Molecular detection of Burkholderia mallei in different geographic regions of Brazil.

Glanders is a contagious disease of equids caused by the Gram-negative bacterium Burkholderia mallei. In Brazil, the disease is considered to be reemerging and has been expanding, with records of equids with positive serology in most of the federative units. However, there are few reports describing the genotypic detection of the agent. This study demonstrated the detection of B. mallei by species-specific PCR directly from tissues or from bacterial cultures, followed by amplicon sequencing in equids (equines, mules, and asinines) with positive serology for glanders in all five geographic regions of Brazil. The molecular evidence of B. mallei infection in serologically positive equids in this study expands the possibility of strain isolation and the conduction of epidemiological characterizations based on molecular information. The microbiological detection of B. mallei in cultures from nasal and palate swabs, even in equids without clinical manifestations, raises the possibility of environmental elimination of the agent.

Fused Pyrroles in Cholestane and Norcholestane Side Chains: Acaricidal and Plant Growth-Promoting Effects.

Herein, we describe the synthesis and characterization of fused pyrroles in cholestane and norcholestane side chains derived from kryptogenin and diosgenin, respectively. Both conventional and microwave heating techniques were used to synthesize the steroidal pyrroles from primary amines, with the microwave method producing the highest yields. In particular, the norcholestane pyrroles were tested as acaricides against the two-spotted spider mite (Tetranychus urticae Koch) under laboratory conditions and as plant growth promoters on habanero pepper (Capsicum chinense Jacq) under greenhouse conditions.

Augmentation of the Esophageal Sphincter Using LINX.

Gastroesophageal reflux disease (GERD) is the retrograde flow of gastric contents into the distal esophagus and may be treated medically or surgically. Magnetic sphincter augmentation surgery using LINX has recently demonstrated comparable results to Nissen fundoplication. We aimed to evaluate preoperative patient risk factors that were associated with LINX removal rates or postoperative EGD with dilation rates (POEGDD). This is a single institution retrospective review of patients undergoing LINX between 2015 and 2021. One hundred and twelve patients were reviewed, 106 included within the study; those excluded had prior foregut surgery or device fracture. Variables including age, sex, BMI, size of device, DeMeester score, manometry, GERD Health-Related Quality of Life (GERD HRQL) questionnaires, POEGDD, and removal rates were recorded. Comparing removal and dilation status, the chi-square or Fisher's exact test and the Mann-Whitney U test were used to analyze categorical and continuous variables, respectively. A P < .05 was considered to be statistically significant. Eleven LINX devices were removed (10%); of these, 9 (81%) underwent POEGDD (P = .0023). There was no difference in DeMeester scores, size of device, or BMI in patients requiring LINX removal compared to those not removed or POEGDD rates. Patients who required LINX removal had higher GERD HRQL scores both preoperatively (median 34 vs 28) and postoperatively at all visits compared to those patients who did not undergo removal (P = .032). Manometry and DeMeester scores were not associated with LINX removal suggesting a less invasive GERD HRQL questionnaire may be a better predictor of patients who will succeed with LINX surgery.

Microwave-enhanced synthesis of 26-amino-22-oxocholestanes and their cytotoxic activity.

The synthesis of a series of 26-amino-22-oxocholestanes derived from diosgenin was accomplished via the substitution of an iodine atom at C-26 by primary and secondary amines. The reactions were conducted in refluxing acetonitrile and through microwave-assisted heating. The latter shows significant improvements in terms of reaction times going from hours to a few minutes or even seconds for completion. Only one of the selected amines, 4-aminourazole, did not yield the substitution product and the imine formation pathway was investigated instead, achieving the 26-iminourazole-22-oxocholestane. All the final products have been characterized and the cytotoxic activity of three of them has been evaluated in SiHa, MCF-7 and MDA tumor cell lines by the sulforhodamine B assay.

Stereoselective synthesis of (26R)-26-hydroxydiosgenin and its effect on the regulation of rat ovarian function.

The stereoselective cyclization of a C-16 acetylated 22,26-dioxocholestene derivative to give the spirostane E and F rings, under alkaline conditions, yields exclusively the (26R)-26-hydroxydiosgenin. Both experimental and computational data support the formation of a single diastereoisomer. The effect of diosgenin and (26R)-26-hydroxydiosgenin on rat ovary is also investigated.

Splicing and cancer: Challenges and opportunities.

Cancer arises from alterations in several metabolic processes affecting proliferation, growth, replication and death of cells. A fundamental challenge in the study of cancer biology is to uncover molecular mechanisms that lead to malignant cellular transformation. Recent genomic analyses revealed that many molecular alterations observed in cancers come from modifications in the splicing process, including mutations in pre-mRNA regulatory sequences, mutations in spliceosome components, and altered ratio of specific splicing regulators. While alterations in splice site preferences might generate alternative isoforms enabling different biological functions, these might also be responsible for nonfunctional isoforms that can eventually cause dysregulation in cellular processes. Molecular characteristics of regulatory sequences and proteins might also be important prognostic tools revealing a cancer-specific splicing pattern and linking splicing control to cancer development. The connection between cancer biology and splicing regulation is of primary importance to understand the mechanisms leading to disease and also to improve development of therapeutic approaches. Splicing modulation is being explored in new anti-cancer therapies and further investigation of targeted splicing factors is critical for the success of these strategies. This article is categorized under: RNA Processing > Splicing Mechanisms RNA-Based Catalysis > RNA Catalysis in Splicing and Translation RNA Processing > Splicing Regulation/Alternative Splicing RNA in Disease and Development > RNA in Disease.

Revisiting the Formation Mechanism of 1,3,4-Oxadiazole-2(3 H)-ones from Hydrazonyl Chloride and Carbon Dioxide.

The reaction mechanism for the synthesis of 1,3,4-oxadiazole-2(3 H)-ones from hydrazonyl chloride and CO2 in the presence of CsF/18-crown-6 and toluene, is revisited via density functional theory computations. Although this reaction was earlier classified as a 1,3-dipolar cycloaddition, we found some competing pathways involved therein. The mechanisms including the (F-CO2)- anion and the nitrile imine intermediate are some options. The dimerization of nitrile imine is another competing mechanism in this reaction. Our results show that the most favorable mechanism proceeds via a stepwise pathway without involving any nitrile imine intermediate or the (F-CO2)- anion. The F- anion, resulting from the formation of a complex between 18-crown-6 and Cs+ cation, deprotonates the nitrile imine precursor easily, which acts then as a nucleophilic anion, enhancing the reactivity of CO2 toward it. The mechanism for the reaction with COS, an isoelectronic analogue of CO2, is also explored.

Both Dietary Fatty Acids and Those Present in the Cecotrophs Contribute to the Distinctive Chemical Characteristics of New Zealand Rabbit Milk Fat.

The relationship between the fatty acid (FA) profile of cecotrophs and that of the milk fat was evaluated in nine multiparous New Zealand does during the first 12 days of lactation. Milk samples were obtained manually on days 6, 8, 10, and 12 postpartum and cecotrophs and feces were collected on days 7, 9, and 11 postpartum. The FA profiles of feed, milk, cecotrophs, and feces were determined using gas chromatography. The principal FA found in rabbits' milk were 8:0, 10:0, 16:0, 18:1 cis-9, and 18:2 n-6. Bacteria-derived FA found in the milk fat included branched FA from 14 to 16 carbons, and 18:1 trans. Two isomers of conjugated linoleic acid (CLA) were also present, namely cis-9,trans-11 (0.09 ± 0.006 mol%) and trans-10,cis-12 (0.06 ± 0.01 mol%). The content of total FA in the cecotrophs was the 1.10 ± 0.08 mg/100 mg freeze-dried sample, with 2.50 ± 0.83 mol% 18:1 trans-11. Significant correlations between cecotroph and milk FA profiles were found for numerous FA, and those with correlation coefficients greater than 0.90 were 12:0, 14:0, 15:0, 16:0, 18:0, 18:1 trans-6/8, 18:1 trans-9, 18:1 cis-9, 18:2 n-6, 18:3 n-3, 20:1 cis-9, 20:2 n-6, and 22:0. Cecum biohydrogenation processes were evident based on the greater content of saturated FA (p = 0.008) found (54.46 ± 4.37 mol%) in the cecotrophs relative to that in feces (43.08 ± 4.37 mol%). Under conditions of the present study, the milk FA profile was influenced by the FA profile of diet and the cecotrophs consumed by lactating does.

Association between Pro12Ala, Pvull, Avall, Sstl and ADIPOQ single-nucleotide polymorphisms with lipid and glycemic profiles of patients with Berardinelli-Seip syndrome.

BACKGROUND/AIMS: Berardinelli-Seip syndrome (BSS) is a recessive autosomal genetic disorder characterized by the near loss of adipose tissue with disturbance in lipid metabolism. METHODS: Biochemical and hormonal parameters and Pro12Ala, Pvull, Avall, Sstl and ADIPOQ polymorphisms in 22 patients with BSS were analyzed and examined for a possible association with lipid profiles. RESULTS: Parental consanguinity, insulin resistance and diabetes mellitus were observed in 63.6, 81.8 and 59.1% of patients, respectively. All individuals presented high triglyceride levels, and 68.1% of patients showed high cholesterol levels. The Pro/Pro genotype of the Pro12Ala polymorphism of the PPARγ2 gene was found in 86.3% of patients; the Ala/Ala variant was not observed in any patient. The PvuII polymorphism of the LPL gene showed a frequency of 50% for the P1P2 variant. The AvaII polymorphism of the LDLR gene showed a similar frequency of 40.9% for both CT and TT variants. The S1S1 genotype of the Sstl polymorphism of the APOC3 gene had a frequency of 86.3%. The CC allele of the ADIPOQ polymorphism of the adiponectin gene was found in 54.6% of patients. CONCLUSIONS: No association was found between lipid parameters and the relevant Pvull, Avall and Sstl polymorphisms. However, we did observe an association of the Pro12Ala and ADIPOQ polymorphisms with higher lipid levels, suggesting a close relationship between these factors.

Family names and the length of the y chromosome in Brazilian blacks

A variabilidade das regiöes heterocromática e eucromática do cromossomo Y humano foi estudada, pelo emprego de uma metodologia da análise quantitativa e através de medidas densitométricas, em 60 negros normais e näo aparentados (30 com sobrenomes de conotaçäo religiosa e 30 sem sobrenome de conotaçäo religiosa) de Salvador, Bahia. Trinta indivíduos caucasóides de origem européia, normais e näo aparentados, de Curitiba, Paraná, constituíram o grupo controle. A regiäo heterocromática e o tamanho total do cromossomo Y foram, em média, maiores nos caucasóides do que nos negros com e sem sobrenomes de conotaçäo religiosa, sendo as médias observadas nestes últimos intermediárias entre as dos caucasóides e dos negros com sobrenome de conotaçäo religiosa. Estes dados estäo de acordo com os de publicaçöes anteriores, que demostram que nos negros com sobrenomes de conotaçäo religiosa há mais ancestrais negros do que naqueles sem sobrenomes de conotaçäo religiosa.