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The polycondensation of the cis and cis-trans-cis stereoisomers of (tetrahydroxy)(tetraphenyl)cyclotetrasiloxane in different ratios in solution in the presence of montmorillonite affords polyphenylsilsesquioxanes with different unit conformations and cyclolinear siloxane framework configuration as confirmed by 29 Si NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Climate models indicate that dry extremes will be exacerbated in many regions of the world 1,2 . However, confidence in the magnitude and timing of these projected changes remains low 3,4 , leaving societies largely unprepared 5,6 . Here we show that constraining model projections with observations using a newly proposed emergent constraint (EC) reduces the uncertainty in predictions of a core drought indicator, the longest annual dry spell (LAD), by 10-26% globally. Our EC-corrected projections reveal that the increase in LAD will be 42-44% greater, on average, than 'mid-range' or 'high-end' future forcing scenarios currently indicate. These results imply that by the end of this century, the global mean land-only LAD could be 10 days longer than currently expected. Using two generations of climate models, we further uncover global regions for which historical LAD biases affect the magnitude of projected LAD increases, and we explore the role of land-atmosphere feedbacks therein. Our findings reveal regions with potentially higher- and earlier-than-expected drought risks for societies and ecosystems, and they point to possible mechanisms underlying the biases in the current generation of climate models., (© 2024. The Author(s).)

Background and Purpose: One of the most important mechanisms of tissue regeneration is the high functional activity of cells, including proliferation. Currently, there are practically no effective skin cell activators on the pharmaceutical market. The purpose of this work was to demonstrate the stimulating effect of spiroconjugated 1,2,3-triazolo[5,1- b ]1,3,4-thiadiazine (STT) on the functional activity of fibroblasts., Experimental Approach: STT containing ointment for dermal application was made. To assess in vivo effect of the STT a linear wound model in rats was tested. A combination of histological techniques and mechanical testing was employed to estimate the stimulating effect of STT on the functional activity of fibroblasts., Findings/results: The STT significantly increased the number of fibroblasts as well as the density and order of produced collagen fibers in the dermis during the wound healing process. As a result, a tissue was formed at the site of damage with the structure corresponding to normal skin. In addition, skin functions were restored, in particular mechanically., Conclusion and Implications: The results suggested the stimulating effect of the STT on fibroblast activity and demonstrated its potential for skin regeneration., Competing Interests: The authors declared no conflicts of interest in this study., (Copyright: © 2024 Research in Pharmaceutical Sciences.)

The bites of hard ticks are the major route of transmission of tick-borne infections to humans, causing thousands of cases of diseases worldwide. However, the characteristics of the human population that is exposed to tick bites are still understudied. This work is aimed at characterizing both the structure of the population directly contacting ticks and the human behavioral features associated with tick bites. We studied 25,970 individuals who sought medical help after a tick bite at the Centre for Diagnostics and Prevention of Tick-borne Infections (CDPTBI) in Irkutsk City (Russian Federation). The demographic and behavioral characteristics of the human population were analyzed using z-tests for proportions, the Mann-Whitney U test, and the Spearman rank correlation coefficient. The majority of bitten people were urban residents (70 %), and most of them were either of active ages between 30 and 74 years old (62 %), or children between 0 and 9 years old (approximately 20%). Tick bites occurred mostly in the range of 150 km around the location of the diagnostic facility (83 %). In comparison to the general population, significant differences were revealed in the representation of different age groups among bitten people. The population affected by tick bites included fewer men and women in the ages of 10-29 and over 75 years old than would be predicted based on the demographics of the general population. Vice versa, the proportions of people in the ages of 5-9 and 60-74 increased among bitten people. Among men, such activities (in order of occurrence) as "leisure and recreation", "visiting allotments", "foraging for forest food", and "fulfilling work duties" tend to be more associated with tick bites. Among women, tick bites occurred mainly during "visiting allotments", "leisure and recreation", "visiting cemeteries" and "contact with pets and plants at home". The overall vaccination rate was 12 %; however, significantly more men than women were vaccinated against tick-borne encephalitis (up to 20 % vs. approximately 7 % respectively). The structure of the tick bite - affected population suggests that it is age-specific human behavior that mainly determines the frequency of contact between people and ticks. However, in several age groups, especially among children from 5 to 9 and people aged 30-39 years old, gender-related factors could significantly change the exposure of people to tick bites., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Prime editing is a rapidly developing method of CRISPR/Cas-based genome editing. The increasing number of novel PE applications and improved versions demands constant analysis and evaluation. The present review covers the mechanism of prime editing, the optimization of the method and the possible next step in the evolution of CRISPR/Cas9-associated genome editing. The basic components of a prime editing system are a prime editor fusion protein, consisting of nickase and reverse transcriptase, and prime editing guide RNA, consisting of a protospacer, scaffold, primer binding site and reverse transcription template. Some prime editing systems include other parts, such as additional RNA molecules. All of these components were optimized to achieve better efficiency for different target organisms and/or compactization for viral delivery. Insights into prime editing mechanisms allowed us to increase the efficiency by recruiting mismatch repair inhibitors. However, the next step in prime editing evolution requires the incorporation of new mechanisms. Prime editors combined with integrases allow us to combine the precision of prime editing with the target insertion of large, several-kilobase-long DNA fragments.

Fungi of genus Botrytis are important pathogens of legumes, causing gray mold and chocolate spot diseases. The use of molecular methods to identify pathogens has resulted in the discovery of several new Botrytis species and new associations of pathogens with diseases. Thus, chocolate spot of faba bean is now associated with at least four species: B. fabae , B. cinerea , B. pseudocinerea and B. fabiopsis . Species of Botrytis differ in host plant, pathogenicity, fungicide resistance and other relevant properties that affect disease control. The aim of this study was to identify the species of Botrytis isolated from different legume crops and to evaluate their in vitro pathogenicity. Between 2014 and 2019, 278 isolates of Botrytis were obtained from infected legumes in Latvia. A phylogenetic analysis was carried out by sequencing three nuclear genes, RPB2, HSP60, and G3PDH, considered to be diagnostic for species in this genus. A set of 21 representative isolates was selected for pathogenicity tests on detached leaves of faba bean, field pea, lupin and soybean using 5-mm mycelium-agar plugs. The diameter of the formed lesions under the inoculated plug was measured crosswise each day. The datasets were subjected to analysis of variance with the split-plot design of the experiment and repeated-measures model. Six species were identified: B. cinerea , B. fabae , B. pseudocinerea , B. fabiopsis , B. euroamericana and B. medusae . In addition to the expected combinations of host and pathogen, naturally occurring infections of B. fabiopsis were found on chickpea, B. euroamericana on faba bean and B. medusae in lupin seeds. Species and isolate had significant effects on pathogenicity on all crops tested. Several isolates were pathogenic on two or more host species: two of B. pseudocinerea , two of B. cinerea , two of B. fabiopsis and the one of B. medusae . One isolate of B. pseudocinerea and two of B. fabiopsis caused primary lesions on all five host species. The results show that these Botrytis species have a broad host range that should be borne in mind when planning crop sequences and rotations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Brauna-Morževska, Stoddard, Bankina, Kaņeps, Bimšteine, Petrova, Neusa-Luca, Roga and Fridmanis.)

High-throughput protein assays are crucial for modern diagnostics, drug discovery, proteomics, and other fields of biology and medicine. It allows simultaneous detection of hundreds of analytes and miniaturization of both fabrication and analytical procedures. Photonic crystal surface mode (PC SM) imaging is an effective alternative to surface plasmon resonance (SPR) imaging used in conventional gold-coated, label-free biosensors. PC SM imaging is advantageous as a quick, label-free, and reproducible technique for multiplexed analysis of biomolecular interactions. PC SM sensors are characterized by a longer signal propagation at the cost of a lower spatial resolution, which makes them more sensitive than classical SPR imaging sensors. We describe an approach for designing label-free protein biosensing assays employing PC SM imaging in the microfluidic mode. Label-free, real-time detection of PC SM imaging biosensors using two-dimensional imaging of binding events has been designed to study arrays of model proteins (antibodies, immunoglobulin G-binding proteins, serum proteins, and DNA repair proteins) at 96 points prepared by automated spotting. The data prove feasibility of simultaneous PC SM imaging of multiple protein interactions. The results pave the way to further develop PC SM imaging as an advanced label-free microfluidic assay for the multiplexed detection of protein interactions.

Glycogen storage disease type 1 (GSD1) is a rare hereditary monogenic disease characterized by the disturbed glucose metabolism. The most widespread variant of GSD1 is GSD1a, which is a deficiency of glucose-6-phosphatase-ɑ. Glucose-6-phosphatase-ɑ is expressed only in liver, kidney, and intestine, and these organs are primarily affected by its deficiency, and long-term complications of GSD1a include hepatic tumors and chronic liver disease. This article is a brief overview of existing animal models for GSD1a, from the first mouse model of 1996 to modern CRISPR/Cas9-generated ones. First whole-body murine models demonstrated exact metabolic symptoms of GSD1a, but the animals did not survive weaning. The protocol for glucose treatment allowed prolonged survival of affected animals, but long-term complications, such as hepatic tumorigenesis, could not be investigated. Next, organ-specific knockout models were developed, and most of the metabolic research was performed on liver glucose-6-phosphate-deficient mice. Naturally occuring mutation was also discovered in dogs. All these models are widely used to study GSD1a from metabolic and physiological standpoints and to develop possible treatments involving gene therapy. Research performed using these models helped elucidate the role of glycogen and lipid accumulation, hypoxia, mitochondrial dysfunction, and autophagy impairment in long-term complications of GSD1a, including hepatic tumorigenesis. Recently, gene replacement therapy and genome editing were tested on described models, and some of the developed approaches have reached clinical trials., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Global warming increases the number and severity of deadly heatwaves. Recent heatwaves often coincided with soil droughts that intensify air temperature but lower air humidity. Since lowering air humidity may reduce human heat stress, the net impact of soil desiccation on the morbidity and mortality of heatwaves remains unclear. Combining weather balloon and satellite observations, atmospheric modelling, and meta-analyses of heatwave mortality, we find that soil droughts—despite their warming effect—lead to a mild reduction in heatwave lethality. More specifically, morning dry soils attenuate afternoon heat stress anomaly by ~5%. This occurs because of reduced surface evaporation and increased entrainment of dry air aloft. The benefit appears more pronounced during specific events, such as the Chicago 1995 and Northern U.S. 2006 and 2012 heatwaves. Our findings suggest that irrigated agriculture may intensify lethal heat stress, and question recently proposed heatwave mitigation measures involving surface moistening to increase evaporative cooling.