for each of the vaccines we investigated, coverage gradually increased between 1999 and 2010 but then levelled off. CONCLUSION: The delivery of routine vaccination services to Indian children appears to have improved between 1999 and 2013. There remains considerable scope to improve the recording and reporting of childhood vaccination coverage in India and regular systematic reviews of the coverage data are recommended.