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A leadership perspective of the creation of opportunities for professional teacher development in Diepsloot Combined SchoolKgabo, Veronica 22 June 2011 (has links)
M. Ed. / Professional Teacher Development (PTD) is an ingredient essential to the creation of effective schools, positively impacting learners’ performance and enhancing teachers’ knowledge, skills and attitudes, which are imperative in improving leaner performance. Effective PTD requires considerable time, must be well organised, be carefully structured, purposefully directed and focused on both content and pedagogy. It should be cost effective, in terms of time and effort persistent to teachers’ needs, relevant, practical and educationally sound. It is not a single stroke; one must work hard so as to attain mastery. PTD is an effective transfer of knowledge-sharing from within the institution, supporting critical junctures in its networks, ensuring integration within the externally. When carried out correctly, it is the key to ‘recharging’ teaches, giving them the tool they need. Principals are being challenged about what constitutes quality in education, and are forced to make efforts to change the status quo – instead of cocooning themselves in isolation. They have to design coherent and purposeful programmes effecting learning which is accompanied by change in behaviour, perception, thinking, beliefs, values, and awareness. It also will alter insight, and involve new patterns of operation, new strategies and new procedures. A structural PTD is determined by the specific institution’s context, helping to overcome teachers’ negative reaction to school-based PTD. They will be changed in major ways, both in terms of their teaching practices and their personal behaviour as there is no substitute for on-the-job learning with opportunities to reflect on action. One potential way to enhance PTD is to utilise constructivist strategies with the teacher. For PTD to be effective and bring improvement within the institution, the teachers should meet regularly to explore common problems and seek solutions based on shared experiences and collective wisdom. School-based PTD will cause DCS teachers to shift cultural paradigms, instil new values and goals, and help shape their professional identity, taking the microenvironment of DCS into cognisance. A good PTD needs to be mindful of connecting good theory to classroom practices, as quality PTD is the vehicle for providing the knowledge needed to support effective teaching – an adult institution. No improvement efforts can succeed in the absence of thoughtfully planned and wellimplemented PTD.
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INCENP Translation during Oocyte Maturation Is a Maternal Factor of Xenopus Laevis DevelopmentLeblond, Geoffrey January 2011 (has links)
During vertebrate oocyte maturation, the chromosomes progress to and arrest at metaphase of meiosis II in preparation for fertilization. This process includes emission of the first polar body. The second polar body is emitted after fertilization. A number of proteins are accumulated during oocyte maturation. Inhibition of this de novo translation does not appear to affect the progression of meiosis during oocyte maturation. The role of these pools of proteins has yet to be elucidated. Curiously, several of the upregulated proteins are key players in mitosis, including INCENP, a subunit of the chromosome passenger complex implicated in chromosome segregation and cytokinesis. During early stages of development in Xenopus laevis, the embryo cycles through mitosis, also known as embryo cleavage, every 30min with little to no time for transcription/translation. Our goal is to determine if the de novo translation of these mitotic proteins during oocyte maturation has a role in early embryogenesis. We used morpholino oligonucleotides antisense to INCENP mRNA (INCENPmorpho) to inhibit de novo translation during oocyte maturation. Using confocal imaging and the host transfer technique, these injected oocytes were matured, fertilized and assessed for developmental competency. INCENPmorpho and a control morpholino (ctrlmorpho) had no discernable effect on 1st or 2nd polar body emission. Whereas ctrlmorpho embryos developed normally, INCENPmorpho embryos did not cleave. Thus, de novo translation of INCENP during oocyte maturation is necessary for embryogenesis. Specifically, accumulation of INCENP and other mitotic proteins during oocyte maturation may be a common strategy in this species to prepare for the rapid and synchronous mitoses during early embryogenesis.
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Traits biologiques d'une espèce invasive, la perche soleil (Lepomis gibbosus), dans un réservoir artificiel aux eaux échauffées : reproduction, croissance, longétivité / Biological traits of an invasive specie, the pumpkinseed (Lepomis gibbosus), in an over-heated reservoir : reproduction, growth, longevity and predationValente, Emmanuel 14 November 2008 (has links)
L'étude de la reproduction chez les téléostéens est fondamentale pour comprendre le devenir des populations ichtyologiques déterminantes pour l'équilibre des milieux aquatiques, et ce, dans un contexte de changement climatique global qui aura pour effet de modifier les aires de répartitions des espèces ainsi que leurs stratégies de reproduction afin de garantir la survie de la progéniture. La maturation sexuelle de la perche soleil (Lepomis gibbosus), à partir d'un échantillon de162 femelles et 157 mâles, a été étudiée dans une retenue artificielle du Nord-Est de la France (réservoir du Mirgenbach) recevant les eaux échauffées de la centrale électronucléaire de Cattenom. La perche soleil, de la famille des centrarchidés, est originaire d'Amérique du Nord et a été introduite en Europe en 1880. Depuis son introduction, elle a colonisé tout le réseau hydrographique français. Cette espèce, occupant la zone littorale, est actuellement présente dans 28 pays d'Europe et d'Asie mineure, mais elle n'est considérée invasive que dans le sud et le centre de l'Europe. Dans la présente étude, l'effort de reproduction a été étudié chez les femelles et les mâles, à partir de l'indice gonado-somatique (IGS) et de profils de maturité gonadique, définis à partir d'observations histologiques. Les données acquises concernent, d'autre part, la croissance et la longévité de cette espèce dans ce cas particulier d'écosystème échauffé. Dans ce contexte, la maturation sexuelle est précoce par rapport aux autres populations de perches soleil localisées à des latitudes similaires. (Age de maturité : 1 an), et les mâles entrent en maturation un mois avant les femelles. La croissance des juvéniles est rapide (LT>70mm à 1 an), excepté chez les petits mâles cocufiants, mais la longévité (3 ans) est inférieure à celles rencontrées dans d'autres sites d'Europe (4 à 8 ans). Cette précocité a également été observée chez d'autres espèces dans des sites d'Europe recevant des eaux échauffées, cependant des anomalies ovocytaires avaient été observées, ce qui n'est pas le cas pour les individus du réservoir du Mirgenbach. De part ses conditions thermiques, le réservoir du Mirgenbach constitue un modèle intéressant pour étudier les conséquences du changement climatique global sur la biologie des poissons / The study of teleost reproduction is fundamental in order to understand the future of ichthyologic populations, determinant for the balance in aquatic environments, and this, in a context of global warming which will affect distribution zones of species as well as their reproductive strategies in order to guarantee survival of their progeny. Sexual maturation in pumpkinseed (Lepomis gibbosus) has been studied in an artificial basin in north-eastern France (Mirgenbach Reservoir) which receives over-heated water from the Cattenom nuclear power plant. Pumpkinseed, a centrarchid fish specie, is native to North America but has been introduced in Europe in 1880. Since its introduction, it has colonized the entire French hydrographic network. This specie, predominantly littoral, is already established in at least 28 countries in Europe and Asia Minor, but is currently considered to be invasive mainly in southern and central Europe. In our study, the reproductive effort was studied in both sex, using gonado-somatic index (GSI) and gonadal maturity stages obtained from histological observations. Growth and longevity have also been studied. A sample of 162 females and 157 males was collected for this work. In this context of warm thermal environment, sexual maturation is precocious compared to other pumpkinseed populations located at similar latitudes (age at maturity: 1 year), and the males mature one month before the females. The juvenile growth rate is high (LT>70mm at 1 year old), except for the small male cuckolders, but longevity (3 years) is lower than at the other sites in Europe (4 to 8 years). This precocity was also observed in other species at sites receiving over-heated nuclear plant discharge water, however oocyte abnormalities were observed which was not the case for the pumpkinseed population in the Reservoir Mirgenbach. The thermal conditions of the Mirgenbach Reservoir confer to this site a good opportunity to evaluate the consequences of the Global Warming on fish biology
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Idade relativa : implicações sobre características antropométricas e desempenho motor de jovens jogadores de futebol / Relative age : implications on anthropometric characteristics and motor performance of young soccer playersAltimari, Juliana Melo, 1981- 26 August 2018 (has links)
Orientador: Antonio Carlos de Moraes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Educação Física / Made available in DSpace on 2018-08-26T13:31:01Z (GMT). No. of bitstreams: 1
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Previous issue date: 2014 / Resumo: Este estudo analisou o efeito da idade relativa (EIR) sobre características antropométricas e desempenho motor de jovens jogadores de futebol. Para tanto, foram conduzidos dois estudos. No estudo 1 a amostra foi composta de 400 jogadores de futebol (15,4 ± 0,4 anos) da categoria Sub-15 que participaram da 10° Copa Brasil de Futebol Sub-15. As datas de nascimento, bem como as medidas antropométricas massa corporal (MC), estatura (ET), foram obtidas a partir de dados relatados pelas equipes na ficha de inscrição de cada atleta à organização do evento e a CBF. No estudo 2 a amostra foi composta de 146 jogadores de futebol das categorias Sub-13 (n = 50; 13,6 ± 0,3 anos), Sub-15 (n = 50; 15,5 ± 0,4 anos) e Sub-17 (n = 46; 17,7 ± 0,3 anos). Os sujeitos foram submetidos a diferentes situações experimentais de forma transversal: 1) mensurações antropométricas MC, ET, massa magra (MM) e gordura relativa (%G); 2) avaliação da idade óssea (IO); 3) testes motores para avaliação da resistência aeróbia (RA), velocidade (VL10m e VL30m), força de membros inferiores a partir de salto vertical (SV, SVCSMS e SVCCMS), resistência de velocidade (RSA) e índice de fadiga obtido a partir do teste de RSA (IFRSA). Em ambos os estudos os jogadores foram separados de acordo com a categorização de idade cronológica por quadrimestres, 1? quadrimestre (1? QDT), jovens nascidos entre janeiro e abril; 2? quadrimestre (2? QDT), jovens nascidos entre maio e agosto e 3? quadrimestre (3? QDT), jovens nascidos entre setembro e dezembro. Para o tratamento estatístico foram empregados teste não paramétrico do qui-quadrado (X2), análise de variância (ANOVA) two-way, seguido pelo teste Post-hoc de Scheffé. As correlações entre os parâmetros analisados foram estabelecidas pelo coeficiente de correlação de Pearson. O nível de significância adotado para todas as análises foi de 5%. Os resultados do primeiro estudo demonstram um maior número jogadores nascidos nos primeiros meses do ano (1? QDT > 2? QDT > 3º QDT, P<0,05). Da mesma forma, constatou-se valores significativamente maiores para as variáveis ET e MC dos jogadores nascidos nos primeiros meses do ano (1? QDT > 2? QDT > 3º QDT, P<0,05). No segundo estudo observou-se que as variáveis MC, ET e RSA apresentaram diferenças significativas entre o 1? QDT e 3? QDT, nas categorias Sub-13 e Sub-15 (P<0,05). Enquanto que para a variável MM diferenças significativas foram observadas apenas entre 1? QDT e 3? QDT da categoria Sub-13 (P<0,05). Por outro lado, nenhuma diferença significativa para a variáveis %G, SV, SVCSMS, SVCCMS, RA, VL10 m, VL30 m e IFRSA entre o 1? QDT, 2? QDT e 3? QDT foram observadas em todas as categoria analisadas (P>0,05). Ressalta-se que os valores das variáveis MC, ET, MM, SV, SVCSMS, SVCCMS, RA, RSA, VL10 m, VL30 m, foram significativamente diferentes entre os jogadores da categoria Sub-13 e Sub-17 nos diferentes quadrimestres (P<0,05). Constatou-se também que os jogadores da categoria Sub-13 apresentaram menores valores de estatura, massa corporal e massa magra, em relação aos jogadores da categoria Sub-15 e Sub-17 nos diferentes quadrimestres (P<0,05). Observou-se nas três categorias analisadas, a prevalência de jogadores apresentando estado de maturidade normal nos três quadrimestres (Sub-13 = 72,0%; Sub-15 = 78,0%; Sub-17 = 95,0%). Os achados do primeiro estudo sugerem que o ERI exerce influência na seleção de jovens jogadores brasileiros de elite e que este efeito está associado as características antropométricas estatura e massa corporal. Corroborando com esses achados, os resultados do segundo estudo apontam para influência do ERI nas categorias Sub-13 e Sub-15 para as variáveis massa corporal, estatura e resistência de velocidade, enquanto que para a variável massa muscular isso ocorreu apenas na categoria Sub-13, possibilitando aos jogadores nascidos no 1? QDT (Jan-Abr) dessas categorias vantagens em relação aos nascidos no 3? QDT (Set-Dez) / Abstract: This study examined the effect of relative age (ERA) on anthropometric characteristics and motor performance of young soccer players. To this end, two studies were conducted. In the study, a sample composed of 400 soccer players (15.4 ± 0.4 years) of the U-15 category who participated in the 10th World Cup Football Brazil U-15. Dates of birth and anthropometric measures body mass (BM) and height (H) were obtained from data reported by the teams on the registration form for each athlete to the event organization and CBF. The second study sample was composed of 146 soccer players in the categories U-13 (n = 50, 13.6 ± 0.3 years), U-15 (n = 50, 15.5 ± 0.4 years) and U-17 (n = 46, 17.7 ± 0.3 years). The subjects were submitted to different experimental situations across the board: 1) anthropometric measurements BM, H, lean mass (LM) and fat percent (BF%), 2) assessment of bone age (BA) and 3) motor tests to evaluate aerobic endurance (AE), speed (S10 m and S30 m), lower limb strength from vertical jump (VJ, VJCWUL and VJ SVCAUL), repeated sprint ability (RSA) and fatigue index obtained from the RSA test (FIRSA). In both studies the players were separated according to the categorization of chronological age by four, quarter 1? (1? QT ), young people born between January and April; quarter 2? (2? QT), young people born between May and August and 3? quarter (3? QT), young people born between September and December. For statistical treatment nonparametric chi-square (X2) analysis of variance (ANOVA) two-way, followed by posthoc Scheffé test were used. Correlations between parameters were established by Pearson's correlation coefficient. The significance level for all analyzes was 5%. The results of the first study show a greater number of players born in the first months of the year (1? QT > 2? QT > 3? QT, P<0.05). Likewise, we found significantly higher values for the variables BM and H players born in the first months of the year (1? QT > 2? QT > 3? QT, P< 0.05). In the second study, it was observed that the BM, H and RSA variables showed significant differences between the 1? QT and 3? QT in categories U-13 and U-15 (P<0.05). While for the variable LM significant differences were found between 1? QT and 3? QT category U- 13 (P<0.05). On the other hand, no significant difference for the variables BF%, VJ, VJCWUL, VJ SVCAUL, AE, S10 m, S30 m and IFRSA me between 1? QT, 2? QT and 3? were observed in every category analyzed (P>0.05). It is noteworthy that the values of BM, H and RSA LM, VJ, VJCWUL, VJ SVCAUL, AE, RSA, S10 m, S30 m, variables were significantly different between the players of the category U-13 and U-17 in different quarters (P< 0.05). It was also found that the players of U-13 category had significantly lower height, body mass and lean mass in relation to the category of players U-15 and U-17 in different quarters (P< 0.05). Observed in the three categories analyzed, the prevalence of players showing normal state of maturity in each four (U-13 = 72.0 %, U-15 = 78.0 %, U- 17 = 95.0 %). The findings of the first study suggest that the ERA influences the selection of young Brazilian elite players and that this effect is associated with anthropometric characteristics height and body mass. Corroborating these findings, the results of the second study indicate influence of ERA in categories U-13 and U-15 for the variables body mass, height and repeated sprint ability, while for muscle mass this variable occurred only in the U-13, allowing players born in 1? QDT (Jan-Apr) of these categories advantages compared to those born at 3? QDT (Sep-Dec) / Doutorado / Biodinamica do Movimento e Esporte / Doutora em Educação Física
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A single molecule view of FEN1 remarkable substrate recognition, perfect catalysis and regulationZaher, Manal 05 1900 (has links)
DNA replication is one of the most fundamental processes in all living organisms. Its semi-discontinuous nature dictates that the lagging strand is synthesized in short fragments called Okazaki fragments. In eukaryotes, each Okazaki fragment is initiated by an ~ 30-40 nucleotide-long RNA-DNA hybrid primer that is synthesized by Pol α-primase complex. To ensure genomic stability, the RNA primer has to be excised, any misincorporations by Pol α have to be corrected for and finally the resulting nick has to be sealed generating a contiguous strand. This feat is accomplished by a highly coordinated and regulated process called Okazaki fragment maturation. At the center of this process are 5’ nucleases, which are structure-specific nucleases that catalyze the incision of phosphodiester bonds one nucleotide into the 5’ end of ssDNA/dsDNA junctions.
Previous structural and biochemical studies have shed some light on the mechanism of FEN1 substrate recognition, its catalysis and regulation. However, many gaps in our understanding of this remarkable nuclease still persist. Moreover, the choice between the short- and long-flap pathways is still elusive. Finally, the mechanism of the coordination among the different enzymatic activities of the polymerase, the nuclease and the ligase during Okazaki fragment maturation is still debatable. In this work, we set out to study FEN1 substrate recognition, catalysis and regulation using single molecule techniques. We show that FEN1 employs a sophisticated substrate recognition mechanism through which it actively distorts the DNA to ~100˚ bent angle. It also displays a remarkable selectivity towards its cognate substrate and avoids off-target substrate by a lock-down mechanism that commits the enzyme for catalysis on cognate substrates while promoting the dissociation of non-cognate substrates. We further characterized FEN1 reaction from substrate binding/bending to product handoff and built a comprehensive kinetic scheme that shows FEN1 releasing its product in two steps. Finally, we uncovered an unprecedented role of FEN1 in the choice between short- and long-flap pathways.
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Epigenomics of Post-testicular Sperm MaturationGalan, Carolina 26 August 2021 (has links)
Beyond the haploid genome, mammalian sperm carry a payload of epigenetic information with the potential to modulate offspring phenotype. Morphologically mature sperm exit the testes, but cannot swim or interact with the oocyte without extensive remodeling during epididymal transit; this includes modifications to the lipid composition of the sperm membrane, gain of necessary proteins, and a dramatic shift in sperm RNA content. Epididymal maturation has also been linked to changes in the sperm methylome suggesting that the epididymis might play a broader role in shaping the sperm epigenome. First, we characterized the genome-wide methylation landscape in seven germ cell populations from throughout the male reproductive tract. Our data emphasize the stability of cytosine methylation in mammalian sperm, and identify a surprising, albeit transient, period during which sperm are associated with extracellular DNA. Second, given our interest in the small RNA repertoire of sperm we set out to address known bias in sequencing protocols by comparing several small RNA cloning protocols. We found a protocol recently developed by Kathleen Collins’ lab (OTTR) to be superior to commercially available kits in providing an accurate representation of tRNA fragment levels as compared to Northern blotting. These results not only provide a more accurate representation of tRNA fragments, but also more complexity than previously seen allowing us to reassess the true sperm small RNA content. Taken together, these results provide significant insight into the mechanisms and factors modulating sperm epigenomics during post-testicular sperm maturation.
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Age estimation of living South African individuals : a multifactorial modelUys, Andre January 2019 (has links)
Age estimation in living individuals around the legal age of 18 years remains a difficult challenge, with limited options available. In this study third molar development was used, along with the novel method of anterior inferior vertebral ring apophysis development, to assess the age of living individuals and the probability of being 18 years. For third molar development, panoramic radiographs of 705 white and 563 black South Africans were scored using a 10 stage scoring system. Vertebral apophysis development of C2, C3, and C4 of 496 white and 478 black South Africans were assessed from cephalometric radiographs, using a four-stage scoring system. Likelihood values were determined for individuals in each sex and population group being 18 years, based on developmental stages. For apophysis development, the median ages for attainment of stages 0, 1, and 2 were below the 18-year threshold for all ancestry and sex groups, while stage 3 was also below this threshold in some groups. For third molar development, black South African individuals consistently matured earlier than white South African individuals, while for most of the stages the opposite was true for apophysis development. Differences between the sexes were also noted for third molar, but not for vertebral apophysis development. These age indicators were also combined by using a generalised linear model (GLM). The combined sample comprised of 165 females and 122 males aged between 15 and 18 years. Four additional models were obtained from data sets only containing data for third molar and cervical ring apophysis development respectively. The performance of all the models were quantified and compared using the Akaike information criterion (AIC) as an estimator of the relative quality of the statistical models and the prediction error as a mean square error value. The best performance resulted from third molar development, although the vertebral data adds a component related to skeletal development which may better reflect biological reality. These results show that cervical vertebral apophysis development is a valuable, novel addition to the assessment of age in living individuals. Both these methods are easy to use and can be assessed from standard and routinely used radiographic images. The developed models need to be sex and ancestry specific, as clear differences were noted. / Thesis (PhD)--University of Pretoria, 2019. / Anatomy / PhD / Unrestricted
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The relationship between adiposity indices, dental development and skeletal maturation in orthodonticsBamashmous, Laila Said 22 August 2019 (has links)
OBJECTIVES: The aim of this study is to assess the association between different adiposity indices, dental development and skeletal maturation in children and adolescents.
METHODS: A total of 115 patients who presented to the orthodontic clinics at Boston University were examined for their height, weight, skeletal maturation, and 10 different adiposity indices. Statistical analysis included chi-square, ANOVA, and multiple ordinal regression models.
RESULTS: In the sample (59% female, 41% male) the mean age was 14 years, (SD:2.5), height 160 cm (SD:11.9), weight 61 kg (SD:19.1), and ethnicity was 31% African Americans, 31% Hispanics, 27% Caucasians, and 9% Asians. The Pearson correlation coefficient showed SMI was significantly correlated with (by order of correlation strength) CVMI (P<.01), dental development according to Demirjian (P<.01), root completion (P<.01), eruption (P<.01), fat free mass (FFM) (P<.01), total body water (TBW) (P<.01), body adiposity index (BAI) (P<.01), BMI (P<.01), fat mass (P<.01), right subscapular skinfold (P<.01), BMI percentile (P<.01), fat percentage (P<.01), right triceps skinfold (P<.01), and waist/hip ratio (P<.01). For CVMI, it was significantly correlated in order of strength with SMI (P<.01), BMI % (P<.01), dental development (Demirjian) (P<.01), root completion (P<.01), eruption (P<.01), FFM (P<.01), TBW (P<.01), BAI (P<.01), waist/hip ratio (P<.01), BMI (P<.01), fat mass (P<.01) and right subscapular skinfold (P<.01). However, the Waist/Height ratio was not significantly related with either methods of skeletal assessment. Using the Chisquare test, we found that no adiposity index was statistically significant predictor of any dental outcome (i.e., dental development by Demirjian, root completion and eruption sequence) except for dental development (Demirjian) which was statistically significantly related with the waist/hip ratio. After controlling for other covariates (i.e., age and gender) for skeletal outcomes, all adiposity indices were statistically significant predictors for SMI including BMI percentile, BMI, BAI, fat percentage, fat mass, FFM, TBW, BIA, and waist/height ratio.
CONCLUSIONS: Children and adolescents with increased adiposity values (i.e., BMI percentile, BMI, BAI, fat percentage, fat mass, FFM, TBW, BIA, and waist/height ratio), had higher probability of being skeletally more mature as measured by SMI. / 2021-08-22T00:00:00Z
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Memory-Like Responses of Brain Microglia Are Controlled by Developmental State and Pathogen DoseLajqi, Trim, Stojiljkovic, Milan, Williams, David L., Hudalla, Hannes, Bauer, Michael, Witte, Otto W., Wetzker, Reinhard, Bauer, Reinhard, Schmeer, Christian 25 September 2020 (has links)
Microglia, the innate immune cells of the central nervous system, feature adaptive immune memory with implications for brain homeostasis and pathologies. However, factors involved in the emergence and regulation of these opposing responses in microglia have not been fully addressed. Recently, we showed that microglia from the newborn brain display features of trained immunity and immune tolerance after repeated contact with pathogens in a dose-dependent manner. Here, we evaluate the impact of developmental stage on adaptive immune responses of brain microglia after repeated challenge with ultra-low (1 fg/ml) and high (100 ng/ml) doses of the endotoxin LPS in vitro. We find that priming of naïve microglia derived from newborn but not mature and aged murine brain with ultra-low LPS significantly increased levels of pro-inflammatory mediators TNF-α, IL-6, IL-1β, MMP-9, and iNOS as well as neurotrophic factors indicating induction of trained immunity (p < 0.05). In contrast, stimulation with high doses of LPS led to a robust downregulation of pro-inflammatory cytokines and iNOS independent of the developmental state, indicating induced immune tolerance. Furthermore, high-dose priming with LPS upregulated anti-inflammatory mediators IL-10, Arg-1, TGF- β, MSR1, and IL-4 in newborn microglia (p < 0.05). Our data indicate pronounced plasticity of the immune response of neonate microglia compared with microglia derived from mature and aged mouse brain. Induced trained immunity after priming with ultra-low LPS doses may be responsible for enhanced neuro-inflammatory susceptibility of immature brain. In contrast, the immunosuppressed phenotype following high-dose LPS priming might be prone to attenuate excessive damage after recurrent systemic inflammation.
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Origin and maturation of the pulmonary lymphatic endotheliumNorman Jr., Timothy Alfred 14 June 2019 (has links)
The lymphatic vasculature is composed of lymphatic endothelial cells (LECs) that coalesce into a branched hierarchy of small capillaries and larger collecting vessels that regulate interstitial fluids, lipid uptake and immunity. Few studies have focused on pulmonary lymphatic system. To fill these critical knowledge gaps, we interrogated the fetal maturation program of lymphatic endothelium, and we provide evidence that CSF1R-lineage progenitors contribute to LECs in the lung during a temporally defined period in early postnatal life.
The pulmonary lymphatic system is required for fluid clearance and air breathing at birth, suggesting a prenatal maturation program. To interrogate this, we developed a cell sorting strategy to enrich pulmonary LECs by their unique cell surface immunophenotype (CD45-, EPCAM-, CD31+, VEGFR3+, PDPN+, LYVE1+) for transcriptional profiling. These experiments highlighted the coordinate down-regulation of genes involved in “cell cycle”, and “mRNA processing” along with coordinate upregulation of “complement/coagulation cascade”, “lipid metabolism”, and “angiogenesis” genes from embryonic day E16.5 to E18.5. The most significantly enriched gene set corresponded to the “interferon-alpha/beta signaling” pathway which was confirmed with qRT-PCR and in-situ hybridization. These data provide the first description of the transcriptional landscape of fetal pulmonary LEC maturation.
During development, all LECs are thought to originate from embryonic veins, however multiple studies have suggested a myeloid origin for a subset of LECs. A relationship between myeloid cells and the pulmonary LECs has not been elucidated. Here, we used myeloid-specific inducible CSF1R-CreERtdTomato lineage tracing mice and identified rare, single cells that co-expressed CSF1R- CreERtdTomato and Prox1, the master lymphatic regulator, in the postnatal day 3 lung. This process was temporally restricted to the early postnatal period. Lineage tracing with additional myeloid-Cre mice (CSF1R-iCre and CX3CR1-Cre) also showed contribution to postnatal LECs. To determine the biological significance of CSF1R-derived LECs to postnatal lung biology, we performed conditional Prox1 loss of function experiments. CSF1R-CreER mediated deletion of Prox1 resulted in lymphatic hypoplasia, edematous foci and clotting. These findings suggest that early postnatal CSF1R+ progenitors contribute to the pulmonary lymphatic endothelium and that vascular clotting may result from lymphatic malformation/dysfunction. / 2021-06-14T00:00:00Z
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