RESUMEN
The silkworm Bombyx mori is an important economic insect for producing silk, the "queen of fabrics". The currently available genomes limit the understanding of its genetic diversity and the discovery of valuable alleles for breeding. Here, we deeply re-sequence 1,078 silkworms and assemble long-read genomes for 545 representatives. We construct a high-resolution pan-genome dataset representing almost the entire genomic content in the silkworm. We find that the silkworm population harbors a high density of genomic variants and identify 7308 new genes, 4260 (22%) core genes, and 3,432,266 non-redundant structure variations (SVs). We reveal hundreds of genes and SVs that may contribute to the artificial selection (domestication and breeding) of silkworm. Further, we focus on four genes responsible, respectively, for two economic (silk yield and silk fineness) and two ecologically adaptive traits (egg diapause and aposematic coloration). Taken together, our population-scale genomic resources will promote functional genomics studies and breeding improvement for silkworm.
Asunto(s)
Bombyx , Diapausa , Animales , Bombyx/genética , Domesticación , Genómica , Seda/genéticaRESUMEN
This study examined the effects of sertraline (SER) on glucocorticoid sensitivity in mononuclear leukocytes (MNL) from eight subjects with current post-traumatic stress disorder (PTSD) and nine comparison subjects. In all, 60 ml of blood was withdrawn by venipuncture at 0800, and MNL were isolated from blood and divided into two portions: the first contained live cells incubated with a series of concentrations of dexamethasone (DEX); the second contained cells incubated with similar concentrations of DEX+2 muM SER. Group difference in the concentrations of DEX required to inhibit lysozyme activity by 50% were evaluated under conditions of DEX-only and DEX+SER using analysis of covariance (ANCOVA). A significant Group x Condition interaction reflected that SER altered the lysozyme IC(50-DEX) in the direction of decreasing sensitivity to glucocorticoids in PTSD while having no uniform effect in cells from comparison subjects. The data provide support for the idea that glucocorticoid receptors might be more responsive to antidepressants in PTSD than in persons without PTSD. Insofar as increased sensitivity to glucocorticoids has been linked with PTSD, the actions of SER on the lysozyme IC(50-DEX) suggest that this medication may target a biologic alteration associated with PTSD pathophysiology.
Asunto(s)
Glucocorticoides/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/enzimología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Sertralina/farmacología , Trastornos por Estrés Postraumático/sangre , Adulto , Dexametasona/farmacología , Femenino , Humanos , Hidrocortisona/sangre , Linfocitos/efectos de los fármacos , Linfocitos/enzimología , Masculino , Muramidasa/metabolismo , Receptores de Glucocorticoides/efectos de los fármacosRESUMEN
OBJECTIVE: Studies using the dexamethasone suppression test (DST) have demonstrated an enhanced negative feedback inhibition at the pituitary in PTSD, but have not provided information about central feedback effects, since dexamethasone (DEX) does not penetrate the brain well. The authors therefore examined the change in ACTH and cortisol before and after cortisol administration, which acts at central feedback sites in addition to peripheral targets. METHOD: Blood was obtained from 31 male veterans (18 with PTSD) before, and 8, 40 and 95 min following injection of 17.5 mg cortisol and placebo. RESULTS: A greater decline in ACTH was observed after cortisol injection in PTSD. CONCLUSIONS: Central as well as peripheral negative feedback inhibition may be altered in PTSD.
Asunto(s)
Hormona Adrenocorticotrópica/sangre , Hidrocortisona/sangre , Trastornos por Estrés Postraumático/sangre , Veteranos , Anciano , Trastornos de Combate/sangre , Trastornos de Combate/complicaciones , Trastornos de Combate/fisiopatología , Retroalimentación Fisiológica , Humanos , Hidrocortisona/administración & dosificación , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Estimulación Química , Trastornos por Estrés Postraumático/complicaciones , Trastornos por Estrés Postraumático/fisiopatologíaRESUMEN
BACKGROUND: There is emerging interest in examining the role of plasma neuropeptide Y (NPY) as a protective stress factor. METHODS: To further investigate this possibility, plasma NPY was measured in 11 nonexposed veterans, 11 combat-exposed veterans without posttraumatic stress disorder (PTSD), and 12 veterans with current PTSD. RESULTS: A significant group difference in plasma NPY (F(2,31) = 5.16, p = .012) was observed, reflecting higher NPY levels in exposed veterans without PTSD than in nonexposed but comparable levels in veterans with current PTSD. Among those without current PTSD, veterans with past PTSD had higher NPY levels than those without past PTSD (t(9) = 2.71, p = .024). After controlling for all other variables, NPY levels were significantly predicted by extent of symptom improvement and lower combat exposure and significant at a trend level with positive coping. CONCLUSIONS: Plasma NPY levels may represent a biologic correlate of resilience to or recovery from the adverse effects of stress.
Asunto(s)
Adaptación Psicológica , Neuropéptido Y/metabolismo , Trastornos por Estrés Postraumático/metabolismo , Trastornos por Estrés Postraumático/terapia , Veteranos/psicología , Demografía , Humanos , Masculino , Persona de Mediana Edad , Neuropéptido Y/sangre , Inducción de RemisiónRESUMEN
BACKGROUND: The aim of this study was to determine whether there is increased responsiveness to corticosteroids in posttraumatic stress disorder (PTSD) by examining the differential effects of dexamethasone (DEX) on the inhibition of lysozyme activity. METHODS: 60 mL of blood was withdrawn at 8:00 am, and mononuclear leukocytes were isolated from the blood of 26 men with, and 18 men without, PTSD. An aliquot of live cells was incubated with a series of concentrations of DEX to determine the rate of inhibition of lysozyme activity; a portion of cells was frozen for the determination of glucocorticoid receptors (GR). RESULTS: Subjects with PTSD showed evidence of a greater sensitivity to glucocorticoids as reflected by a significantly lower mean concentration (nmol/L) of dexamethasone at which 50% of lysozyme activity is inhibited (IC(50-DEX)) (PTSD+ = 4.9 +/-.53; PTSD- group = 7.2 +/-.64). The lysozyme IC(50-DEX) was significantly correlated with age at exposure to the first traumatic event in subjects with PTSD (r =.44, n = 26, p =.025). The number of cytosolic glucocorticoid receptors was also correlated with age at exposure to the focal traumatic event (r = -.44, n = 25, p =.03) in PTSD. CONCLUSIONS: This is the first in vitro demonstration of an alteration in target tissue sensitivity to glucocorticoids in PTSD. The lower lysozyme IC(50-DEX) might be related to the risk factor of prior exposure to trauma.
Asunto(s)
Dexametasona/farmacología , Glucocorticoides/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Trastornos por Estrés Postraumático/patología , Adulto , Factores de Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Recuento de Células/métodos , Humanos , Hidrocortisona/sangre , Concentración 50 Inhibidora , Masculino , Persona de Mediana Edad , Muramidasa/metabolismo , Ensayo de Unión Radioligante/métodos , Receptores de Glucocorticoides/metabolismo , Trastornos por Estrés Postraumático/sangreRESUMEN
This study examined the effects of topiramate (TPM) on glucocorticoid receptors (GRs) in mononuclear leukocytes of nine men and four women with chronic and recurring post-traumatic stress disorder (PTSD) and a group of comparison subjects (nine men, four women). A measure of 60 ml of blood was withdrawn by venipuncture at 0800 and mononuclear leukocytes were isolated. The cells were incubated with a series of concentrations of dexamethasone (DEX) without or with 50 micromol/l of TPM to evaluate the effects of DEX to inhibit lysozyme activity and the effect of TPM on it. ANCOVA compared the IC(50) for lysozyme inhibition under conditions of DEX only and TPM+DEX. TPM affected lysozyme IC(50) in the direction of increasing the sensitivity of the receptor in the sample as a whole. This effect was more pronounced in the mononuclear leukocytes from participants in the PTSD group, particularly in cells from subjects whose pretreatment lysozyme IC(50) was relatively higher (eg, reflecting decreased glucococorticoid receptor responsiveness), compared to the rest of the sample. In conclusion, further investigation of the actions of TPM on GR and other neuroendocrine systems may prove useful in understanding some of the other established clinical effects of this agent.
Asunto(s)
Anticonvulsivantes/farmacología , Fructosa/análogos & derivados , Fructosa/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Receptores de Glucocorticoides/fisiología , Adulto , Anciano , Anticonvulsivantes/uso terapéutico , Sitios de Unión , Estudios de Casos y Controles , Demografía , Dexametasona/farmacología , Interacciones Farmacológicas , Femenino , Fructosa/uso terapéutico , Glucocorticoides/farmacología , Humanos , Concentración 50 Inhibidora , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Muramidasa/metabolismo , Receptores de Glucocorticoides/efectos de los fármacos , Trastornos por Estrés Postraumático/sangre , Trastornos por Estrés Postraumático/tratamiento farmacológico , Encuestas y Cuestionarios , TopiramatoRESUMEN
The assessment of lysozyme activity in mononuclear leukocytes (MNLs) following the in vitro administration of dexamethasone (DEX) provides a measure of peripheral glucocorticoid sensitivity. The goal of the present study was to determine the relationship between the IC(50) of lysozyme activity following such challenge, and the cortisol response to oral administration of 0.50 mg DEX in 18 healthy subjects. The results demonstrated a robust association between the IC(50) and both cortisol decline and percent suppression of cortisol in response to low-dose DEX. However, this measure was uncorrelated with pre or post DEX cortisol levels or GR number. The high correlation between the inhibitory effect of DEX on lysozyme synthesis and two measures reflecting cortisol suppression in response to oral DEX reflects the similarities of GC responsiveness in both in vivo and in vitro models, and suggests that the in vitro assessment of lysozyme activity in MNLs may be useful in the study of neuropsychiatric or other clinical disorder.