Nejvíce citovaný článek - PubMed ID 13741297
Second-order spinal cord excitatory neurons play a key role in spinal processing and transmission of pain signals to the brain. Exogenously induced change in developmentally imprinted excitatory neurotransmitter phenotypes of these neurons to inhibitory has not yet been achieved. Here, we use a subpial dorsal horn-targeted delivery of AAV (adeno-associated virus) vector(s) encoding GABA (gamma-aminobutyric acid) synthesizing-releasing inhibitory machinery in mice with neuropathic pain. Treated animals showed a progressive and complete reversal of neuropathic pain (tactile and brush-evoked pain behavior) that persisted for a minimum of 2.5 months post-treatment. The mechanism of this treatment effect results from the switch of excitatory to preferential inhibitory neurotransmitter phenotype in dorsal horn nociceptive neurons and a resulting increase in inhibitory activity in regional spinal circuitry after peripheral nociceptive stimulation. No detectable side effects (e.g., sedation, motor weakness, loss of normal sensation) were seen between 2 and 13 months post-treatment in naive adult mice, pigs, and non-human primates. The use of this treatment approach may represent a potent and safe treatment modality in patients suffering from spinal cord or peripheral nerve injury-induced neuropathic pain.
- Klíčová slova
- GAD65 and VGAT, long-lasting pain reversal, neuropathic pain, precision spinal vector delivery, subpial injection technique, subpial non-human primates, subpial pig, targeted AAV9 delivery,
- MeSH
- buňky zadních rohů míšních MeSH
- mícha MeSH
- myši MeSH
- neuralgie * etiologie terapie MeSH
- nociceptory * MeSH
- prasata MeSH
- technika přenosu genů MeSH
- zadní rohy míšní MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: Trypanosoma theileri species complex includes parasites of Bovidae (cattle, sheep, goat, etc.) and Cervidae (deer) transmitted mainly by Tabanidae (horse flies and deerflies) and keds (Hippoboscidae). While morphological discrimination of species is challenging, two big clades, TthI and TthII, each containing parasites isolated from bovids and cervids, have been identified phylogenetically. To date, the development in the vector has been studied in detail only for the ked-transmitted sheep parasite T. melophagium (TthII), while the fate of trypanosomes in tabanids was described only briefly by light microscopy. METHODS: We collected infected tabanids of various species and identified trypanosomes by molecular phylogenetic analysis. The morphology and development of trypanosomes was studied using the combination of statistical analyses as well as light and electron microscopy. RESULTS: Two trypanosome species belonging to both TthI and TthII clades of the T. theileri complex were identified. The phylogenetic position of these two trypanosomes suggests that they parasitize deer. Both species were indiscernible by morphology in the vector and showed the same development in its intestine. In contrast to the previously described development of T. melophagium, both trypanosomes of tabanids only transiently infected midgut and settled mainly in the ileum, while pylorus and rectum were neglected. Meanwhile, the flagellates developing in the tabanid ileum (pyriform epimastigotes and metacyclic trypomastigotes) showed similarities to the corresponding stages in T. melophagium by morphology, mode of attachment to the host cuticle and formation of the fibrillar matrix surrounding the mass of developing parasites. In addition, for the first time to our knowledge we documented extraintestinal stages in these trypanosomes, located in the space between the epithelium and circular muscles. CONCLUSIONS: The development of different species of flagellates of the T. theileri complex in their insect vectors shows many similarities, which can be explained not only by their common origin, but also the same transmission mode, i.e. contamination of the oral mucosa with the gut content released after squashing the insect either by tongue or teeth. The observed differences (concerning primarily the distribution of developmental stages in the intestine) are associated rather with the identity of vectors than the phylogenetic position of parasites.
- Klíčová slova
- Deerflies, Horseflies, Life cycle, Trypanosomes, Vector,
- MeSH
- Diptera * parazitologie MeSH
- fylogeneze MeSH
- hmyz - vektory parazitologie MeSH
- ovce MeSH
- skot MeSH
- Trypanosoma * MeSH
- vysoká zvěř * parazitologie MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Aging depicts one of the major challenges in pharmacology owing to its complexity and heterogeneity. Thereby, advanced glycated end-products modify extracellular matrix proteins, but the consequences on the skin barrier function remain heavily understudied. Herein, we utilized transmission electron microscopy for the ultrastructural analysis of ribose-induced glycated reconstructed human skin (RHS). Molecular and functional insights substantiated the ultrastructural characterization and proved the relevance of glycated RHS beyond skin aging. In particular, electron microscopy mapped the accumulation and altered spatial orientation of fibrils and filaments in the dermal compartment of glycated RHS. Moreover, the epidermal basement membrane appeared thicker in glycated than in non-glycated RHS, but electron microscopy identified longitudinal clusters of the finest collagen fibrils instead of real thickening. The stratum granulosum contained more cell layers, the morphology of keratohyalin granules decidedly differed, and the stratum corneum lipid order increased in ribose-induced glycated RHS, while the skin barrier function was almost not affected. In conclusion, dermal advanced glycated end-products markedly changed the epidermal morphology, underlining the importance of matrix⁻cell interactions. The phenotype of ribose-induced glycated RHS emulated aged skin in the dermis, while the two to three times increased thickness of the stratum granulosum resembled poorer cornification.
- Klíčová slova
- advanced glycated end products, aging, diabetes, electron microscopy, nanomedicine, reconstructed human skin, ribose, skin absorption,
- MeSH
- bazální membrána účinky léků ultrastruktura MeSH
- buněčná diferenciace účinky léků MeSH
- epidermis účinky léků ultrastruktura MeSH
- fibroblasty účinky léků ultrastruktura MeSH
- keratinocyty účinky léků ultrastruktura MeSH
- kůže účinky léků ultrastruktura MeSH
- lidé MeSH
- produkty pokročilé glykace metabolismus MeSH
- ribosa farmakologie MeSH
- škára účinky léků ultrastruktura MeSH
- stárnutí kůže účinky léků MeSH
- transmisní elektronová mikroskopie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- produkty pokročilé glykace MeSH
- ribosa MeSH
In order to avoid sperm competition, males of many taxa apply physical barriers, so-called mating plugs, into female genitalia. Females may control which males deposit a plug through pre-copulatory mate choice or by influencing plug efficacy to avoid costs imposed by plugging. However, subsequent suitors might remove the plugs. We investigated behavioural and morphological aspects of plug deposition and removal in a promiscuous spider, Philodromus cespitum (Philodromidae). We performed mating trials to investigate factors affecting plugging. To identify the plug origin, we conducted a morphological analysis using 3D X-ray microtomography and histology of the male copulatory organ and the female genital tract. In P. cespitum, the plug material is produced in the male genital bulb and transferred to the female together with sperm. The copulation is brief and terminated by the female. After mating, plugging material was found in the genital atrium of all females, covering it to a varying degree (10-100%). The extent of coverage was associated with the duration of movements of male copulatory organ connected with sperm transfer (i.e. full haematodochal expansions) and with the number of taps a male delivered with his legs to the female during courtship. Males larger than the female performed more tapping movements. Mating trials with plugged females revealed that males could remove plugs partly or entirely. Removal success increased with increasing foreleg length ratio between the male who removed the plug and the one who deposited it. We discuss our results in the light of the potential female control of plug deposition and removal.
- Klíčová slova
- Courtship, Female mate choice, Genital morphology, Polyandry, Sperm competition, X-ray microscopy,
- MeSH
- pavouci fyziologie MeSH
- rozmnožování fyziologie MeSH
- sexuální chování zvířat fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The primary function of male copulatory organs is depositing spermatozoa directly into the female reproductive tract. Typical male copulatory organs are sensorily active. This is in contrast to the copulatory organs of male spiders (i.e. palpal bulbi), which have been assumed to lack nerves and muscles until recently. Neurons have been found within the bulbus of the spider Hickmania troglodytes, a taxon basal to all Neocribellata. We provide the first evidence for neurons and an internalized multi-sensillar sensory organ in the bulbus of an entelegyne spider (Philodromus cespitum). The sensory organ likely provides mechanical or chemical feedback from the intromitting structure, the embolus. We found further neurons associated with two glands within the bulbus, one of which is likely responsible for sperm extrusion during mating. These findings provide a new framework for studies on reproductive behaviour and sexual selection in spiders.
- MeSH
- čití, cítění fyziologie MeSH
- mužské pohlavní orgány inervace ultrastruktura MeSH
- neurony fyziologie ultrastruktura MeSH
- pavouci fyziologie MeSH
- sensilla fyziologie ultrastruktura MeSH
- sexuální chování zvířat fyziologie MeSH
- transmisní elektronová mikroskopie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Sperm competition imposes a strong selective pressure on males, leading to the evolution of various physiological, morphological and behavioral traits. Sperm competition can be prevented by blocking or impeding the access to female genitalia by means of a mating plug. We investigated the factors responsible for plug production and function in the promiscuous female-cannibalistic spider Micaria sociabilis (Gnaphosidae). RESULTS: We performed mating trials using females with and without a plug that consists of an amorphous mass. The mating trials demonstrated that the probability of male plugging increased non-linearly with the duration of copulation. Copulation duration and plug production seem to be controlled by the female. We found that females terminated matings later if males were fast at genital coupling. Whereas incomplete plugs had disappeared on the day following copulation, complete plugs persisted (40%). In matings with females with complete plugs, only a small proportion of males (7%) were able to remove the plug, indicating the high effectiveness of plugging. Moreover, males ceased attempts to copulate with plugged females with higher probability. 3D X-ray microscopy of the female and male genitalia showed that the plug material can extend far into the female genital tract and that the plug material is produced by a massive gland inside the palpal organ of the modified male pedipalps. CONCLUSIONS: Our study demonstrates that the mating plug in M. sociabilis constitutes an effective male strategy to avoid sperm competition that seems to be under female control.
