RESUMO
Trees structure the Earth's most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1-6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth's 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world's most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.
Assuntos
Florestas , Árvores , Clima Tropical , Biodiversidade , Árvores/anatomia & histologia , Árvores/classificação , Árvores/crescimento & desenvolvimento , África , Sudeste AsiáticoRESUMO
This quantitative study tested hypotheses derived from a previous qualitative study of the factors that facilitated and hindered compersion (the positive feelings derived from one's partner's intimate relations with others) in consensually non-monogamous (CNM) relationships. A total of 255 participants recruited from online CNM and Alt-Sex communities reported on demographic and relationship characteristics as well as individual, relationship, and metamour-related variables in an online anonymous survey. In Flicker et al. (2022), we identified various factors that predicted three subtypes of compersion: contentment with one's partner's relationships with established metamours (intimate partners of one's partners), excitement sparked by one's partner's new/potentially new intimate connections, and sexual excitement elicited by thinking about one's partner with another person. The current findings were consistent with the Flicker et al. qualitative study, with some hypotheses from the previous study more strongly supported than others. The predictors of compersion most strongly supported by the current data include closeness with one's metamour and knowledge about the partner/metamour relationship, in a positive direction, as well as jealousy, envy, and attachment anxiety, in a negative direction. Individual-level predictors were weak predictors of compersion. The sexual arousal subtype of compersion was weakly endorsed by the current sample and predictors of this subtype were distinct from predictors of the other subtypes of compersion. The findings suggest that the development of new interventions that target reducing jealousy and envy and increasing attachment security within the unique context of CNM relationships could have the added benefit of increasing compersion. The development of these interventions stands to benefit a growing population of individuals involved in CNM relationships.
Assuntos
Felicidade , Comportamento Sexual , Humanos , Parceiros Sexuais , Ciúme , Casamento , Relações InterpessoaisRESUMO
The Semliki Forest virus capsid protein (C) is an RNA binding protein which exhibits both specific and unspecific affinities to single-strand nucleic acids. The putative use of the self-amplifying RNAs (saRNAs) of alphaviruses for biotechnological purpose is one of the main studied strategies concerning RNA-based therapies or immunization. In this work, a recombinant C protein from SFV was expressed and purified from bacteria and used to associate in vitro with a saRNA derived from SFV. Results showed that the purified form of C protein can associate with the saRNA even after high temperature treatment. The C protein was associated with a modified saRNA coding for the green fluorescent protein (GFP) and delivered to murine macrophage cells which expressed the GFP, showing that the saRNA was functional after being associated with the recombinant purified C protein.
Assuntos
Proteínas do Capsídeo , Macrófagos , RNA Viral , Proteínas Recombinantes , Vírus da Floresta de Semliki , Vírus da Floresta de Semliki/genética , Animais , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , Camundongos , Macrófagos/metabolismo , Macrófagos/virologia , Proteínas Recombinantes/genética , RNA Viral/genética , Linhagem Celular , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismoRESUMO
Cancer is a complex disease characterized by several alterations, which confer, to the cells, the capacity to proliferate uncontrollably and to resist cellular death. Multiresistance to conventional chemotherapy drugs is often the cause of treatment failure; thus, the search for natural products or their derivatives with therapeutic action is essential. Chiral derivatives of xanthones (CDXs) have shown potential inhibitory activity against the growth of some human tumor cell lines. This work reports the screening of a library of CDXs, through viability assays, in different cancer cell lines: A375-C5, MCF-7, NCI-H460, and HCT-15. CDXs' effect was analyzed based on several parameters of cancer cells, and it was also verified if these compounds were substrates of glycoprotein-P (Pgp), one of the main mechanisms of resistance in cancer therapy. Pgp expression was evaluated in all cell lines, but no expression was observed, except for HCT-15. Also, when a humanized yeast expressing the human gene MDR1 was used, no conclusions could be drawn about CDXs as Pgp substrates. The selected CDXs did not induce significant differences in the metabolic parameters analyzed. These results show that some CDXs present promising antitumor activity, but other mechanisms should be triggered by these compounds.
Assuntos
Aminoácidos , Xantonas , Humanos , Xantonas/farmacologia , Xantonas/química , Linhagem Celular Tumoral , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genéticaRESUMO
AbstractLife history theory aims to understand how different environments result in differential investment in fitness-related traits. While trade-offs between traits are expected, many studies show positive or no correlation between pairs of costly traits. One hypothesis that may explain the inconsistency of trade-offs in the literature is that trait investment may occur in a dichotomous hierarchy (the tree model), which allows for differential trait investment weighted by the traits' respective positions within the hierarchy. Previous mathematical models predict different covariances between traits depending on their position on the allocation tree. While hierarchical differential investment is often used to discuss findings in life history theory, the role of an allocation hierarchy in trait covariances has not been directly tested. In turn, this study aims to identify trait covariances between behavioral and morphological phenotypes on different branches of an allocation tree for the bean beetle, Callosobruchus maculatus. While trade-offs between copulatory behaviors and morphology were found for both males and females, only traits at the base and far from each other in the hierarchy negatively covaried. This study empirically shows that trade-offs may be the result of hierarchical investment.
Assuntos
Besouros , Características de História de Vida , Animais , Feminino , Larva , Masculino , FenótipoRESUMO
Personality variables, including sensation-seeking, interpersonal trust, avoidance of uncertainty, endorsement of social conformity, and love styles (Ludus, Eros, Pragma, Storge, Mania, and Agape), were examined as predictors of prejudicial attitudes toward individuals who practice polyamory and personal interest in engaging in consensual non-monogamy (CNM) among 1831 participants who completed anonymous surveys online. Personality characteristics were also compared between individuals who currently practice CNM (n = 67) and case-matched controls involved in monogamous relationships. As predicted, prejudicial attitudes and willingness to engage in CNM were positively and moderately correlated and there was substantial overlap in the predictors of both variables. However, the strongest predictors differed: prejudicial attitudes were best predicted, in a positive direction, by endorsement of social conformity and, to a lesser extent, Pragma love style, while willingness to engage in CNM was best predicted by the Ludus (positive) and Eros (negative) love styles. Individuals who practice monogamy and CNM were more similar than different: only two of the 12 variables tested significantly differed. CNM individuals are more ludic and more tolerant of cognitive uncertainty. Difficulty interpreting some of the results laid bare the need for relationship measures that are valid for individuals who practice CNM. Improving our understanding of the relation between personality traits and CNM may help us develop better interventions for clients who seek to transition from monogamy to CNM but struggle to adapt to the new challenges as well as design better efforts to increase acceptance and reduce discrimination against those who practice CNM.
Assuntos
Atitude , Amor , Humanos , Casamento , Preconceito , Personalidade , Comportamento Sexual/psicologia , Parceiros Sexuais/psicologiaRESUMO
INTRODUCTION: Heterozygotes (HZs) for 21-hydroxylase deficiency (21OHD) are highly prevalent, ranging from 1:60 to 1:11 for classic and nonclassic (NC) forms, respectively. Detection of HZ and asymptomatic NC by CYP21A2 genotyping is valuable for genetic counselling, but costly, complex and narrowly available. Adrenocorticotropic hormone (ACTH)-stimulated serum 17-hydroxyprogesterone (17P) and 21-deoxycortisol (21DF) discriminate 21OHD phenotypes effectively, notably if measured simultaneously by liquid chromatography-tandem mass spectrometry (LC-MS/MS). OBJECTIVE: This study was performed to reassess former LC-MS/MS-defined post-ACTH 21DF, 17P and cortisol (F) cutoffs in family members at risk for 21OHD. DESIGN AND PATIENTS: Prospective study in which we screened 58 asymptomatic relatives from families with 21OHD patients and compared post-ACTH steroid phenotypes with subsequent genotypes. RESULTS: Post-ACTH 21DF, 17P, F and (21DF + 17P)/F ratio segregate NC, HZ and wild-type (WT) phenotypes (subsequently genotyped) with some overlap. New receiver operating characteristic curve-defined cutoffs for post-ACTH 21DF, 17P and (21DF + 17P)/F ratio are 60 ng/dl, 310 ng/dl and 12 (unitless). Twenty-six of 33 HZ and all 6 NC (82.1%) had post-ACTH 21DF > 60 and 17P > 310 ng/dl, whereas 17/19 WT (89.5%) had values below cutoffs. Post-ACTH 21DF and 17P had a strong positive correlation (r = .9558; p < .001). A (21DF + 17P)/F ratio > 12 correctly identified 36 of 39 HZ plus NC (92.3% sensitivity) with 84.2% specificity (16 of 19 WT). Given the high frequency of 21OHD HZ, the negative prediction of ratio values below 12 excludes heterozygosity in 99.8% and 99.1% for classic and NC mutations, respectively. CONCLUSIONS: Reassessed ACTH-stimulated 21DF and 17P cutoffs by LC-MS/MS (60 and 310 ng/dl, respectively) correctly recognised 82.5% HZ plus NC, but combined precursor-to-product ratio ([21DF + 17P]/F) cutoff of 12 was superior, identifying 92.3% HZ plus NC. Since one WT subject is an outlier (potential HZ), these values would be somewhat better reinforcing their utility for screening asymptomatic relatives at risk for 21OHD.
Assuntos
Hiperplasia Suprarrenal Congênita , Hormônio Adrenocorticotrópico , 17-alfa-Hidroxiprogesterona , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/genética , Cromatografia Líquida , Cortodoxona , Heterozigoto , Humanos , Estudos Prospectivos , Esteroide 21-Hidroxilase/genética , Espectrometria de Massas em TandemRESUMO
Although polyamorous relationships have received increasing attention from researchers over the past decade, little attention has been paid to differences in relationship configurations: some individuals arrange their relationships hierarchically, prioritizing a primary partner; other relationship structures are non-hierarchical with no relationships prioritized over others. Across two samples (NStudy1= 225; NStudy2= 360), we compared relationship satisfaction and attachment security between individuals in hierarchical and non-hierarchical configurations. Greater variability in attachment security was found between partners in hierarchical relationships than those in non-hierarchical relationships; no significant differences were found in variability in relationships satisfaction across these groups. Furthermore, individuals in hierarchical relationships reported lower overall relationship satisfaction and attachment security compared to individuals in non-hierarchical relationships. More specifically, although no significant differences were found between non-hierarchical and primary partners, participants reported lower relationship satisfaction and attachment security with secondary and tertiary partners compared to non-hierarchical and primary partners. Findings suggest that these differences may attenuate with time. Although previous research has found that differences (e.g., in investment) between partners exist in both non-hierarchical and hierarchical configurations, the current research suggests that differences that occur organically rather than in a predetermined manner may be related to greater similarities in attachment security across partners as well as greater overall levels of relationship satisfaction and attachment security for individuals in non-hierarchical configurations. More research is needed to determine whether the observed between-partner differences are consistent with the relationship goals of individuals in hierarchical relationships.
Assuntos
Satisfação Pessoal , Parceiros Sexuais , Humanos , Relações Interpessoais , Apego ao Objeto , Comportamento SexualRESUMO
BACKGROUND: Adrenal hypoplasia congenita (AHC) is an X-linked disorder that affects the adrenal cortex and hypothalamus-pituitary-gonadal axis (HPG), leading to primary adrenocortical insufficiency (PAI) and hypogonadotropic hypogonadism. AHC is caused by a mutation in the DAX-1 gene (NR0B1). More commonly, this disease is characterized by early-onset PAI, with symptoms in the first months of life. However, a less severe phenotype termed late-onset AHC has been described, as PAI signs and symptoms may begin in adolescence and adulthood. Here we describe a family report of a novel mutation within NR0B1 gene and variable reproductive phenotypes, including spontaneous fertility, in a very late-onset X-linked AHC kindred. CASE PRESENTATION: Three affected maternal male relatives had confirmed PAI diagnosis between 30 y and at late 64 y. The X-linked pattern has made the endocrinology team to AHC suspicion. Regarding the HPG axis, all males presented a distinct degree of testosterone deficiency and fertility phenotypes, varying from a variable degree of hypogonadism, oligoasthenoteratozoospermia to spontaneous fertility. Interestingly, the other five maternal male relatives unexpectedly died during early adulthood, most likely due to undiagnosed PAI/adrenal crisis as the probable cause of their premature deaths. Sequencing analysis of the NR0B1 gene has shown a novel NR0B1 mutation (p.Tyr378Cys) that segregated in three AHC family members. CONCLUSIONS: NR0B1 p.Tyr378Cys segregates in an AHC family with a variable degree of adrenal and gonadal phenotypes, and its hemizygous trait explains the disease in affected family members. We recommend that NR0B1 mutation carriers, even those that are allegedly asymptomatic, be carefully monitored while reinforcing education to prevent PAI and consider early sperm banking when spermatogenesis still viable.
Assuntos
Insuficiência Adrenal/genética , Insuficiência Adrenal/patologia , Receptor Nuclear Órfão DAX-1/genética , Fertilidade , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Reprodução , Adulto , Idade de Início , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Fenótipo , PrognósticoRESUMO
Attachment theory posits that in adulthood, romantic partners typically fill the role of primary attachment figure, yet few studies have examined whether these findings hold in cultures that practice arranged marriage or that emphasise collectivistic values and filial piety. In the current study, we compared attachment hierarchies in 116 Bangladeshi women engaged to be married or in the first 3 years of couple-initiated (also known as love) marriages and arranged marriages. Women in couple-initiated marriages reported greater use of their partners for the attachment functions of safe haven and secure base than women in arranged marriages. However, women in both groups were more likely to identify one of their parents than their partner as their primary attachment figure. Although replication is necessary, these findings suggest that partners may not be universally prioritised above parents in the attachment hierarchy and that attachment theory's assumptions of individuation from parents in adulthood may not apply cross-culturally. Findings are discussed in terms of cultural differences from samples previously represented in attachment research, such as kinship structures, the meaning of marriage and filial piety.
Assuntos
Casamento/etnologia , Casamento/psicologia , Adolescente , Adulto , Bangladesh , Feminino , Humanos , Adulto JovemRESUMO
Previous comparisons of relationship quality between individuals in couple-initiated and arranged marriage have yielded inconsistent findings. One factor which may help to explain this inconsistency is variability in the way in which arranged and couple-initiated marriages are practiced. To test this, we recruited 116 Bangladeshi women engaged to be married or within the first 3 years of couple-initiated and arranged marriages. We tested to see which of three models (type of marriage only, perceived influence over partner selection only, and a model that included both relationship type and influence over partner selection) best accounted for variance in self-reported intimacy, passion, commitment as well as positive and negative relationship quality. Results suggest that influence over partner selection is a better predictor of these outcomes than marriage type, with marriage type offering little if any information beyond that provided by perceived influence. Regardless of marriage type, women with greater influence over their partner selection reported higher levels of intimacy, passion, commitment and positive marital quality. Negative marital quality was unrelated. Future research may benefit from reconceptualising the arranged/couple-initiated marriage dichotomy as a continuum.
Assuntos
Casamento/psicologia , Cônjuges/psicologia , Adulto , Feminino , Humanos , Relações Interpessoais , MasculinoRESUMO
The cauda epididymis (CE), the site of sperm storage until the ejaculation, is densely innervated by the sympathetic nervous system. Contraction of CE smooth muscle via α1-adrenoceptors (α1-ARs) plays a key role during the seminal emission phase of ejaculation and α1-AR antagonism has been suggested as a nonhormonal and reversible male contraceptive target. Since the α1-AR subtype mediating contraction of rat CE is not known, this study investigates the expression and role of α1-AR subtypes on the proximal and distal rat CE duct contraction to norepinephrine in vitro. Alpha1a, α1b, and α1d transcripts were detected by real-time quantitative polymerase chain reaction in proximal and distal CE segments and α1a and α1d were shown to predominate over α1b The inhibition of [3H]prazosin specific binding to intact CE segments from proximal and distal CE by RS 100329 and 5-methylurapidil (α1A-selective) and BMY 7378 (α1D-selective) showed that α1A- and α1D-ARs are expressed at similar densities. Norepinephrine-induced contractions of CE were competitively antagonized with high affinity by RS 100329 (pKB ≈ 9.50) and 5-methylurapidil (pKB ≈ 9.0) and with low affinity by BMY 7378 (pKB ≈ 7.0) and the α1B-selective L-765,314 (pA2 < 7.0), suggesting contractions are mediated by α1A-ARs. The clinically used α1A/D-ARs antagonist tamsulosin potently (pA2 ≈ 10.0) inhibited the norepinephrine-induced CE contractions. Altogether, our results show that α1A- and α1D-ARs are expressed in the CE duct and α1A-AR is the main subtype mediating contraction to norepinephrine. Our results highlight the importance of α1A-AR in the peripheral control of ejaculation and strengthen the α1A-AR as a target for a nonhormonal approach to male contraception.
Assuntos
Epididimo/fisiologia , Contração Muscular , Músculo Liso/fisiologia , Receptores Adrenérgicos alfa 1/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Animais , Epididimo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Receptores Adrenérgicos alfa 1/genéticaRESUMO
Goblet cells (GCs) are specialized secretory cells that produce mucins and a variety of other proteins. Significant conjunctival GC loss occurs in both experimental dry eye models and patients with keratoconjunctivitis sicca due to the induction of interferon (IFN)-γ. With the use of a primary murine culture model, we found that GCs are highly sensitive to IFN-γ with significantly reduced proliferation and altered structure with low concentrations. GC cultures treated with IFN-γ have increased gene expression of Muc2 and Muc5AC but do not express these mucin glycoproteins. We hypothesized that IFN-γ induces endoplasmic reticulum stress and the unfolded protein response (UPR) in GCs. Cultures treated with IFN-γ increased expression of UPR-associated genes and proteins. Increased GRP78 and sXBP1 expression was found in experimental dry eye and Sjögren syndrome models and was GC specific. Increased GRP78 was also found in the conjunctiva of patients with Sjögren syndrome at the gene and protein levels. Treatment with dexamethasone inhibited expression of UPR-associated genes and increased mucin production. These results indicate that induction of UPR by IFN-γ is an important cause of GC-associated mucin deficiency observed in aqueous-deficient dry eye. Therapies to block the effects of IFN-γ on the metabolically active endoplasmic reticulum in these cells might enhance synthesis and secretion of the protective GC mucins on the ocular surface.
Assuntos
Células Caliciformes/metabolismo , Interferon gama/metabolismo , Mucinas/deficiência , Síndrome de Sjogren/metabolismo , Resposta a Proteínas não Dobradas/fisiologia , Animais , Western Blotting , Células Cultivadas , Túnica Conjuntiva/metabolismo , Chaperona BiP do Retículo Endoplasmático , Imunofluorescência , Humanos , Immunoblotting , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Post-menopause hyperandrogenism is a condition that needs careful evaluation. Aromatase inhibitors (AI), which are important in the management of positive estrogen breast cancer, and chronic kidney disease (CKD) can puzzle the evaluation of this condition. A postmenopause female with type-2 diabetes and advanced CKD was attended due to progressive virilization, which has started after the introduction of an AI for breast cancer 5 years earlier. Clinical and radiological investigation has confirmed a pure Leydig cell tumor as source of hyperandrogenism. Re-evaluation of the breast tumor immunohistochemistry has shown positive androgen receptor expression and negative expression for estrogen, progesterone and HER-2 receptors. Even though an ovarian tumor was the source of androgen excess, we discuss that AI could exert a slight contribution to patient's virilization by reducing estradiol counterbalance. Also, although the onset of hyperandrogenic symptoms was unclear, we could not exclude that the ovarian tumor had produced enough androgens to play a role in breast tumor progression. This case report supports the literature regarding the possible association between Leydig cell tumor and androgen-receptor-positive breast cancer development. Finally, progressive hyperandrogenic symptoms in postmenopause, even under AI therapy or the presence of advanced CKD, impose a more detailed investigation.
Assuntos
Neoplasias da Mama/patologia , Tumor de Células de Leydig/patologia , Neoplasias Ovarianas/patologia , Idoso , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Hiperandrogenismo/etiologia , Tumor de Células de Leydig/complicações , Neoplasias Ovarianas/complicações , Pós-Menopausa , Virilismo/etiologiaRESUMO
Conjunctival goblet cell (GC) loss in dry eye is associated with ocular surface inflammation. This study investigated if conjunctival GCs contribute to ocular surface immune tolerance. Antigens applied to the ocular surface, imaged by confocal microscopy, passed into the conjunctival stroma through goblet cell associated passages (GAPs) in wild type C57BL/6 (WT), while ovalbumin (OVA) was retained in the epithelium of SAM pointed domain containing ETS transcription factor (Spdef) knockout mice (Spdef-/-) that lack GCs and are a novel model of dry eye. Stimulated GC degranulation increased antigen binding to GC mucins. Induction of tolerance to topically applied OVA measured by cutaneous delayed type hypersensitivity (DTH) was observed in WT, but not Spdef-/-. OTII CD4⺠T cells primed by dendritic cells (DCs) from the conjunctival draining lymph nodes of Spdef-/- had greater IFN-γ production and lower Foxp3 positivity than those primed by WT DCs. These findings indicate that conjunctival GCs contribute to ocular surface immune tolerance by modulating antigen distribution and antigen specific immune response. GC loss may contribute to the abrogation of ocular surface immune tolerance that is observed in dry eye.
Assuntos
Túnica Conjuntiva/citologia , Síndromes do Olho Seco/imunologia , Células Caliciformes/imunologia , Tolerância Imunológica , Animais , Anticorpos/metabolismo , Linfócitos T CD4-Positivos/imunologia , Túnica Conjuntiva/imunologia , Células Dendríticas/imunologia , Síndromes do Olho Seco/genética , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Interferon gama/genética , Interferon gama/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mucinas/metabolismo , Ovalbumina/metabolismo , Proteínas Proto-Oncogênicas c-ets/genéticaRESUMO
The Th1-associated chemokines CXCL9, CXCL10, and CXCL11 coordinate migration of CXCR3(+) Th1 cells. The objective of this study was to evaluate the role of the innate immune system in stimulating chemokine expression in an experimental model of dry eye and bridge the gap between innate and adaptive immunity. Desiccating stress (DS) induced very early (6 h) expression and production of Th1-associated chemokines in cornea and conjunctiva of C57BL/6 and RAG1 knockout (KO) mice, demonstrating that chemokine expression does not require innate T cells. We then demonstrated that activating the innate immune system prior to adoptive transfer of T cells to RAG1KO mice increased disease severity. Interestingly, lack of induction of chemokines CXCL9, CXCL10, and CXCL11 in IFN-γKO mice provided evidence that their expression requires IFN-γ for induction. Treatment of RAG1KO mice with anti-NK1.1 prevented the increase of CXCL9, CXCL10, and CXCL11 in response to DS, compared with isotype controls. Additionally, DS increased the expression of NKG2D in the conjunctiva. The expression of the NKG2D ligand, retinoic acid early inducible gene 1, also increased at the ocular surface at both the protein and gene levels. Neutralization of NKG2D at the ocular surface decreased the expression of CXCL9, CXCL10, CXCL11, and IFN-γ. In summary, upregulation of CXCL9, CXCL10, and CXCL11 expression in experimental dry eye is T cell-independent, requiring IFN-γ-producing NKG2D(+) NK cells that are activated in response to DS-induced stress signals. This study provides insight into the events that trigger the initial immune response in dry eye pathology.
Assuntos
Epitélio Corneano/imunologia , Imunidade Inata , Interferon gama/imunologia , Proteínas de Membrana/imunologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/imunologia , Xeroftalmia/imunologia , Transferência Adotiva , Animais , Anticorpos/farmacologia , Antígenos Ly/genética , Antígenos Ly/imunologia , Quimiocina CXCL10/genética , Quimiocina CXCL10/imunologia , Quimiocina CXCL11/genética , Quimiocina CXCL11/imunologia , Quimiocina CXCL9/genética , Quimiocina CXCL9/imunologia , Túnica Conjuntiva/imunologia , Túnica Conjuntiva/patologia , Dessecação , Modelos Animais de Doenças , Epitélio Corneano/patologia , Feminino , Deleção de Genes , Regulação da Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/imunologia , Interferon gama/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Subfamília B de Receptores Semelhantes a Lectina de Células NK/antagonistas & inibidores , Subfamília B de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília B de Receptores Semelhantes a Lectina de Células NK/imunologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Linfócitos T/imunologia , Linfócitos T/patologia , Linfócitos T/transplante , Xeroftalmia/genética , Xeroftalmia/patologiaRESUMO
The purpose of this study was to test the hypotheses that development of mature vimentin+/α-smooth muscle actin+/desmin+ (V+A+D+) myofibroblasts from corneal fibroblasts is regulated by transforming growth factor (TGF) ß and platelet-derived growth factor (PDGF); and that myofibroblast development in vitro follows a similar developmental pathway as it does in vivo. Mouse corneal stromal fibroblasts (MSF) were isolated from the corneas of Swiss Webster mice and cultured in serum-free media augmented with DMEM/F12 and varying doses of TGFß (0.1-2.0 ng/ml), with and without mouse PDGF-AA and/or PDGF-BB (2.0 ng/ml), to study the transition of the MSF to V+A+D+ myofibroblasts. The mean percentage of vimentin+, α-SMA+ and desmin+ cells was determined at each time point (2-15 days), with each growth factor concentration. MSF in vitro were noted to undergo the same developmental transition from V+A-D- to V+A+D- to V+A+D+ myofibroblasts as precursors undergo in vivo. TGFß at a dose of 0.5 ng/ml and 1.0 ng/ml with 2.0 ng/ml PDGF-AA and 2.0 ng/ml PDGF-BB in DMEM/F12 serum-free media was optimal for the development of V+A+D+ myofibroblasts. This study defines optimal in vitro conditions to monitor the development of MSF into myofibroblasts. The combined effects of TGFß and PDGF promote the full development of V+A+D+ myofibroblasts from MSF.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Ceratócitos da Córnea/citologia , Miofibroblastos/citologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteínas Proto-Oncogênicas c-sis/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Actinas/metabolismo , Animais , Becaplermina , Células Cultivadas , Ceratócitos da Córnea/metabolismo , Substância Própria/citologia , Desmina/metabolismo , Combinação de Medicamentos , Imuno-Histoquímica , Camundongos , Miofibroblastos/metabolismo , Vimentina/metabolismoRESUMO
OBJECTIVES: Obesity is the main risk factor for the development of obstructive sleep apnea (OSA). Hyperprolactinemia has also been related to obesity. To determine the OSA prevalence in patients with prolactinoma before and after dopamine agonist (DA) and to evaluate the correlation between the apnea-hypopnea index (AHI) and prolactin levels, body mass index (BMI), waist circumference (WC), visceral fat volume (VFV), subcutaneous fat volume, and other metabolic parameters. METHODS: Thirty-five patients with prolactinoma at baseline and twenty-one who completed the 6-month DA treatment were submitted to clinical/laboratorial evaluations, polysomnography and abdominal imaging. RESULTS: Before treatment, the prevalence of obesity/overweight and OSA were, respectively, 68.5 and 34.2 %. We found a positive correlation between AHI and weight (r = 0.57; p < 0.001), BMI (r = 0.56; p < 0.001), WC (r = 0.61; p < 0.001), VFV (r = 0.55; p = 0.002), insulin levels (r = 0.57; p < 0.001), and HOMA-IR index (r = 0.57; p < 0.001); and a negative correlation between AHI and HDL-cholesterol (r = -0.47; p = 0.005). After multivariate analysis, VFV and insulin levels were the most important predictors for AHI (p = 0.001 and p = 0.02, respectively). After DA, the obesity/overweight and OSA prevalence did not change. CONCLUSIONS: The OSA prevalence in patients with prolactinoma is similar to the obese subjects and did not change after treatment. Higher BMI and visceral obesity, but not prolactin levels, seem to be the major factor involved in the occurrence of OSA in these patients.
Assuntos
Agonistas de Dopamina/uso terapêutico , Prolactinoma/tratamento farmacológico , Prolactinoma/epidemiologia , Apneia Obstrutiva do Sono/tratamento farmacológico , Apneia Obstrutiva do Sono/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , Agonistas de Dopamina/farmacologia , Feminino , Humanos , Hiperprolactinemia/tratamento farmacológico , Hiperprolactinemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prolactina/sangue , Prolactinoma/sangue , Prolactinoma/complicações , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/complicações , Circunferência da Cintura/efeitos dos fármacos , Adulto JovemRESUMO
Chapman's claim that the key to marital happiness is "speaking" your partner's primary "love language" has been highly influential in pop culture and incorporated into therapeutic practice. However, the theory has not yet been empirically validated. The current study tests his theory, examining the hypothesis that satisfaction with one's partner's primary love language behavior predicts relationship satisfaction better than satisfaction with one's partner's nonprimary love language behavior. We recruited a sample (n = 696, M = 43.8 years, 70% married, 97.3% cohabitating) through Amazon CloudResearch. Chapman's hypothesis was not supported. Participants' satisfaction with their partners' primary love language behavior no better-predicted relationship satisfaction or perceived love than the lower-ranked love languages. Words of Affirmation and Quality Time better predicted perceived love and relationship satisfaction than participants' primary love language. These results replicate previous research and suggest that these should remain targets of intervention for relationship therapists.