By I. Surus. Luther Seminary.
Although there are sequence similarities between rpr and the death domain of tumor necrosis factor receptor-1 family members discount 30 gm v-gel otc, including the low-affinity neurotrophin receptor p75 buy discount v-gel 30gm on line, mutational analysis does not support the functional similarity suggested by this sequence (Chen et al. Apart from a short, interrupted polyglutamine tract in grim, none of these gene products shows other motifs with known homology to vertebrate proteins. Nonetheless, cell death induced by expression of rpr and hid in mammalian cell culture systems suggests that certain aspects of cell death pathways utilized by these proteins are more widely conserved, despite the apparent absence of homologs (Claveria et al. Directed expression of each of these genes in the eye results in massive cell death with the appearance of reduced, rough eyes (Grether et al. The viral gene P35, which is required for apoptosis of insect cells by the baculovirus Autographa californica (Clem et al. Both genes are homologous to apoptosis inhibitors found in a wide range of organisms, from viruses to C. Loss-of-function mutations in this pathway enhance hid- induced cell death, whereas gain-of-functions mutations suppress it. Thus, intriguing links between regulation of widely conserved signaling pathways and cell death exist; others are likely to be identified. The search for caspases in Drosophila homologous to those previously identified in vertebrates led to identification of the first Drosophila caspase, Dcp-1 (Song et al. Homozygous loss-of-function alleles of Dcp-1 show larval lethality and melanotic tumors. Impaired transfer of nurse cell cytoplasm to oocytes in Dcp-1 mutants demonstrates a requirement for this caspase in oogenesis (McCall and Steller, 1998). Loss of dredd function (using a deficiency line that deletes other genes, as well) serves as an enhancer of eye-specific rpr expression in vivo (Chen et al. Interestingly, the sequence surround- ing the catalytic cysteine of dredd differs from the canonical caspase sequence in that it contains a glutamate residue rather than a glycine, suggesting dredd may have novel substrate specificity. Neurodegenerative Disease in the Fruit Fly 379 Akt or protein kinase B, a downstream target of phosphatidyl inositol-3 kinase, has been implicated in regulating the survival of neurons in response to extracellular signals (Hemmings, 1997). As information becomes available about the function of these genes, it will be interesting to determine if their products interact with polyglutamine- expanded proteins in vivo and, if so, how this affects neuronal dysfunction and degeneration in the fly. Although such developmental cell death is not strictly comparable to late-onset neurodegenerative disease in humans, consider- ation of such mutants may provide valuable insight into mechanisms of neurodegenerative disease. Precise development of appropriate connections between neuronal processes and their targets is required for survival of neurons; such a target-dependent survival phenomenon also occurs in Drosophila. Photoreceptor neurons that fail to establish connections with the optic lobe degenerate. Conversely, optic ganglion neurons that fail to establish contact with photoreceptors in mutants of genes required for eye 380 Jackson specification such as sine oculis differentiate normally but subsequently degenerate (Cheyette et al. In the disconnected mutant, there is a defect in the pathfinding of the larval optic nerve, result- ing in the formation of photoreceptor neurons disconnected from the optic lobe (Steller et al. Such disconnected photoreceptors subsequently degenerate, as does the optic lobe target tissue, demonstrating a reciprocal requirement between neurons and their targets for survival. As noted earlier, loss-of-function mutants in eye-specification genes such as sine oculis result in failure of eyes to develop, associated with increased cell death anterior to the morphogenetic furrow, prior to specification of imaginal disc epithelia as eye progenitors. Developmental cell death is also observed in mutants for genes required for progression of the morphoge- netic furrow. This results in increased cell death anterior to the furrow, fail- ure of differentiation, and the appearance of a scar in the adult eye (Heberlein et al. Mutants acting within the morphogenetic furrow may also show abnormal cell death during imaginal disc develop- ment, resulting in eye abnormalities in the adult. This wave of death eliminates supernumerary cells in each ommatidium to form the perfect crystalline lattice of the adult eye. Inhibition of pupal cell death by eye-specific expression of P35 also disrupts perfection of the lattice structure, resulting in a mildly rough eye (Hay et al. How can an understanding of specific developmental mutants in Droso- phila contribute to the treatment of human diseases? A dramatic example has come from study of Math1, the mouse atonal homolog (Bermingham et al. Hair cells of the inner ear fail to develop in Math1 null embryos, raising the intriguing possibility that ectopic expression of Math1 might provide a treatment for some cases of deafness. Without Drosophila genetic studies to lay the groundwork for analysis of Math1, such an exciting prospect might never have arrived. A number of mutants Neurodegenerative Disease in the Fruit Fly 381 have demonstrated that aberrant regulation of phototransduction results in death of photoreceptor neurons. Despite fundamental differences in the physiology of phototransduction between invertebrates and man, a number of fly retinal degeneration mutants have provided insight into mechanism of retinal degeneration in man.
In this study we hypothesized that expression of varisin would provide protection in D buy v-gel 30 gm with amex. Surprisingly v-gel 30 gm overnight delivery, the results derived from this research were contrary to our hypothesis and demonstrated that silencing of varisin resulted in signicantly reduced A. Further studies are needed to determine whether defensin may be necessary for the development of A. Larvae and nymphs were fed on rabbits and male ticks derived from the engorged nymphs were used for these studies. Male ticks were used for these studies because they become persistently infected with A. Off-host ticks were maintained in a L12:D12 photoperiod at 22 25 C and 95% relative humidity. Acquisition was done by feeding the ticks for 7 days on a splenectomized calf that was experimentally-infected with the Virginia isolate of A. The ticks were then removed and maintained off-host for 4 days, after which they were allowed to feed for 7 days on a sheep to allow for development of A. Two days after infestation of the sheep all unattached ticks were removed and discarded. All ticks were removed after 7 days of feeding and held in the humidity chamber for 4 days. The ticks were held in a humidity chamber for 24 h after which they were allowed to feed on an experimentally infected calf. Midguts and salivary glands were also collected from another ve ticks and xed for microscopy studies (see following section). Injected ticks were allowed to feed on a calf for 3 days after which they were removed with forceps. Two primers were Diseases of Mites and Ticks 21 synthesized based on the sequences of D. Photomicrographs were recorded using a light microscope equipped with a 3-chip digital camera. In contrast, varisin levels were signicantly higher in the salivary glands from A. Amplication efciencies were normalized against b-actin using the comparative Ct method. Two of these ticks appeared to be systemically infected with microbes of unknown identity. Large numbers of these organisms were observed in most tissues, including midguts (Fig. Discussion Ticks are exposed to a wide variety of organisms from mammalian hosts during their extended feeding periods. While some of these organisms are not infective for ticks, others infect tick midguts, where they undergo development and are subsequently transmitted to other hosts during feeding or when the ticks are ingested by the host. During attachment and blood feeding, tick genes express a variety of proteins and peptides involved in the innate immune response that function to inhibit microbial infection, as well as mitigating the oxidative stress and the toxic byproducts (e. These proteins may include several stress reducing proteins such as glutathione-S-transferases (Dreher-Lesnick et al. In addition, anti-microbial peptides in ticks have been reported to be upregulated in response to microbial challenge. For example, lysozyme was found to be upregulated in tick hemolymph after challenge-exposure with E. The small cationic peptides, defensins, are a notable part of the innate response in ticks. Upregulation of tick defensins has also been reported in response to gram negative bacteria such as the intracellular rickettsia, R. The reports cited above suggest that ticks are able to eliminate or at least curtail most microbial infections to which they are exposed. In this research we tested the hypothesis that one of the defensins identied in D. While expression of varisin was conrmed to be silenced in the midguts and hemocytes of the male D. Although these studies were not designed to quantify morphologic changes, the appearance and integrity of the A. Finally, due to the redundant gene function of other defensin genes (Ceraul et al. We observed that two of ve ticks appeared to have a systemic infection with an unknown microbe. Further studies are needed to dene the relationship between other microbes and A. However, whether either of these observations were directly related to varisin knockdown is not known. Since ticks and the pathogens they transmit have co-evolved molecular interactions to assure their survival, these interactions are likely to involve loci in both the pathogen and the tick. Further studies are needed to fully explore the impact of defensins on the infection and development of A.
Several patients recalled walk- ing through a spider web before developing the rash cheap v-gel 30 gm mastercard. The crushing of Paederus beetles on the skin has no immediate effect as well cheap v-gel 30 gm with amex, but in clin- ical experience and observations acute dermatitis appears within 12 36 hours after contact with the irritant. Due to delayed onset of symptoms, contact with the insect is only rarely recalled. Skin lesions correspond in shape and dimension to the area over which the substance was released. Clinically, Paederus dermatitis in characterized by sudden onset of sting- ing and burning sensations with vesicles and pustules on erythematous skin. Blisters are usually described as being multiple and minute, although many cases with bullae up to 1 cm of diameter are described. Lesions typi- cally appear linear and striking diagnostic clues are kissing ulcers and drip marks. Pederin caused skin lesions are usually of a greater severity than those caused by cantharidin. Skin lesions usually heal within 1 2 weeks, but in some cases, lesions persist for a longer time and may remain itchy for 280 Imported Skin Diseases some time. Complications comprise postinammatory hyperpigmentation, secondary infections, and extensive exfoliating or ulcering dermatitis . It is usually caused by transfer of pederin from the skin to the eyes by the nger, although ocu- lar symptoms may be the only manifestation. It usually presents with uni- lateral perorbital dermatitis, but some patients develop severe periorbital edema or keratoconjunctivitis ( Nairobi eye ) . Systemic involvement due to pederin intoxication is described in only a few anecdotic cases. Diagnostic procedures Diagnosis of beetle dermatitis can be easily made in most cases by the clin- ical history and the typical cutaneous lesions However, histopathology may provide useful information. Early lesions are characterized by a neutrophilic spongiosis with intraepidermal vesic- ulation. In contrast, late lesions show epidermal necrosis with a surviv- ing layer of suprabasal cells. In some areas even the basal layer may be destroyed and rarely epithelial necrosis extends down to hair follicles to the level of the sebaceous duct. There is also a moderate perivascular and interstitial inltrate of lymphocytes and histiocytes in the supercial and mid-dermis. Neutrophils are found supercially and associated with papil- lary edema, whereas eosinophils are rare. Exposure to pederin causes a wider spectrum of histopathologic changes, ranging from epidermal necrosis and blistering in the acute stages to marked acanthosis with mitotic gures in the late stages. Pederin der- matitis is an entomologic model of irritant contact dermatitis, having histopathologic features of intraepidermal and subepidermal blistering, epidermal necrosis, and acanthosis . Differential diagnosis Beetle dermatitis may be confused with herpes virus infections, liquid burns, phototoxic reactions, and allergic and irritant contact dermatitis. Prevention and treatment However, insecticides are an efcient not always very environment- friendly way to reduce the number of insects including beetles. In Beetle Dermatitis 281 densely populated buildings such as hospitals, it is sometimes mandatory to treat rooms with insecticides to prevent epidemics of beetle dermatitis [12, 13]. Repellents, which by denition are used to remove arthropods from the host, are effective only at a certain extent to avoid beetle con- tact. An effective way to prevent beetle contact during the night is the use of mosquito nets treated with insecticides as used very effectively in the prophylaxis of malaria. People living in endemic areas furthermore should learn to recognize beetles in order to avoid crushing them on the skin . The rst treatment approach especially in fresh lesions should be to rinse the skin lesion with water . Topical corticosteroids and systemic antihistamines may be helpful in case of severe itch; nevertheless both treatments are of limited effect. In many cases, analgesics are needed due to sometimes very strong pain related to the skin lesions. Defensive secretions of the carabid beetle Chlaenius cordicollis: chemical components and their geographic patterns of variation. Proceedings of the National Academy of Sciences of the United States of America, 99(22), 14002 14007. Gaastra Centrum Oosterwal, Clinic for Dermatology and Flebology, Alkmaar, the Netherlands Key points r Aquatic skin disorders are more frequently seen.
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