RESUMEN
Acute decompensated Wilson's disease (WD) that presents as fulminant hepatic failure carries significant mortality without hepatic replacement. The abnormal gene implicated in WD, ATP7B, has been mapped to chromosome 13, and leads to decreased passage of copper from hepatocytes to bile. Excess copper accumulation exceeds hepatocyte storage capacity resulting in intracellular necrosis, apoptosis and cell death in various organs of the body. The hepatic injury induced by the abnormal accumulation of copper in WD has variable presentation such as acute hepatitis, rapid hepatic deterioration resembling fulminant hepatic failure, or as progressive chronic liver disease in the form of chronic active hepatitis or cirrhosis. There are reports in the literature describing monozygotic (identical) twins with similar hepatic progression requiring liver transplantation, however, with different neurological outcome after transplant. We report a case of one monozygotic twin presenting with acute liver failure requiring emergent liver transplantation while the other twin presented with mild liver disease, when both shared an identical genetic mutation.
Asunto(s)
Degeneración Hepatolenticular , Hepatopatías/cirugía , Trasplante de Hígado , Mutación , Gemelos Monocigóticos/genética , Enfermedad Aguda , Adolescente , Cromosomas Humanos Par 13/metabolismo , Cobre/metabolismo , Progresión de la Enfermedad , Femenino , Degeneración Hepatolenticular/genética , Degeneración Hepatolenticular/metabolismo , Degeneración Hepatolenticular/cirugía , Humanos , Hígado/metabolismo , Hígado/cirugía , Hepatopatías/genética , Hepatopatías/metabolismo , Fallo Hepático Agudo/genética , Fallo Hepático Agudo/metabolismo , Fallo Hepático Agudo/cirugíaRESUMEN
Three inherited autosomal dominant conditions-BRCA-related hereditary breast and ovarian cancer (HBOC), Lynch syndrome (LS) and familial hypercholesterolemia (FH)-have been termed the Centers for Disease Control and Prevention Tier 1 (CDCT1) genetic conditions, for which early identification and intervention have a meaningful potential for clinical actionability and a positive impact on public health1. In typical medical practice, genetic testing for these conditions is based on personal or family history, ethnic background or other demographic characteristics2. In this study of a cohort of 26,906 participants in the Healthy Nevada Project (HNP), we first evaluated whether population screening could efficiently identify carriers of these genetic conditions and, second, we evaluated the impact of genetic risk on health outcomes for these participants. We found a 1.33% combined carrier rate for pathogenic and likely pathogenic (P/LP) genetic variants for HBOC, LS and FH. Of these carriers, 21.9% of participants had clinically relevant disease, among whom 70% had been diagnosed with relevant disease before age 65. Moreover, 90% of the risk carriers had not been previously identified, and less than 19.8% of these had documentation in their medical records of inherited genetic disease risk, including family history. In a direct follow-up survey with all carriers, only 25.2% of individuals reported a family history of relevant disease. Our experience with the HNP suggests that genetic screening in patients could identify at-risk carriers, who would not be otherwise identified in routine care.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Pruebas Genéticas , Genética de Población , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Hiperlipoproteinemia Tipo II/genética , Adolescente , Adulto , Anciano , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Femenino , Tamización de Portadores Genéticos/métodos , Síndrome de Cáncer de Mama y Ovario Hereditario/diagnóstico , Síndrome de Cáncer de Mama y Ovario Hereditario/patología , Heterocigoto , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/patología , Persona de Mediana EdadRESUMEN
Chronic infections with the hepatitis B virus (HBV) and high-risk human papillomaviruses (HPVs) are important risk factors for hepatocellular carcinoma (HCC) and cervical cancer (CC), respectively. HBV and HPV are DNA viruses that almost invariably integrate into the host genome in invasive tumors. The viral integration sites occur throughout the genome, leading to the presumption that there are no preferred sites of integration. A number of viral integrations have been shown to occur within the vicinity of important cancer-related genes. In studies of HBV-induced HCC and HPV-induced CC, we have identified two HBV and three HPV integrations into the human telomerase reverse transcriptase (hTERT) gene. Detailed characterization of the integrations revealed that four integrations occurred within the hTERT promoter and upstream region and the fifth integration occurred in intron 3 of the hTERT gene. None of the integrations altered the hTERT coding sequence and all resulted in juxtaposition of viral enhancers near hTERT, with potential activation of hTERT expression. Our work supports the hypothesis that the sites of oncogenic viral integration are nonrandom and that genes at the sites of viral integration may play important roles in carcinogenesis.
Asunto(s)
Virus de la Hepatitis B/genética , Neoplasias Hepáticas/virología , Papillomaviridae/genética , Telomerasa/genética , Neoplasias del Cuello Uterino/virología , Integración Viral , Secuencia de Bases , Proteínas de Unión al ADN , Femenino , Regulación Enzimológica de la Expresión Génica , Humanos , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/etiología , Datos de Secuencia Molecular , Células Tumorales Cultivadas , Neoplasias del Cuello Uterino/enzimología , Neoplasias del Cuello Uterino/etiologíaRESUMEN
Cellular RNAs play fundamental roles as genetic messages, structural components and, in some cases, as catalytic agents. The ability to create vast combinatorial libraries of random RNA sequences has previously been exploited in vitro to identify RNA aptamers with desirable binding specificities, and to isolate RNAs with novel catalytic properties. Despite the advantages of in vitro selections from RNA libraries, there is no way to predict if the identified RNAs can function in living cells. We are therefore exploring random RNA expression libraries in Escherichia coli to search for small RNAs with novel functions. Here we describe selections that identified a small RNA (approximately 260 nucleotides) capable of altering the copy-number control circuitry of IncFII plasmids. The novel RNA appears to function by annealing to a region of the mRNA encoding the plasmid replicator protein. The resulting RNA-RNA hybrid permits translation of the replicator protein, but blocks base-pairing with a natural negative regulatory RNA. Implications of this in vivo selection strategy are discussed.
Asunto(s)
Replicación del ADN/genética , Escherichia coli/genética , Plásmidos/genética , ARN Bacteriano/química , Antibacterianos/farmacología , Secuencia de Bases , Resistencia a Medicamentos/genética , Amplificación de Genes/genética , Regulación Bacteriana de la Expresión Génica/genética , Datos de Secuencia Molecular , Mutagénesis/genética , Conformación de Ácido Nucleico , Hibridación de Ácido Nucleico/genética , Regiones Operadoras Genéticas/genética , ARN Mensajero/metabolismoRESUMEN
The anatomy and physiology of neurones with axons in left and right homologous nerves was studied in abdominal ganglia of the migratory locust, Locusta migratoria, by using a differential cobalt/nickel staining method. These neurones reside within two clusters at the anterior and posterior ends of all unfused abdominal ganglia. Each cluster contains at least seven neurones with bilaterally projecting axons. All neurones of the anterior cluster possess bilaterally projecting axons which leave the ganglion through nerve 2 (= sternal nerve) or nerve 1 (= tergal nerve). Additional axon collaterals, which are present in some of these neurones leave through either nerve 1 or nerve 2 of the right or left side of the ganglion. With few exceptions, the neurones show further asymmetries in their dendritic arborizations. Neurones of the posterior group also have bilaterally projecting axons that leave the ganglion through nerve 1 or nerve 2. Among these neurones are the two large posterior dorsal unpaired median (DUM) neurones with bilaterally symmetrical axons that were described earlier as DUM1 and DUM2. They innervate the skeletal muscles of an abdominal segment. Two other cells of this cluster have anatomical properties similar to the DUM1 neurone and were termed DUMheart1A and DUMheart1B. The rest resemble the bilaterally projecting neurones of the anterior group. With the exception of the two classic DUM neurones (DUM1 and DUM2), all neurones of the anterior and posterior cluster innervate the heart or a neurohaemal area.
Asunto(s)
Ganglios/anatomía & histología , Saltamontes/anatomía & histología , Neuronas/citología , Animales , Transporte Axonal , Axones/fisiología , Femenino , Ganglios/fisiología , Neuronas/fisiología , Coloración y EtiquetadoRESUMEN
The progress of two groups of 10 calves, which had previously been exposed to trichostrongyle infections by grazing infected pastures, was monitored from housing in October to slaughter the following April. Each of the animals of one group had received a morantel sustained release bolus, the other control group remained untreated. The high faecal egg counts and serum pepsinogen concentrations, together with the clinical signs of ostertagiosis observed in the controls in October, persisted during the first month of housing but improved thereafter. From late November onwards, no difference in feed intake and digestive efficiency was observed between the groups. The control calves exhibited a significantly greater feed conversion efficiency over the period February-April, (7.5 vs. 12.3 kg feed kg-1 liveweight gain, P less than 0.001). This reduced the liveweight advantage of the MSRB group over the controls at housing to 25 kg.
Asunto(s)
Enfermedades de los Bovinos/metabolismo , Digestión , Ingestión de Alimentos , Parasitosis Intestinales/veterinaria , Infecciones por Nematodos/veterinaria , Alimentación Animal , Animales , Apetito , Bovinos , Heces/parasitología , Vivienda para Animales , Parasitosis Intestinales/metabolismo , Carne/normas , Infecciones por Nematodos/metabolismo , Ostertagia/aislamiento & purificación , Recuento de Huevos de Parásitos/veterinaria , Estaciones del Año , Trichostrongylus/aislamiento & purificaciónRESUMEN
Herbage intake was measured in two groups of 20 first-year grazing cattle. The animals in one group each received a morantel sustained release bolus at turnout to control nematode parasitism and the animals in the other group remained untreated. The latter group showed a mean peak faecal egg count of 655 eggs per gram (e.p.g.) in October associated with high serum pepsinogen concentration and clinical signs of ostertagiasis, compared with a peak of 119 e.p.g. in the treated group which remained in good health. In September the daily voluntary feed intake of the untreated animals was significantly depressed (94 g kg-1 body weight vs. 77 g kg-1 P less than 0.001), but no difference in digestive efficiency was recorded between the two groups. This difference in feed intake was associated with a 47 kg mean live weight advantage of the treated animals at housing.
Asunto(s)
Enfermedades de los Bovinos/prevención & control , Ingestión de Alimentos , Parasitosis Intestinales/veterinaria , Morantel/uso terapéutico , Pirimidinas/uso terapéutico , Tricostrongiloidiasis/veterinaria , Animales , Peso Corporal , Bovinos , Enfermedades de los Bovinos/fisiopatología , Preparaciones de Acción Retardada , Digestión , Parasitosis Intestinales/fisiopatología , Parasitosis Intestinales/prevención & control , Masculino , Morantel/administración & dosificación , Ostertagia/crecimiento & desarrollo , Ostertagiasis/fisiopatología , Ostertagiasis/prevención & control , Ostertagiasis/veterinaria , Estaciones del Año , Trichostrongyloidea/crecimiento & desarrollo , Tricostrongiloidiasis/fisiopatología , Tricostrongiloidiasis/prevención & control , Trichostrongylus/crecimiento & desarrolloRESUMEN
A crossover study was carried out in cattle to determine the serum pharmacokinetics of a standard dose (20 mg/kg bodyweight) of oxytetracycline given either as a conventional injectable formulation or as a long acting formulation. For reference purposes, an intravenous treatment (also given at 20 mg/kg) was included in the trial protocol. A comparison of the two treatment regimes showed that the long acting formulation gave a significantly lower peak oxytetracycline serum concentration, with a significant extension of drug serum concentration. The long acting formulation also showed a longer serum half life and a significantly greater area under the curve value, calculated from 36 hours onwards, together with serum oxytetracycline concentrations which exceeded 0.5 microgram/ml for 86.8 as opposed to 51.5 hours for the conventional formulation. It is concluded that the use of the long acting formulation in cattle leads to a more sustained serum oxytetracycline concentration than does the same dose of conventional formulation.
Asunto(s)
Animales Domésticos/sangre , Oxitetraciclina/administración & dosificación , Animales , Disponibilidad Biológica , Bovinos , Preparaciones de Acción Retardada , Inyecciones Intramusculares , Inyecciones Intravenosas , Cinética , Masculino , Oxitetraciclina/sangre , Oxitetraciclina/metabolismoRESUMEN
Using a survey of two cohorts of men and women who received Ph.D.s in the years 1958-63 and 1967-72, the authors test two hypotheses: (1) that the relatively lower earnings of highly educated women can be explained largely by their career interruptions and by their lesser willingness to accumulate human capital in anticipation of such interruptions, and (2) that the differential in earnings between men and women increases with age because of career interruptions and that the gap narrows once women reenter the labor force on a permanent basis The findings do not lend support to either of these hypotheses, leading the authors to reject the proposition that the lower rewards of women Ph.D.s are primarily caused by their own voluntary decisions.
Asunto(s)
Salarios y Beneficios , Factores Sexuales , Escolaridad , Femenino , Humanos , Masculino , Estados Unidos , Derechos de la MujerRESUMEN
The rapid rise in women's labor-force participation and the great increase in diversity of family and household structures raise serious questions about the equity and adequacy of a Social Security system developed primarily to meet the needs of traditional families with male wage earners and female homemakers. This article examines the changes in women's roles in the home and in the labor market, then goes on to consider possible reforms in the Social Security system that might help it to better meet the requirements of this profoundly altered society.
Asunto(s)
Familia , Renta , Seguridad Social/economía , Mujeres Trabajadoras , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Predicción , Humanos , Masculino , Persona de Mediana Edad , Salarios y Beneficios , Factores SocioeconómicosRESUMEN
Adoptive cell transfer using engineered T cells is emerging as a promising treatment for metastatic melanoma. Such an approach allows one to introduce T cell receptor (TCR) modifications that, while maintaining the specificity for the targeted antigen, can enhance the binding and kinetic parameters for the interaction with peptides (p) bound to major histocompatibility complexes (MHC). Using the well-characterized 2C TCR/SIYR/H-2K(b) structure as a model system, we demonstrated that a binding free energy decomposition based on the MM-GBSA approach provides a detailed and reliable description of the TCR/pMHC interactions at the structural and thermodynamic levels. Starting from this result, we developed a new structure-based approach, to rationally design new TCR sequences, and applied it to the BC1 TCR targeting the HLA-A2 restricted NY-ESO-1157-165 cancer-testis epitope. Fifty-four percent of the designed sequence replacements exhibited improved pMHC binding as compared to the native TCR, with up to 150-fold increase in affinity, while preserving specificity. Genetically engineered CD8(+) T cells expressing these modified TCRs showed an improved functional activity compared to those expressing BC1 TCR. We measured maximum levels of activities for TCRs within the upper limit of natural affinity, K D = â¼1 - 5 µM. Beyond the affinity threshold at K D < 1 µM we observed an attenuation in cellular function, in line with the "half-life" model of T cell activation. Our computer-aided protein-engineering approach requires the 3D-structure of the TCR-pMHC complex of interest, which can be obtained from X-ray crystallography. We have also developed a homology modeling-based approach, TCRep 3D, to obtain accurate structural models of any TCR-pMHC complexes when experimental data is not available. Since the accuracy of the models depends on the prediction of the TCR orientation over pMHC, we have complemented the approach with a simplified rigid method to predict this orientation and successfully assessed it using all non-redundant TCR-pMHC crystal structures available. These methods potentially extend the use of our TCR engineering method to entire TCR repertoires for which no X-ray structure is available. We have also performed a steered molecular dynamics study of the unbinding of the TCR-pMHC complex to get a better understanding of how TCRs interact with pMHCs. This entire rational TCR design pipeline is now being used to produce rationally optimized TCRs for adoptive cell therapies of stage IV melanoma.
Asunto(s)
Vectores Genéticos , Nucleopoliedrovirus/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Bombyx , Línea Celular , Clonación Molecular/métodos , ADN Circular/genética , ADN Recombinante/genética , ADN Viral/genética , Genes Virales , Genoma Viral , Larva , Datos de Secuencia Molecular , Mariposas Nocturnas , Nucleopoliedrovirus/fisiología , Proteínas de la Matriz de Cuerpos de Oclusión , Plásmidos/genética , Regiones Promotoras Genéticas , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Virales/genética , Proteínas Estructurales ViralesRESUMEN
The females of the palaearctic digger wasp species Liris niger hunt crickets (e.g., Acheta domesticus) as food for their future brood. The wasps paralyze the prey by injecting their venom directly into each of the three thoracic ganglia and the suboesophageal ganglion. This study describes the effects produced by the Liris venom at the level of the intact prey animal (by chronic electromyogram) and at the level of a dissected preparation (by extra- and intracellular records) during the immediate action. Natural or artificial injections of the Liris venom into various ganglia revealed that: (a) The venom injection induced an about 15- to 35-s long tonical discharge of the neurons located in the stung ganglion. This discharge is usually accompanied by convulsions of the prey's limbs. (b) Subsequently, the generation and propagation of action potentials are blocked for up to 30 min (total paralysis). (c) During total paralysis, the venom blocks synaptic transmission. (d) The effects of the venom are restricted to the stung ganglion. Responses of mechanoreceptors in the legs can be recorded from the peripheral nerves of the stung ganglion during the whole period of total paralysis. (e) The neurons almost completely recover after this period. The venom does not selectively affect leg motoneurons, but affects any neuron (e.g., internerneurons or neurosecretory neurons) in any part of the central nervous system of the prey where it was released.
Asunto(s)
Sistema Nervioso Central/efectos de los fármacos , Gryllidae/fisiología , Venenos de Avispas/toxicidad , Avispas/fisiología , Potenciales de Acción/efectos de los fármacos , Animales , Electrofisiología , Femenino , Músculos/efectos de los fármacos , Músculos/fisiología , Parálisis/inducido químicamente , Parálisis/fisiopatología , Transmisión Sináptica/efectos de los fármacosRESUMEN
The oviposition of female locusts requires longitudinal muscles to tolerate remarkable lengthening. Whether this ability together with concomitant properties develops during maturation or is present throughout life was investigated. The properties of the locust abdominal muscles involved in oviposition behaviour were investigated with respect to their maturation, segment- and gender-specificity and regulation by juvenile hormone (JH). Muscles from the sixth abdominal segment (an oviposition segment) of mature females (>18 days old) were able to tolerate large extensions (>8 mm). At this length, muscles were still able to generate considerable neurally evoked twitch tension. In contrast, muscle fibres from females less than 5 days old did not tolerate extension of more than 4 mm. At this length, tension generation was negligible. The maximum tension generated at different stimulus frequencies was significantly higher in muscles of females more than 18 days old than in females less than 5 days old. Furthermore, the cross-sectional area of muscle fibres increased significantly during reproductive development. Current-clamp recordings from denervated muscle fibres of females more than 18 days old revealed their ability to generate overshooting action potentials. The potentials were tetrodotoxin (TTX)-insensitive (0.5 micromol l(-1) TTX), but were blocked by Cd(2+) (50 micromol l(-1)) or nifedipine (50 micromol l(-1)), which suggests the involvement of L-type Ca(2+) channels. Action potentials recorded from females less than 5 days old differed considerably in amplitude and shape from those recorded from females more than 18 days old, suggesting their maturation during the first 2 weeks of adult life. Inactivation of the corpora allata (CA) by precocene inhibited the maturation of these muscle properties, whereas injection of JH into precocene-treated females reversed this effect. Homologous muscles from the third abdominal segment (a non-oviposition segment, M169) and muscles from males (M214) revealed no comparable changes, although some minor changes occurred during reproductive development. The results suggest a gender- and segment-specific maturation of muscle properties that is related to reproductive behaviour and controlled by JH.
Asunto(s)
Saltamontes/crecimiento & desarrollo , Hormonas Juveniles/farmacología , Desarrollo de Músculos , Músculos/fisiología , Músculos Abdominales/efectos de los fármacos , Músculos Abdominales/crecimiento & desarrollo , Músculos Abdominales/fisiología , Potenciales de Acción , Animales , Canales de Calcio Tipo L/fisiología , Femenino , Saltamontes/fisiología , Masculino , Desnervación Muscular , Fibras Musculares Esqueléticas/fisiología , Músculos/efectos de los fármacos , Oviposición/fisiología , Caracteres SexualesRESUMEN
Determining the affinities of oligonucleotides for duplex DNA is an important analytical problem that arises during the design of potential gene repressors based on triple helix recognition. Quantitative DNa-seI footprinting assays (QDFA) offer a rigorous technique for this purpose. Electrophoretic mobility shift assays (EMSA) have proven to be simpler and more rapid. Although EMSA can separate triplex and duplex complexes, there is concern that this technique does not afford as rigorous an equilibrium measurement as is provided by QDFA. We show that QDFA and EMSA techniques provide Kd estimates that agree within one order of magnitude under common experimental conditions. Agreement is best in buffers with low concentrations of monovalent cations. Surprisingly, EMSA appears to slightly overestimate triplex stabilities relative to QDFA in the presence of physiological concentrations of monovalent cations (100 mM). Under these conditions, agreement between the techniques can be improved by quenching EMSA samples with excess unlabeled competitor duplex just prior to gel loading. The data suggest that EMSA can provide results in reasonable agreement with QDFA and offer some insight into sources of deviation between the two methods.
Asunto(s)
ADN/metabolismo , Oligonucleótidos/metabolismo , Huella de ADN , Electroforesis en Gel de Poliacrilamida , Cinética , Conformación de Ácido NucleicoRESUMEN
Three antisera were used to study the distribution and anatomy of bovine pancreatic polypeptide (BPP)-like/FMRFamide-like immunoreactive neurones within the unfused abdominal ganglia of the migratory locust, Locusta migratoria. All the antisera used stained two or more clusters of perikarya, localized anteriorly and posteriorly near the midline within each unfused abdominal ganglion. Double labelling experiments with intracellular dye injection, or differential backfilling, combined with subsequent immunostaining were carried out to identify these neurones. Two of the antisera (antisera 1 and 2, both raised against FMRFamide) stained three groups of midline neurones, located anterior dorsal, anterior ventral and posterior dorsal within the ganglion. Neurones of the former of these two clusters projected via the anterior median nerve to a neurohaemal organ. The posterior cluster of midline cells comprised immunopositive perikarya all but one of which also projected via the anterior median nerve to innervate the neurohaemal organ. Double labelling with Lucifer yellow and antisera 1 and 2 showed that the remaining neurone was the previously identified dorsal unpaired median (DUM)heart 1 neurone. The third antiserum (AK141), also raised against FMRFamide, stained neurones within an anterior dorsal cluster, and in a posterior cluster. Double labelling with differential Co2+/Ni(2+)-backfilling and the antiserum 3 (AK141) demonstrated that the large neurones of both clusters belonged to the population of bilaterally projecting neurones (BPNs), including the DUMheart1 neurone. Since the antisera cross-react with BPP and fail to label neurones when preadsorped with BPP or FMRFamide, we conclude that the labelled neurones contain polypeptides of the FMRFamide/BPP-family.
Asunto(s)
Ganglios/metabolismo , Saltamontes/metabolismo , Neuropéptidos/metabolismo , Animales , FMRFamida , Saltamontes/anatomía & histología , Inmunohistoquímica , Neuronas/metabolismo , Polipéptido Pancreático/metabolismoRESUMEN
This study was conducted to determine whether hospital emergency department (ED) use has been affected by the presence of freestanding emergency centers (FECs) in hospitals' service areas. A sample of FECs was drawn and hospitals in their service areas identified. ED visits to those hospitals from 1970 to 1980 were compared with those of a comparison group of hospitals not studied. The presence of FECs did not lead to a decline in ED visits to hospitals in their service areas. The study documented that FECs are located near hospitals that are larger than average and that have busier EDs. Because of the relative newness of FEC development, future studies of this type should be conducted. This study could not answer the question of whether FECs caused the growth of hospital ED visits to slow. It did not attempt to measure the impact FECs have on private medical practices or determine whether FECs attract currently underserved patient groups.
Asunto(s)
Instituciones de Atención Ambulatoria/estadística & datos numéricos , Servicios Médicos de Urgencia/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Recolección de Datos , Humanos , Factores de Tiempo , Estados UnidosRESUMEN
The data presented here describe neurophysiological experiments addressing the question of cellular mechanisms underlying the total paralysis of locomotor behavior in crickets occurring after being stung by females of the digger wasp species Liris niger. The Liris venom effects have been studied by both in vivo recordings from identified neurons of the well-described giant fiber pathway and in vitro recordings from cultured neurons isolated from the terminal ganglion of crickets. The total paralysis of the prey is characterized by a general block of action potential generation as well as by a block of synaptic transmission. Intracellular recordings from neurons in intact ganglia under single electrode voltage-clamp conditions, as well as whole-cell patch-clamp recordings from cultured cricket neurons consistently show that the block of action potential generation by the Liris venom is due to a block of voltage-gated sodium inward currents in neurons of the stung ganglia. Furthermore, our data provide evidence that the Liris venom also blocks calcium currents in identified neurosecretory neurons. On the other hand, outward currents are not affected by the Liris venom. The in vitro recordings suggest that the Liris venom contains active venom components, which, at least for the observed block of inward currents, do not require a metabolic modification. Because venom application does not affect the ACh-induced EPSPs in giant interneurons, the Liris venom does not seem to influence the postsynaptic ACh receptors. The possible pre- and postsynaptic sites of venom action and the functional consequences on synaptic transmission within the giant fiber system are discussed.
Asunto(s)
Gryllidae/fisiología , Parálisis/inducido químicamente , Venenos de Avispas , Animales , Tamaño de la Célula , Células Cultivadas , Conductividad Eléctrica , Femenino , Interneuronas/efectos de los fármacos , Interneuronas/patología , Interneuronas/fisiología , Masculino , Sistemas Neurosecretores/efectos de los fármacos , Sistemas Neurosecretores/patología , Sistemas Neurosecretores/fisiopatología , Técnicas de Placa-Clamp , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología , Venenos de Avispas/farmacología , AvispasRESUMEN
Genetic differences between strains of a baculovirus are often limited to some restriction sites, short DNA deletions or absence of some nonessential genes. The recently coined bro gene family, represents a new major source of intraspecific variability. A comparison between two bro gene sets of Bombyx mori nucleopolyhedroviruses (NPV) shows that bro genes are distributed in three regions for the -T3 and -SC7 virus strains. In BmNPV T3, five bro genes are distributed in three genome locations, whereas the BmNPV SC7 strain possess a single bro copy in each region. In addition, each of the BmNPV SC7 bro genes belongs to one of the three subfamilies present in BmNPV T3. Analysis of bro copy sequences and of adjacent sequences suggests an active redistribution of sequences due to intraspecific recombination. The maintenance of one allele of each subfamily suggests that they play different roles in the viral cycle, and that they are essential.