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Introduction. Cadmium (Cd) is one of the most powerful and dangerous pollutants. Cd exposure is associated with multiple organ damage in both animals and humans. The mechanism of Cd toxicity is the disruption of the body’s antioxidant system (AOS), which leads to transformation of the functional integrity of the liver. The extent of target organ damage can be examined by measuring concentrations of key indicators of hepatocellular injury. The purpose of the work is to evaluate changes in the activity of enzyme markers of hepatotoxicity in the blood serum of laboratory animals after oral exposure to an aqueous solution of cadmium chloride (CdCl2) under the conditions of a subchronic experimental model with a period of remission. Materials and methods. The study was conducted on 40 white outbred rats. Animals of three experimental groups were intragastrically administered a pollutant in various dosages for 3 months. The duration of the remission stage was 1 month. The activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) was determined in the blood serum of animals. Results. When CdCl2 was administered to animals at a dose of 1 μg/kg, an increase in AST activity was observed by 45.9% relative to the control (p=0.006). An increase in the concentration of ALT and LDH is shown. A dose-dependent decrease in the level of alkaline phosphatase was revealed in three groups of animals by 24.7%, 37.5% and 55.4%, respectively (p=0.002). The noted trends indicate pathological processes occurring in hepatocytes. Conclusion. In the course of this study, it was found that under the conditions of a subchronic model of the experiment with a period of remission, cadmium, having a pronounced hepatoxic effect, induces liver damage in experimental animals.

Contrary to the 4′- and 5′-nitro- and aminofluoresceins, the corresponding 3′-derivatives are practically unexplored. In this paper, we describe the synthesis and spectral properties of 3′-nitrofluorescein and 3′-aminofluorescein, as well as their methyl esters. Among other methods, X-ray analysis, 13C NMR spectroscopy, and ESI mass spectrometry made it possible to establish the molecular structure of the target compounds as well as intermediates and by-products. Some unexpected products, though in small amounts, were revealed within the course of study. Whereas the fluorescence of the double-charged R2− ion of 3′-nitrofluorescein in both aqueous and organic solvents is weak, the R2− anion of 3′-aminofluorescein in a non-hydrogen bonding donor solvent, but not in water, exhibits intensive fluorescence, analogous to the case of 4′- and 5′-aminofluoresceins. Interestingly, the λ max values in water of the R2− ions bearing an NO2 group in the 3′- and 6′-positions are 7 to 10 nm higher than those of the 4′- and 5′-nitro derivatives. The difference was also observed in dimethyl sulfoxide. This correlates with the angles between the xanthene and phthalic planes of the dyes. The dye 3′-aminofluorescein could be used as a fluorescent indicator sensitive to hydrogen bonding ability of the solvent. It could also serve as a platform for synthesizing fluorescent molecular probes for biochemical research, analogous to the very popular application of 4′- and 5′-amino derivatives. [ABSTRACT FROM AUTHOR]

The study of the metabolism in the body of cows, depending on the physiological state, factors of feeding and the conditions of content in different seasons of the year, is a necessary condition for the direct effect on their reproductive capacity and productivity. In particular, the scientific and practical interest is the disclosure of physiological and biochemical mechanisms, which are associated with the characteristics of metabolism in the body of cows during pregnancy. The purpose of the research was to study the features of protein metabolism in highly productive deep-calving cows in different seasons of the year. The object for the study is served cows with milk production of 5–6 thousand kg for lactation at 8–9 months of pregnancy and blood samples taken from them. Biochemical study of cows blood plasma was carried out according to generally accepted methods. The recorded seasonal changes in protein exchange of deep-calving cows (Table) were cyclic. In contrast to the total protein content, seasonal differences in its fractional composition were also detected. The dynamics of the change in protein ratio is similar to that of albumin. During the summer, the content of a-globulins increased by 20.1 %, b-globulins by 17.3 %, g-globulins per 20.5 % compared with the spring period. In dry-bodied cows, the activity of ALT and AST in winter increases, reaching its maximum value but in the summer activity of ALT significantly decreased, and its activity was even less than the physiological limits. ACT activity was the lowest in the autumn. Determined that seasonal changes in the protein metabolism of dry cows were cyclic character. A decrease in the content of globulins (due to α-, β- and γ-globulins) was observed during the winter period compared to the summer period. This characterizes the high activity of protein metabolism in the summer with the decline in winter. In dry cows, the albumin content and protein ratio reached a maximum in winter with a significant decrease in spring and summer, and in the autumn they again started to rise. The degree and direction of changes in ALT and AST activity were similar to seasonal changes in albumin content. This indicates a low intensity of proteinsynthesizing processes in the liver in summer. [ABSTRACT FROM AUTHOR]

The period of stable keeping of cows is one of the most difficult periods for the body, as it is the most saturated with stressful influences, and precisely due to the lack of solar insolation and exercise, the action of potentially pathogenic microflora and increased gassing of livestock premises, shortage vitamins, microand macroelements in feed. Deep calving animals have metabolic disorders without clinical signs. Such a form pathologies can be detected only through biochemical research.The content of total protein was determined by biuret`s method, albumins ‒ by reaction with bromocresol green, activity alanine and aspartate aminotransferase ‒ by the Reitman-Frenkel method, activity alkaline phosphatase ‒ with disodium phenyl phosphate, acid capacity ‒ by Bolshakov-Belyaev technique, carotene content ‒ by photometric method, content of total calcium ‒ by the complexometric method, the content of carotene ‒ photometric method. The purpose of our work was to study the dynamics of protein and mineral meabolism in cows during the dry period for stall keeping. The object of the study was cows (15 heads) of the Holstein breed with a milk yield of 5‒6 thousand kg per lactation for 8‒9 months of pregnancy. It was found that the total protein of the cows organism decreased in the last months of pregnancy during the dry period from 87.25 ± 1.20 to 81.60 ± 1.20 g/l (Р < 0.05), including the globulin fraction from 51.96 ± 2.08 to 43.75 ± 2.07 g/l (Р < 0.05) and other indicators of protein metabolism changed. The -globulin fraction significantly decreased from 28.53 g/l to 22.97 g/l (Р < 0.01). In our opinion, this is due to a decrease in the activity of the mother's body defenses to prevent the development of a reaction to the fetal tissue, which is a foreign organism. The activity of aspartate aminotransferase decreased by 8.5 months of pregnancy to 150.26 ± 13.59 nM/sꞏL (Р < 0.01), and then tended to increase to 187.19 ± 9.21 nM/sꞏL (Р < 0.05). Such a change in the activity of this enzyme in late pregnancy is associated with an increase in the processes of self-renewal of proteins due to transamination, which can be used more intensively by the fetus. The calcium content decreased by 1.14 times during the dry period. This fact, in our opinion, is associated with the intensive development and formation of the fetal skeleton. This is also evidenced by a significant increase in the activity of alkaline phosphatase (1.29 times, Р < 0.01). Changes in total calcium and inorganic phosphorus were strongly correlated (r = 1.0). The results obtained allow us to point out the causes of the identified deviations and offer recommendations for their elimination and correction of animal feeding. [ABSTRACT FROM AUTHOR]

The article reports that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to Ipsen's Iqirvo (elafibranor) as a second-line treatment for primary biliary cholangitis (PBC), addressing an unmet medical need. Topics include the drug's efficacy in reducing alkaline phosphatase levels and achieving biochemical response, its potential benefits and limitations based on the ELATIVE trial, and the need for further research to confirm long-term clinical benefits.

β‐Glucosidase is a key enzyme that hydrolyzes nonvolatile glycosylated precursors of aroma compounds and enhances the organoleptic quality of wines. In this study, a novel β‐glucosidase from Hanseniaspora uvarum Yun268 was localized, purified, and characterized. Results indicated that β‐glucosidase activity was mainly distributed within the cells. After purification via ammonium sulfate precipitation combined with chromatography, β‐glucosidase specific activity increased 8.36 times, and the activity recovery was 56.90%. The enzyme had a molecular mass of 74.22 kDa. It has a Michaelis constant (Km) of 0.65 mmol/L, and a maximum velocity (Vmax) of 5.1 nmol/min under optimum conditions; and Km of 0.94 mmol/L, and Vmax of 2.8 nmol/min under typical winemaking conditions. It exhibited the highest activity at 50°C and pH 5.0 and was stable at a temperature range of 20–80°C and pH range of 3.0–8.0. The enzyme has good tolerance to Fe3+, especially maintaining 93.68% of its activity with 10 mmol/L of Fe3+. Ethanol (<20%) and glucose (<150 g/L) inhibited its activity only slightly. Therefore, β‐glucosidase from H. uvarum Yun268 has excellent biochemical properties and a good application potential in winemaking. Practical Application: Winemaking is a biotechnological process in which exogenous β‐glucosidase is used to overcome the deficiency of endogenous β‐glucosidase activity in grapes. By localizing, purifying, and characterizing of β‐glucosidase from Hanseniaspora uvarum Yun268, it is expected to reveal its physical and chemical characteristics to evaluate its oenological properties in winemaking. The results may provide the basis for promoting the release of varietal aroma and improving wine sensory quality in the wine industry. [ABSTRACT FROM AUTHOR]

The experiment was carried out in the Scientific Centre of Agriculture – Sredets with indigenous East Balkan pigs divided in three age groups – suckling piglets (n = 10), growers (n = 10) and sows (n = 10). Seven hematological and nine blood biochemical parameters were determined. The pigs raised under extensive breeding system – in semi-open buildings without providing the optimum temperature for the different pig categories a depends on the outside temperature. The changes in haematological and blood biochemical parameters at four temperature ranges (TR) – I (up to 8 °С), II (9–15 °С), III (16–22 °С) and IV (over 23 °С) were controlled. Blood samples were taken during the months of February, May, July and October. The results were analyzed through two-way ANOVA to assess the influence of the age and temperature on the hematological profile of the animals. The lowest monthly average values were measured in the period from December to March – 1,8 °С–6,0 °С. The next temperature interval – from 9.6 °С to 14.6 °С was observed in the months of April, October and November and optimal temperature values – from 16 °С to 20 °С, in May, June and September. The highest average monthly temperature was established during the period July– August – above 23.0 °С. The leukocyte´s number is influenced by both the temperature and the age of the pigs. For all controlled categories values were lower in II and III compared to I and IV TR, which could be explained by differences in temperature. The differences obtained for the number of lymphocytes and granulocytes are not significant and does not show any age and temperature dependence. Significant influence was found at the red blood cells number (P < 0.001), hemoglobin (P < 0.001) and hematocrit (P < 0.01), as well as in the most biochemical parameters including glucose, creatinine (P < 0.001), total protein (P < 0.001), albumin (P < 0.001), alanine aminotransferase (P < 0.001), aspartate aminotransferase (P < 0.01), triglycerides (P < 0.05) and cholesterol (P < 0.01). [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is one of the deadly and highly drug-resistant. The aim of the present study was isolation and identification of Pseudomonas aeruginosa from different clinical samples. A total of 100 clinical specimen have been collected from Urine, sputum samples, burn, ear, wound swabs and bronchial wash that were obtained from 100 patients include both gender and different age groups from the beginning of November 2019 to the end of February 2020. The results showed that out of 100 samples, 36 (36%) samples have been detected for Pseudomonas aeruginosa depending on the morphologic characteristics of this bacterium on the culture media and biochemical tests, which included manual, conventional, biochemical tests and automated biochemical tests such as Vitek 2 test and by using Polymerase Chain Reaction (PCR) technique for gyrA gene with 121 bp. The results confirmed that these isolates were belong to Pseudomonas aeruginosa. [ABSTRACT FROM AUTHOR]

The development of modern clinical medicine and the truthful medical diagnosis require hard physicochemical data. Furthermore, the social demands for more accurate and collected data, which refer to human health in real conditions and in real time, force the quest for techniques which would be possible to be applied in a broadly understood clinical field. In this article two techniques are described. A high vacuum technique which is an X-ray photoelectron spectroscopy (XPS), and a functional near infrared spectroscopy (fNIRS), which might be applied in vivo condition. For the both techniques, the results pointing their applicability in the clinical and modern biochemical research are described. [ABSTRACT FROM AUTHOR]

The effects of chemicals commonly used in Cameroon to eliminate slime from the flesh of the African giant land snail, Archachatina marginata, during processing on some nutritional and biochemical parameters were investigated. Groups of snails were processed with these chemicals at three different concentrations. Proximate analysis of all the treated snail groups was carried out, and groups with the highest concentration of each chemical were used to compose diets for experimental rats. Thirty weanling male Wistar albino rats (31.25 ± 3.09 g) aged 21days old were distributed into four groups and fed with 10% protein based diets of A. marginata named D1 (washed with only water), D2 (lime C-treated), D3 (alum C-treated), and D4 (salt C-treated). The crude protein contents of the treated groups reduced significantly when compared with the control (CW), with lime C-treated (LC) having the least here and in crude fiber, but higher (LC, LB, and LA) in dry matter. There was a significant reduction in the crude lipid of alum C-treated (AC) and salt A-treated (SA). In vivo studies showed a general decrease in food consumption, weight gained, efficiency of feed utilization (EFU), true protein digestibility (TD) (except D2), and hematological indices (RBCs (red blood cells), PCV (packed cell volume) of the treated groups (D2, D3, D4) when compared to the control (D1). On the other hand, an increase in the relative weight of the liver (RWL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total cholesterol was observed with some of the treated diets; meanwhile, protein efficiency ratio (PER), net protein ratio (NPR), relative weight of the kidneys (RWK), HDL cholesterol, and triglycerides were not affected by these diets. These chemicals should only be used at low concentrations or not at all because of its toxicity at high concentrations. [ABSTRACT FROM AUTHOR]

Fifteen male rats, Albino Dawley rats, approximately age 7- 8 week were utilized for this study that divided into three groups, Group A: control received equivalent quantity sterile distilled water for the same period, Group B: treated orally with 0.5 g Flaxseed that dissolved in 5 ml of sterile distilled water, Group C : treated orally with 1 g Flaxseed that dissolved in 5 ml of sterile distilled water. The levels of some blood biochemical parameters (Glucose, Total protein, Albumin, Globuline, Blood urea, Uric acid and Creatinine) of male rat have been estimated in all subjects. The levels of serum Total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST),alkaline phosphatase (ALP) and lipids profile have been determined in all subjects also. The results showed a significant (p< 0.05) decrease in serum glucose, blood urea, uric acid, creatinine, cholesterol, LDL and VLDL in groups B and C as compared to group A, While the levels of globuline and HDL showed a significant increase in the same groups as mention above. However total bilirubin, ALT and AST levels appear significant differences when compared group C to group A . The levels of albumin and ALP did not show any statistical significant alterations. [ABSTRACT FROM AUTHOR]

Relationship between dietary habits and disease risk was demonstrated by numerous epidemiological studies which led to the conclusion that food has a direct impact on health. On the other hand, recent researches established some correlations between the consumption of fresh fruits and vegetables and their health benefits. Lettuce (Lactuca sativa L.) is an important dietary leafy vegetable mainly consumed fresh or in salad mixes for its good taste, but also because it is perceived as being amongst healthy food since a number of lettuce varieties have been investigated and reported to contain some compounds with antioxidant activities. Lettuce cultivation has been greatly expanded in recent times, so that researchers have been looking for solutions for growing it in confined spaces using artificial LED lighting (light emitting diodes). The objective of this research was to investigate the effect of LED lighting on biochemical characteristics of some lettuce varieties in order to establish the best light treatment during cultivation for enhancing the plants growth, yield and nutritional value. Different combinations of LED wavelengths against conventional light sources were investigated and the researches performed demonstrated that LEDs variably influenced growth characteristics and increased biochemical compounds content in the analyzed lettuce varieties. [ABSTRACT FROM AUTHOR]

The study was conducted to determine the pollen composition, diversity and biochemical constituents of honey samples from five states of Nigeria. A total of 104 pollen types belonging to 57 plant families were recorded. The honey samples were classified into three botanical groups on basis of major contributing plants; Unifloral, bifloral and polyfloral honeys. Shannon-Wiener Diversity and Pielou's Evenness Indices ranged from 1.987 -- 2.676 and 0.580 -- 0.705 respectively indicating high plant heterogeneity foraged by the honeybees. The common plant sources of nectar and pollen include Combretaceae- Melastomataceae, Phyllanthus muelerianus, Elaeis guineensis, Alchornea cordifolia and Syzygium guineense. The biochemical analyses conformed to the Codex and EU Council standard for all parameters tested except moisture content from Akpanya and Anyigba samples that exceeded the limit. The highest crude protein content was recorded in Calabar sample (1.71 ± 0.01 %) while ash content was highest in Anyigba (0.29 ± 0.02 %). Calabar and Akpanya samples had the highest fibre value (0.80 ± 0.01 %). The hydroxymethylfurfural value was highest in Abakaliki (4.46 ± 0.02 mg/kg). Sample from Calabar had the highest free acidity (0.12 ± 0.01 meg/kg), while electrical conductivity was highest in Akpanya (17.70 ± 0.01 µS/cm) sample. The pH and refractive index values, 4.72 ± 0.01 and 1.50 ± 0.01 respectively were highest in Abakaliki sample. The sum of fructose and glucose ranged from 68.8 ± 0.01 -- 82.62 ± 0.01 % in the samples and had ratios greater than one in the samples making them subject to low crystallization. [ABSTRACT FROM AUTHOR]

The efficacy of inspiratory muscle training (IMT) has been the subject of considerable controversy in terms of whether it is beneficial to endurance athletes and because a convincing physiological rationale has not been identified to explain its mechanism of action. Early studies suggested that IMT was an ineffectual intervention for gains in either maximal aerobic power or endurance-specific performance. More rigorous recent research supports the observation that maximal aerobic power is not receptive to IMT; however, closer evaluation of both early and contemporary research indicates that responses to endurance-specific performance tests are sensitive to IMT. As the aim of endurance training is to improve endurance performance rather than maximal aerobic power, it is plausible that IMT may be useful in specific performance-related circumstances. Performance adaptations following IMT appear to be connected with posttraining reports of attenuated effort sensations, but this common observation has tended to be overlooked by researchers in preference for a reductionist explanation. This commentary examines the pertinent research and practical performance implications of IMT from the holistic perspective of complex central metabolic control. [ABSTRACT FROM AUTHOR]

We present a simple method for determining the exact noise power spectra and related statistical properties for linear chemical reaction networks. The method is applied to reaction networks which are representative of biochemical processes such as gene expression. We find, for example, that a post-translational modification reaction can reduce the noise associated with gene expression. Our results also indicate how to coarse grain networks by the elimination of fast reactions. In this context we have discovered a breakdown of the sum rule which relates the noise power spectrum to the total noise. The breakdown can be quantified by a sum rule deficit, which is found to be universal, and can be attributed to the high-frequency noise in the fast reactions. [ABSTRACT FROM AUTHOR]

Aim: To investigate the possible therapeutic effects of alpha‐lipoic acid (ALA) in a model of chronic apical periodontitis in rats by analysing biochemical, histopathological and micro‐CT parameters. Methodology: The study was approved by the Animal Ethics Committee of the Near East University. Thirty‐two Wistar rats were divided into four groups of eight rats each: Control Group; ALA Group; AP Group; AP + ALA Group. In the AP and AP + ALA groups, the pulp chambers of the mandibular first molars were surgically exposed and were left open to the oral environment for 4‐weeks to allow the establishment of periapical lesions. The rats in the Control and AP groups were treated intraperitoneally with saline solution (with a daily dose of 100 mg kg−1, for 28 days after periapical lesion induction). The rats in the ALA and AP + ALA groups were treated intraperitoneally with ALA (with a daily dose of 100 mg kg−1, for 28 days after periapical lesion induction). After decapitation, the trunk blood was collected for the assessment of biochemical parameters. The mandibles were surgically removed and dissected for histopathologic analysis and further scanned with micro‐CT. Groups of data were compared with a two‐way analysis of variance (two‐way anova) followed by Sidak's multiple comparison tests. Values of P < 0.05 were regarded as significant. Results: TNF‐α, IL‐1β, MMP‐1, MMP‐2 levels were significantly lower in AP + ALA group compared with AP group (P < 0.05). There was a significant difference between the AP and AP + ALA groups according to assessment of the inflammatory scores (P < 0.05). The periapical inflammatory infiltrates were significantly more severe (P < 0.05) in the AP group. The AP + ALA group exhibited lower values both in terms of surface area and volume of resorption cavities than the AP group and this difference was significant (P < 0.05). Conclusion: alpha‐lipoic acid treatment provided therapeutic effects on the inhibition of periapical bone loss. [ABSTRACT FROM AUTHOR]

Ethanamizuril is a novel triazine compound that exhibits remarkable anticoccidial activity. Owing to its pharmacological properties, this study was conducted to evaluate the acute and 30-day oral toxicity of ethanamizuril. In the acute study, ethanamizuril was administered once by oral gavage to mice and rats. The calculated LD50 values for mice and rats were 5776 and 4743 mg per kg b.w, respectively, but the LD50 value for male rats was higher than that of female rats. In the subchronic study, male and female rats were fed with diets supplemented with 0, 20, 60 or 120 mg kg−1 ethanamizuril for 30 days. Treatment related clinical signs of alopecia on the back and neck of the animals were observed in the 60 and 120 mg kg−1 dose groups from the third week of treatment. Significant differences in haematological and biochemical parameters as well as organ-to-body weight ratios were detected between the 60 and 120 mg kg−1 groups. Histopathological observations revealed that 60 and 120 mg kg−1 ethanamizuril could induce focal hepatocellular necrosis and split phase. Slight renal tubule protein casts in the kidneys and alveolar wall thickening in the lungs were also observed in the high dose groups of both genders. The dietary no-observed-adverse-effect level (NOAEL) of ethanamizuril for 30 days was 20 mg kg−1 feed. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the association between metabolic syndrome (MetS) and periodontitis among young adults, and also to compare results using observed and latent variables for MetS and periodontitis.Methods: Data from the 1982 Pelotas Birth Cohort, Brazil, were used. Metabolic syndrome at the age of 23 years was measured using clinical and biochemical analysis and set as the main exposure. Periodontitis at the age of 31 years was clinically measured and set as the outcome. Confounding variables included sex and maternal education, assessed at birth, family income at 23 years, and smoking status at the age of 23 and 30 years. Factor analyses (exploratory and confirmatory) were performed to define latent variables for MetS and periodontitis. In addition, both conditions were also defined as categorical observed variables. The association between MetS and periodontitis was tested in structural equation models.Results: Two latent periodontal variables were identified: "initial" and "advanced" periodontitis, while one latent variable was identified for MetS. Metabolic syndrome is positively associated with "advanced" (coefficient 0.11; P value < 0.01), but not with "initial" (coefficient -0.01; P value = 0.79) periodontitis. When MetS and periodontitis were set as observed variables in the structural equation models, no association was found irrespective of the criteria used for periodontitis classification.Conclusions: There was a positive association between metabolic syndrome and "advanced" periodontitis, when the multiple dimensions of both diseases were accounted in latent variables. Nevertheless, when MetS and periodontitis were treated as observed variables, no association was detected irrespective of the criteria used for periodontitis classification. [ABSTRACT FROM AUTHOR]

Background: Analyses of replicates in sets of discrete data, typically acquired in multi-well plate formats, is a recurring task in many contemporary areas in the Life Sciences. The availability of accessible cross-platform data analysis tools for such fundamental tasks in varied projects and environments is an important prerequisite to ensuring a reliable and timely turnaround as well as to provide practical analytical tools for student training. Results: We have developed an easy-to-use, interactive software tool for the analysis of multiple data sets comprising replicates of discrete bivariate data points. For each dataset, the software identifies the replicate data points from a defined matrix layout and calculates their means and standard errors. The averaged values are then automatically fitted using either a linear or a logistic dose response function. Conclusions: DRfit is a practical and convenient tool for the analysis of one or multiple sets of discrete data points acquired as replicates from multi-well plate assays. The design of the graphical user interface and the built-in analysis features make it a flexible and useful tool for a wide range of different assays. [ABSTRACT FROM AUTHOR]

Gastric abscess is one of the ututmost serious sicknesses. Utmost classical dealing lines produce negative prescription rejoinders. Therefore, this learning aims to explore the preventive properties of normal quotations, namely, marshmallow quotations, on gastric abscesss caused by aspirin in rats. Fifty rats of the adult Wistar family were divided into five groups for each group of 10 rats; the normal rheostat group distilled water, gastric abscess induction by Asprine (20 mg / kg BW), Famotidin dealing groups receiving (20 mg / kg) (100 mg / kg) and dealing of combinations with Famotidin and Marshmallow Oral dealings were administered daily for 21 days before ip direction of aspirin (20 mg / kg) except for the normal group. Aspirin direction lead to in a important predisposed consequence from important rises in the number of abscesss, abscess index and high blood pressure demosotase activity, with important reductions in nitric oxide echelons in gastric mucosa and glutathione echelons. Furthermore, rises in mucosal mucous peroxides in the stomach content were observed. Instead, predealing with famotidin, marshmallow important corrects the visual and biochemistry marks and the real time analysis to TNF-Q was fixed of consequence of marshmallow on the gasteric abscess. These marks suggest that eating marshmallow quotation can shiled against gastric abscesss caused by aspirin in rats through their antioxidant properties. [ABSTRACT FROM AUTHOR]

Abstract Throughout the years an increase has been observed in research output on biochemical markers for determining the postmortem interval (PMI). However, to date, a complete overview is missing on the results of postmortem biochemical markers (PBM's) for PMI estimation. In this paper, literature was reviewed in order to identify the knowledge lacunae of PBM research from a practical point of view. A three-step approach was undertaken in order to achieve the set goal. Literature was collected, the PBM's were evaluated for completeness by means of a scorings index based on set criteria, and PBM's were subsequently evaluated in light of the Daubert & Frye criteria for scientific evidence in court. Seven PBM's were found to be well investigated, from which potassium had the highest completion score. However, none of these PBM's could be qualified as suitable for court evidence. Further, this study revealed that the majority of PBM's (94%) is not well investigated. Consequently, these PBM's did not meet Daubert & Frye criteria. In order to improve the assessment for use of PBM's as evidence in court regarding PMI estimation, PBM's should be investigated more thoroughly and data should be made readily available. Highlights • Systematic review of data on postmortem biochemical markers (PBM's). • Scoring index for assessing a PBM's research completeness and practicality. • For many PBM's, assessment is impossible due to insufficient data. [ABSTRACT FROM AUTHOR]

Circadian oscillators are networks of biochemical feedback loops that generate 24-hour rhythms in organisms from bacteria to animals. These periodic rhythms result from a complex interplay among clock components that are specific to the organism, but share molecular mechanisms across kingdoms. A full understanding of these processes requires detailed knowledge, not only of the biochemical properties of clock proteins and their interactions, but also of the three-dimensional structure of clockwork components. Posttranslational modifications and protein–protein interactions have become a recent focus, in particular the complex interactions mediated by the phosphorylation of clock proteins and the formation of multimeric protein complexes that regulate clock genes at transcriptional and translational levels. This review covers the structural aspects of circadian oscillators, and serves as a primer for this exciting realm of structural biology. [ABSTRACT FROM AUTHOR]

Abstract A synopsis of in-cell NMR spectroscopic approaches to study interaction proteomics in prokaryotic and eukaryotic cells is presented. We describe the use of in-cell NMR spectroscopy to resolve high resolution protein structures, discuss methodologies for determining and analyzing high and low affinity protein-target structural interactions, including intrinsically disordered proteins, and detail important functional interactions that result from these interactions. Significance The ultimate goal of structural and biochemical research is to understand how macromolecular interactions give rise to and regulate biological activity in living cells. The challenge is formidable due to the complexity that arises not only from the number of proteins (genes) expressed by the organism, but also from the combinatorial interactions between them. Despite ongoing efforts to decipher the complex nature of protein interactions, new methods for structurally characterizing protein complexes are needed to fully understand molecular networks. With the onset of in-cell NMR spectroscopy, molecular structures and interactions can be studied under physiological conditions shedding light on the structural underpinning of biological activity. [ABSTRACT FROM AUTHOR]

The results of the field observations and biochemical researches of plum (Prunus rossica Erem.) fruits grown in the garden of intensive type with agrogenic soil in row spacing are presented in the article. The fruits of plum breeds Kubanskaya kometa and Naidena were gathered from the trees grafted on different stocks. The influence of the stock on the trees productivity, the fruit weight and biochemical structure of the plum fruits were studied. Basic chemical analyses, ascorbic acid concentration, antioxidant activity and fruit ash content were determined. The variation limits of the parameters under study depending on the used stock were shown. The best degustation evaluation parameters were found at the combinations of Kubanskaya kometa on stocks OPA-15-2 and Novinka, Naidena on stocks OPA-15-2 (more than 4,5 points). The high positive correlation (r =0.92) was marked between soluble solids and sugars content. The researches about the stock influence on the plum fruits titratable acidity change we have not found. The correlation between AA and ascorbic acid content in the fruits was determined (r =0.7). The decreasing row of the elements content in the plum fruits ash is the following: K>P>Mg>Ca>Mo>Cu>S>Ni>Fe≈Si>Mn. The proportion of K is from 18.67 (Naidena/OPA-15-2) to 27.48 (Kubanskaya kometa/Novinka); P from 3.35 (Kubanskaya kometa/seedlings P. cerasifera Ehrh. to 6.39 (Kubanskaya kometa/Novinka), Mg from 1.11 (Naidena/OPA-15-2) to 2.43 (Naidena/seedlings P. cerasifera Ehrh.) and Ca from 0.39 (Naidena/13-113) to 1.85 (Naidena/OPA-15-2) mass % respectively. The proportion of the rest elements is not more than 1 mass %. Under the OPA-15-2 stock influence the trees productivity and the single fruit weight increased, soluble solids, sugars and ascorbic acid concentration in the fruit in comparison with standard stock by the seedling rootstock of alycha (Prunus cerasifera Ehrh. seedlings). While ingrafting by Novinka stocks the parameters under study decreased. [ABSTRACT FROM AUTHOR]

Abstract Nanosecond pulsed electric field (nsPEF) has the ability to induce a host of intracellular biochemical processes in living cells as a function of parameter setting. In vitro experiments proved that nsPEF stimulation could remarkably promote biomineralization processes and new bone formation. However, the impact of nsPEF parameter settings on the calcium flux of osteoblasts, as well as the intracellular mechanisms underlying those observations have yet to be elucidated. In this study, live osteoblast-like MG63 cells were loaded with fluorescence indicator dye fluo-4 AM. nsPEF stimulation could induce intracellular calcium mobilization in MG63 cells with no refractory period. We confirmed that moderate output voltage (4–8 KV) and large pulse number (25) were required for efficient nsPEF irritation of MG63 cells. Additionally, nsPEF stimulation-induced calcium flux in MG63 cells was dramatically reduced with the treatment by ethylene glycol tetraacetic acid (EGTA), proving that the intake of extracellular calcium ions is crucial for increasing intracellular calcium concentration of nsPEF-treated MG63 cells. Our preliminary study investigated the mechanisms underlying nsPEF stimulation-induced calcium mobilization in osteoblast-like cells, and it has the potential to accelerate the application of nsPEF stimulation in new bone formation. Highlights • The calcium flux in osteoblasts induced by nsPEF stimulation was investigated. • nsPEF stimulation induced calcium mobilization in MG63 cells had no refractory. • Output voltage and pulse number affect nsPEF stimulation on MG63 cells. • EGTA could inhibit nsPEF induced calcium immobilization in MG63 cells. [ABSTRACT FROM AUTHOR]

The article discusses the classes of transmembrane proteins that help alter large bifunctional molecules drugs across the cell membrane. Topics include challenges in optimizing biochemical potency and membrane permeability remains one of the biggest challenges in drug development; and Large macrocyclic peptides from natural products serve as counter examples to the long-held assumption that the passive mechanism to low molecular weight drugs such as Cyclosporine, an immunosuppressive drug.

Microbes belonging to the genus Metallosphaera oxidize sulfidic minerals. These organisms thrive at temperature extremes and are members of the archaeal phylum Crenarchaeota. Because they can employ a lithoautotrophic metabolism, energy availability likely limits their activity raising questions about how they conduct biogeochemical activity. Vesicles are membrane encapsulated structures produced by all biological lineages but using very different mechanisms. Across the Crenarchaeota, it has been proposed that a eukaryotic‐like Endosomal Sorting Complex Required for Transport system promotes formation of these structures but in response to unknown signals and for undefined purposes. To address such questions, Metallosphaera sedula vesicle formation and function were studied under lithoautotrophic conditions. Energy deprivation was evaluated and found to stimulate vesicle synthesis while energy excess repressed vesicle formation. Purified vesicles adhered rapidly to the primary copper ore, chalcopyrite, and formed compact monolayers. These vesicle monolayers catalyzed iron oxidation and solubilization of mineralized copper in a time‐dependent process. As these activities were membrane associated, their potential transfer by vesicle fusion to M. sedula cells was examined. Fluorophore‐loaded vesicles rapidly transferred fluorescence under environmentally relevant conditions. Vesicles from a related archaeal species were also capable of fusion; however, this process was species‐specific as vesicles from different species were incapable of fusion. In addition, vesicles produced by a copper‐resistant M. sedula cell line transferred copper extrusion capacity along with improved viability over mutant M. sedula cells lacking copper transport proteins. Membrane vesicles may therefore play a role in modulating energy‐related traits in geochemical environments by fusion‐mediated protein delivery. [ABSTRACT FROM AUTHOR]

Abstract Chitooligosaccharides are widely used in functional food, medicaments and agriculture. Controllable conversion of chitosan to chitooligosaccharides with desired degree of polymerization (DP) is of great value. Herein, a novel glycoside hydrolase family 46 chitosanase (BaCsn46A) was cloned and expressed from Bacillus amyloliquefaciens. BaCsn46A exhibited good enzymatic properties with high specific activity (1031.2 U/mg) under optimal hydrolysis conditions of pH 6.0 and 50 °C. BaCsn46A is an endo-type chitosanase, which could be utilized to yield abundant chitooligosaccharides. Furthermore, the preparation of high degree of polymerization chitooligosaccharides (DP 5–10) was investigated by BaCsn46A in an enzymatic reactor with a subsequent series of membranes. The maximum concentration of total chitooligosaccharides (DP 2–10) was 28.11 g/L (93.70% yield). The proportion of high degree of polymerization chitooligosaccharides (DP 5–10) occupied 56.17% (w/w) of total chitooligosaccharides. This study provided a cleaner production process for the controllable preparation of chitooligosaccharides with specific degree of polymerization. Graphical abstract Image 1 Highlights • A high-activity chitosanase from B.amyloliquefaciens (BaCsn46A) was identified. • BaCsn46A could be used for controllable producing chitooligosaccharides in membrane reactor. • High degree polymerized chitooligosaccharides was accumulated by enzyme-membrane coupling process. • This study provided a cleaner production process for controllable producing chitooligosaccharides. [ABSTRACT FROM AUTHOR]

Background: Bronchial asthma is one of the top disabling diseases in pediatrics. Limited research has been studied the association of the widely used plastic monomer bisphenol A (BPA) with childhood asthma. Objective: To compare the levels of urinary BPA in asthmatic and control children and to investigate the implication of BPA among other risk factors for the development of asthma. Subjects and methods: This case–control study included 97 children (45 asthmatic and 52 healthy controls) aged 3–8 years. Asthmatic children were diagnosed according to Global initiative for asthma (GINA) guidelines. Sociodemographic factors were assessed and urinary levels of BPA were determined in spot urine samples using high-performance liquid chromatography. The contribution of BPA among predictors for developing asthma was studied in asthmatic children. Results: Median total urinary BPA levels were significantly higher in asthmatic children than in control group (1.56 ng/mL in asthmatic children compared to 0.790 ng/mL in control group, p = 0.001). Children who had total urinary BPA levels >1.3 ng/mL were more likely to be asthmatic (odds ratio: 2.84, 95% confidence interval 1.22–6.59, p = 0.015). Multiple logistic regression analysis for predictors of asthma showed the importance of higher levels of BPA (>1.3 ng/mL) as a more significant predictor than passive smoking (p = 0.006 for BPA categories vs. p = 0.049 for passive smoking). Conclusion: Association of higher levels of urinary BPA with the diagnosis of asthma in children may indicate the potential risk of BPA exposure in the precipitation of bronchial asthma. Further clinical and biochemical research are needed to clarify the proper mechanism explaining this association. [ABSTRACT FROM AUTHOR]

Abstract Caenorhabditis elegans is a model organism for the study of different molecular, biochemical, microbial and immunity-related mechanisms. In its natural habitat, C. elegans survives by feeding microorganisms (mainly bacteria), though majorly on Escherichia coli OP50 when grown in the laboratory. Numerous bacteria are shown to influence the lifespan, behavioural responses and innate immunity of C. elegans. The secondary metabolites produced by bacteria have shown to play key role in C. elegans longevity. This behaviour provides insights for potential development of new strategies for the treatment of diseases in other species, including humans. This review explains the concept of C. elegans microbiome, different mechanisms employed in its longevity and resistance against bacterial pathogens and the effects of various bacteria (both beneficial and harmful) as well as their products on the life cycle of C. elegans. [ABSTRACT FROM AUTHOR]

The current study has covered key issues related to the adverse effects of Nitazoxanide (18mg/kg, orally once daily). Blood samples were collected on the 1st, 7th, 14th and 21th days post-treatment. The results indicated that Nitazoxanide caused the elevation of the liver enzymes ALT, AST, ALP, creatinine and urea. Obvious decline was observed in all blood parameters with a respectable decline in CAT, SOD, GPX and a significant increase in MDA. Histopathological results of liver in 7th day showed markedly dilated congested central vein surrounded by the rows and cords of hepatocytes with clean cytoplasm due to the severe fatty changes. On 14th day, the dilated congested central vein with a mild fatty change of the hepatocyte was observed. Histopathological results on 7th day, showed the dilated congested vascular space between renal tissues and heavy aggregations of chronic inflammatory cells. On 14th day, the dilated congested vascular space and the mild aggregation of chronic inflammatory cell was observed. [ABSTRACT FROM AUTHOR]

The particle support volume is crucial for simulating reactive transport with Lagrangian methods as it dictates the interaction among particles. Assuming that it is constant in space, the particle support volume can be selected by means of kernel density estimation theory, an approach that has been shown to provide accurate estimates in simple setups. However, the particle support volume should intuitively vary with the particle position and evolve with time so as to mimic the local behavior of the solute plume. In this paper, we present a new approach to select a locally optimal particle support volume in reactive transport simulations. We consider that each particle has a different support volume that can locally adapt its shape and size with time based on the nearby particle distribution. By introducing a new optimality criterion, closed‐form expressions of the particle support volume are presented under certain assumptions. In advection‐dominated transport, we propose to orient the support volume along the local velocities. Numerical simulations of solute transport in a randomly heterogeneous porous medium demonstrate that the new approach can substantially increase accuracy with a more rapid convergence to the true solution with the number of particles. The error reduction seen in local approaches is particularly important in regions with extreme (high and low) density of particles. The method is shown to be computationally efficient, displaying better results than traditional histogram or global kernel methods for the same computational effort. Key Points: We present a locally adaptive kernel density estimator for computation of chemical reactions in random walk models of solute transportThe support volume adapts to the nearby particle distribution, adjusting its size and stretching along the direction of minimum curvatureThe local approach outperforms the existing methods when estimating concentrations and reaction rates in a heterogeneous porous medium [ABSTRACT FROM AUTHOR]

Rotary ATPases are a family of enzymes that are thought of as molecular nanomotors and are classified in three types: F, A, and V-type ATPases. Two members (F and A-type) can synthesize and hydrolyze ATP, depending on the energetic needs of the cell, while the V-type enzyme exhibits only a hydrolytic activity. The overall architecture of all these enzymes is conserved and three main sectors are distinguished: a catalytic core, a rotor and a stator or peripheral stalk. The peripheral stalks of the A and V-types are highly conserved in both structure and function, however, the F-type peripheral stalks have divergent structures. Furthermore, the peripheral stalk has other roles beyond its stator function, as evidenced by several biochemical and recent structural studies. This review describes the information regarding the organization of the peripheral stalk components of F, A, and V-ATPases, highlighting the key differences between the studied enzymes, as well as the different processes in which the structure is involved. [ABSTRACT FROM AUTHOR]

The results of pigs' research of different technological groups (sows, boars-producers, repair young) with the aim of determining of biochemical indexes informativity in serum blood, including the biopolymers of connective tissue, in diagnosis of musculoskeletal systems' diseases, are represented in the article. It was identified, that the lowering in serum blood the content of chondroitinsulfates, activity of transaminases in boars, which didn't do the sledge on the phantom, can be the criteria of development of stress myopathy, weakness of ligamentous apparatus and osteochondrosis. The lowering of content in serum blood of chondroitinsulfates and the activity of aspartate aminotransferase in pigs, in which was observed the lameness symptom, can be the criteria not only of weakness of muscles, but and the declining of biosynthesis of proteoglycans of extracellular matrix of joint's hyaline cartilage, that adducts to osteochondrosis. The declining of body mass, the absence of growth and periodical tremor of pelvic limbs in pigs are going with the increasing in serum blood of the glycoproteins level, a significant decreasing of the transaminase activity, concentration of creatinine and points on the development in pigs of degenerative-dystrophic process in organism and stress myopathy without the injury of joints' cartilage structure. The using of complex of biochemical researches with the determining of transaminase activity, content of creatinine and, especially, the indexes of connective tissue state - glycoproteins and total chondroitinsulfates in the time of leading of medical examination and survey of pigs in specialized farms we are considering as a perspective. [ABSTRACT FROM AUTHOR]

By the end of the century, atmospheric CO 2 concentration ([CO 2 ] a ) could reach 800 ppm, having risen from ∼200 ppm ∼24 Myr ago. Carbon dioxide enters plant leaves through stomata that limit CO 2 diffusion and assimilation, imposing stomatal limitation ( L S ). Other factors limiting assimilation are collectively called non-stomatal limitations ( L NS ). C 4 photosynthesis concentrates CO 2 around Rubisco, typically reducing L S . C 4 -dominated savanna grasslands expanded under low [CO 2 ] a and are metastable ecosystems where the response of trees and C 4 grasses to rising [CO 2 ] a will determine shifting vegetation patterns. How L S and L NS differ between savanna trees and C 4 grasses under different [CO 2 ] a will govern the responses of CO 2 fixation and plant cover to [CO 2 ] a – but quantitative comparisons are lacking. We measured assimilation, within soil wetting–drying cycles, of three C 3 trees and three C 4 grasses grown at 200, 400 or 800 ppm [CO 2 ] a . Using assimilation–response curves, we resolved L S and L NS and show that rising [CO 2 ] a alleviated L S , particularly for the C 3 trees, but L NS was unaffected and remained substantially higher for the grasses across all [CO 2 ] a treatments. Because L NS incurs higher metabolic costs and recovery compared with L S , our findings indicate that C 4 grasses will be comparatively disadvantaged as [CO 2 ] a rises. [ABSTRACT FROM AUTHOR]

BET5 is a component of trafficking protein particle (TRAPP) which has been studied extensively in non-plant organisms where they are involved in membrane trafficking within Golgi and between Golgi and early endosomes. Recent analysis of TRAPP in different classes of organisms indicates that TRAPP function might exhibit differences among organisms. A single copy of the BET5 gene named AtBET5 was found in the Arabidopsis genome based on sequence similarity. Developmental phenotype and the underlying mechanisms have been characterized upon transcriptional knock-down lines generated by both T-DNA insertion and RNAi. Pollen grains of the T-DNA insertional line present reduced fertility and pilate exine instead of tectate exine. Perturbation of the AtBET5 expression by RNAi leads to apical meristematic organization defects and reduced fertility as well. The reduced fertility was due to the pollination barrier caused by an altered composition and structure of pollen walls. Auxin response in root tip cells is altered and there is a severe disruption in polar localization of PIN1-GFP, but to a less extent of PIN2-GFP in the root tips, which causes the apical meristematic organization defects and might also be responsible for the secretion of sporopollenin precursor or polar targeting of sporopollenin precursor transporters. [ABSTRACT FROM AUTHOR]

Ethanol is a substrate for the chemical synthesis of fatty acid ethyl esters (FAEE) during storage of virgin olive oil whose contents are officially regulated. Given the impact that the ethanol content might have on the olive oil commercialization, the level of this metabolite has been studied in an array of olive genotypes representing the diversity available in olive ( Olea europaea L.). Substantial levels of ethanol have been found in the oils of all genotypes under study. Moreover, increasing levels of alcohol dehydrogenase activity have been found during olive fruit ripening in good correspondence with the accumulation of ethanol in advanced stages of fruit maturation. The results suggest that ethanol has a ubiquitous character in the fruits of Olea europaea and, therefore, in all the oils obtained from them. Besides, their concentration seems to depend on the cultivar, ripening stage and climatology, not discarding the influence of the growing conditions. Data suggest that the application of olive oil regulation for FAEE levels should consider the presence of basal levels of ethanol in the oils, which are quite high in many cultivars. [ABSTRACT FROM AUTHOR]

Laboratory-scale bioreactors represent an important part of microbiological, biotechnological, and biochemical researches. The small volume bioreactors enable the biomass growth, extracellular metabolite production, solid-state fermentation, and biocatalytic processes in a controlled open system. Using the lab-scale bioreactors, the processes which were optimized in experiments can be scaled up to a pilot level. In turn, the manufacturing scale processes can be scaled down to study the heterogeneity of the system and its effect on the producer. This mini-review is focused on a short description of features of the most popular designs of continuous and semi-continuous bioreactors applied at the present time as well as their application area. [ABSTRACT FROM AUTHOR]

The article discusses the use of enzyme immunoassays (EIAs) for cortisol detection in fish scales. Topics include the use of water and isopropanol as wash solvents for goldfish scales, the biochemical validation of the EIA process, and statistical aspects of the determination of cortisol concentrations.

Background: The objective of this work was to isolate, optimize, and characterize protease from Burnatia enneandra which is an endemic plant found abundantly in the Far-Nord Region of Cameroon. The optimum condition to extract maximum quantity of protease from B. enneandra with respect to pH, the ratio (m/v), and agitation frequency was defined as 5.1%, 4%, and 100 rpm, respectively. Materials and Methods: The enzyme was purified using ammonium sulphate precipitation, double gel filtration chromatography sephadex G200 followed by sephadex G75 and the purified protease was further characterized. With an apparent molecular weight of 23 kDa on SDS-PAGE, the purified protease showed maximum activity at 5.1 and 40°C respectively for pH and temperature. Its activity was enhanced by metal ions such as Ca2+ and Ni2+, while Fe2+and Zn2+ showed significant inhibition. Results: B. enneandra protease activity was not affected by proteases inhibitors such as phenylmethylsulfonyl fluoride, aprotinin, and iodoacetamide but was strongly inhibited by Pepstatin A and ethylenediaminetetraacetic acid which allowed to classify this new protease as aspartic-metalloproteases. Using casein as substrate, protease from B. enneandra had a maximum rate of reaction (Vmax) and Michaelis-Menten constant (Km) of 64.935 (U/mL) and 373.941 (μg/mL), respectively. Abbreviations used: CCD: Central composite design; Km: Michaelis–Menten constant; Vmax: Maximum Velocity; PBD: Plackett–Burman design; PMSF: Phenylmethylsulfonyl floride; AAD: Absolute Average Deviation; AF: Accuracy Factor; BSA : Bovine serum albumin; BF: Bias factor; EDTA: Ethylene diamine tetraacetic acid; RSM: Response surface methodology; SDS-PAGE: Sodium dodecyl sulfate polyacrylamide gel electrophoresis. [ABSTRACT FROM AUTHOR]

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Giant vesicles (GVs) are commonly used as artificial membranes and microcompartments in biochemical and biophysical studies. The efficiency and/or yield of their production can be strongly affected by the conditions and procedures used, and thus many protocols have been developed. A reverse-phase protocol has been used to prepare liposomes for decades, and is reported to be suitable for preparing GVs. By revisiting a reverse-phase (W/O/W emulsification) mechanism, in this study we verified how simply and efficiently GVs could be generated using the following alternative method. First, phospholipid/diethyl ether was mixed with an aqueous solution containing sucrose to form an emulsion, and the mixture was centrifuged. The resulting GVs together with tubular and sheet aggregates in the lower water phases could be purified by a second centrifugation after the addition of a glucose aqueous solution. This “reverse-phase/centrifugation” method provided a large amount of GVs of ∼20 μm in diameter from egg phosphatidylcholine as well as multiple lipid components. Spherical GVs were obtained in the presence of physiological salt concentrations (phosphate-buffered saline, PBS) when phosphatidylglycerol was included. The appearance of microdomains on the vesicle membranes may indicate that giant unilamellar vesicles (GUVs) can form through this process. [ABSTRACT FROM AUTHOR]

Selective modification of native proteins in live cells is one of the central challenges in recent chemical biology. As a unique bioorthogonal approach, ligand-directed chemistry recently emerged, but the slow kinetics limits its scope. Here we successfully overcome this obstacle using N-acyl-N-alkyl sulfonamide as a reactive group. Quantitative kinetic analyses reveal that ligand-directed N-acyl-N-alkyl sulfonamide chemistry allows for rapid modification of a lysine residue proximal to the ligand binding site of a target protein, with a rate constant of ~104M-1 s-1, comparable to the fastest bioorthogonal chemistry. Despite some off-target reactions, this method can selectively label both intracellular and membrane-bound endogenous proteins. Moreover, the unique reactivity of N-acyl-N-alkyl sulfonamide enables the rational design of a lysine-targeted covalent inhibitor that shows durable suppression of the activity of Hsp90 in cancer cells. This work provides possibilities to extend the covalent inhibition approach that is currently being reassessed in drug discovery. [ABSTRACT FROM AUTHOR]