Molecular and Historical Aspects of Corn Belt Dent Diversity

Tens-of-thousands of open-pollinated cultivars of corn (Zea mays L.) are being maintained in germplasm banks. Knowledge of the amount and distribution of genetic variation within and among accessions can aid end users in choosing among them. We estimated molecular genetic variation and looked for influences of pedigree, adaptation, and migration in the genetic makeup of conserved Corn-Belt Dent-related germplasm. Plants sampled from 57 accessions representing Corn-Belt Dents, Northern Flints, Southern Dents, plus 12 public inbreds, were genotyped at 20 simple sequence repeat (SSR) loci. For 47 of the accessions, between 5 and 23 plants per accession were genotyped (mean = 9.3). Mean number of alleles per locus was 6.5 overall, 3.17 within accessions, and 3.20 within pooled inbreds. Mean gene diversity was 0.53 within accessions and 0.61 within pooled inbreds. Open-pollinated accessions showed a tendency toward inbreeding (FIS = 0.09), and 85% of genetic variation was shared among them. A Fitch-Margoliash tree strongly supported the distinctiveness of flint from dent germplasm but did not otherwise reveal evidence of genetic structure. Mantel tests revealed significant correlations between genetic distance and geographical (r = 0.54, P= 0.04) or maturity zone (r = 0.33, P = 0.03) distance only if flint germplasm was included in the analyses. A significant correlation (r = 0.76, P \u3c 0.01) was found between days to pollen shed and maturity zone of accession origin. Pedigree, rather than migration or selection, has most influenced the genetic structure of the extant representatives of the open-pollinated cultivars at these SSR loci

Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets?

This review covers the current knowledge of the cytochrome P450 enzymes (CYPs) of the human pathogen Mycobacterium tuberculosis (Mtb) and their endogenous redox partners, focusing on their biological function, expression, regulation, involvement in antibiotic resistance, and suitability for exploitation as antitubercular targets. The Mtb genome encodes twenty CYPs and nine associated redox partners required for CYP catalytic activity. Transposon insertion mutagenesis studies have established the (conditional) essentiality of several of these enzymes for in vitro growth and host infection. Biochemical characterization of a handful of Mtb CYPs has revealed that they have specific physiological functions in bacterial virulence and persistence in the host. Analysis of the transcriptional response of Mtb CYPs and redox partners to external insults and to first-line antibiotics used to treat tuberculosis showed a diverse expression landscape, suggesting for some enzymes a potential role in drug resistance. Combining the knowledge about the physiological roles and expression profiles indicates that, at least five Mtb CYPs, CYP121A1, CYP125A1, CYP139A1, CYP142A1, and CYP143A1, as well as two ferredoxins, FdxA and FdxC, can be considered promising novel therapeutic targets

Colgajo sural reverso neurotizado en el tratamiento de úlcera postraumática del talón Neurotization in reverse sural flap in treatment of postraumatic heel ulcer

En la reconstrucción de la región plantar se debe de cumplir el objetivo de proporcionar una sensibilidad protectora para las zonas de presión del talón y de las epífisis dístales del primer y del quinto metatarsianos. La reconstrucción dependerá del defecto y de las estructuras a restituir, pudiendo emplear colgajos locales, a distancia o microquirúrgicos. El colgajo sural reverso es muy eficaz para cubrir la zona del talón, con vascularización constante, fácil diseño, disección y poca morbilidad del sitio donante. Inicialmente fue considerado neurocutáneo, debido a la inclusión del nervio sural en su pedículo; sin embargo, éste no consta con las características de un colgajo sensitivo. Presentamos el caso de una mujer de 23 años de edad con ulceración crónica del talón izquierdo secundaria a traumatismo y tratada con colgajo sural reverso con exteriorización de pedículo para realizar retardos intermitentes; a los 22 días se realizó sección del pedículo y coaptación de la porción proximal del nervio sural al nervio peroneo medio, obteniendo una cubierta cutánea definitiva, sin recurrencia de la ulceración, con adecuada sensibilidad protectora y con discriminación táctil de dos puntos a los 6 meses.The main goal in the plantar area reconstruction is to restore the protective sensation in the zones of pressure of the heel and distal epiphysis of the first and fifth metatarsals. The reconstruction is in dependence of the defect and of the structures to be replaced that can be treated with local, distant or microvascular free flaps. The reverse sural flap is very efficient for the heel coverage, with constant vascularity, easy tailoring, dissection, and low morbidity of the donor site. Initially the flap was term neurofasciocutaneos due to sural nerve inclusion in the pedicle; never the less, it does not fulfill the characteristics of a sensitive flap. We present the case of a 23 year old female patient with chronic ulceration of the left heel due to trauma, treated with a reverse sural flap, not burying its pedicle, with intermittent delays, and release 22 days later, performing the coaptation of the proximal stump of the sural nerve to the medial peroneal nerve. Definitive cutaneous cover was achieved without recurrence of ulceration and appropriate protective sensibility, with a two-point discrimination in 6 months

Polar vectors as a method for evaluating the effectiveness of irritable bowel syndrome treatments: An analysis with pinaverium bromide 100 mg plus simethicone 300 mg po bid

Background: Irritable Bowel Syndrome (IBS) is a disorder characterized by abdominal pain or discomfort associated with changes in bowel habit. Currently there are no objective outcome measures for evaluating the effectiveness of treatments for this disorder. Aims: To determine the usefulness of a method of analysis that employs polar vectors to evaluate the effectiveness of IBS treatments. Methods: Data from a Phase IV clinical study with 1677 active IBS-Rome III patients who received 100 mg of pinaverium bromide + 300 mg of simethicone (PB + S) po bid for a period of four weeks were used for the analysis. Using the Bristol Stool Scale as a reference, the consistency and frequency of each type of bowel movement were recorded weekly in a Bristol Matrix (BM) and the data were expressed as polar vectors. Results: The analysis showed a differential response to the PB + S treatment among the IBS subtypes: in reference to the IBS with constipation subtype, the magnitude of the vector increased from 10.2 to 12.5, reaching maximum improvement at two weeks of treatment (p < 0.05, Scheffé). In the IBS with diarrhea and mixed IBS subtypes, the magnitude of the vector decreased from 19 to 14 (p<0.05) and from 16.5 to 13 (p < 0.05), respectively, with continuous improvement for a period of four weeks. There was no definable vectorial pattern in the unsubtyped IBS group. Conclusions: Analysis with polar vectors enables treatment response to be measured in different IBS subtypes. All the groups showed improvement with PB + S, but each one had its own characteristic response in relation to vector magnitude and direction. The proposed method can be implemented in clinical studies to evaluate the efficacy of IBS treatments

Linking cytochrome P450 enzymes from Mycobacterium tuberculosis to their cognate ferredoxin partners

Mycobacterium tuberculosis (Mtb) codes for 20 cytochrome P450 enzymes (CYPs), considered potential drug-targets due to their essential roles in bacterial viability and host infection. Catalytic activity of mycobacterial CYPs is dependent on electron transfer from a NAD (P)H-ferredoxin-reductase (FNR) and a ferredoxin (Fd). Two FNRs (FdrA and FprA) and five ferredoxins (Fdx, FdxA, FdxC, FdxD, and Rv1786) have been found in the Mtb genome. However, as of yet, the cognate redox partnerships have not been fully established. This is confounded by the fact that heterologous redox partners are routinely used to reconstitute Mtb CYP metabolism. To this end, this study aimed to biochemically characterize and identify cognate redox partnerships for Mtb CYPs. Interestingly, all combinations of FNRs and ferredoxins were active in the reduction of oxidized cytochrome c, but steady-state kinetic assays revealed FdxD as the most efficient redox partner for FdrA, whereas Fdx coupled preferably with FprA. CYP121A1, CYP124A1, CYP125A1, and CYP142A1 metabolism with the cognate redox partners was reconstituted in vitro showing an unanticipated selectivity in the requirement for electron transfer partnership, which did not necessarily correlate with proximity in the genome. This is the first description of microbial P450 metabolism in which multiple ferredoxins are functionally linked to multiple CYPs