Cereal type and conditioning temperature altered protein and carbohydrate molecular structure, nutrient retention and performance in broilers fed pellet diets during starter and grower period.

1. Effects of cereal type and conditioning temperature (CT) on protein and carbohydrate (CHO) molecular structures, nutrient retention, carcass and blood characteristics, caecal microbial population and growth criteria of broilers fed pellet diet were evaluated for a total period of 35 d.2. In total, 336-day-old Cobb 500 broiler chicks were randomly allotted into a 2 × 2 factorial arrangement with two different cereal types (maize or wheat) processed in two different temperatures (CT; 68°C or 90°C) with seven pen replicates containing 12 birds each.3. Chicks fed the maize-based diets significantly gained higher body weight (BW) and lower feed conversion ratio (FCR) in comparison to the chicks fed wheat-based diets during the whole grow-out period (p < 0.01). Overall, the highest BW and feed intake (FI) were seen in birds fed wheat-based diets conditioned at 68°C, but the lowest FCR was observed in maize-based diet conditioned at 90°C at 7, 14 and 21 d of age (p < 0.01). However, BW was higher and FCR lower in chicks fed maize-based diets conditioned at 90°C in the grower period (28 and 35 d; p < 0.01).4. The α-helix height was higher in wheat-based starter diets in comparison to the maize-based diet (p < 0.01). Ratio of amide I to II area and total CHO peak height were increased when diets were processed at 90°C in both maize and wheat-based starter diet (p < 0.05). Increasing the CT from 68°C to 90°C reduced CHO peak 1 and 2 height by 11.6% and 3.95%, respectively, in maize-based starter diets, while increasing the CT from 68°C to 90°C reduced CHO peak 1 and 2 height by 54.3% and 57.2%, respectively, in wheat-based starter diets. In the grower diets, increasing the CT from 68°C to 90°C increased CHO peak 1 by 23% in maize-based diets, but reduced CHO peak 1 by 24.5% in wheat-based diets.5. Calcium and phosphorous retention were highest in chicks fed wheat-based diets conditioned at 90°C and lowest in chicks fed maize-based diets conditioned at 90°C (p < 0.01). Salmonella, E. coli and coliforms in the caeca reduced significantly (p < 0.05) in chicks fed wheat-based diets conditioned at 90°C on d 11 and increased with the same diet at 35 d of age compared to the chicks fed maize-based diets conditioned at both 68°C and 90°C or wheat-based diets conditioned at 68°C.6. Conditioning the wheat-based diets at 68°C improved production responses without causing any adverse effects on protein and CHO molecular structures, however increasing the conditioning temperature to 90°C impaired performance due to alteration of protein and CHO molecular structures. In contrast, conditioning of the maize-based diets at 90°C had the opposite effect, and improved production performance compared to diets conditioned at 68°C.

Boosting Single-Cell RNA Sequencing Analysis with Simple Neural Attention.

A limitation of current deep learning (DL) approaches for single-cell RNA sequencing (scRNAseq) analysis is the lack of interpretability. Moreover, existing pipelines are designed and trained for specific tasks used disjointly for different stages of analysis. We present scANNA, a novel interpretable DL model for scRNAseq studies that leverages neural attention to learn gene associations. After training, the learned gene importance (interpretability) is used to perform downstream analyses (e.g., global marker selection and cell-type classification) without retraining. ScANNA's performance is comparable to or better than state-of-the-art methods designed and trained for specific standard scRNAseq analyses even though scANNA was not trained for these tasks explicitly. ScANNA enables researchers to discover meaningful results without extensive prior knowledge or training separate task-specific models, saving time and enhancing scRNAseq analyses.

Deep learning applications in single-cell genomics and transcriptomics data analysis.

Traditional bulk sequencing methods are limited to measuring the average signal in a group of cells, potentially masking heterogeneity, and rare populations. The single-cell resolution, however, enhances our understanding of complex biological systems and diseases, such as cancer, the immune system, and chronic diseases. However, the single-cell technologies generate massive amounts of data that are often high-dimensional, sparse, and complex, thus making analysis with traditional computational approaches difficult and unfeasible. To tackle these challenges, many are turning to deep learning (DL) methods as potential alternatives to the conventional machine learning (ML) algorithms for single-cell studies. DL is a branch of ML capable of extracting high-level features from raw inputs in multiple stages. Compared to traditional ML, DL models have provided significant improvements across many domains and applications. In this work, we examine DL applications in genomics, transcriptomics, spatial transcriptomics, and multi-omics integration, and address whether DL techniques will prove to be advantageous or if the single-cell omics domain poses unique challenges. Through a systematic literature review, we have found that DL has not yet revolutionized the most pressing challenges of the single-cell omics field. However, using DL models for single-cell omics has shown promising results (in many cases outperforming the previous state-of-the-art models) in data preprocessing and downstream analysis. Although developments of DL algorithms for single-cell omics have generally been gradual, recent advances reveal that DL can offer valuable resources in fast-tracking and advancing research in single-cell.

Deep learning in spatial transcriptomics: Learning from the next next-generation sequencing.

Spatial transcriptomics (ST) technologies are rapidly becoming the extension of single-cell RNA sequencing (scRNAseq), holding the potential of profiling gene expression at a single-cell resolution while maintaining cellular compositions within a tissue. Having both expression profiles and tissue organization enables researchers to better understand cellular interactions and heterogeneity, providing insight into complex biological processes that would not be possible with traditional sequencing technologies. Data generated by ST technologies are inherently noisy, high-dimensional, sparse, and multi-modal (including histological images, count matrices, etc.), thus requiring specialized computational tools for accurate and robust analysis. However, many ST studies currently utilize traditional scRNAseq tools, which are inadequate for analyzing complex ST datasets. On the other hand, many of the existing ST-specific methods are built upon traditional statistical or machine learning frameworks, which have shown to be sub-optimal in many applications due to the scale, multi-modality, and limitations of spatially resolved data (such as spatial resolution, sensitivity, and gene coverage). Given these intricacies, researchers have developed deep learning (DL)-based models to alleviate ST-specific challenges. These methods include new state-of-the-art models in alignment, spatial reconstruction, and spatial clustering, among others. However, DL models for ST analysis are nascent and remain largely underexplored. In this review, we provide an overview of existing state-of-the-art tools for analyzing spatially resolved transcriptomics while delving deeper into the DL-based approaches. We discuss the new frontiers and the open questions in this field and highlight domains in which we anticipate transformational DL applications.

ACTIVA: realistic single-cell RNA-seq generation with automatic cell-type identification using introspective variational autoencoders.

MOTIVATION: Single-cell RNA sequencing (scRNAseq) technologies allow for measurements of gene expression at a single-cell resolution. This provides researchers with a tremendous advantage for detecting heterogeneity, delineating cellular maps or identifying rare subpopulations. However, a critical complication remains: the low number of single-cell observations due to limitations by rarity of subpopulation, tissue degradation or cost. This absence of sufficient data may cause inaccuracy or irreproducibility of downstream analysis. In this work, we present Automated Cell-Type-informed Introspective Variational Autoencoder (ACTIVA): a novel framework for generating realistic synthetic data using a single-stream adversarial variational autoencoder conditioned with cell-type information. Within a single framework, ACTIVA can enlarge existing datasets and generate specific subpopulations on demand, as opposed to two separate models [such as single-cell GAN (scGAN) and conditional scGAN (cscGAN)]. Data generation and augmentation with ACTIVA can enhance scRNAseq pipelines and analysis, such as benchmarking new algorithms, studying the accuracy of classifiers and detecting marker genes. ACTIVA will facilitate analysis of smaller datasets, potentially reducing the number of patients and animals necessary in initial studies. RESULTS: We train and evaluate models on multiple public scRNAseq datasets. In comparison to GAN-based models (scGAN and cscGAN), we demonstrate that ACTIVA generates cells that are more realistic and harder for classifiers to identify as synthetic which also have better pair-wise correlation between genes. Data augmentation with ACTIVA significantly improves classification of rare subtypes (more than 45% improvement compared with not augmenting and 4% better than cscGAN) all while reducing run-time by an order of magnitude in comparison to both models. AVAILABILITY AND IMPLEMENTATION: The codes and datasets are hosted on Zenodo (https://doi.org/10.5281/zenodo.5879639). Tutorials are available at https://github.com/SindiLab/ACTIVA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Challenges in the Management of Care of Brain-Dead Patients in the Donation Process: A Qualitative Content Analysis.

BACKGROUND: In care of brain-dead patients, nurses face several challenges. It is important to determine the context behind these challenges since they affect the performance of nurses and the organ donation process. OBJECTIVE: To identify factors affecting the emergence of challenges related to the management of brain-dead patients by nurses in the donation process. METHODS: In this qualitative conventional content analysis, data were collected by performing 28 semi-structured and in-depth interviews with nurses working in the ICUs. Purposive sampling started from March 2014 until saturation, which was reached in June 2016. Data analysis occurred simultaneously with data collection. RESULTS: Qualitative analysis of contents provided from interviews led to the extraction of themes that showed the experience of nurses about the challenges of caring for brain-dead patients in the donation process. These themes included "doubt and conflict in accepting the situation" and "defects in an effective and targeted care system." In the end, the main theme of "inconsistency and incompatibility of care management" was abstracted. CONCLUSION: According to the results of the study, factors involved in the emergence of challenges for nurses in care management included defects in education or managerial problems, which increased tension for nurses.

Molecular and dissociative adsorption of tetrachlorodibenzodioxin on M-doped graphenes (M = B, Al, N, P): pure DFT and DFT + VdW calculations.

Tetrachlorodibenzodioxin (TCDD) is one of the most famous dioxin families that is hazardous to humans and the environment. Designing cheap and novel catalysts for its detecting and removing is an essential need for the environment. In this work, DFT + VdW is used to investigate the potentiality of proposed catalysts in adsorbing and dissociating TCDD. P-type and N-type charge carrier effects on the adsorption process are modeled by doping of B/Al and N/P atoms in the graphene. Al-doped graphene, with - 1.27 eV adsorption energy, has the highest possibility to adsorb TCDD. P-type dopants have higher interactions with TCDD in comparing with N-type dopants. Introducing positive and negative charges on the studied complexes shows that in all complexes, the driving force of complexation is π-π stacking except for the Al-doped graphene. Dissociative adsorption studies show that unlike literature data, chlorine atoms on the surface of studied catalysts are not dissociated from TCDD, and instead, C-O bonds in TCDD are dissociated symmetrically and asymmetrically. Data show that Al-doped graphene is the best catalyst for symmetrical dissociation, and pure graphene is the best one for asymmetrical dissociation of TCDD.

Epidemiology and pathophysiology of malignancy in common variable immunodeficiency?

Common variable immunodeficiency (CVID) is a diagnostic category of primary immunodeficiency (PID) which may present with heterogeneous disorders including recurrent infections, autoimmunity, granulomatous diseases, lymphoid and other types of malignancies. Generally, the incidence of malignancy in CVID patients is around 1.5-20.7% and usually occurs during the 4th-6th decade of life. Non-Hodgkin lymphoma is the most frequent malignancy, followed by epithelial tumours of stomach, breast, bladder and cervix. The exact pathological mechanisms for cancer development in CVID are not fully determined; however, several mechanisms including impaired genetic stability, genetic predisposition, immune dysregulation, impaired clearance of oncogenic viruses and bacterial infections, and iatrogenic causes have been proposed to contribute to the high susceptibility of these patients to malignancies.

The effect of celecoxib and its combination with imatinib on human HT-29 colorectal cancer cells: Involvement of COX-2, Caspase-3, VEGF and NF-κB genes expression.

It has been shown that combination of imatinib (IM) with other agents may have some advantages in avoiding toxicity and resistance caused by this drug. The selective cyclooxygenase-2 inhibitor, celecoxib (CX), has been known to have antitumor and chemo-sensitizing effect in the treatment of colorectal cancer. In this study, we investigated the effectiveness of CX and its combination with anticancer agent IM on human colorectal cancer HT-29 cell and their probable molecular targets. Cultured HT-29 cells were exposed to IC50 dose of CX, IM, and their combination (half dose of IC50) for 24 hours to assess their effect on proliferation inhibition by MTT assay. The caspase-3 activity was estimated in HT-29 cells with colorimetric kit. COX-2, Caspase-3, VEGF and NF-κB genes expression was also investigated using real-time PCR method. Combined treatment with IM and CX, resulted in a significant (P˂0.05) decrease in cell viability and increased caspase-3 enzyme activity. Decreased COX-2 gene expression has been found in CX and combined treated group. Significant increase in Caspase-3 gene expression has been shown in IM and combined treated cells. In conclusion, the present in vitro study with colon cancer cell line demonstrated that CX and its combination with IM improved the anticancer activity of each component. Caspase-3 and COX-2 dependent molecular targets seem to be involved in mediating the anti-proliferative effects of IM and CX combination. Of course, the other molecular pathways are also likely to play the role and should be explored in future studies.

The effects of transportation stress on Japanese quail (Coturnix Coturnix japonica) fed corn-based diet in comparison with wheat-based diet supplemented with xylanase and phytase.

Harvesting, handling and transporting quails to the slaughterhouses, other farms and laboratories might covertly reduce their welfare. The aim of this study was to evaluate the effects of two major sources of energy in poultry nutrition on reducing transportation stress in Japanese quail (Coturnix Coturnix japonica). Male quails (n = 60) were divided into two groups. The first group was fed corn-based diet, and the second was fed wheat-based diet supplemented with xylanase and phytase. At the end of the experiment (day 35), quails were subjected to 80 km of transportation. Immediately on arrival and after 24 h, heterophil counts, lymphocyte counts and H:L ratios were measured. On arrival, H counts were lower, L counts were higher, and H:L ratios were lower for corn-fed group. After 24 h, wheat-fed group showed lower increment of H counts, greater increment of L counts and also decrement of H:L ratios rather than corn-fed group which showed increment of H:L ratios. However, these ratios were still lower in corn-fed group. Results indicate that corn-based diets can help Japanese quail to better resist transportation stress, although it seems that feeding wheat-based diets supplemented with xylanase and phytase could have positive effects for coping better with stress after journeys.

Multicentre observational study of the Gatekeeper for faecal incontinence.

BACKGROUND: A variety of therapeutic approaches are available for faecal incontinence. Implantation of Gatekeeper prostheses is a new promising option. The primary endpoint of this prospective observational multicentre study was to assess the clinical efficacy of Gatekeeper implantation in patients with faecal incontinence. Secondary endpoints included the assessment of patients' quality of life, and the feasibility and safety of implantation. METHODS: Patients with faecal incontinence, with either intact sphincters or internal anal sphincter lesions extending for less than 60° of the anal circumference, were selected. Intersphincteric implantation of six prostheses was performed. At baseline, and 1, 3 and 12 months after implantation, the number of faecal incontinence episodes, Cleveland Clinic Faecal Incontinence, Vaizey and American Medical Systems, Faecal Incontinence Quality of Life Scale and Short Form 36 Health Survey scores were recorded. Endoanal ultrasonography was performed at baseline and follow-up. RESULTS: Fifty-four patients were implanted. After Gatekeeper implantation, incontinence to gas, liquid and solid stool improved significantly, soiling was reduced, and ability to defer defaecation enhanced. All faecal incontinence severity scores were significantly reduced, and patients' quality of life improved. At 12 months, 30 patients (56 per cent) showed at least 75 per cent improvement in all faecal incontinence parameters, and seven (13 per cent) became fully continent. In three patients a single prosthesis was extruded during surgery, but was replaced immediately. After implantation, prosthesis dislodgement occurred in three patients; no replacement was required. CONCLUSION: Anal implantation of the Gatekeeper in patients with faecal incontinence was effective and safe. Clinical benefits were sustained at 1-year follow-up.

Exploring the needs and perceptions of Iranian families faced with brain death news and request to donate organ: a qualitative study.

BACKGROUND: Learning that one of your beloved ones is passing away and you have to decide on organ donation is a very stressful experience. OBJECTIVE: To explore the specific needs of families with a brain-dead patient during organ donation process. METHODS: A qualitative research using content analysis was used to obtain data from 26 purposely selected families in a transplantation center in Mashhad, northeastern Iran, regarding how they would face organ donation decisions. RESULTS: Data saturation was reached after 38 unstructured in-depth interviews and field notes, once data was transcribed and tabulated. Four major themes emerged as 1) family needs for emotional support, 2) empathy and compassion, 3) team efforts to assure family, and 4) shouldering grief. CONCLUSION: Study results highlighted the essential need for an expert team with specialized training to help families in despair deciding in favor or against organ donation. Moreover, discovering and explaining these specific needs help policy makers and administrators to plan interventions in relation to condition-building to facilitate safe passing of the families through this difficult situation.

Effect of short-term lead exposure on PTZ-induced seizure threshold in mice.

This study was designed to determine the effect of different concentrations of lead acetate on seizure threshold. Balb\c male mice were randomly divided into one control group provided with tap water and four experimental groups received lead acetate in drinking water for 30 days at concentrations of 50, 100, 200 and 400 ppm. Intravenous infusion of pentylenetetrazole (PTZ) was used to induce seizure signs and elapsed time was recorded to calculate the threshold dose. At the end of the experiments blood samples were taken to measure the blood lead level. Threshold doses of PTZ were significantly lower in 100, 200 and 400 ppm lead exposed groups for the induction of all seizure stages. Blood lead level increased in all experimental groups compared to control dose-dependently. Considering the lack of any response induced by 50 ppm concentration of lead, it may be concluded that 100 ppm of lead was the minimal effective dose. Therefore, lead acetate at a concentration of 100 ppm that produces similar blood level in human populations approves the enhancement of convulsive attack risk. Considering the effect of low levels of lead in the reduction of seizure threshold, more investigations should be carried out to clarify the exact mechanisms.

What is the most common complication after one-stage transanal pull-through in infants with Hirschsprung's disease?

BACKGROUND: Hirschsprung's disease (HD) is a relatively common congenital disease that could be suspected by clinical symptoms, abdominal plain X-ray, and finally diagnosed by rectal biopsy. In 80% cases, rectosigmoid junction is involved. Recently, one-stage transanal pull-through (TAPT) procedure has been popular and may have several complications. METHODS AND PATIENTS: During a 4-year period, 86 infants (28 girls, 58 boys) with mean age 8 days (3-33) and clinically suspected to HD were admitted in our center. HD was proved by rectal biopsy. All patients after full bowel preparation and rectal washout were candidates for TAPT operation. A Swenson-like procedure was performed and the anastomosis was done between the well blood supply ganglionic colon and the rectum at 1 cm above dentate line. Interrupted suture with 5-0 Vicryl was used. Nelaton tube (12 F) inserted in the pelvis via transprineal for drainage of blood or collection. From February 2008 in 30 cases, prophylactic Hegar dilatation was performed 2 weeks after operation. RESULTS: Anal stricture in 12 cases (14%) was treated by anal dilation in 10 cases and 2 cases corrected by surgical management. Entrocolitis in 4 cases (5%) was treated by medical management. In two cases, retrocolic abscess had spontaneous drainage via tube drain. There was no anastomotic stricture after starting prophylactic anal bouginage. CONCLUSION: TAPT has many advantages, low complications and the results are excellent. It seems the most common complication is anastomotic stricture that responds well to prophylactic bouginage. We recommend prophylactic anal bouginage with Hegar probe at 2 weeks after operation. Long-term follow-up is needed to evaluate the outcomes of our operations.

Adipogenic human adenovirus-36 reduces leptin expression and secretion and increases glucose uptake by fat cells.

OBJECTIVE: Human adenovirus Ad-36 causes adiposity in animal models and enhances differentiation and lipid accumulation in human and 3T3-L1 preadipocytes, which may, in part, explain the adipogenic effect of Ad-36. We determined the consequences of Ad-36 infection on leptin and glucose metabolism in fat cells. DESIGN: 3T3-L1 preadipocytes were used to determine the effect of infection by human adenoviruses Ad-36, Ad-2, Ad-9 and Ad-37 on leptin secretion and lipid accumulation. Rat primary adipocytes were used to determine the effect of Ad-36 infection on leptin secretion and glucose uptake in vitro. Furthermore, the effect of Ad-36 on expressions of leptin and selected genes of de novo lipogenesis pathway of visceral adipose tissue were compared ex vivo, between Ad-36 infected and uninfected control rats. RESULTS: Ad-36 suppressed the expression of leptin mRNA in 3T3-L1 cells by approximately 58 and 52% on days 3 and 5 post-infection, respectively. Leptin release normalized to cellular lipid content was 51% lower (P<0.002) in the Ad-36 infected 3T3-L1 cells. Lipid accumulation was significantly greater and leptin secretion was lower for the 3T3-L1 cells infected with other human adenoviruses Ad-9, Ad-36, or Ad-37. Whereas, human adenovirus Ad-2 did not influence cellular lipid accumulation or the leptin release. In rat primary adipocytes, Ad-36 reduced leptin release by about 40% in presence of 0.48 (P<0.01) or 1.6 nM insulin (P<0.05) and increased glucose uptake by 93% (P<0.001) or 18% (P<0.05) in presence of 0 or 0.48 nM insulin, respectively. Next, the adipose tissue of Ad-36 infected rats showed two to fivefold lower leptin mRNA expression, and 1.6- to 21-fold greater expressions for acetyl Co-A carboxylase-1 and 1.2- to 6.3-fold greater expressions for fatty acid synthase, key genes of de novo lipogenesis, compared to the uninfected weight and adiposity matched controls. CONCLUSION: The in vitro and ex vivo studies show that Ad-36 modulates adipocyte differentiation, leptin production and glucose metabolism. Whether such a modulation contributes to enhanced adipogenesis and consequent adiposity in Ad-36 infected animals or humans needs to be determined.

Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes.

OBJECTIVE: Human adenovirus Ad-36 causes adiposity in animal models and shows association with human obesity. Ad-36 enhances differentiation of 3T3-L1 and human preadipocytes, without cell lysis, a characteristic that may contribute to its adipogenic effect observed in vivo. Ad-2, another human adenovirus is nonadipogenic in animals and in 3T3-L1 cells and shows no correlation with human obesity. The objective of this study was to determine the adipogenic roles of viral mRNA and DNA, which may explain the differential effects of Ad-36 and Ad-2 on preadipocyte differentiation. METHODS: This study determined the duration of selected Ad-36 gene expression in 3T3-L1 cells, and the effect on preadipocytes differentiation, when Ad-36 gene expression was attenuated by Cidofovir, an antiadenoviral agent. RESULTS: The results showed that Ad-36, but not Ad-2, expresses viral mRNA. Ad-36 gene expression peaked at 2-4 days postinoculation and very low levels persisted after day 7. Despite the viral mRNA expression, Ad-36 infection of 3T3-L1 cells was abortive as indicated by a progressive decrease in viral DNA quantity. Attenuation of Ad-36 mRNA expression by Cidofovir reduced the adipogenic effect of the virus. CONCLUSION: In conclusion, viral mRNA expression, although transient, is a prerequisite for enhancing differentiation of preadipocytes by Ad-36. Viral DNA replication was not required for the effect. This is the first evidence for the role of gene expression of an adipogenic human virus in enhancing preadipocytes differentiation. This study provides the basis for further understanding novel regulatory modulators of preadipocytes differentiation.

Study on the role of common weeds in survival of Verticillium dahliae the causal agent of cotton wilt disease.

This study was carried out to investigate the roles of common weeds in the survival of Verticillium dahliae and the incidence of cotton wilt disease in Moghan and Neishabour area of Iran during 2003-2005 cropping seasons. The design of the experiment was Randomized Complete Blocks (RCB) with ten treatments (No. of weeds) and four replications (No. of cotton fields). Populations of V. dahliae in the roots of weeds and their surrounding soil was determined every year and were compared in different treatments. The cotton wilt disease index was also evaluated in different fields in each experimental site. Results indicated that the fungal population was variable depending on weed species, experimental site and the year of study. In general, Pigweed (Amaranthus retroflexus), Nightshde (Solanum nigrum), Spiny cockleburr (Xanthium spinosum) and common purslane (Portulaca oleraceea) showed the highest fungal populations in their roots and surrounding soil. Disease index in Moghan cotton fields in different years varied and were higher than Neishabour fields.

Investigation of the effect of heating, vesicular arbuscular mycorrhiza and thermophilic fungus on cotton wilt disease.

In this study, combinations of spores of a thermophilic fungus (Talaromyces flavus), Vesicular Arbuscular Mycorrhiza (VAM) and microsclerotia of Verticillium dahliae under various temperature treatment (31-38 degrees C) in triplicate trial, were investigated and results were compared with those of non-treated controls. Five cotton seeds were planted in each pot containing 3 kg of pasteurized soil. In each pot, combinations of 4x10(3) VAM spores, 2.5x10(9) spores of thermophilic fungus (T. flavus) and 5x10(5) microsclerotia of V. dahliae were added. Symptoms of Verticillium wilt were observed after 45 days. Index of disease severity was measured. Results indicated that pre-heating of microsclerotia at 31 and 35 degrees C for 10 and 14 h, respectively, caused a 15% reduction in leaf infection index. Presence of VAM and thermophilic fungus (T. flavus) spores caused 23 and 50% reductions in the disease development, respectively. Concurrent presence of mycorrhiza and thermophilic fungus spores caused a 10-20% reduction in disease development. These findings provide a promising approach to the control of Verticillium wilt of cotton. However, heat treatment of soil may prove difficult. Further studies in this regard are required and useful agricultural practices such as seasonal heating may be applied in the cotton fields.

Mechanism-based inactivation of CYP2D6 by methylenedioxymethamphetamine.

The potency of methylenedioxymethamphetamine (MDMA) as a mechanism-based inhibitor of CYP2D6 has been defined using microsomes prepared from yeast expressing the enzyme and from three human livers. The inhibitory effect was increased by preincubation through formation of a metabolic intermediate complex. Inactivation parameters (kinact and KI), defined with respect to the O-demethylation of dextromethorphan, were 0.29 +/- 0.03 (S.E.) min(-1) and 12.9 +/- 3.6 (S.E.) microM for yeast-expressed CYP2D6, and 0.26 +/- 0.02 min(-1) and 14.4 +/- 2.5 microM, 0.15 +/- 0.01 min(-1) and 8.8 +/- 2.6 microM, and 0.12 +/- 0.05 min(-1) and 45.3 +/- 32.1 microM for the liver microsomal preparations. The rate of inactivation of CYP2D6 by MDMA decreased when quinidine, a competitive inhibitor of CYP2D6, was added to the primary incubation mixture. However, inactivation was unaffected by the addition of glutathione. The results indicate that MDMA is a potent mechanism-based inhibitor of CYP2D6, with implications for understanding its in vivo disposition and drug interaction potential.