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The 2019 coronavirus disease (COVID-19) has infected people in many countries around the world. The discovery of an effective treatment for this disease, especially in severe cases, has been the subject of intensive scientific research. Therefore, the aim of this study was to evaluate the effectiveness of intravenous immunoglobulin (IVIG) administration in patients with severe COVID-19 infection. Patients with acute respiratory disease COVID-19 who received intravenous immunoglobulin in the intensive care unit were exami­ned. All patients underwent non-invasive ventilation and all patients had concomitant pathology. Twenty patients participated in the study, 10 patients received an infusion of intravenous immunoglobulin. Patients who received IVIG were on invasive pulmonary ventilation for an average of 7 days, the condition of patients improved by days 2–3. At the time of transfer to adjacent departments (on ave­rage, day 14), the dynamics of the disease improved. Respiration rate was 23 per 1 min. SpO2 without O2 was 92 %. All patients presented with lymphopenia and increased transaminases level, the values of which normalized by days 2–3. When ultrasound examination of the lungs, there were no pulmonary consolidations in patients. Mortality in the group of patients who received IVIG was lower compared to patients who did not receive IVIG.

Large clostridial toxins (LCTs) are a family of six homologous disease-causing proteins characterised by their large size (>200 kDa) and conserved multidomain architectures. Using their central translocation and receptor-binding domain (T domain), LCTs bind host cell receptors and translocate their upstream glycosyltransferase and cysteine protease domain across the endosomal membrane and into the cytosol. The recent discovery of hundreds of LCT-like T domains in diverse genomic contexts and domain architectures from bacteria other than clostridia has provided significant new insights into the enigmatic process of LCT translocation, but also has put the definition of what constitutes an LCT into question. In this opinion article, we discuss how these findings have expanded our understanding of LCT translocation and reshaped the scope of the LCT family.

The availability of millions of SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) sequences in public databases such as GISAID (Global Initiative on Sharing All Influenza Data) and EMBL-EBI (European Molecular Biology Laboratory-European Bioinformatics Institute) (the United Kingdom) allows a detailed study of the evolution, genomic diversity, and dynamics of a virus such as never before. Here, we identify novel variants and subtypes of SARS-CoV-2 by clustering sequences in adapting methods originally designed for haplotyping intrahost viral populations. We asses our results using clustering entropy—the first time it has been used in this context. Our clustering approach reaches lower entropies compared with other methods, and we are able to boost this even further through gap filling and Monte Carlo-based entropy minimization. Moreover, our method clearly identifies the well-known Alpha variant in the U.K. and GISAID data sets, and is also able to detect the much less represented (

BACKGROUND. Among countries of Europe in Ukraine the incidence and mortality rate from tuberculosis (TB), including the incidence of the relapses in patients with pulmonary tuberculosis (RPT), remain high. Absence of the national program of fight from TB, lack of financing of anti-TB measures, unsatisfactory statistical information confirm the necessity of study of situation from relapses in patients with RPT and development of measures on their warning. OBJECTIVE. To estimate the features of dynamics of the incidence of RPT in the last few years and consisting of epidemic situation of TB in a country. MATERIALS AND METHODS. An analysis of official statistical reports of anti-TB establishments of administrative territories of Ukraine, information of SI “Center of Public Health of the Ministry of Health of Ukraine” and SI “Center of Medical Statistics of the Ministry of Health of Ukraine” in the last few years. RESULTS AND DISCUSSION. By the features of dynamics of the incidence of RPT in the last few years in a country are high the incidence in patients with RPT with sputum positive smears with comparison in the incidence in patients with RPT with sputum negative smears; decline of index on 46,0 %; high part of RPT with sputum positive smears among patients with TB sputum positive smears (the TB new cases + relapses); diminishing of amount of cases of TB which the diagnosis of multidrug-resistant TB is confirmed, from them growth of percent of patients with extended resistant of Mycobacterium tuberculosis. The signs of epidemic situation are: decline of the TB incidence of lights (the new cases + relapses); high percent of patients sputum positive smears; high TB incidence among children by age 15-17; diminishing of the TB mortality rate and his prevalence; absence of changes of index prevalence of TB among children by age 0-17 and 0-14. CONCLUSIONS. The analysis of statistical data testifies to the presence of failings in an exposure and treatment of patients with the relapses of TB, on the necessity of introduction of complex anti-TB measures for warning of relapses within the framework of the national program of fight from TB.

У діагностиці кардіоренального синдрому (КРС) знаходять широке застосування біологічні маркери, що можуть бути використані для ідентифікації патофізіологічної стадії кардіоренального синдрому, оцінки величини ризику, прогнозу та результату, а також моніторування ефективності лікування. Терапія КРС включає призначення діуретиків, вазодилататорів, інгібіторів ангіотензинперетворюючого ферменту, антагоністів рецепторів ангіотензину II, нітратів і серцевих глікозидів. Одним з ефективних методів лікування КРС є застосування методів замісної ниркової терапії.

The systematic position and modern state of populations of the rare species of Ukrainian flora Carlina cirsioides Klokov (Asteraceae) are considered. Since this species is included into the Red Data Book of Ukraine (2009) and the European List of Globally Threatened Animals and Plants (1991), it is well-known for European botanists as an endemic of the Ukrainian flora. However, neither the authors of Flora Europaea (1976), nor monographers of the genus Carlina recognize Carlina cirsioides as a separate species. Comparative morphological, chorological, and coenotic analyzes does not allow Carlina cirsioides to be considered as a separate species, endemic and relic of the Ukrainian flora. According to morphological features, specimens from the plains of Ukraine are referred to the subspecies Carlina acaulis caulescens, which is distributed mainly in plain regions of Europe. Ecological and coenotic conditions of habitats of Carlina acaulis in the lowland part of Ukraine are different from its habitats in the Carpathians and Alps and are close to xerotherme grass communities with Carlina acaulis of plains of Central Europe. Steppe communities of Festuco-Brometea class with Carlina acaulis in the Volhynian-Podolian Upland are similar to xerotherme communities with Carlina acaulis of Central Europe. Erico-Pinetea class communities are common habitats for Carlina acaulis in the Ukrainian Polissia and north-eastern Poland. Lowering the species status of Carlina cirsioides from separate species to subspecies Carlina acaulis caulescens does not diminish its phytosozological value. Due to the low number of Carlina acaulis populations in the Volhynian-Podolian Upland and Polissia, all localities of this species in the lowland part of Ukraine need to be provided by protection.

The unresolved problem of quail is feed stress and high sensitivity of poultry of this species to feed quality. To eliminate such consequences it is possible with the use of various biologically active feed additives. However, their introduction into the diet automatically raises questions about the quality and safety of the products for the consumer. The purpose of the research is to conduct a veterinary and sanitary assessment of the quality of quail meat for feeding NDC. The purpose of the research is to conduct a veterinary and sanitary assessment of the quality of quail meat for feeding NDC. The object of study were the quails of the Pharaoh breed, at the age of 24 were divided into two groups: experimental and control 30 heads each. The birds were kept in cages with free access to food and water. Quails of the experimental group were added to drinking water feed additive "Nanocerium" at a dose of 8.6 mg per liter of drinking water. Nanocerium feed additive is an aqueous dispersion of NDC with average nanoparticle sizes of 2–7 nm. Antemortem examination of quails of both groups revealed a satisfactory clinical condition of birds. The average weight of the gut carcass of quails of the experimental group was higher by 8.3% compared to the control. Examination of 20 carcasses of quails showed that they can be classified as first class. According to organoleptic parameters, quail meat is of good quality in veterinary and sanitary terms. Microbiological studies of quail meat indicate no effect of NDC in the applied doses on its bacterial contamination. Chemical parameters of meat (pH, aminoammonia nitrogen, volatile fatty acids during storage in the refrigerator) (5 days, t = 4–5 ° C) tended to increase and were within the normal range for fresh product. Tissue in quails of both groups was not detected. The biological value of quail meat in both groups was identical and no toxicity. Tasting evaluation of the broth and meat showed that NDC did not affect the studied taste. The obtained results show that the quails that received the feed additive "Nanocerium" with water according to the indicators of veterinary and sanitary examination are of good quality, which allows to use it in human food without restrictions. Key words: poultry, nanocerium, organoleptic evaluation, microbial contamination, biological value, tasting evaluation.

The study of egg-laying patterns and defining ways of increasing egg-laying productivity is a necessary condition for the development and increased efficiency of ostrich breeding. Therefore, some studies deal with egg productivity of ostriches of different age groups (group 1 - age 8-9 years, group 2 - age 4-5 years) for their long-term keeping under a semi-intensive system forest-steppe zone of Ukraine. The sex ratio in the families was 1: 2-3. Behavioral patterns of poultry during the breeding season are close to natural ones. Older individuals are characterized with a longer productive period (January-October) than younger ones (March-September). According to the most extended daylight hours at this time of year, the higher level of egg-laying performance is established in May and summer months. The females’ egg-laying performance analysis shows their significant individual features - 9-42 eggs were obtained from one female. It is worth mentioning that the productivity period’s duration does not continuously regulate the number of eggs. There is a high positive correlation between the duration of the egg-laying process and total egglaying performance in group 1 (r = 0.7981); in group 2 � there is no relation between these features (r = -0.0843). The variability of egg-laying cycles of ostrich females has been confirmed, and it requires further studies. According to the intensity of lying during the breeding season, there are differences between younger and older poultry groups. The first two months and the last month of egg-laying are the least productive for all. It was established that the egg weight of older females is higher compared to young ones, with a potential difference between the groups (P> 0.999) and a significant level of individual variability (Cv = 1.78-8.06%). This indicates the necessity of successive work with the herd to optimize egg weight, as a significant variation in egg weight affects the duration of incubation and embryonic development of ostriches. It also leads to the elongation of the “hatch window” that causes heterogeneity of ostrich weight. New data allow characterizing the peculiarities of ostrich physiology, their ability to adapt to industrial conditions of breeding at farms located in the northern part of the forest-steppe zone of Ukrai.

The study of the current state and habitats of rare and threatened species of plants is a relevant task of ecological research. The paper presents the results of the study of systematic position, habitats and modern state of populations of a rare species included in the Red DataBook of Ukraine Carlina cirsioides Klokov (=C. acaulis L.). Carlina cirsioides is well-known to European phytosozologists as an endemic and relic species of the Flora of Ukraine. At the same time, the species independence of this taxon is not recognized by the authors of monographs on the Carlina genus and by the authors of “Flora Europaea”. Comparative morphological, chorological and ecological-coenotic analyses do not give sufficient reasons to consider C. cirsioides described by Klokov as a separate species, endemic and relic species of the Flora of Ukraine. According to the morphological traits, the specimens from the lowland part of Ukraine belong to the C. acaulis caulescens subspecies, which is distributed mostly in the lowlaand regions of Europe. Ecological-coenotic conditions of habitats of C. acaulis in the plains of Ukraine are different from those in the mountain regions and are close to the plains habitats of this species in Central Europe. Steppe communities of class Festuco-Brometea, of which C. acaulis is component in the plains part of Ukraine, are close to xerothermic herbaceous communities of Central Europe; forest communities of Erico-Pinetea with C. cirsioides in Ukrainian Polissia and the North-East Poland are very сlose by floristic composition. The removal of separate species status of the plains populations of C. acaulis near the eastern border of the range does not at all downplay its sozological significance. Taking into account the low number of C. acaulis in the Volhynian-Podolian Upland and in the Polesian Lowland, all localities of this species in the lowland part of the range in Ukraine must be taken under protection in situ.

To evaluate maize lines on the basis of the high content of lysine and tryptophan and waxiness using SSR markers.

Purpose:Somatic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), which encodes the p110α catalytic subunit of PI3K, are found in multiple human cancers. While recurrent mutations in PIK3CA helical, regulatory, and kinase domains lead to constitutive PI3K pathway activation, other mutations remain uncharacterized. To further evaluate their clinical actionability, we designed a basket study for patients with PIK3CA-mutant cancers with the isoform-specific PI3K inhibitor taselisib.Patients and Methods:Patients were enrolled on the basis of local PIK3CA mutation testing into one of 11 histology-specific cohorts and treated with taselisib at 6 or 4 mg daily until progression. Tumor DNA from baseline and progression (when available) was sequenced using a next-generation sequencing panel. Exploratory analyses correlating genomic alterations with treatment outcomes were performed.Results:A total of 166 patients with PIK3CA-mutant cancers were enrolled. The confirmed response rate was 9%. Activity varied by tumor type and mutant allele, with confirmed responses observed in head and neck squamous (15.4%), cervical (10%), and other cancers, plus in tumors containing helical domain mutations. Genomic analyses identified mutations potentially associated with resistance to PI3K inhibition upfront (TP53 and PTEN) and postprogression through reactivation of the PI3K pathway (PTEN, STK11, and PIK3R1). Higher rates of dose modification occurred at higher doses of taselisib, indicating a narrow therapeutic index.Conclusions:Taselisib had limited activity in the tumor types tested and is no longer in development. This genome-driven study improves understanding of the activity, limitations, and resistance mechanisms of using PI3K inhibitors as monotherapy to target PIK3CA-mutant tumors.

In the article there were considered the problematic aspects of accountants’ certification in Ukraine, as well as the relevance of professional certification as a universal tool for recognition of qualifications in accounting in professional circles and in the labor market. The most popular institutions and organizations which are specializing in the training of accounting professionals in the field of accounting ACCA, CIPA, IFA, CPA, CIMA, ITFA, CAP, CFA are cited. The problematic approaches to organization of education in the country are analyzed in comparison with the international experience, where higher education is not required for the professional activity of accountant, but the emphasis are made on proceeding of professional development. The reasons for the lack of readiness of enterprises and companies to finance training programs for improving the skills of accountants and obtaining certificates are justified. A detailed analysis of the functional differences in work between traditional and certified accountants has been carried out. It has proved that the key indicator that can confirm the qualification and professional training of an employee in all aspects of accounting according to International standards is a relevant certificate, which is not only recognized by international accounting experts, but also the fundamental basis for creating a confidence base for foreign investors and business-partners.

Objective The aim of the study is to reveal in the experiment the morphological features of the infected skin wounds healing, which are a manifestation of acne vulgaris severe and very severe forms, using a gel with carbon dioxide extract of hops. Patients and methods Materials and methods: An experimental study was carried out on 80 male WAG rats of three months of age. The animals were divided into 9 groups. Group 1 consisted of intact animals (n=6). Group 2 was represented by animals (n=6), which had hair epilation on the dorsal surface of the body in an area of 1 сm2, followed by application of 2 ml of placebo gel to this area. Group 3 included animals (n=6), which were epilated on the dorsal surface of the body in an area of 1 сm2 and applied 2 ml of 1 % gel with carbon dioxide extract of hops. Group 4 included rats (n=6), which were epilated on the dorsal surface of the body in an area of 1 сm2 and simulated thermal damage. Group 5 was represented by 10 rats, who were epilated on the dorsal surface of the body in an area of 1 сm2, simulated thermal damage, followed by applying 2 ml of placebo gel to the wound surface. Group 6 included rats (n=10), who underwent measures similar to group 5, followed by application of 2 ml of 1 % gel with carbon dioxide extract of hops to the wound surface. In group 7, there were 6 rats, which were epilated on the dorsal surface of the body in an area of 1 сm2, thermal damage to the skin with underlying soft tissues was simulated, followed by application to the wound surface the reference strains of Staphylococcus aureus, Streptococcus pyogenes, Proteus vulgaris, Propionibacterium acnes, Escherichia coli, Pseudomonas aeruginosa, Malassezia slooffiae, Malassezia pachydermatis, Candida albicans, Candida parapsilosis. In groups 8 and 9, there were 15 rats each, which underwent measures similar to group 7, followed by applying 2 ml of placebo gel on its surface on the next day after infection of the wound in group 8, and in group 9 - 2 ml of 1 % gel with carbon dioxide extract hops. The material for the study was the skin with underlying soft tissues. It was used histological, histochemical, morphometric and statistical methods. Results Results: This experimentally created gel with carbon dioxide extract of hops activates separation processes of horny masses from the surface of the epidermis, cleaning the pores of the skin; stimulating the proliferative activity of the epidermis, which is located in the marginal sections of the wound or covers the surface of the regenerate; activating the processes of cleansing the wound from necrotic tissue; activating the growth and maturation of granulation tissue with its subsequent transformation into connective tissue. It has anti-inflammatory, bactericidal and antimycotic effects, normalizing skin microbiocenosis. Conclusion Conclusions: The complex morphological study has showed that gel with carbon dioxide extract of hops is a highly effective drug in treatment of severe and very severe acne vulgaris, characterized by the development of deep and infected wound defects.

Acute small bowel obstruction remains one of the most challenging nosologies in emergency surgery, leading to a pronounced imbalance between lipid peroxidation and the antioxidant defense system. We aimed to study changes in the anti- and prooxidant status of serum and small intestine wall in an experiment modeling acute small bowel obstruction. The control group included 11 rats, and the main group included 42 rats (simulation of mechanical bowel obstruction on day 1 was conducted in 14 rats, on day 2 – in 12 rats, on day 3 – in 16 rats). Acute small bowel obstruction was modeled by ligation. Serum analysis and removal of the small intestinal wall were performed on days 1, 2, and 3. Indicators of lipid peroxidation and antioxidant protection were determined by the spectrophotometric method, and the imbalance between lipid peroxidation and antioxidant protection gradually increased from 1 to 3 days of observation. On day 3, the low level of aldehyde increased 1.3 times, and the level of superoxide dismutase decreased 1.2 times compared to the control group. Pathophysiological changes in the wall of the small intestine are caused by the activation of lipid peroxidation and the exhaustion antioxidant protection, whereby the degree of their severity increases depending on the increase in time from the moment of modeling of acute obstruction of the small intestine.

Characteristics of watermelon seed formation in intercropping were studied. Different growing methods of watermelon seeds depending on its interaction with intercrops (sugar maize and common bean) and their planting schemes in melon fields were investigated. The developed elements of the watermelon seed growing technology reduced the impact of high temperatures on this melon crop (the number of fruits with sunburn decreased by 7.1 % compared to control). The results of phenological observations and analysis of yield components, seed productivity and quality of Favoryt watermelon variety in the intercropping with sugar maize and common bean were presented. It was established that the developed elements of the watermelon growing technology in intercropping under high temperatures and low relative air humidity in the Northern Steppe of Ukraine increased of watermelon yield and the full-value seed formation. It was found that intercropping of watermelon with sweet corn under proper cultivation gave positive results (watermelon seed yield gain by 12.4 % and 0.7 t/ha ears of sweet maize in milky-wax ripeness were received additionally), and with common bean (watermelon seed yield gain by 8.9 % and additional 75 kg/ha of beans). Methods and planting schemes of watermelon and intercrops were established: sugar maize in the rows of watermelon according to scheme 2.8 x 1 m, common bean in the rows of watermelon according to scheme 1.4 x 0.5 m. It was found that under intercropping of watermelon with sweet maize the full-value seed yield per one fruit increased up to 88.5 %, and with common bean – to 84.9 %. Key words: watermelon, sugar maize, common bean, intercropping, seed yield.

Ginkgo biloba is one of the oldest relict plants in the existing seed plants. It is a historical heritage and living fossil. It is a world natural heritage unimaginable by human beings and a milestone in revealing nature's mysteries. The primary study areas with G. biloba plants are located in North-East Ukraine (Sumy region). A comparative analysis of the condition of seedlings in 2018 and 2019 was conducted. The plants were examined for the following morphological parameters: plant height, annual growth size, shoot diameter at the base, and the number of leaves. In two variants, about 100 plants were examined. The vitality analysis of seedlings with the establishment of their quality index is carried out. Studies of G. biloba leaves' morphological parameters from artificial plantations in Ukraine (Sumy) and natural plantations of China from the province were also carried out. Zhejiang province covers an area of 105,500 square kilometers and is located on the southeast coast of China. 118°01'-123°10'E bounds Zhejiang Province, 27°02'-31°11' N, east of the East China Sea, north of Shanghai, which is China's largest city, and Qiantang River is the largest river in Zhejiang. Its climate is Subtropical monsoon. The average annual rainfall is 980-2 000 mm, the average annual sunshine is 1710-2100 hours, and the average annual temperature is 15-18 °C. We selected three G. biloba groups for investigation and data collection. These three places are located west of Zhuji City, Zhejiang Province, about 5 kilometers apart. The G. biloba tree group in Guanshan, Lingshanwu, and Wuxie Village Zhejiang Province, China, were measured in 2019. The age of the trees ranges from 20 years to 500 years. The height is generally more than 15 meters, and the breast diameter is more than 20 cm. In order to ensure the randomness of the data, we choose a tree every 50 meters. Studies have shown a statistically significant difference between leaves from China and Ukraine. Simultaneously, the leaf blade's size was more extensive in the leaves of G. biloba from artificial plantations in Ukraine. Morphometric analysis of G. biloba plantations (Ukraine) showed statistically significant differences between plant morphological parameters in 2018 compared to 2019, which indicates the intensity of growth and the positive trends in plants' vegetative growth mass. Plant height increased from 26.68 ± 1.01 cm in 2018 to 40.07 ± 1.72 cm in 2019, the annual increase, respectively, from 10.34 ± 0.89 to 13.90 ± 0.92. Such an indicator as the shoot diameter at the base has tripled (from 0.42 ± 0.02 cm in 2018 to 1.41 ± 0.02 cm in 2019). Differences between all morphological parameters have high statistical reliability (from 0.01 to 0.001). The differences were confirmed by the results of vitality analysis, which showed an increase in plant quality and their transition from equilibrium in 2018 (Q = 0.300) to prosperous in 2019 (Q = 0.465), which indicates optimal growth conditions and confirms the possibility of growing G. biloba plantation method for obtaining medicinal raw materials in North-East Ukraine.

Goal. was to research biological preparations efficiency usage in alternaria blight harmfulness decrease and to develop effective cultivar protection system. Methods. Field and laboratory — vegetative researches. Tubers were treated by allowed biological preparations as Lists of pesticides: Planrise (Pseudomonas fluorescens, strain AR-33), Phytodoctor (Bacillus subtilis); MicoHelp (Trichoderma, Bacillus subtilis, Azotobacter, Enterobacter, Enterococcus) for disease developing decrease. The present preparations were used for spraying in future. The treating during the growing period favoured the plant organism resistance to stress conditions of environment. The first plant treating was conducted at the blossoming beginning before alternaria blight appearing on plant’s leaves plants. The second spraying was conducted during the first spots appearing on the plates of early potato varieties. Results. The researches results biological preparations: Planrise, Phytodoctor, MicoHelp treating potato defeated plants by alternaria blight were proposed. The biological preparations relative high efficiency was determined. Conclusions. The researched preparations technical efficiency was also depended upon the conducting testing variety. The biological preparation MicoHelp (variety Serpanok) showed the highest technical efficiency (46.2%) during the plant treating against potato alternaria blight. The preparation MicoHelp (variety Svitanok Kyivskyi) showed the highest efficiency during the potato treating in vegetation period. So the biological control protection means usage in the modern potato varieties allows to decrease negative impact of used preparations and put into production effective and ecologically — friendly means for alternaria blight limit in terms of Western Foreststeppe of Ukraine.

The article presents the results of the study of the possibilities of using neural networks to solve the problem of determining the active set of a wind farm (WF), taking into account the efficiency of each wind turbines (WT). The comparative analysis of the obtained results with the known methods of determining the active composition of WF, such as: the method of dynamic programming; the method of dynamic programming with increasing the load on the experimentally set percentage; modified method of dynamic programming. The advantages and disadvantages of using each of the studied methods in terms of the possibility of achieving a given generation power at the maximum efficiency of the selected WT are determined. It is established that when using recurrent neural networks to solve the problem of determining the active composition of WF, the minimum direct linear variation of the difference between the power to be generated and the actual power of the determined active set of WF is 2.7%. Under the same conditions, the use of other known methods, in particular, the modified method of dynamic programming ensures the achievement of this parameter at the level of 0.05%. This significantly increases the time to solve the problem. By computer simulation, it was found that under equal conditions, the time to solve the problem using neural networks - 0.04 s, and using a modified method of dynamic programming 3.4 s. The obtained results provide an opportunity to implement effective decision support systems in energy flow management.

The prenatal period is a critical window for the development of autism spectrum disorder (ASD). The relationship between prenatal nutrients and gestational gene expression in mothers of children later diagnosed with ASD or non-typical development (Non-TD) is poorly understood. Maternal blood collected prospectively during pregnancy provides insights into the effects of nutrition, particularly one-carbon metabolites, on gene pathways and neurodevelopment. Genome-wide transcriptomes were measured with microarrays in 300 maternal blood samples in Markers of Autism Risk in Babies-Learning Early Signs. Sixteen different one-carbon metabolites, including folic acid, betaine, 5'-methyltretrahydrofolate (5-MeTHF), and dimethylglycine (DMG) were measured. Differential expression analysis and weighted gene correlation network analysis (WGCNA) were used to compare gene expression between children later diagnosed as typical development (TD), Non-TD and ASD, and to one-carbon metabolites. Using differential gene expression analysis, six transcripts (TGR-AS1, SQSTM1, HLA-C, and RFESD) were associated with child outcomes (ASD, Non-TD, and TD) with genome-wide significance. Genes nominally differentially expressed between ASD and TD significantly overlapped with seven high confidence ASD genes. WGCNA identified co-expressed gene modules significantly correlated with 5-MeTHF, folic acid, DMG, and betaine. A module enriched in DNA methylation functions showed a suggestive protective association with folic acid/5-MeTHF concentrations and ASD risk. Maternal plasma betaine and DMG concentrations were associated with a block of co-expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results suggest that the prenatal maternal blood transcriptome is a sensitive indicator of gestational one-carbon metabolite status and changes relevant to children's later neurodevelopmental outcomes. LAY SUMMARY: Pregnancy is a time when maternal nutrition could interact with genetic risk for autism spectrum disorder. Blood samples collected during pregnancy from mothers who had a prior child with autism were examined for gene expression and nutrient metabolites, then compared to the diagnosis of the child at age three. Expression differences in gene pathways related to the immune system and gene regulation were observed for pregnancies of children with autism and non-typical neurodevelopment and were associated with maternal nutrients.

Perosis is one of the most common leg pathologies in broiler chickens, during the period of intense weight gain – at the age of 14–35 days. Due to manganese deficiency, the number of sick birds can reach up to 5% of the flock. These studies were carried out in order to establish changes in some indicators of protein, macro- and micromineral metabolism in the blood serum of clinically healthy broiler chickens and birds with perosis at 14, 21 and 28 days of age. A batch of 2,000 Cobb-500 crossbred broiler chickens was selected. Two groups of chickens were directly involved in the research, in which blood was taken at the age of 14, 21 and 28 days: healthy birds and those with perosis signs. Clinical studies showed that 8.0% of chickens on 28th day suffered from perosis. Trace mineral biochemical parameters of serum and blood of broiler chickens with perosis on the 28th day of life significantly differed from those of healthy birds (manganese and zinc). It was found that on the 28th day of life the weight of chickens with perosis was reduced by 42.7%, causing a loss of weight 88 kg per batch of 2000 birds, with a consumption of feed 140 kg. The obtained data will allow the development of early perosis prevention schemes in broiler chickens, which will help manage production losses and increase its profitability. On farms, to prevent the occurrence of perosis, it is necessary to take into account the technological factors of the production of compound feed. Also, an increase in the level of total protein and albumin in serum in the blood may indicate inflammatory processes and dehydration of the body. Therefore, it is better to site a sick bird separately for rearing or hand over to a sanitary culling.

A detailed study of the geographical distribution and populations status in historical aspects of Daphne cneorum (Thymelaceae), a rare species in Europe, was conducted to establish the dynamics of its range in Ukraine. Analysis of phytogeographic and paleological data showed that this is a migratory relict species (sensu Szafer, 1975). As a tertiary relic, D. cneorum survived in the Volhynian-Podolian Upland. From this refugium, it migrated to the Polissya and Dnipro lowlands as well as the Dnipro and Lublin uplands in the interglacial and postglacial periods. The range of D. cneorum in Ukraine currently consists of two separate areas, Volhynian-Podolian and Dnipro fragments. The disjunction apparently arose as a result of inconsistency of the ecological conditions (acid soils on crystalline rocks) of the Ukrainian shield and physiological needs of the calcephilous species D. cneorum. In our opinion, the disjunctions between the Volhynian-Podolian, Belarus and Lublin parts of the range are of anthropogenic origin. Over the last century, an intensive degradation of populations and fragmentation of the range of D. cneorum took place in Ukraine. Anthropogenic pressure has led to regressive changes in the species range in the country. Due to low seed productivity, plant death is not compensated by replenishment and therefore in disturbed habitats populations of D. cneorum are completely eliminated. The species has apparently disappeared from the flora of Roztocze, Volhynian Upland and the Kremenets Mountains. Since the absolute protection regime is ineffective for D. cneorum populations, the need to develop conservation management for this species in natural habitats is emphasized.

A new wood-boring ichnospecies is described from transgressive (lagoonal) deposits of the Lower Cretaceous Sparky Formation (Mannville Group) in west-central Saskatchewan, Canada. Apectoichnus lignummasticans new ichnospecies is a trace fossil that occurs in a thin coal bed and that was emplaced in an in situ xylic substratum (woodground). The ichnofossil is thin, elongate, unbranched, and straight to gently curved with a circular cross section and uniform diameter. Apectoichnus lignummasticans n. isp. is similar in many respects to modern borings in wood that are produced by marine isopods, e.g., Limnoria lignorum Rathke, 1799, for feeding and refugia. The recognition of Apectoichnus lignummasticans n. isp. in the rock record aligns with the modern observation that fossilized wood-boring assemblages should display higher ichnofossil diversities than commonly reported. Additionally, the stratigraphic occurrence of Apectoichnus lignummasticans n. isp. in association with other evidence of marine deposition reaffirms that certain wood boring morphologies (i.e., ichnotaxa) are useful as indicators of marine transgressions.UUID: http://zoobank.org/880e722f-8944-42d7-bc38-423cc5a46413

Goal. To determine the technical efficiency of the novel fungicides against root rot of pumpkins in the area of ​​the Right Bank Forest-Steppe of Ukraine. Methods. The experiments were conducted in 2016—2018 in the Right-Bank Forest-Steppe of Ukraine (Khmelnytsky region) on the following varieties: common pumpkins — Ukrainskyi bahatoplidnyi, hull-less pumpkins — Shtyriiskyi. Assessment of severity, spread of root rot, technical and farm efficiency was carried out according to generally accepted methods. To control the development of the disease, the following preparations were investigated: Maxim 480 FS, FS, Inshur perform, TK, Phytocide, s., Trichoderma blend Bio-Green Microzyme TR, EC. Results. During the study period, root rot was observed on pumpkins of both studied varieties annually. In the laboratory, it was found that the causative agents of root rot on pumpkins were fungi of the genus Fusarium Link. The development of the disease in control ranged from 11.2 to 17.6%. When biological preparations were used on the variety Ukrainskyi bahatoplidnyi, technical efficiency was at the level of 52.6—62.8%, on the variety Shtyriiskyi — 43.4—59.2%. The best effect against fusarium root rot was recorded for seed treatment with Trichoderma blend Bio-Green Microzyme TR. Pre-sowing treatment of seeds with Inshur Perform and Maxim 480 FS reduced the development of the disease by 3.6—4 times. On both varieties, biological products showed lower technical efficiency compared to chemical preparations. The use of pesticides made it possible to obtain a yield of pumpkin seeds with the use of biological products at the level of 0,431—0,435 t/ha on the variety Ukrainskyi bahatoplidnyi and 0,308—0,315 t/ha — on the variety Shtyriiskyi. When seeds were treated with chemical pesticides, the yield was 0,456—0,465 t/ha and 0,319—0,325 t/ha, respectively. That is, pre-sowing seed treatment allows to save from 4.1 to 12.9% of crop yield. Conclusions. Under conditions of the Right-Bank Forest-Steppe of Ukraine pumpkin plants are annually affected by fusarium root rot. The use of pesticides allows to save the seed yield in the range from 0.012 to 0.053 t/ha. The best technical efficiency was observed on the variants with the disinfectant Maxim 480 FS, TH with a consumption rate of 1.0 l/t and the biological product Trichoderma blend Bio-Green Microzyme TR, EC with a consumption rate of 50 ml/t.

Goal. To do analyze phitosanitary state of wart potato sources in Carpathian region of Ukraine with determining infectious load of soil. Identify existing anti-cancer patatoes in Ukraine. Methods. The selection of soil’s samples for zoosporangia of wart pathogen was provided by standard method as per DSTU 3355-96. The sample’s selection points fixed by GPS-navigator Garmin eTrex Legend. The potato wart zoosporangia extraction was conducted by floatation in solution of sodium iodide. The solution Coomassi blue G-250 used for zoosporangia viability determining. Results. Of potato wart pathogens infectious load in Carpathian region of Ukraine 2016—2018 showed the different level of zoosporangia soil’s infection in researched areas. In the hearths of the Chernivtsi region the infectious load was reached 56—68 zoosporangia/1g in sources of Carpathian region, 42—48 zoosporangioa was in the sources of Zakarpattia region, 40—45/1g zoosporangia was determined in Ivano-Frankivsk region, 49 zoosporangia /1g was determined in town Turka Lviv region. The common (D1) pathotype and four aggressive pathotypes of wart potato: 11 (M1) - Mizhgirrya, 13 (R2) - Rachiv, 18 (Ya) - Yasynya and 22 (B1) - Bystrytsya were determined by pathotypes identification in old sources of Zakarpattia, Ivano-Frankivsk, Lviv and Chernivtsi region Conclusions. Analysis of phitosanitary state of wart potato sources in Carpathian region of Ukraine showed the different level of soil’s infectious load in researched areas. There is a common pathotype (D1) and 4 aggressive pathogen disease in Ukraine for present time. The identification of Ukrainian wart pothotypes is planned to identify by European potato cultivar test-assortment usage in perspective.

The effect of early-spring stimulation of bee families on protein partial substitutes (low-fat soy bean meal and soy peptone) on the eff ectiveness of winter rapeseed pollination has been studied. Cross-pollination in the evolution of the fl ora has become dominant, because about 80 % of vegetation requires its application. There are two types of cross-pollination of plants: within one plant (geetonogamy) and within several plants (xenogamy). The transfer of pollen within one fl ower or several occurs by wind, water, birds and insects. However, the most widespread was insect pollination, which amounts 4/5 of the total number of plants that are needed to be pollinated. It is established that only with high organization of pollination of entomophilous crops it is possible to achieve the maximum eff ect. The intensity of development of bee families depends on: the age of the queen bee, the quality of the bee nest, the temperature of the air and the presence of carbohydrate and protein feed in their nests. In the early spring, bees may not always provide themselves with carbohydrate and protein feed, which reduces breeding and delaying bee growth until the beginning of pollination of spring agricultural honey plants. The eff ectiveness of entomophilic bee pollination depends on many factors, including the forces of the bee families, the distance from the source of honey, temperature and humidity. Therefore, there is a need to replenish feed stocks in early spring in order to stimulate rapid growth of bees. It has been found that stimulation of bee growth in bee families by partial protein substitutes of pollen in early spring helps to increase their strength from 6.6 % to 16.6 % and the amount of pollen collected from winter rape from 12.3% to 34.1% indicating a higher intensity of pollination of this crop. Key words: bee families, winter rapeseed, soy fl our, soy peptone, forces of the bee families, pollination, development.

T cell epitopes are mostly nonmodified peptides, although posttranslationally modified peptide epitopes have been described, but they originated from viral or self-proteins. In this study, we provide evidence of a bacterial methylated T cell peptide epitope. The mycobacterial heparin-binding hemagglutinin (HBHA) is a protein Ag with a complex C-terminal methylation pattern and is recognized by T cells from humans latently infected with Mycobacterium tuberculosis. By comparing native HBHAwith recombinant HBHA produced in Mycobacterium smegmatis (rHBHA-Ms), we could link antigenic differences to differences in the methylation profile. Peptide scan analyses led to the discovery of a peptide containing methyl lysines recognized by a mAb that binds to native HBHA ∼100-fold better than to rHBHA-Ms. This peptide was also recognized by T cells from latently infected humans, as evidenced by IFN-g release upon peptide stimulation. The nonmethylated peptide did not induce IFN-g, arguing that the methyl lysines are part of the T cell epitope., SCOPUS: ar.j, info:eu-repo/semantics/published

Одержано нові продукти біосинтезу штаму Pseudomonas sp. PS-17: біогенні поверхнево-активні речовини (рамноліпідний біокомплекс, дирамноліпід та екзополісахарид) і біополімер полігідроксіалканоат. Вивчено процес термічного перетворення цих продуктів у повітряному середовищі в інтервалі температур 293–1273 К. За результатами термолізу та ІЧ-спектроскопії виявлено утворення рамноліпідного біокомплексу між рамноліпідами та екзополісахаридом при підкисленні супернатанту культуральної рідини до рН=3. Методом UV-Vis спектроскопії (за максимумом поглинання при 239 нм) ідентифіковано клітинний полімер – полігідроксіалканоат. За даними термічного аналізу визначено температуру плавлення полігідроксіалканоату (319 К) та температуру початку його деструкції (499 К). З використанням методу Віка визначено теплостійкість полімеру, що склала 321 К. Biogenic surfactants (rhamnolipid biocomplex, dirhamnolipid and exopolysaccharide) and polyhydroxyalkanoate biopolymer which are the new biosynthesis products of Pseudomonas sp. PS-17 strain have been obtained. The thermal transformation of these products has been studied in the air in the temperature range of 293–1273 K. Thermolysis and IR spectroscopy revealed a formation of rhamnolipid biocomplex between rhamnolipids and exopolysaccharide upon acidification of the culture fluid supernatant to pH = 3. Cellular polymer – polyhydroxyalkanoate – was identified by UV-Vis spectroscopy. According to the thermal analysis, the melting point and initial degradation temperature of polyhydroxyalkanoate were determined. Using the Vicat method, the heat resistance of the polymer was determined.

Trichloroethylene (TCE) is an environmental contaminant associated with immune-mediated inflammatory disorders and neurotoxicity. Based on known negative effects of developmental overnutrition on neurodevelopment, we hypothesized that developmental exposure to high fat diet (HFD) consisting of 40% kcal fat would enhance neurotoxicity of low-level (6 μg per kg per day) TCE exposure in offspring over either stressor alone. Male offspring were evaluated at ∼6 weeks of age after exposure beginning 4 weeks preconception in the dams until weaning. TCE, whether used as a single exposure or together with HFD, appeared to be more robust than HFD alone in altering one-carbon metabolites involved in glutathione redox homeostasis and methylation capacity. In contrast, opposing effects of expression of key enzymes related to DNA methylation related to HFD and TCE exposure were observed. The mice generated unique patterns of anti-brain antibodies detected by western blotting attributable to both TCE and HFD. Taken together, developmental exposure to TCE and/or HFD appear to act in complex ways to alter brain biomarkers in offspring.

It is proved that the satellite segment is a necessary component of the national information infrastructure. From this position, the state and development trends of satellite telecommunication systems and satellite channel organization technologies are analyzed. It is shown that there are two ways to build a satellite segment: based on the use of leased resources of satellite operators operating in the satellite communications market; based on the resources of the national satellite communications system, which still needs to be created. It is shown that satellite telecommunication systems have a steady tendency to increase the number of spacecraft, until the launch of “heavyˮ satellites with a payload of more than 70 transponders and to increase the frequency resource. The diagram of satellites location density of in orbit is given. In the case of orientation to rent the resources of active spacecraft, the criteria for their selection is indicated. The arc of the geostationary orbit, on which the satellite should be selected, is calculated. For satellites located on this arc, diagrams of equivalent isotropically radiated power values in the C and Ku bands, which they provide in Ukraine, are shown. A list of satellites that you can focus on, recommendations for selection and a list of recommended for the satellite segment is indicated. The technology standards used in payload and methods for organizing satellite communications channels is noticed. To select the parameters of the satellite segment, the results of calculations of the effectiveness of signal-code structures are provided. Approaches to creating a satellite segment of the national information infrastructure are proposed. It is shown that the orientation to the Lybid national satellite does not make sense; a new frequency-orbit resource is required. The types of platforms that can be used on a national satellite are considered.

Large Clostridial Toxins (LCTs) are a family of six homologous protein toxins that are implicated in severe disease. LCTs infiltrate host cells using a translocation domain (LCT-T) that contains both cell-surface receptor binding sites and a membrane translocation apparatus. Despite much effort, LCT translocation remains poorly understood. Here we report the identification of 1104 LCT-T homologs, with 769 proteins from bacteria outside of clostridia. Sequences are widely distributed in pathogenic and host-associated species, in a variety of contexts and architectures. Consistent with these homologs being functional toxins, we show that a distant LCT-T homolog from Serratia marcescens acts as a pH-dependent translocase to deliver its effector into host cells. Based on evolutionary footprinting of LCT-T homologs, we further define an evolutionarily conserved translocase region that we show is an autonomous translocase capable of delivering heterologous cargo into host cells. Our work uncovers a broad class of translocating toxins and provides insights into LCT translocation., Large Clostridial toxins infiltrate host cells using a translocation domain (LCT-T). Here, using a genomics-driven approach and functional assays, the authors uncover the presence of distant LCT-T homologs in bacteria outside clostridia and provide evidence for a toxic effector function in the gammaproteobacterium Serratia marcescens.

Plants show an unparalleled regenerative capacity, allowing them to survive severe stress conditions, such as injury, herbivory attack and harsh weather conditions. This potential not only replenishes tissues and restores damaged organs, but can also give rise to whole plant bodies, highlighting the intertwined nature of development and regeneration. It suggests that regeneration and developmental processes respond to the same upstream signals, but how a cell knows which of the two processes to engage is currently unknown. Here, we demonstrate that next to being regulators of regeneration, ETHYENE RESPONSE FACTOR 114 (ERF114) and ERF115 govern developmental growth in the absence of wounding or injury. Increased ERF114 and ERF115 activity is correlated with enhanced xylem maturation and lateral root formation, whereas their knockout results in a decrease in lateral roots and xylem connectivity following grafting. Moreover, we provide evidence that mechanical cues contribute to ERF114 and ERF115 expression in correlation with BZR1 mediated brassinosteroid signaling under both regenerative and developmental conditions. Antagonistically, negative regulation of cell wall extensibility via cell wall-associated mechanosensory FERONIA signaling suppresses their expression under both conditions. Our data suggest a molecular framework in which mechanical perturbations too great to be compensated by adaptive cell wall remodeling results in strong ERF114 and ERF115 expression, switching their role from developmental to regenerative regulators. One-Sentence SummaryMechanical cues drive ERF114/ERF115 expression during lateral root development as well as regeneration.

Production of environmentally friendly multitasking materials is among the urgent challenges of chemistry and ecotechnology. The current research paper describes the synthesis of amino–/silica and amino–/phenyl–/silica particles using a one-pot sol–gel technique. CHNS analysis and titration demonstrated a high content of functional groups, while scanning electron microscopy revealed their spherical form and ∼200 nm in size. X-ray photoelectron spectroscopy data testified that hydrophobic groups reduced the number of water molecules and protonated amino groups on the surface, increasing the portion of free amino groups. The complexation with Cu(II) cations was used to analyze the sorption capacity and reactivity of the aminopropyl groups and to enhance the antimicrobial action of the samples. Antibacterial activities of suspensions of aminosilica particles and their derivative forms containing adsorbed copper(II) ions were assayed against Gram-positive (Staphylococcus aureus ATCC 25923) and Gram-negative bacteria (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). Meanwhile, antifungal activity was tested against fungi (Candida albicans UCM Y-690). According to zeta potential measurements, its value could be depended on the suspension concentration, and it was demonstrated that the positively charged suspension had higher antibacterial efficiency. SiO2/–C6H5/–NH2 + Cu(II) sample’s water suspension (1%) showed complete growth inhibition of the bacterial culture on the solid medium. The antimicrobial activity could be due to occurrence of multiple and nonspecific interactions between the particle surfaces and the surface layers of bacteria or fungi.

Досліджено вплив виду ферментного препарату бактеріальної α-амілази і температури на накопичення розчинних сухих речовин та редукуючих цукрів у процесі термоферментативної обробки замісу з пшениці. Показано кореляцію між термічною стабільністю α-амілази і показниками процесу. Встановлено, що початкова активність ферментного препарату впливає на інтенсивність гідролізу крохмалю, а зміна активності ферментів внаслідок їх інактивації за високої температури – на максимальний вміст сухих речовин і редукуючих цукрів у розрідженіймасі. The influence of the bacterial α-amylase type and temperature on the accumulation of soluble dry matter and reducing sugars during fermentation of wheat batch has been investigated. The correlation between thermal stability of α-amylase and process parameters is shown. The initial activity of the enzyme preparation affects the starch hydrolysis intensity. The change in the enzymes activity, occurred due to their inactivation at high temperatures, affects the maximum content of dry matter and reducing sugars in the liquefied matter.

The chloroquinoline scaffold is characteristic of anti-malarial drugs such as chloroquine (CQ) or amodiaquine (AQ). These drugs are also described for their potential effectiveness against prion disease, HCV, EBV, Ebola virus, cancer, Parkinson or Alzheimer diseases. Amyloid precursor protein (APP) metabolism is deregulated in Alzheimer’s disease. Indeed, CQ modifies amyloid precursor protein (APP) metabolism by precluding the release of amyloid-beta peptides (Aβ), which accumulate in the brain of Alzheimer patients to form the so-called amyloid plaques. We showed that AQ and analogs have similar effects although having a higher cytotoxicity. Herein, two new series of compounds were synthesized by replacing 7-chloroquinolin-4-amine moiety of AQ by 2-aminomethylaniline and 2-aminomethylphenyle moieties. Their structure activity relationship was based on their ability to modulate APP metabolism, Aβ release, and their cytotoxicity similarly to CQ. Two compounds 15a, 16a showed interesting and potent effect on the redirection of APP metabolism toward a decrease of Aβ peptide release (in the same range compared to AQ), and a 3–10-fold increased stability of APP carboxy terminal fragments (CTFα and AICD) without obvious cellular toxicity at 100 µM.

Plants form commensal associations with soil microorganisms, creating a root microbiome that provides benefits to the host including protection against pathogens. While bacteria can inhibit pathogens through production of antimicrobial compounds in vitro, it is largely unknown how microbiota contribute to pathogen protection in planta. We developed a gnotobiotic model system consisting of Arabidopsis thaliana, and an opportunistic pathogen Pseudomonas sp. N2C3, to identify mechanisms that determine the outcome of plant-pathogen-microbiome interactions in the rhizosphere. We screened 25 phylogenetically diverse Pseudomonas strains for their ability to protect against N2C3 and found that commensal strains closely related to N2C3 were more likely to protect against pathogenesis. We used a comparative genomics approach to identify unique genes in the protective strains that revealed no genes that correlate with protection, suggesting that variable regulation of components of the core Pseudomonas genome may contribute to pathogen protection. We found that commensal colonization level was highly predictive of protection and so tested deletions in genes previously shown to be required for Arabidopsis rhizosphere colonization. We identified a response regulator colR that is required for Pseudomonas protection from N2C3 and fitness in competition with N2C3 indicating that competitive exclusion may contribute to pathogen protection. We found that Pseudomonas WCS365 also protects against the agricultural pathogen Pseudomonas fuscovaginae SE-1, the causal agent of bacterial sheath brown rot of rice. This work establishes a gnotobiotic model to uncover mechanisms by which members of the microbiome can protect hosts from pathogens and informs our understanding of the use of beneficial strains for microbiome engineering in dysbiotic soil systems.

Large clostridial toxins (LCTs) are a family of bacterial exotoxins that infiltrate and destroy target cells. Members of the LCT family include Clostridioides difficile toxins TcdA and TcdB, Paeniclostridium sordellii toxins TcsL and TcsH, Clostridium novyi toxin TcnA, and Clostridium perfringens toxin TpeL. Since the 19th century, LCT-secreting bacteria have been isolated from the blood, organs, and wounds of diseased individuals, and LCTs have been implicated as the primary virulence factors in a variety of infections, including C. difficile infection and some cases of wound-associated gas gangrene. Clostridia express and secrete LCTs in response to various physiological signals. LCTs invade host cells by binding specific cell surface receptors, ultimately leading to internalization into acidified vesicles. Acidic pH promotes conformational changes within LCTs, which culminates in translocation of the N-terminal glycosyltransferase and cysteine protease domain across the endosomal membrane and into the cytosol, leading first to cytopathic effects and later to cytotoxic effects. The focus of this review is on the role of LCTs in infection and disease, the mechanism of LCT intoxication, with emphasis on recent structural work and toxin subtyping analysis, and the genomic discovery and characterization of LCT homologues. We provide a comprehensive review of these topics and offer our perspective on emerging questions and future research directions for this enigmatic family of toxins.

Diphtheria toxin (DT) is the archetype of bacterial exotoxins implicated in human diseases and has played a central role in defining the field of toxinology since its discovery in 1888. Despite being one of the most extensively characterized bacterial toxins, the origins and molecular evolution of DT host specialization remain unknown. Here, we determined high-resolution structures of two recently discovered distant homologs of DT. These DT-like proteins from non-human associatedStreptomyces albireticuli(17% identity to DT) andSeinonella peptonophila(20% identity to DT) display remarkable structural similarity to DT enabling a comparative investigation into DT’s unique toxicity toward mammalian cells. We find that the individual domains of DT-like toxins retain two critical features of DT’s activity: full catalytic function and ability to translocate across mammalian cell membranes. However, we show that receptor-binding, pH-dependent pore-formation and proteolytic release of the cytotoxic enzyme into the cytosol are not optimized for human cell physiology and thus unable to efficiently deliver the cytotoxic cargo into human hosts. Our work provides structural insights into DT’s evolutionary history, and implies key transitions required for the emergence of human-specificity of a major bacterial exotoxin with an important history in human disease.

Cellular regeneration in response to wounding is fundamental to maintain tissue integrity. Various internal factors including hormones and developmental pathways affect wound healing but little is known about how external factors influence regeneration. To better understand how the environment affects regeneration, we investigated the effects of temperature using the horticulturally relevant process of plant grafting. We found that elevated temperatures accelerated vascular regeneration of Arabidopsis thaliana and tomato (Solanum lycopersicum) grafts. Leaves were critical for this effect since blocking auxin transport or mutating PHYTOCHROME INTERACTING FACTOR4 (PIF4) or YUCCA2/5/8/9 in the cotyledons abolished the temperature enhancement. However, these perturbations had no effect upon graft healing at ambient temperatures and mutations in PIF4 did not affect the temperature enhancement of callus formation or tissue adhesion, suggesting that leaf-derived auxin was specific for enhancing vascular regeneration in response to elevated temperatures. Tissue-specific perturbations of auxin response using a BODENLOS (BDL) mutant revealed an asymmetric effect of temperature upon regeneration: the presence of bdl above the cut prevented temperature enhancement whereas the presence of bdl below the cut prevented graft healing regardless of temperature. Promotion of tissue regeneration by elevated temperatures was not specific for graft healing and we found that elevated temperatures accelerated xylem formation between the parasite Phtheirospermum japonicum and host Arabidopsis thaliana, and this effect required shoot-derived auxin from the parasite. Taken together, our results identify a pathway by which elevated temperatures accelerate vascular development which could be of relevance for improving regeneration and better understanding inter-plant vascular connections.