Paralytic Effects Research Articles

Extraction, Purification, Quantification, and Stability of Bioactive Spilanthol from Acmella oleracea.

Acmella oleracea is an ethnobotanically significant plant with a relatiwely high content of spilanthol. Due to its broad spectrum of activity, including anti-inflammatory, antioxidant, analgesic, antifungal, and bacteriostatic properties, it is considered a valuable bioactive natural product. In addition, spilanthol as its main bioactive component inhibits facial muscle contractions, making it an attractive ingredient in anti-wrinkle and anti-aging cosmetics. Due to its muscle paralyzing effects, it is called herbal botox. The commercial interest in spilanthol encourages the development of effective methods of isolating it from plant material. The methodology used in this paper allows for the obtaining of extracts from Acmella oleracea with a relatively high content of spilanthol. An effective method of spilanthol extraction from all aerial parts of Acmella oleracea as well as methods of enriching spilanthol concentration in extracts achieved by removing polar and acidic substances from crude extracts was developed. To quantify the concentration of spilanthol, a simple, fast and economically feasible quantification protocol that uses nuclear magnetic resonance (HNMR) was developed. In addition, it has been proven, that oxidation of spilanthol by air gives (2E,7Z)-6,9-endoperoxy-N-(2-methylpropyl)-2,7-decadienamide. The studies on spilanthol solutions stability were carried out and the conditions for the long-time storage of spilanthol solutions have also been developed. Additionally, for confirmation of obtained results a sensitive (LOQ=1 ng/mL), precise (RSD lower than 7%) and accurate (RE lower than 7.5%), new HPLC-MS/MS method was applied.

The complete mitochondrial genome of Pyemotes zhonghuajia (Acari: Pyemotidae)

Pyemotes zhonghuajia (Acari: Pyemotidae) has paralyzing and lethal effects on a variety of important agricultural and forestry pests in Lepidoptera, Coleoptera, and Hymenoptera pests. A single P. zhonghuajia mite can paralyze and kill a host 680,000 times its own weight within 3 hours. However, although it is an efficient and broad-spectrum natural enemy that is unique to China, its mitochondrial genome is still unknown. In this study, the complete mitochondrial genome of P. zhonghuajia was sequenced and annotated. It consists of two circular genomes. The complete mitogenome of P. zhonghuajia is 14,772 bp in length and contains 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and two control regions. The phylogenetic tree of 29 species suggests that P. zhonghuajia belongs to Eleutherengona.

Temporal Structuring in Sensemaking – How an Entrepreneurial Team Deals with Radical Uncertainty

Understanding ways in which teams and organizations manage, negotiate and navigate uncertain futures is paramount, as high uncertainty can significantly harm employee and volunteer engagement. Recently, scholars have taken a keen interest in exploring collective sensemaking in uncertain contexts. Previous studies have examined how teams restore action after disruptive events and retrospectively make sense of the disruptions. However, the strategies teams utilize to deal with dynamic uncertainty “on the ground” have been largely missing. In this study, we examined team-level sensemaking during high uncertainty. We identified three strategies of temporal structuring that helped the team cope with and tame the uncertainty that could cripple their organizing efforts: (1) freezing the future (2) bracketing the future and (3) abstracting the future. Our study contributes to the literature on sensemaking and uncertainty by demonstrating the significance of temporal structuring as a way of moving forward and dealing with uncertainty as well as mitigating the potentially paralyzing effect of radical uncertainty. In addition, our study contributes to the literature on prospective and temporal sensemaking by focusing on the present-future connection and showing how a team constructs sensemaking anchors in the future rather than retrospectively in the past.

Emerging Therapies in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the loss of cortical and spinal motor neurons, leading to weakness, muscle atrophy, and, in a substantial number of patients, cognitive impairment. Most patients die within 2 to 5 years of diagnosis. The disease initiates from the death of upper and lower motor neurons leading to a degeneration of motor pathways and the paralytic effects of the disease. The disease has huge economic costs as well. FDA has approved two drugs, riluzole, and edaravone for the treatment of ALS. However, these drugs provide modest benefits in mortality and/or function. Recent developments in the understanding of the underlying pathophysiologic processes that contribute to ALS have led to the development of numerous investigational therapies, with several now in phase 3 trials. This article highlights the epidemiology, pathophysiology, and several current and emerging treatment options for ALS including stem cell therapy.

46. Nanomaterial-based Neuromodulators for Extended Duration of Therapeutic Effect

Purpose: Neuromodulators of the botulinum toxin family are highly effective therapeutics for aesthetic and medical indications. However, wider use of these agents is hampered by their limited duration of effect which necessitates in frequent redosing. In addition, diffusion away from the target site resulting in off-target activity with unwanted muscle paralysis. The aim of this study was to (1) develop a novel nanoparticle-based delivery system for neuromodulators that enables sustained release at target tissue sites and (2) assess the efficacy of locally delivered neuromodulation in prolonging muscle paralysis. Methods: Botulinum toxin A (BoNTA), BoNTA toxoid (chemically inactivated form of the toxin) Neuromodulators were each encapsulated within polymeric nanoparticles (NPs). BoNTA or its toxoid were mixed with carrier molecules and fabricated into polymeric nanoparticles. Release kinetics were of the nanomaterial-based neuromodulator formulation were evaluated in vitro using enzyme-linked immunosorbent assays. The bioactivity of released neuromodulator was assessed using a substrate hydrolysis assay. The therapeutic potential was assessed in vivo using a quantitative forelimb grip strength model in rats. The nanomaterial-based neuromodulator formulations were injected into the muscles of the anterior compartment in the forearm and the paralytic effect was quantified by assessing functional recovery using stimulated grip strength testing. Functional recovery was assessed weekly and compared to baseline grip strength as percentage recovery from baseline until this was complete at which point animals were sacrificed for histologic analyses. Results: Reference protein-loaded NPs showed superior localization when injected in rodent models when compared to unencapsulated proteins. Rodents injected with unencapsulated BoNTA (1X BoNTA) fully regained grip strength fastest with 80% recovery in only 8 weeks. Doubling the dose of unencapsulated BoNTA (2X BoNTA) delayed 80% recovery to 18 weeks. Strikingly, the nanoparticle encapsulated BoNTA (1X BoNTA/NP) at the original 1X dose outperformed even this group with 65% recovery at 18 weeks. Conclusion: Our novel nanomaterial-based neuromodulator formulation provides linear, long-acting release while the encapsulation process did not diminish the bioactivity of BoNTA. This prolongation of effect is achieved without increasing BoNTA dosing. Such a sustained release formulation and local delivery modality promises superior therapeutic outcomes with less frequent re-dosing.

Genetic Survey of Psilocybe Natural Products.

Psilocybe magic mushrooms are best known for their main natural product, psilocybin, and its dephosphorylated congener, the psychedelic metabolite psilocin. Beyond tryptamines, the secondary metabolome of these fungi is poorly understood. The genomes of five species (P. azurescens, P. cubensis, P. cyanescens, P. mexicana, and P. serbica) were browsed to understand more profoundly common and species‐specific metabolic capacities. The genomic analyses revealed a much greater and yet unexplored metabolic diversity than evident from parallel chemical analyses. P. cyanescens and P. mexicana were identified as aeruginascin producers. Lumichrome and verpacamide A were also detected as Psilocybe metabolites. The observations concerning the potential secondary metabolome of this fungal genus support pharmacological and toxicological efforts to find a rational basis for yet elusive phenomena, such as paralytic effects, attributed to consumption of some magic mushrooms.

Descriptive Study: Attitude and Behaviour Regarding Oral Corticosteroid Use in Bebita Clinic Cicurug, Sukabumi in 2019

Background: Corticosteroids are derivatives of steroid hormones that have the effect of inhibiting the inflammatory response. Glucocorticoid is the type of corticosteroid that is easy to obtain and has a high anti-inflammatory effect. Therefore, glucocorticoids are often used in various therapies. However, the use of this drug should be monitored since its side effects can be harmful to the health as paralytic effects or even lethal effects. Purposes: This study aims to determine the behavior of using oral corticosteroids in patients at the Bebita Cicurug Clinic, Sukabumi. Methods: This is a descriptive quantitative research study. Data collection was done from September to December 2019. The respondents of this study were 96 subjects of Bebita Cicurug Clinic with a history of oral glucocorticoid usage. The data was taken using a questionnaire and medical records. Result: The most widely used glucocorticoid type is Methylprednisolone 4 mg and dexamethasone 0,5 mg. Overall, 89.6% of respondents used corticosteroids for a week or less. A total of 21.9% had tried to get corticosteroids without a prescription (self-medication), and all of them didn't get restricted on purchasing corticosteroids. Conclusion: In general, patients in this study had good behavior in using corticosteroids (using steroids according to a doctor's prescription), but 21.9% had tried to get corticosteroids without a prescription, and all of them didn't get restricted on purchasing corticosteroids. Doctors and health workers must clearly explain prescribed drugs' benefits and side effects, especially in patients with chronic diseases. Then ensure that the patient has understood the benefits and side effects of the medications used.

Comparative Pharmacodynamics of Three Different Botulinum Toxin Type A Preparations following Repeated Intramuscular Administration in Mice.

Botulinum neurotoxin type A (BoNT/A) causes muscle paralysis by blocking cholinergic signaling at neuromuscular junctions and is widely used to temporarily correct spasticity-related disorders and deformities. The paralytic effects of BoNT/A are time-limited and require repeated injections at regular intervals to achieve long-term therapeutic benefits. Differences in the level and duration of effectivity among various BoNT/A products can be attributed to their unique manufacturing processes, formulation, and noninterchangeable potency units. Herein, we compared the pharmacodynamics of three BoNT/A formulations, i.e., Botox® (onabotulinumtoxinA), Xeomin® (incobotulinumtoxinA), and Coretox®, following repeated intramuscular (IM) injections in mice. Three IM injections of BoNT/A formulations (12 U/kg per dose), 12-weeks apart, were administered at the right gastrocnemius. Local paresis and chemodenervation efficacy were evaluated over 36 weeks using the digit abduction score (DAS) and compound muscle action potential (CMAP), respectively. One week after administration, all three BoNT/A formulations induced peak DAS and maximal reduction of CMAP amplitudes. Among the three BoNT/A formulations, only Coretox® afforded a significant increase in paretic effects and chemodenervation with a prolonged duration of action after repeated injections. These findings suggest that Coretox® may offer a better overall therapeutic performance in clinical settings.

Stomach-affecting intestinal parasites as a precursor model of Pheretima posthuma treated with anthelmintic drug from Dodonaea viscosa Linn.

Abstract The preponderance of helminth contagions is constrained to tropical regions and can cause massive vulnerability to malnutrition, anemia, pneumonia, and eosinophilia. Many human parasitic diseases cause severe illness in endemic populations. The helminths transmitting through the gastro-intestinal tract may develop resistance to anthelmintic drugs. The phytotherapy, anthelmintic, and antimicrobial efficacy of Dodonaea viscosa leaf solvent extracts were examined. Phytochemical screening was carried out by ultraviolet (UV) and Fourier transform infrared spectroscopy (FTIR). The anthelmintic activity was performed against a South Indian earth worm as a model by measuring the paralytic time. The antibacterial activity was performed against Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus, which stimulate the stomach helminths. Phytochemical screening revealed the presence of chemical compounds from the UV spectrum, and alkenes and aromatic compounds were confirmed by FTIR. Higher concentrations of the D. viscosa extract showed a rapid paralytic effect with a rapid death rate and histopathology. The zone-of-inhibition study indicated the potent antibacterial activity of the ethanolic and methanolic extracts of D. viscosa against different bacterial species. The current research revealed that D. viscosa has significant anthelmintic and antibacterial activities and it can be used for further elucidation and characterization.

Dynamic muscle paralytic effects of a novel botulinum toxin A free of neurotoxin-associated proteins.

Structurally, botulinum toxin type A (BTX‐A) is composed of neurotoxin and nontoxic complexing proteins (CPs), and the neurotoxin has the function of blocking acetylcholine release from the neuromuscular junction and therefore paralyzing muscles. Nowadays, a novel botulinum toxin A free of CPs (chinbotulinumtoxin A, A/Chin) is produced, and the present study comprehensively evaluated the dynamic paralytic effect of A/Chin on the gastrocnemius muscle of rats. Different doses (0.01, 0.1, 0.5, 1, 2, and 4 U) of A/Chin and other BTX‐As with and without CPs were administered to the gastrocnemius muscles of rats and muscle strength was measured and compared at different postinjection timepoints (from day 0 to 84). With the dose increased, time‐to‐peak paralytic effect of other BTX‐As varied from day 3 to day 14, while A/Chin groups showed rapid and steady time to peak on day 3. At the lowest dose of 0.01 U, A/Chin showed significantly better peak paralytic effect than the others on day 3. When the dose increased to 0.5 U and more, A/Chin group also showed significant paralytic effect when the paralytic effect of other BTX‐As was worn off. Moreover, the paralytic effect of A/Chin was confirmed as muscle atrophy while hematoxylin–eosin staining was performed. In conclusion, compared with other BTX‐As, A/Chin showed rapid and steady time‐to‐peak paralytic effect and long‐term paralytic efficacy at the same dose level. And it might lay a solid foundation for further wide application of A/Chin in both clinical and cosmetic areas.

“We Were Born from Beauty”: Dis/Inheriting Genealogies of Refugee and Queer Shame in Ocean Vuong’sOn Earth We’re Briefly Gorgeous

AbstractI examine how Ocean Vuong’s 2019 novel On Earth We’re Briefly Gorgeous reconceives intergenerational shame produced through processes of refugee and queer becoming and identification in the United States. I posit that the affective condition of shame is both a result of and intrinsic to the social formation of queer and refugee identities. I also trace how these identities that at times can exclude the Other also intersect in On Earth as a way of revealing and critiquing the parallel forms of heteropatriarchal violence enacted upon the queer/refugee subject. Through Vuong’s presentation of Little Dog’s queer Vietnamese identity, I consider how Little Dog must reconcile himself to the loyalties that bind him to his matrilineal family and Vietnam and also to American idealizations of white masculinity and heterosexuality. These tensions are animated through the shame resulting from Little Dog’s sexual encounters with his white American love interest, Trevor, and in Little Dog and his family’s social “failures” to integrate into the United States and become model minorities. The sustained incompatibility between the matrilineal past of Vietnam (and the metonymic war the country signifies) and the American present belonging to the white fathers who fill the text also shows the limits of the dominant narratives that situate the United States in benevolent relation to the powerless refugees it saved and rehomed. Although I focus on the paralyzing effects of shame that attend experiences of racial and sexual difference, I explore how Vuong reimagines shame as a generative site that not only creates new intimacies and grammars across bodies that have been deemed socially abject but also conjures a Vietnam outside the familiar US war narrative of rescue.

Effects of Threat and Motivation on Classical Musicians’ Professional Performance Practice During the COVID-19 Pandemic

In the past 2 years our world has experienced huge disruptions because of COVID-19. The performing arts has not been insulated from these tumultuous events with the entire music industry being thrown into a state of instability due to the paralyzing effects of the COVID-19 pandemic. In this study, we examined how classical professional musicians’ ability to cope with uncertainty, economic struggles, and work-life interplay during COVID-19 was influenced by various factors that affect a crucial part of the development and sustainment of music careers: musicians’ practice. We analyzed responses to an online survey of 309 classical performing musicians from 41 countries in Europe and Latin America across three pandemic stages: immediately before the pandemic, during the pandemic, and when vaccines were being made available and lockdowns were being reduced or lifted. Structural equation modeling indicates relationships between perceptions of threat at the peak of the pandemic and the musicians Self- or External-Based Motivation for the three periods in which respondents were asked to reflect. Findings suggest that musicians who are more internally self-motivated seemed to be more resilient to the pandemic threats and more capable of managing their practicing routines, whereas more externally motivated musicians experienced a reduction in their dedicated time to practice during lockdown. We suggest pedagogical and policy implications, as well as future lines of research that are oriented toward supporting professional musicians in assessing and understanding their motivational drives so that they can cope with situations that disrupt their professional lives.

A wireless controlled intelligent healthcare system for diplegia patients.

Rehabilitation engineering is playing a more vital role in the field of healthcare for humanity. It is providing many assistive devices to diplegia patients (The patients whose conditions are weak in terms of muscle mobility on both sides of the body and their paralyzing effects are high either in the arms or in the legs). Therefore, in order to rehabilitate such types of patients, an intelligent healthcare system is proposed in this research. The electric sticks and chairs are also a type of this system which was used previously to facilitate the diplegia patients. It is worth noting that a voice recognition system along with wireless control feature has been integrated intelligently in the proposed healthcare system in order to replace the common and conventional assistive tools for diplegia patients. These features will make the proposed system more user friendly, convenient and comfortable. The voice recognition system has been used for movements of system in any desired direction along with the ultrasonic sensor and light detecting technology. These sensors detect the obstacles and low light environment intelligently during the movement of the wheelchair and then take the necessary actions accordingly.

Hybrid Antibody-Aptamer Assay for Detection of Tetrodotoxin in Pufferfish.

The marine toxin tetrodotoxin (TTX) poses a great risk to public health safety due to its severe paralytic effects after ingestion. Seafood poisoning caused by the consumption of contaminated marine species like pufferfish due to its expansion to nonendemic areas has increased the need for fast and reliable detection of the toxin to effectively implement prevention strategies. Liquid chromatography-mass spectrometry is considered the most accurate method, although competitive immunoassays have also been reported. In this work, we sought to develop an aptamer-based assay for the rapid, sensitive, and cost-effective detection of TTX in pufferfish. Using capture-SELEX combined with next-generation sequencing, aptamers were identified, and their binding properties were evaluated. Finally, a highly sensitive and user-friendly hybrid antibody–aptamer sandwich assay was developed with superior performance compared to several assays reported in the literature and commercial immunoassay kits. The assay was successfully applied to the quantification of TTX in pufferfish extracts, and the results obtained correlated very well with a competitive magnetic bead-based immunoassay performed in parallel for comparison. This is one of the very few works reported in the literature of such hybrid assays for small-molecule analytes whose compatibility with field samples is also demonstrated.

INVESTIGATION OF ANTHELMINTIC EFFECT OF NEOLAMARCKIA CADAMBA FRUIT EXTRACTS IN ASCARIASIS

Objective: Investigation of Anthelmintic effect of Neolamarckia Cadamba fruit extracts (Ethanol, Aquaous, Phenyl ether, Chloroform) in Ascariasis.
 Methods: The experiment was conducted on an adult Indian earthworm, Eiseniafoetida, owing of its morphological and physiological similarities to the human intestine roundworm parasite. Six sets of six earthworms were discharged sequentially into different extracts of N. cadamba fruits at dose levels of 5,10,15,20, and 25 mg/ml, respectively, and 25 mg/ml of albendazole solutions. Albendazole was employed as the standard reference medication.
 Results: The results showed that Ethanolic extract has the greatest degree of activity. When compared to any other extract or conventional medicine, it produces a paralytic effect sooner and has a shorter time to death (Albendazole). An ethanol extract included alkaloid, saponin, tannins, flavonoids, proteins, and amino acids. As a result, it is possible to infer that the ethenolic fruit extract of Neolomarckia Cadamba showed much more anthelmintic activity against Indian earthworms than the usual treatment (Albendazole).
 Conclusion: The solvents Ethanol, Chloroform, Phenyl Ether, and Aquaous were used to extract the Neolamarckia Cadamba. The results showed that Ethanolic extract has the greatest degree of activity. When compared to any other extract or conventional medicine, it produces a paralytic effect sooner and has a shorter time to death (Albendazole).

Street Fighters with Insurance Coverage: The Insurance System of the Nazi Storm Section (Sturmabteilung)

AbstractThe Storm Section (Sturmabteilung, or SA) was organized throughout the Weimar Republic as a paramilitary force entrusted with the ‘fight for the streets’ during the so‐called ‘time of struggle’ (Kampfzeit). To offset the potentially paralyzing effects of activism entailing risks of injury or death, the leaders of the movement devised and implemented an insurance system, which was retained throughout the following years. This insurance system smoothed the way for the most radical uncivility to hold sway without restriction during the final years of the Republic. Starting from late 1926, the National Socialist mechanism for overcoming the barriers to participation in violent activities that could potentially involve a high cost was to introduce an insurance system to facilitate their activists' willingness to ‘sacrifice’ themselves. The visceral anti‐Semitism of the Nazis was central to the negotiations and agreements reached with different insurers. The Nazis introduced an insurance policy for their activists that would cover them while carrying out their obligations as militants in the ‘fight’ against Social Democrats and, more often, Communists. By lowering the potential costs of participation in a high‐risk instance of activism, the insurance system contributed to stoking a ‘latent civil war’ in the German streets during the final years of the Republic. Relaying on archival and other primary sources and looking at them from a collective action perspective, this paper delves into the history of the SA insurance system, as well as on its functions.

Investigation In Vitro Anthelmintic Activity of Methanolic Extracts From Five Different Geophyte Plant Species

Helminth infections are among the commonest infections in the developing world. The present study was designed to investigate in vitro anthelmintic activities of methanolic extract of Hyacinthella lineata, Ornithogalum umbellatum, Allium reuterianum, Cyclamen coum, Sternbergia clusiana. Evaluation of anthelmintic activity was done by counting of paralyzed time and death time on the indian earth worm Cosmocerca ornata. Three different concentrations, (5,10 and 20 mg mL-1) of methanol extracts were used to determine their effect as time taken to paralysis and time to induce death in the worms. Albendazole (15 mg mL-1) was used, as reference standard drug. The higher concentrations of plant extracts 20 mg mL-1 produced faster paralytic effects and showed shorter time of death. Results revealed that Sternbergia clusiana killed all the test worms within 20±0.6 min post exposure being 100% effective. Among all five plants extracts, S. clusiana was found to be highly effective against earthworms (Cosmocerca ornata) and give significant results. The results will help us to understand the importance and usage of this medicinal plant species in the food industry, traditional medicine and pharmaceutical applications

Botulinum toxin-induced blepharoptosis: Anatomy, etiology, prevention, and therapeutic options.

BackgroundBotulinum toxin A (BoNT‐A) has grown tremendously in aesthetic dermatology since 2002 when the United States Food and Drug Administration (FDA) first approved its use for treating moderate‐to‐severe glabellar lines. Blepharoptosis, due to local spread of toxin, is a reported side effect of BoNT‐A which, although rare, more frequently occurs among inexperienced practitioners.ObjectivesThe purpose of this review is to highlight the causes and management of eyelid ptosis secondary to BoNT‐A administration including new anatomic pathways for BoNT‐A spread from the brow area to the levator palpebrae superioris muscle.MethodsA literature search was conducted using electronic databases (PubMed, Science Direct, MEDLINE, Embase, CINAHL, EBSCO) regarding eyelid anatomy and the underlying pathogenesis, presentation, prevention, and treatment of eyelid ptosis secondary to BoNT‐A. Anatomic dissection has been performed to assess the role of neurovascular pedicles and supraorbital foramen anatomic variations.ResultsBlepharoptosis occurs due to weakness of the levator palpebrae superioris muscle. Mean onset is 3–14 days after injection and eventually self‐resolves after the paralytic effect of BoNT‐A wanes. Administration of medications, such as oxymetazoline hydrochloride or apraclonidine hydrochloride eye drops, anticholinesterase agents, or transdermal BoNT‐A injections to the pre‐tarsal orbicularis, can at least partially reverse eyelid ptosis. Anatomic study shows that a supraorbital foramen may be present in some patients and constitutes a shortcut from the brow area directly into the orbital roof, following the supraorbital neurovascular pedicle.ConclusionProviders should understand the anatomy and be aware of the causes and treatment for blepharoptosis when injecting BoNT‐A for the reduction of facial wrinkles. Thorough anatomic knowledge of the supraorbital area and orbital roof is paramount to preventing incorrect injection into “danger zones,” which increase the risk of eyelid ptosis.

«Табиғи катаклизм» ұғымы: заңдылықтары мен себеп-салдарлық байланыстары

Мақалада географиялық қабықта тікелей болатын табиғи апаттар туралы айтылған. Мақала мазмұнында авторлар «табиғи апат» ұғымына өзіндік түсінік берген. Табиғи апаттардың жіктемесі ұсынылды және олардың өзара әрекеттестігі орнатылды. Табиғи апаттардың себеп-салдарлық байланыстары олардың факторларын, көрсеткіштерін және олардың салдарын анықтай отырып ашылды. Қауіпті табиғи процестерге баға берілді, сондай-ақ катаклизмдердің көріну масштабы, уақыты, шығу тегі, көріну ауданы, сондай-ақ әсер ету сипаты бойынша жіктеу жүргізілді. Табиғи апаттардың мына типологиясы ұсынылған: деструктивті әсерге ие (дауыл, тайфун, торнадо, жер сілкінісі, жәндіктермен зақымдануы); көлік қозғалысын тоқтатуға әсер ететін (қар жаууы, су басу, нөсер, тұман); сарқылушы әсерге ие (өнімді, топырақтың құнарлылығын, сумен жабдықтауды және басқа табиғи ресурстарды азайту); технологиялық апаттарды (табиғи және техникалық апаттарды) тудыруы мүмкін табиғи апаттар (найзағай, мұз, мұздану, биохимиялық коррозия және т.б.). Сонымен бірге мақалада табиғи апаттарды бақылау және болжау міндеттері қарастырылған. Осы мәселелерді шешу үшін қажетті ақпаратты жинауды, сақтауды және өңдеуді қамтамасыз ететін экологиялық бақылау жүйелерінің синтезіне ерекше назар аударылған. Экоинформатиканың алгоритмдері мен әдістеріне негізделген және ақпараттық технологиялар мен экологиялық кіші жүйелер эволюциясы модельдерін бірлесіп пайдаланудан тұратын аэроғарыштық бақылау жүйелерінің синтезінің жаңа тұжырымдамасы сипатталды. Табиғи апаттардың нақты жағдайлары талданды.

A C. elegans genome-wide RNAi screen for altered levamisole sensitivity identifies genes required for muscle function.

At the neuromuscular junction (NMJ), postsynaptic ionotropic acetylcholine receptors (AChRs) transduce a chemical signal released from a cholinergic motor neuron into an electrical signal to induce muscle contraction. To identify regulators of postsynaptic function, we conducted a genome-wide RNAi screen for genes required for proper response to levamisole, a pharmacological agonist of ionotropic L-AChRs at the Caenorhabditis elegans NMJ. A total of 117 gene knockdowns were found to cause levamisole hypersensitivity, while 18 resulted in levamisole resistance. Our screen identified conserved genes important for muscle function including some that are mutated in congenital myasthenic syndrome, congenital muscular dystrophy, congenital myopathy, myotonic dystrophy, and mitochondrial myopathy. Of the genes found in the screen, we further investigated those predicted to play a role in endocytosis of cell surface receptors. Loss of the Epsin homolog epn-1 caused levamisole hypersensitivity and had opposing effects on the levels of postsynaptic L-AChRs and GABAA receptors, resulting in increased and decreased abundance, respectively. We also examined other genes that resulted in a levamisole-hypersensitive phenotype when knocked down including gas-1, which functions in Complex I of the mitochondrial electron transport chain. Consistent with altered ATP synthesis impacting levamisole response, treatment of wild-type animals with levamisole resulted in L-AChR–dependent depletion of ATP levels. These results suggest that the paralytic effects of levamisole ultimately lead to metabolic exhaustion.