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The aim of the work was to study serum biochemical parameters and qualitative composition of milk of cows with various genotypes of the LEP gene. The research was conducted in 148 Holstein cow-heifers of Integrated Agricultural Production Centre “Stud farm named after Lenin” of the Atninsky district of the Republic of Tatarstan. Cattle genotyping was conducted by the AC-PCR method at the laboratory of the Department of Agrobiological Research of Tatar Research Institute of Agriculture of FRC KazanSC of RAS. The findings of allele and genotype calling of the LEP gene showed that the population under study is polymorphic and differs in genetic biodiversity. The study of serum biochemical parameters of experimental animals testified that the level of triglycerides, cholesterol and lipase is meaningfully lower in the blood of animals with the TT genotype. This indicates the rate of lipid metabolism in their body. During the analysis of milk productivity and parameters of the qualitative composition of milk, it was found that cow-heifers with the TT genotype of the LEP gene were superior to animals with other LEP gene genotypes in terms of milk yield for standard lactation (305 days), fat mass fraction, milk fat yield, milk fat and milk protein yield in total. Thus, it may be concluded that the TT genotype of the LEP gene has a positive effect on the economically important characters of cattle, which can be used in breeding in the future.

The aim of the work was to study the traits of dairy productivity of Holstein heifers with different genotypes of the paraoxonase-1 (PON1) gene. The research was conducted in 148 animals of Integrated Agricultural Production Centre “Stud farm named after Lenin” of Atninsky district of the Republic of Tatarstan. Genotyping of cattle was carried out by the PCR-RFLP method at the laboratory of the Department of Agrobiological Research of Tatar Scientific Research Institute of Agriculture, FRC Kazan Scientific Center, Russian Academy of Sciences. The results of allele and genotype calling of the PON1 gene showed that the study population is polymorphic and differs in genetic biodiversity. During the analysis of daity productivity, qualitative composition of milk and lactational activity, it was found that cow-heifers with the GG genotype of the PON1 gene were superior to animals with other genotypes in all the test parameters. Thus, it follows that the GG genotype of the PON1 gene has a positive effect on the economic characters of cattle, which can be used in breeding in the future.

The research presents the findings of DNA testing of allelic polymorphism by the PCR-RFLP method of the SCD1 gene and the relationship of genotypes with the milk fatty acid composition of Holstein cows of Tatarstan population. The research was conducted among 172 Holstein cows at the Integrated Agricultural Production Centre “Stud farm named after Lenin” in Atninsky district of the Republic of Tatarstan in 2017–2018. All genotypes of the SCD1 gene were identified through the research. The milk yield test showed that the maximum content of the mass fraction of fat was in animals with the TT genotype. The significant difference between the content of the mass fraction of fat in milk in individuals by the locus of the SCD1-Fsp4H I gene was: TT to CC – 0.32 % (p < 0.05) and TT to TC – 0.40 % (p < 0.01). The results of chromatography indicate the balance of the milk fatty acid composition of cows with the TT genotype and, as a consequence, its positive effect on the human body. Cows with a homozygous TT genotype are characterized by the optimum ratio of fatty acids in milk fat. The maximum value of the oxygen desaturation index is also observed in animals with the TT genotype by the SCD1 gene.

The research presents the findings of DNA testing of allelic polymorphism by the AC-PCR method of the LEP gene. The research was conducted among 172 Holstein cows at Integrated Agricultural Production Centre “Stud farm named after Lenin” in Atninsky district of the Republic of Tatarstan in 2017–2018. All genotypes of the LEP gene were identified through the research. Associations of the leptin gene polymorphism with dynamics of milk production during three lactations of Holstein cows were established. The best indicators for all three lactations were found in a group of animals with the TT genotype of the LEP gene. These individuals are characterized by increased milk yield, a high yield index, and tend to increase the average daily milk yield during three lactations. These individuals are characterized by increased milk yield, a high milk yield index, and tend to increase the average daily milk yield during three lactations.

The study presents the results obtained in DNA testing of allelic polymorphism by PCR-RFLP based methods for the leptin and stearoyl-coenzyme A desaturase genes and the interaction of their complex genotypes on the milk productivity indicators of Holstein heifers of Tatarstan population. The study was carried out among 471 Holstein cow-heifers by Integrated Agricultural Production Centre “Stud farm named after Lenin” of Atninsky district of the Republic of Tatarstan in 2016–2018. All complex LEP/SCD1 genotypes were identified through the study. The maximum frequency was observed in the combination of heterozygous genotypes LEPTCSCD1TC 149 animals (31.5 %). Milk productivity test, based on the complex genotypes LEP and SCD1, showed that a significantly high level of productivity for 305 days of lactation was 7314.4 kg, and in heifers with a complex genotype LEPTTSCD1CC was minimal (6337.4 kg) in comparison with indicators of milk yield of heifers with other complex genotypes. According to the content of the mass fraction of fat, reliably the best indicators were established in a subpopulation of animals with a complex TT/TC genotype 3.87 %. The content of the mass fraction of protein was maximal for animals with a complex CC/CC genotype.

Air- and sun-dried raisins from Thompson Seedless (TS) grapes were analyzed under GC/MS to evaluate fatty acids (FAs) and their derived volatile compounds, coming from unsaturated fatty acids oxidation. A total of 16 FAs were identified in TS raisins, including 10 saturated fatty acids (SFAs) and 6 unsaturated fatty acids (USFAs). The contents of C18:0, C15:0, and C16:0 among SFAs and C18:3, C18:2 and C18:1 in USFAs were significantly higher. Furthermore, USFAs such as C16:1 and C20:1 were only identified in air-dried raisins. The principal component analysis showed the increased content of FAs and FA-derived compounds were in air-dried and sun-dried raisins, respectively. Among FA-derived compounds, 2-pentyl furan, 3-octen-2-one, 1-hexanol and heptanoic acid were more potent. This study shows that air-drying is more favorable for the production of fatty acids (SFAs and USFAs), whereas sun-drying is more advantageous in terms of fatty acid-derived volatiles.

ABSTRACT Bitter gourd is of great importance due to its usage against the treatment of numerous ailments in human beings. A comprehensive survey at four localities of Southern Punjab, Pakistan was carried out to determine the severity of Myrothecium leaf spot. Maximum disease severity was at C1 (Chak 11/NP) and least at C2 (Kot Mehtab). Among isolated species Myrothecium roridum was found more prevalent and pathogenic as compared to M. verrucaria. Antifungal activity using solvent extracts of five medicinal plants (Mangifera indica, Melia azedarach, Nicotiana tabacum, Moringa oleifera and Eucalyptus globosum) were evaluated against isolated species by agar well diffusion method at various concentrations (0.01, 0.10, 1.0 and 10.0 µg / mL). N. tabacum revealed maximum zone size (13.40 mm and 8.28 mm) with ethanol and chloroform solvents respectively followed by M. azedarach (9.00mm and 6.48mm). However, least inhibition was observed with ethanol and chloroform extracts of E. globosum (6.04mm and 3.88mm zone size respectively). Ethanol extracts showed highest activity when compared to chloroform extracts. Qualitative phytochemical analysis showed that all the selected plants are rich in chemical compounds such as alkaloids, terpenoids, flavonoids and phenols whereas Saponins was only present in N. tabacum while absent in rest of the extracts.

Osteopathia Striata with Cranial Sclerosis (OSCS) is a rare genetic condition primarily characterized by metaphyseal striations of long bones, bone sclerosis, macrocephaly, and other congenital anomalies. It is caused by pathogenic variants in AMER1, a tumor suppressor and a WNT signaling repressor gene with key roles in tissue regeneration, neurodevelopment, tumorigenesis, and other developmental processes. While somatic AMER1 pathogenic variants have frequently been identified in several tumor types (e.g., Wilms tumor and colorectal cancer), whether OSCS (i.e., with AMER1 germline variants) is a tumor predisposition syndrome is not clear, with only nine cases reported with tumors. We here report the first case of neuroblastoma diagnosed in a male child with OSCS, review all previously reported tumors diagnosed in individuals with OSCS, and discuss potential tumorigenic mechanisms of AMER1. Our report adds to the accumulating evidence suggesting OSCS is a tumor predisposition condition, highlighting the importance of maintaining a high index of suspicion for the associated tumors when evaluating patients with OSCS. Importantly, Wilms tumor stands out as the most commonly observed tumor in OSCS patients, underscoring the need for regular surveillance., (© 2024 Wiley Periodicals LLC.)

Purpose: Dominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12., Methods: We used in vitro transcriptional assays and in silico structural analysis to assess the functional relevance of RARB variants in affecting the normal response to retinoids., Results: We found that all RARB variants tested in our assays exhibited either a gain-of-function or a loss-of-function activity. Loss-of-function variants disrupted RARB function through a dominant-negative effect, possibly by disrupting ligand binding and/or coactivators' recruitment. By reviewing clinical data from 52 affected individuals, we found that disruption of RARB is associated with a more variable phenotype than initially suspected, with the absence in some individuals of cardinal features of MCOPS12, such as developmental eye anomaly or motor impairment., Conclusion: Our study indicates that pathogenic variants in RARB are functionally heterogeneous and associated with extensive clinical heterogeneity., Competing Interests: Conflict of Interest J.R.L. owns stock in 23andMe and is a paid consultant for Genome International. All other authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Nicolaides-Baraitser syndrome (NCBRS) is a neurodevelopmental disorder caused by pathogenic sequence variants in SMARCA2 which encodes the catalytic component of the chromatin remodeling BAF complex. Pathogenic variants in genes that encode epigenetic regulators have been associated with genome-wide changes in DNA methylation (DNAm) in affected individuals termed DNAm signatures., Methods: Genome-wide DNAm was assessed in whole-blood samples from the individuals with pathogenic SMARCA2 variants and NCBRS diagnosis (n = 8) compared to neurotypical controls (n = 23) using the Illumina MethylationEPIC array. Differential methylated CpGs between groups (DNAm signature) were identified and used to generate a model enabling classification variants of uncertain significance (VUS; n = 9) in SMARCA2 as "pathogenic" or "benign". A validation cohort of NCBRS cases (n = 8) and controls (n = 96) demonstrated 100% model sensitivity and specificity., Results: We identified a DNAm signature of 429 differentially methylated CpG sites in individuals with NCBRS. The genes to which these CpG sites map are involved in cell differentiation, calcium signaling, and neuronal function consistent with NCBRS pathophysiology. DNAm model classifications of VUS were concordant with the clinical phenotype; those within the SMARCA2 ATPase/helicase domain classified as "pathogenic". A patient with a mild neurodevelopmental NCBRS phenotype and a VUS distal to the ATPase/helicase domain did not score as pathogenic, clustering away from cases and controls. She demonstrated an intermediate DNAm profile consisting of one subset of signature CpGs with methylation levels characteristic of controls and another characteristic of NCBRS cases; each mapped to genes with ontologies consistent with the patient's unique clinical presentation., Conclusions: Here we find that a DNAm signature of SMARCA2 pathogenic variants in NCBRS maps to CpGs relevant to disorder pathophysiology, classifies VUS, and is sensitive to the position of the variant in SMARCA2. The patient with an intermediate model score demonstrating a unique genotype-epigenotype-phenotype correlation underscores the potential utility of this signature as a functionally relevant VUS classification system scalable beyond binary "benign" versus "pathogenic" scoring. This is a novel feature of DNAm signatures that could enable phenotypic predictions from genotype data. Our findings also demonstrate that DNAm signatures can be domain-specific, highlighting the precision with which they can reflect genotypic variation.

Deleterious variants in the same gene present in two or more families with overlapping clinical features provide convincing evidence of a disease-gene association; this can be a challenge in the study of ultrarare diseases. To facilitate the identification of additional families, several groups have created "matching" platforms. We describe four individuals from three unrelated families "matched" by GeneMatcher and MatchMakerExchange. Individuals had microcephaly, developmental delay, epilepsy, and recessive mutations in TRIT1. A single homozygous mutation in TRIT1 associated with similar features had previously been reported in one family. The identification of these individuals provides additional evidence to support TRIT1 as the disease-causing gene and interprets the variants as "pathogenic." TRIT1 functions to modify mitochondrial tRNAs and is necessary for protein translation. We show that dysfunctional TRIT1 results in decreased levels of select mitochondrial proteins. Our findings confirm the TRIT1 disease association and advance the phenotypic and molecular understanding of this disorder., (© 2017 Wiley Periodicals, Inc.)

In anaesthetized white outbred male rats we investigated the change of respiratory mechanoreceptors sensitivity to morphine and phenibut. Bilateral transection of the vagus nerves causes a severely slowdown of respiratory rate in 30 minutes after the systemic administration of morphine, however after administration of phenibut the respiratory rate and other respiration parameters have not changed significantly. It means that the activation of opioid receptors by morphine does not significantly affect the function of the respiratory mechanoreceptor control loop, and transection of the vagus nerves on this background increases the probability of respiratory rhythm disorders. Activation of GABAergic system by phenibut significantly weakened the impact of the regulating contour of the respiratory mechanoreceptor on breathing parameters, up to effect of "central vagotomy": that is, to no changes in respiratory parameters after cutting the vagus nerves.

Neurodevelopmental disorders (NDDs) affect more than 3% of children and are attributable to single-gene mutations at more than 1000 loci. Traditional methods yield molecular diagnoses in less than one-half of children with NDD. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) can enable diagnosis of NDD, but their clinical and cost-effectiveness are unknown. One hundred families with 119 children affected by NDD received diagnostic WGS and/or WES of parent-child trios, wherein the sequencing approach was guided by acuity of illness. Forty-five percent received molecular diagnoses. An accelerated sequencing modality, rapid WGS, yielded diagnoses in 73% of families with acutely ill children (11 of 15). Forty percent of families with children with nonacute NDD, followed in ambulatory care clinics (34 of 85), received diagnoses: 33 by WES and 1 by staged WES then WGS. The cost of prior negative tests in the nonacute patients was $19,100 per family, suggesting sequencing to be cost-effective at up to $7640 per family. A change in clinical care or impression of the pathophysiology was reported in 49% of newly diagnosed families. If WES or WGS had been performed at symptom onset, genomic diagnoses may have been made 77 months earlier than occurred in this study. It is suggested that initial diagnostic evaluation of children with NDD should include trio WGS or WES, with extension of accelerated sequencing modalities to high-acuity patients., (Copyright © 2014, American Association for the Advancement of Science.)

Aim: To evaluate the fecal level of neutrophil gelatinase-associated lipocalin (NGAL) in different behavior of inflammatory bowel disease (IBD)., Materials and Methods: We prospectively included 41 people into the study--30 patients with active IBD and 11 healthy volunteers. The concentration of NGAL in faeces was determined by enzyme immunoassay method., Results: Fecal NGAL level was increased in both UC and CD: in CD--5924.27 ± 2067.6 ng/ml (p < 0.05), in UC--5826.09 ± 891.8 ng/ml (p < 0.05) NGAL levels were higher than in the control group (658.8 ± 237.7 ng/ml). Maximal changes were seen in colonic involvement. NGAL levels increased with the increasing extension of lesion in UC (p < 0.05), while in CD concentration was higher in colitis than in ileitis and ileocolitis (p > 0.05) . NGAL level increased with severity of CD (p < 0.05), in patients with UC difference was not significant. In UC NGAL level was increased with increasing extension of lesions (p < 0.05), in CD this pattern was not marked. Correlation NGAL level with some clinical and laboratory indicators in CD was established. Sensitivity of test in evaluation of exacerbation of IBD was 80%, specificity--90.9%, area under the ROC curve (AUC)--0.9, positive predictive value--96%, negative predictive value--62.5%; positive likelihood ratio--8.8 and negative likelihood ratio--0.22., Conclusions: The fecal concentration of NGAL significantly increased during IBD. With increasing severity and activity of disease level ofNGAL was increased in CD (p < 0.05). Lipocalin-2 values was higher with the increasing extension of lesions in UC (p < 0.05). There has been established the high diagnostic value of the detection of fecal NGAL as a marker of the active phase of IBD.

The authors describe a case of malignant vulvar soft tissue myoepithelioma in a 41-year-old woman. Microscopically, epithelioid and spindle cells were located in the myxoid stroma. Tumor cells co-expressed pan-cytokeratin, EMA, and cytokeratin 18, vimentin, protein S100, and smooth muscle actin. The tumor was found to have a very high proliferative activity (Ki-67 was as high as 80%). The disease was fulminant with a fatal outcome 4 months after the occurrence of the first symptoms of the tumor.

The specific activity of serine, metal dependent and thiolic Ig proteases in the coprofiltrates of children with manifestations of intestinal dysbacteriosis was determined by the enzyme immunoassay. 56 children with pronounced symptoms of intestinal disorders (37 children aged up to 1 year and 19 children over 1 year) were examined. A group of 25 clinically healthy children was used as control. Simultaneously with protease activity of coprofiltrates, there was detected the level of Ig-degrading activity of the opportunistic bacteria islolates of different taxonomic groups from feces of children with dysbacteriosis of different severity (as determined by the classical bacteriological method). The evaluation of the Ig-proteolytic activity of fecal supernatants, associated with the presence of serine, metal-dependent and thiolic proteases in the intestine, as well as detection of such proteases in microbial isolates, seems to be highly important for the diagnosis of intestinal disorders in children and is recommended for screening of intestinal dysbacteriosis.

Biological effects of ozone on the lipid peroxidation (LPO)--antioxidation system was studied in blood serum of patients with various forms of chronic bronchitis. Breathing ozone was shown to intensify LPO processes and lead to a more considerable deviation of the parameters of non-enzymatic but not enzymatic antioxidants in patients.

The enzyme immunoassay system (EIA) for differentiation of antibodies in therapeutic heterogeneous antitoxic serum and antibodies to Corynebacterium diphtheriae toxigenic strains in patients and carriers was developed. The use of EIA permitted the dynamic evaluation of the characteristics of humoral antitoxic and antibacterial immune response in 50 patients with the localized and disseminated forms of stomatopharyngeal diphtheria and 14 "healthy" carriers of toxigenic C. diphtheriae. As revealed in this study, the symptoms of the disease in patients with disseminated forms of stomatopharyngeal diphtheria developed in the presence of statistically significant low quantitative values of antitoxic and antibacterial antibodies to C. diphtheriae antigens. In the group of patients with the localized forms of the disease the initially low level of antitoxic antibodies was detected with the concentration of antibacterial antibodies remaining unchanged. During the period of convalescence the levels of antitoxic antibodies in both groups reached those of healthy persons. In case of localized forms of the disease the level of antibacterial antibodies decreased as compared with healthy persons, starting from the second week of the disease. The period of convalescence in the disseminated forms was characterized by the low concentration of antibacterial antibodies. Carrier state was formed in the presence of high levels of antitoxic antibodies and significantly low levels of antibacterial ones.

Hemosplenoperfusion (HSP) through the donor porcine spleen was used in complex treatment of 75 patients aged from 16 to 75 with pyo-septic complications of diseases and traumas of the abdominal cavity. The influence of HSP on the state of humoral immunity was estimated by the level of antibacterial antibodies to the antigens of E. coli, Ps. aeruginosa, Pr. mirabilis, St. aureus, Bact. fragilis, Bact. bifidum and antiendotoxin antibodies to glycolipid S. Minnesota RE 595, general cortical part of the lipopolysaccharide of Gram-negative bacteria. The use of HPS promoted the resolving of endogenous intoxication, elevation of the strain of humoral antibacterial immunity and is characterized by a reliable increase of the level of antibacterial antibodies in the dynamics of treatment.

Data on lipid metabolism in 109 cases of endometrial carcinoma and 33 patients in control are presented. Relevant disorders were detected in 72.5% of the study group [stage I obesity--23 (21.1%); II--29 (26.6%); III--25 (22.9%); IV--2 (1.9%)] which was 1.5 times the mean level in controls (51.5%). The abdominal pattern of obesity was predominant (77.7%). Symptoms of cardiosclerosis were identified in 93 patients with endometrial tumors (85.3%), 93.5% of the latter group presenting with concomitant hyperglyceridemia. In 68.8% of endometrial carcinoma patients, incidence of arterial hypertension was higher than in controls (54.5%). Lipoproteins played a major role in dyslipoproteid pathogenesis involved in obesity and high blood pressure. A study of the insertion-deletion (I/D) polymorphism of apolipoprotein AI genes showed two deletion alleles (DD--6%) and one heterozygote (ID--3%) in control group; no deletion alleles were identified in endometrial tumor patients (0.1 (p(0.05). An investigation of the I/D polymorphism of angiotensin-converting enzyme genes identified deletion homozygotes in 30, insertion homozygotes (II)--27, and heterozygotes--41% (control). In endometrial cancer group, the deletion allele distribution was: DD--29; II--28 and ID--45%. Deletion allele frequency in control was 0.485 while in endometrial carcinoma--0.484 (p(0.05), i.e. with out significant difference.

The state of antibacterial humoral immunity in young children with acute bronchitis, acute obstructive bronchitis and bronchial asthma at the period of exacerbation has been shown with the use of the enzyme immunoassay. The concentration of antibodies to endotoxin positively correlates with the severity of clinical manifestations of the endogenic intoxication of the body. As the inflammatory process in the bronchial tree increases, the spectrum bacterial agents to which elevated concentrations of specific antibodies can be detected becomes wider, and this finds its maximum reflection in bronchial asthma.

Plasma level of fibronectin and its biological activity were assessed in 33 females suffering ovarian cancer; 13 cases had stage I or II disease whereas 20-stage III or IV tumors. Fibronectin level, as measured by immunoelectrophoresis, proved normal. This was accompanied by a statistically significant (p less than 0.05) rise in gelatin--binding activity of the glycoprotein in patients with stage I-II cancer which accounted for an increased value registered for the entire group studied. However, no such rise was observed in cases of stage III and IV disease.

Hemocoagulation system state and plasmatic fibronectin level at experimental associated craniocerebral trauma have been studied at 29 mongrel white rats (males). It has been revealed that associated craniocerebral trauma, complicated by disseminated intravascular blood coagulation, is accompanied by reliable decrease of plasmatic fibronectin concentration. It has been established that hypofibronectinemia has temporal coincidence with the reaction of hemocoagulation system on trauma and direct quantitative correlation with the decrease of coagulating fibrinogen level and fibrinolytic system activation.

The levels of plasma fibronectin (FN) were investigated in patients during heart surgery using artificial circulation. Plasma FN levels were assessed by electroimmunoassay (rocket immunoelectrophoresis) and bioassay (aggregation of gelatin-coated microparticles). The application of gelatinol in hemodilution++ composition led to the depletion of bioactive Fn from 140 to 0 micrograms/ml, whereas immunoreactive Fn levels were slightly elevated. The in vitro experiments have shown that gelatinol inhibits the aggregation of gelatinol-coated microparticles and chemiluminiscence of neutrophils, stimulated by gelatin-coated particles. Gelatinol elimination from hemodilution++ composition resulted in the reduction of postoperative mortality and accelerated tissue reparation.

Effect of some fibronectin preparations on luminol-dependent chemiluminescence of neutrophils was studied. These fibronectin preparations were obtained after heat denaturation and tryptic digestion. Native fibronectin cause aggregation of gelatin-coated particles and dose-dependent promotion of chemiluminescence of neutrophils, while the rate of these reactions was distinctly decreased if the heat denaturated preparations of fibronectin were used. Structural integrity of fibronectin molecule appears to be responsible for promotion of the neutrophil chemiluminescence.

As many as 89 infants with acute respiratory viral infections (ARVI) were examined to establish a decrease of the levels of immunochemical and bioactive fibronectin, seen during the marked clinical manifestations of the disease. Changes in the level of fibronectin in the course of ARVI are reversible in nature, being related to the intensity of the general toxic manifestations. Measurements of bioactive fibronectin are most informative for assessing the degree of intoxication. Profound and long-term reduction of the level of bioactive fibronectin may be seen in grave focal confluent and polysegmental pneumonia.

The suggested method is based on the ability of fibronectin intact molecules to agglutinate gelatin-coated particles. Gelatin-coated particles have been prepared with the use of specially treated Staphylococcus epidermidis cells. The concentration of biologically active fibronectin has been measured using laser nephelometry and agglutination test in microtitre plates. The accuracy of the test is 4 mg/ml (laser nephelometer) and 0.1 mg/ml (agglutination test).