Partial Maturation Research Articles

Spontaneous Puberty in a Male with Heterozygous PROK2 Gene Mutation Presenting with Micropenis and Synkinesis

Male idiopathic hypogonadotropic hypogonadism is characterized by absent or partial sexual maturation. The Prok2/ProkR2 genes are among the genes implicated in this condition. Objective: Reporting a case harbouring a missense mutation in the PROK2 gene, presenting, at 7 1/2 years with micropenis and synkinesis. History and Examination: Born at full term, with no pre/post-natal complications. On presentation his penile stretched length was 3.8 cm, (-2.5 SDS). Both testes were descended, with a testicular volume of 2ml. Results: On follow up, the testicular volume of 4ml bilaterally, was detected at 11 1/2 years, after 3 testosterone monthly injections. The penile length increased to 5.2 cm. Puberty continued to progress spontaneously. Genetic Analysis revealed a heterozygous missense mutation in PROK2 gene, exon 4, chromosome 3. Conclusion: Heterozygous mutations in the PROK2 gene can present with reproductive and non-reproductive manifestations. They may progress spontaneously into puberty, in the absence of micro/cryptorchidism.

Curie Point Depth from Spectral Analysis of Magnetic Data in Potiskum and Environs, Yobe State, Nigeria

The area under investigation, is part of Chad basin of northeastern Nigeria, located between latitudes 11o00´ to 12o00´N and Longitudes 11o30´ to 12o30´E, with the objective to discover more about the thermal structure of the crust in the area, a research was carried out over Potiskum and surrounding regions in Yobe State, Nigeria to estimate the curie point depth, geothermal gradient, and heat flow using spectrum analysis and empirical formula of aeromagnetic data. To acquire the regional and residual data, polynomial fitting was applied to the high-resolution digital aeromagnetic data. In order to calculate the depth to the centroid and the depth to the top boundary, the upward continued residual data was processed to produce the upward continued data, that was subjected to spectral analysis. The depth to the centroid is between 10.50 and 11.50 kilometers, the depth to the top boundary is between 5.90 and 7.16 kilometers, the depth to the Curie point is between 14.84 and 16.83 kilometers, the geothermal gradient is between 34.462 and 39.083 oCkm-1, and the heat flow is between 86.135 and 97.707 mWm-2. The Curie point depth inferred from the study indicates that the crust is thinning due to thermal upwhirling of magma and is moderately decreasing toward areas of volcanic activity that occurred in the area during the Tertiary Period. The Geothermal gradient shows that the area is a moderate temperature zone, which could likely result in partial thermal maturation of sediments and hence probable oil generation as time goes on with an increase in temperature. In the research area, the geothermal gradient is proportional to the heat flow, whereas the connection between curie depth and heat flow is inversely linear. These findings are in line with the geotectonic regime that is now in effect in the research area. However, this analysis shows that the heat flow that was obtained from the study is sufficient to be utilized as a geothermal energy source.

Steroidogenesis and androgen/estrogen signaling pathways are altered in in vitro matured testicular tissues of prepubertal mice

Children undergoing cancer treatments are at risk for impaired fertility. Cryopreserved prepubertal testicular biopsies could theoretically be later matured in vitro to produce spermatozoa for assisted reproductive technology. A complete in vitro spermatogenesis has been obtained from mouse prepubertal testicular tissue, although with low efficiency. Steroid hormones are essential for the progression of spermatogenesis, the aim of this study was to investigate steroidogenesis and steroid signaling in organotypic cultures. Histological, RT-qPCR, western blot analyses, and steroid hormone measurements were performed on in vitro cultured mouse prepubertal testicular tissues and age-matched in vivo controls. Despite a conserved density of Leydig cells after 30 days of culture (D30), transcript levels of adult Leydig cells and steroidogenic markers were decreased. Increased amounts of progesterone and estradiol and reduced androstenedione levels were observed at D30, together with decreased transcript levels of steroid metabolizing genes and steroid target genes. hCG was insufficient to facilitate Leydig cell differentiation, restore steroidogenesis, and improve sperm yield. In conclusion, this study reports the failure of adult Leydig cell development and altered steroid production and signaling in tissue cultures. The organotypic culture system will need to be further improved before it can be translated into clinics for childhood cancer survivors.

Male minipuberty in human and non-human primates: planting the seeds of future fertility.

Minipuberty is a transient activity period of the hypothalamic-pituitary-gonadal axis in the postnatal and infant period including surging serum concentrations of reproductive hormones. Increasing evidence points to an important role of this period for maturation of the testes and thereby for male reproductive function. Minipuberty is a transient activity period of the hypothalamic-pituitary-gonadal (HPG) axis in the postnatal and infant period in humans and non-human primates. Hallmarks of this period are surging serum concentrations of reproductive hormones. While in females, the role of minipuberty seems to be dispensable for future fertility, in males, it is significantly associated with reproductive function in later life. In males, this activity period promotes further masculinization, including testicular and penile growth, as well as completion of testicular descent if not already achieved at birth. At the testicular level, both, somatic and germ cells undergo proliferation and partial maturation during this period. Minipuberty is thought to prime male gonadal tissue for subsequent growth and maturation. Notably, perturbed or absent minipuberty is associated with reduced male reproductive function in adulthood. While the sustained HPG axis activity during adulthood is known to control reproductive function, minipuberty appears to be a prerequisite for obtaining full male reproductive function in later life, thereby determining future fertility potential, i.e. the ability to father a child. This review maps the role of male minipuberty for reproductive function and presents suitable animal models to study minipuberty. Also, it describes the development and maturation of testicular cell types, discusses short- and long-term effects of minipuberty and highlights future research perspectives.

Systematization of Nursing Care: how did the concept mature?

to analyze the Systematization of Nursing Care conceptual maturation from the perspective of pragmatic utility. a concept analysis study. The stages were: select the concept; elaborate analytical questions; comprehensively review the literature; and determine concept structural components. Sixty-one documents were analyzed after a search carried out until October 2019. four temporal periods of contextual changes have occurred since the emergence of ideas of a systematization in the 1960s. This first lasted until 1990. It was followed by those from 1990 to 2002, from 2002 to 2009 and from 2009 onwards. Partial conceptual maturity was identified, operationalization over the years, based on multiple definitions, and, currently, a concept of Systematization of Nursing Care with managerial and organizational attributes. the concept of Systematization of Nursing Care is partially mature, presents multiple definitions, being operationalized in uncertain connections with other concepts.

Innate and adaptive immune evasion by dengue virus.

Dengue is a mosquito-borne disease which causes significant public health concerns in tropical and subtropical countries. Dengue virus (DENV) has evolved various strategies to manipulate the innate immune responses of the host such as ‘hiding’ in the ultrastructure of the host, interfering with the signaling pathway through RNA modifications, inhibiting type 1 IFN production, as well as inhibiting STAT1 phosphorylation. DENV is also able to evade the adaptive immune responses of the host through antigenic variation, antigen-dependent enhancement (ADE), partial maturation of prM proteins, and inhibition of antigen presentation. miRNAs are important regulators of both innate and adaptive immunity and they have been shown to play important roles in DENV replication and pathogenesis. This makes them suitable candidates for the development of anti-dengue therapeutics. This review discusses the various strategies employed by DENV to evade innate and adaptive immunity. The role of miRNAs and DENV non-structural proteins (NS) are promising targets for the development of anti-dengue therapeutics.

Measuring innovative capability maturity model of trucking companies in Indonesia

Trucking companies are important part of supply chains, as they connect most of product movements. While a lot of studies have been done to assess supply chain maturity level, very limited studies have been done to specifically address trucking companies. In this study we develop a model and measurement instruments to assess maturity of trucking companies in terms of their innovative capabilities. Innovative capabilities are critical in today's fast technological development such as industry 4.0 and trucking companies have opportunities to use those technologies to play a better role in the supply chain they involve in. We then use the instruments to assess the maturity level of 52 companies that involved in transporting goods using trucks. The results show that the maturity level has a widespread, ranging from the lowest to the highest level, but most of them are in the category of partial maturity to mature. This indicates that most companies have an opportunity to improve their innovative capabilities.

Mid-Liver Stage Arrest of Plasmodium falciparum Schizonts in Primary Porcine Hepatocytes.

During co-evolution Plasmodium parasites and vertebrates went through a process of selection resulting in defined and preferred parasite-host combinations. As such, Plasmodium falciparum (Pf) sporozoites can infect human hepatocytes while seemingly incompatible with host cellular machinery of other species. The compatibility between parasite invasion ligands and their respective human hepatocyte receptors plays a key role in Pf host selectivity. However, it is unclear whether the ability of Pf sporozoites to mature in cross-species infection also plays a role in host tropism. Here we used fresh hepatocytes isolated from porcine livers to study permissiveness to Pf sporozoite invasion and development. We monitored intra-hepatic development via immunofluorescence using anti-HSP70, MSP1, EXP1, and EXP2 antibodies. Our data shows that Pf sporozoites can invade non-human hepatocytes and undergo partial maturation with a significant decrease in schizont numbers between day three and day five. A possible explanation is that Pf sporozoites fail to form a parasitophorous vacuolar membrane (PVM) during invasion. Indeed, the observed aberrant EXP1 and EXP2 staining supports the presence of an atypical PVM. Functions of the PVM include the transport of nutrients, export of waste, and offering a protective barrier against intracellular host effectors. Therefore, an atypical PVM likely results in deficiencies that may detrimentally impact parasite development at multiple levels. In summary, despite successful invasion of porcine hepatocytes, Pf development arrests at mid-stage, possibly due to an inability to mobilize critical nutrients across the PVM. These findings underscore the potential of a porcine liver model for understanding the importance of host factors required for Pf mid-liver stage development.

Benefits of a Single Dose of Betamethasone in Imminent Preterm Labour.

Background: A complete course of prenatal corticosteroids reduces the possibility of morbimortality and neonatal respiratory distress syndrome (RDS). Occasionally, it is not possible to initiate or complete the maturation regimen, and the preterm neonate is born in a non-tertiary hospital. This study aimed to assess the effects of a single dose of betamethasone within 3 h before delivery on serious outcomes (mortality and serious sequelae) and RDS in preterm neonates born in tertiary vs. non-tertiary hospitals. Materials and methods: Preterm neonates who were <35 weeks and ≤1500 g, treated during a period of five years in a level IIIC NICU, were included in this retrospective cohort study. Participants were divided into groups as follows: NM, non-matured; PM, partial maturation (one dose of betamethasone up to 3 h antepartum). They were further divided based on their place of birth (NICU-IIIC vs. non-tertiary hospitals). The morbimortality rates and the severity of neonatal RDS were evaluated. Results: A total of 76 preterm neonates were included. A decrease in serious outcomes was found in the PM group in comparison to the NM group (OR = 0.2; 95%CI (0.07–0.9)), as well as reduced need for mechanical ventilation (54% vs. 68%). The mean time between maternal admission and birth was similar in both cohorts. The mean time from the administration of betamethasone to delivery was 1 h in the PM cohort. With regard to births in NICU-IIIC, the PM group performed better in terms of serious outcomes (32% vs. 45%) and the duration of mechanical ventilation (117.75 vs. 132.18 h) compared to the NM group. In neonates born in non-tertiary hospitals with PM in comparison to the NM group, a trend towards a reduced serious outcome (28.5% vs. 62.2%) and a decreased need for mechanical ventilation (OR = 0.09; 95%CI (0.01–0.8)) and maximum FiO2 (p = 0.01) was observed. Conclusions: A single dose of betamethasone up to 3 h antepartum may reduce the rate of serious outcomes and the severity of neonatal RDS, especially in non-tertiary hospitals.

Use of the e-Delphi Method to Validate the Corporate Reputation Management Maturity Model (CR3M)

Information and communication technologies (ICT) have allowed the modification of many research methods based on communication. One of them is the Delphi method, especially e-Delphi. The two main areas of application of the Delphi method are traditional forecasting, but recently also the conceptual framework development of a model or theory, especially in complex domains and those where empirical research is lacking. The aim of the study was to assess the substantive accuracy (validation) of the enterprise reputation management maturity model (CR3M) using the modified e-Delphi. The final model will be tested in selected companies in the future (in the next stage of the research). Maturity models have long been regarded as tools for assessing skills in some field. The CR3M model originally included 96 practices (in four areas: communication management, corporate social responsibility, reputational risk and quality), the implementation of which was considered to be a maturity indicator. The basis for the development of the model was the literature on the subject and the existing partial maturity models. Ten experts (five theorists and five practitioners) participated in the study and assessed the appropriateness of including practices in the model and their validity, using a 5-point Likert scale. The questionnaire consisted of three questions. In two rounds of the Delphi study, an expert consensus was reached (in accordance with a priori established indicators) regarding the retention 70 out of 96 practices originally included in the model (26 deleted). The model retained 18 practices in the area of Communication Management, 14 practices in the area of Corporate Social Responsibility, 18 practices in the field of Reputation Risk Management and 20 practices in the field of Quality Management. Modification of the maturity model-reducing the number of practices included in the model increased its applicability. At the same time, 89% of experts found the presented maturity model a useful tool for self-assessment and improvement of reputation management. The modified e-Delphi procedure can be considered as an effective methodology for validating complex conceptual models.

‘Zeitoun Ennour’: A new olive (Olea europaea L.) cultivar in Tunisia with high oil quality

An olive breeding program was started in Tunisia in 1993 in order mainly to improve the fatty acid composition of the local cultivar ‘Chemlali Sfax’. ‘Zeitoun Ennour’ is a new cultivar obtained from a cross between ‘Chemlali Sfax’ and the local dual-purpose use cultivar ‘Chemchali Gafsa’. The morphological study of this cultivar showed that eleven characters dealing with fruit and endocarp differed from ‘Chemlali Sfax’, mainly regarding to their respective weights. This new cultivar had the same sensitivity to Verticillium dahliae Kleb and earlier bearing than the original variety. Its olive production was considered as high as for ‘Chemlali Sfax’ but with partial self-compatibility and late maturity. The new cultivar realized a net improvement in comparison with the original cultivar particularly regarding its fatty acid composition with very high oleic acid content (&gt;75 %) and low palmitic and linoleic acid contents (&lt;10 %). The new cultivar was recently released and will be available for growers as soon as possible.

‘Zeitoun Ennour’: A new olive (Olea europaea L.) cultivar in Tunisia with high oil quality

An olive breeding program was started in Tunisia in 1993 in order mainly to improve the fatty acid composition of the local cultivar ‘Chemlali Sfax’. ‘Zeitoun Ennour’ is a new cultivar obtained from a cross between ‘Chemlali Sfax’ and the local dual-purpose use cultivar ‘Chemchali Gafsa’. The morphological study of this cultivar showed that eleven characters dealing with fruit and endocarp differed from ‘Chemlali Sfax’, mainly regarding to their respective weights. This new cultivar had the same sensitivity to Verticillium dahliae Kleb and earlier bearing than the original variety. Its olive production was considered as high as for ‘Chemlali Sfax’ but with partial self-compatibility and late maturity. The new cultivar realized a net improvement in comparison with the original cultivar particularly regarding its fatty acid composition with very high oleic acid content (&gt;75 %) and low palmitic and linoleic acid contents (&lt;10 %). The new cultivar was recently released and will be available for growers as soon as possible.

Effect of different thawing methods on the quality of mackerel (Pneumatophorus japonicus)

Five thawing methods such as flow water thawing, ultrasonic flowing water thawing, air thawing, microwave thawing and low temperature thawing were used, and the physical, chemical properties and structure of mackerels after thawing were assessed. The results showed that the low temperature thawing had the best water retention, lower protein and fat oxidation. The microwave thawing had the shortest thawing time, but uneven heating leads to partial maturation. Air thawing prolonged exposure to air leads to high levels of protein and fat oxidation. The flow water thawing had better water retention than that of the ultrasonic flowing water thawing, only the thawing time was slightly longer than that of the ultrasonic flowing water thawing. In general, the low temperature thawing performed well after thawing. The flow water thawing used only 1/43 of the low temperature thawing's elapsed time after sacrificing some acceptable qualities. Thus, flow water thawing is more suitable for thawing frozen mackerel.

Crosstalk Between Dermal Fibroblasts and Dendritic Cells During Dengue Virus Infection.

Dengue virus infection (DENV-2) is transmitted by infected mosquitoes via the skin, where many dermal and epidermal cells are potentially susceptible to infection. Most of the cells in an area of infection will establish an antiviral microenvironment to control viral replication. Although cumulative studies report permissive DENV-2 infection in dendritic cells, keratinocytes, and fibroblasts, among other cells also infected, little information is available regarding cell-to-cell crosstalk and the effect of this on the outcome of the infection. Therefore, our study focused on understanding the contribution of fibroblast and dendritic cell crosstalk to the control or promotion of dengue. Our results suggest that dendritic cells promote an antiviral state over fibroblasts by enhancing the production of type I interferon, but not proinflammatory cytokines. Infected and non-infected fibroblasts promoted partial dendritic cell maturation, and the fibroblast-matured cells were less permissive to infection and showed enhanced type I interferon production. We also observed that the soluble mediators produced by non-infected or Poly (I:C) transfected fibroblasts induced allogenic T cell proliferation, but mediators produced by DENV-2 infected fibroblasts inhibited this phenomenon. Additionally, the effects of fibroblast soluble mediators on CD14+ monocytes were analyzed to assess whether they affected the differentiation of monocyte derived dendritic cells (moDC). Our data showed that mediators produced by infected fibroblasts induced variable levels of monocyte differentiation into dendritic cells, even in the presence of recombinant GM-CSF and IL-4. Cells with dendritic cell-like morphology appeared in the culture; however, flow cytometry analysis showed that the mediators did not fully downregulate CD14 nor did they upregulate CD1a. Our data revealed that fibroblast-dendritic cell crosstalk promoted an antiviral response mediated manly by type I interferons over fibroblasts. Furthermore, the maturation of dendritic cells and T cell proliferation were promoted, which was inhibited by DENV-2-induced mediators. Together, our results suggest that activation of the adaptive immune response is influenced by the crosstalk of skin resident cells and the intensity of innate immune responses established in the microenvironment of the infected skin.

Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment.

Simple SummarySubstantial strides have been made in treating childhood cancers; however, as a result of chemotherapy and radiotherapy, young males experience long-term side effects, including impaired fertility. Whilst prepubertal testicular tissue can be cryopreserved prior to gonadotoxic treatments, it remains to be determined how to generate mature gametes from the immature human testis tissue. Development of immature germ cells into sperm is a complex process, which is supported by mature Sertoli cells and testosterone produced from Leydig cells. We used an established testicular xenotransplantation model to investigate the effect of puberty hormones, known as gonadotrophins, on functional maturation of the spermatogonial stem cell (SSC) niche. Limited testosterone production and partial maturation of Sertoli cells occurred in prepubertal testis grafts, suggesting that longer periods of grafting and/or identification of additional factors are required to develop testicular transplantation as a model for fertility preservation in male survivors of childhood cancer.Survivors of childhood cancer are at risk for long-term treatment-induced health sequelae, including gonadotoxicity and iatrogenic infertility. At present, for prepubertal boys there are no viable clinical options to preserve future reproductive potential. We investigated the effect of a pubertal induction regimen with gonadotrophins on prepubertal human testis xenograft development. Human testis tissue was obtained from patients with cancer and non-malignant haematological disorders (n = 6; aged 1–14 years) who underwent testis tissue cryopreservation for fertility preservation. Fresh and frozen-thawed testis fragments were transplanted subcutaneously or intratesticularly into immunocompromised mice. Graft-bearing mice received injections of vehicle or exogenous gonadotrophins, human chorionic gonadotrophin (hCG, 20 IU), and follicle-stimulating hormone (FSH, 12.5 IU) three times a week for 12 weeks. The gross morphology of vehicle and gonadotrophin-exposed grafts was similar for both transplantation sites. Exposure of prepubertal human testis tissue xenografts to exogenous gonadotrophins resulted in limited endocrine function of grafts, as demonstrated by the occasional expression of the steroidogenic cholesterol side-chain cleavage enzyme (CYP11A1). Plasma testosterone concentrations (0.13 vs. 0.25 ng/mL; p = 0.594) and seminal vesicle weights (10.02 vs. 13.93 mg; p = 0.431) in gonadotrophin-exposed recipient mice were comparable to vehicle-exposed controls. Regardless of the transplantation site and treatment, initiation and maintenance of androgen receptor (AR) expression were observed in Sertoli cells, indicating commitment towards a more differentiated status. However, neither exogenous gonadotrophins (in castrated host mice) nor endogenous testosterone (in intact host mice) were sufficient to repress the expression of markers associated with immature Sertoli cells, such as anti-Müllerian hormone (AMH) and Ki67, or to induce the redistribution of junctional proteins (connexin 43, CX43; claudin 11, CLDN11) to areas adjacent to the basement membrane. Spermatogonia did not progress developmentally but remained the most advanced germ cell type in testis xenografts. Overall, these findings demonstrate that exogenous gonadotrophins promote partial activation and maturation of the somatic environment in prepubertal testis xenografts. However, alternative hormone regimens or additional factors for pubertal induction are required to complete the functional maturation of the spermatogonial stem cell (SSC) niche.

Spatial attention and representation of time intervals in childhood

Spatial attention and spatial representation of time are strictly linked in the human brain. In young adults, a leftward shift of spatial attention by prismatic adaptation (PA), is associated with an underestimation whereas a rightward shift is associated with an overestimation of time both for visual and auditory stimuli. These results suggest a supra-modal representation of time left-to-right oriented that is modulated by a bilateral attentional shift. However, there is evidence of unilateral, instead of bilateral, effects of PA on time in elderly adults suggesting an influence of age on these effects. Here we studied the effects of spatial attention on time representation focusing on childhood. Fifty-four children aged from 5 to 11 years-old performed a temporal bisection task with visual and auditory stimuli before and after PA inducing a leftward or a rightward attentional shift. Results showed that children underestimated time after a leftward attentional shift either for visual or auditory stimuli, whereas a rightward attentional shift had null effect on time. Our results are discussed as a partial maturation of the link between spatial attention and time representation in childhood, due to immaturity of interhemispheric interactions or of executive functions necessary for the attentional complete influence on time representation.

Multidimensional study of the heterogeneity of leukemia cells in t(8;21) acute myelogenous leukemia identifies the subtype with poor outcome

t(8;21)(q22;q22) acute myelogenous leukemia (AML) is morphologically characterized by a continuum of heterogeneous leukemia cells from myeloblasts to differentiated myeloid elements. Thus, t(8;21) AML is an excellent model for studying heterogeneous cell populations and cellular evolution during disease progression. Using integrative analyses of immunophenotype, RNA-sequencing (RNA-seq), and single-cell RNA-sequencing (scRNA-seq), we identified three distinct intrapatient leukemic cell populations that were arrested at different stages of myeloid differentiation: CD34+CD117dim blasts, CD34+CD117bri blasts, and abnormal myeloid cells with partial maturation (AM). CD117 is also known as c-KIT protein. CD34+CD117dim cells were blocked in the G0/G1 phase at disease onset, presenting with the regular morphology of myeloblasts showing features of granulocyte-monocyte progenitors (GMP), and were drug-resistant to chemotherapy. Genes associated with cell migration and adhesion (LGALS1, EMP3, and ANXA2) were highly expressed in the CD34+CD117dim population. CD34+CD117bri blasts were blocked a bit later than the CD34+CD117dim population in the hematopoietic differentiation stage and displayed high proliferation ability. AM cells, which bear abnormal myelocyte morphology, especially overexpressed granule genes AZU1, ELANE, and PRTN3 and were sensitive to chemotherapy. scRNA-seq at different time points identified CD34+CD117dim blasts as an important leukemic cluster that expanded at postrelapse refractory stage after several cycles of chemotherapy. Patients with t(8;21) AML with a higher proportion of CD34+CD117dim cells had significantly worse clinical outcomes than those with a lower CD34+CD117dim proportion. Univariate and multivariate analyses identified CD34+CD117dim proportion as an independent factor for poor disease outcome. Our study provides evidence for the multidimensional heterogeneity of t(8;21)AML and may offer new tools for future disease stratification.

Nested Protein Lattices in a Giant Phage Capsid Suggest Partial Maturation and a Residual Scaffold

Nested Protein Lattices in a Giant Phage Capsid Suggest Partial Maturation and a Residual Scaffold

Understanding the transfer of contemporary temperature signals into lake sediments via paired oxygen isotope ratios in carbonates and diatom silica: Problems and potential

Although the oxygen isotope composition (δ18O) of calcite (δ18Ocalcite) and, to a lesser extent, diatom silica (δ18Odiatom) are widely used tracers of past hydroclimates (especially temperature and surface water hydrology), the degree to which these two hosts simultaneously acquire their isotope signals in modern lacustrine environments, or how these are altered during initial sedimentation, is poorly understood. Here, we present a unique dataset from a natural limnological laboratory to explore these issues. This study compares oxygen and hydrogen isotope data (δ18O, δ2H) of contemporary lake water samples at ~2-weekly intervals over a 2-year period (2010–12) with matching collections of diatoms (δ18Odiatom) and calcite (δ18Ocalcite) from sediment traps (at 10 m and 25 m) at Rostherne Mere (maximum depth 30 m), a well-monitored, eutrophic, seasonally stratified monomictic lake in the UK. The epilimnion shows a seasonal pattern of rising temperature and summer evaporative enrichment in 18O, and while there is a temperature imprint in both δ18Odiatom and δ18Ocalcite, there is significant inter-annual variability in both of these signals. The interpretation of δ18Odiatom and δ18Ocalcite values is complicated due to in-lake processes (e.g. non-equilibrium calcite precipitation, especially in spring, leading to significant 18Ocalcite depletion), and for δ18Odiatom, by post-mortem, depositional and possibly dissolution or diagenetic effects. For 2010 and 2011 respectively, there is a strong temperature dependence of δ18Ocalcite and δ18Odiatom in fresh trap material, with the fractionation slope for δ18Odiatom of ca. −0.2‰/°C, in agreement with several other studies. The δ18Odiatom data indicate the initiation of rapid post-mortem secondary alteration of fresh diatom silica (within ~6 months), with some trap material undergoing partial maturation in situ. Diatom δ18O of the trap material is also influenced by resuspension of diatom frustules from surface sediments (notably in summer 2011), with the net effect seen as an enrichment of deep-trap 18Odiatom by about +0.7‰ relative to shallow-trap values. Contact with anoxic water and anaerobic bacteria are potentially key to initiating this silica maturation process, as deep-trap samples that were removed prior to anoxia developing do not show enrichment. Dissolution (perhaps enhanced by anaerobic bacterial communities) may also be responsible for changes to δ18Odiatom that lead to increasing, but potentially predictable, error in inferred temperatures using this proxy. High resolution, multi-year monitoring can shed light on the complex dynamics affecting δ18Odiatom and δ18Ocalcite and supports the careful use of sedimentary δ18Odiatom and δ18Ocalcite as containing valuable hydroclimatic signals especially at a multi-annual resolution, although there remain substantial challenges to developing a reliable geothermometer on paired δ18Odiatom and δ18Ocalcite. In particular, δ18Odiatom needs cautious interpretation where silica post-mortem secondary alteration is incomplete and diatom preservation is not perfect, and we recommend dissolution be routinely assessed on diatom samples used for isotopic analyses.

ДЕЙСТВИЕ КОРЕВОЙ ВАКЦИНЫ НА СОЗРЕВАНИЕ ДЕНДРИТНЫХ КЛЕТОК ЧЕЛОВЕКА IN VITRO

The most important means of measles control is live measles vaccine, the high epidemiological effectiveness of which is confirmed by half a century of its use. There is a question of the need to further improve the effectiveness of vaccine prophylaxis, in particular, by increasing the immunogenicity of the used vaccine given the increase in the morbidity of measles in recent years. Investigation of effect features of existing vaccine variants is necessary to identify possible ways to increase their immunogenicity. We investigated the effect of measles culture live vaccine on the maturation of human dendritic cells – the most specialized antigen-presenting cells involved in the induction of an immune response. In vitro incubation of monocytic derived immature dendritic cells with the vaccine initiates the process of their partial maturation, which is manifested in an increase in the number of cells carrying molecules CD86, CD83 and ICOSL (CD275).At the same time they have a reduced expression level of the HLA-DR molecule and chemokine receptors CCR7 and CXCR5 involved in the migration of dendritic cells to peripheral lymphoid organs. In our opinion, the relative weak side of measles vaccine effect on dendritic cell maturation is a factor limiting the immunogenicity of the vaccine, which must be taken into account when developing new measles vaccines.