Epithelial cell distribution and abundance in rhesus monkey airways during postnatal lung growth and development.

Lung development is both a pre- and postnatal process. Although many lung diseases have their origins in early childhood, few quantitative data are available on the normal growth and differentiation of both the conducting airways and the airway epithelium during the postnatal period. We examined rhesus monkey lungs from five postnatal ages: 4-6 days and 1, 2, 3, and 6 mo. Airways increase significantly in both length and circumference as monkeys increase significantly in body weight from 5 days to 6 mo. In this study we asked: as basement membrane surface area increases, does the epithelial cell organization change? To answer this question, we quantified total epithelial cell mass using high-resolution light micrographs and morphometric techniques on sections from defined airway regions: trachea, proximal intrapulmonary bronchus (generations 1 or 2), and distal intrapulmonary bronchus (generations 6-8). Epithelial thickness decreased in the smaller, more distal, airways compared with trachea but did not change with age in the trachea and proximal bronchus. The volume fraction of all cell types measured did not change significantly. Ciliated cells in the distal bronchus and goblet cells in the trachea both decreased in abundance with increasing age. Overall, the epithelial cell populations changed little in terms of mass or relative abundance to each other during this period of active postnatal lung growth. Regarding the proximal conducting airway epithelium, we conclude that 1) the steady-state abundance is tightly regulated to keep the proportion of cell types constant, and 2) establishment of these cell types occurs before 4-6 days postnatal age. We conclude that growth of the proximal airways occurs primarily in length and lags behind that of the lung parenchyma.     

Verification of a European corn borer (Lepidoptera: Crambidae) loss equation in the major corn production region of the northeastern United States

Field studies in Pennsylvania and Maryland were conducted during 2000, 2001, and 2002 to test the applicability of published yield loss relationships developed in central Pennsylvania for European corn borer, Ostrinia nubilalis (Hübner), management in warmer, longer season corn, Zea mays L., grain production regions of the northeastern United States. Both isoline hybrids and non-Bt lead hybrids were compared against Bacillus thuringiensis (Bt) hybrids to measure effects of the pest on yield. The European corn borer economic analysis model was used to make site-specific predictions of loss per European corn borer larva for comparison with measured yield loss per larva. Although the model did not predict loss per larva at a field level, it did predict loss at a regional level. The model predicted an overall percentage of yield loss per larva of 2.69+/-0.12% over the region, which was similar to the measured yield loss per larva of 2.66+/-0.59% for isoline hybrids and 3.08+/-0.51% for lead hybrids. The model, on average, provided a good prediction of percentage of yield loss per larva within the climatic zones of 1100-1700 degree-days (DD) (base threshold 12.5 degrees C). Our results suggest that the yield loss relationship developed in Central Pennsylvania, when matched to the timing of third instar second generation European corn borer stalk tunneling is adequate for major corn grain production zones of the northeast United States.     

MTHFR Glu429Ala and ERCC5 His46His Polymorphisms Are Associated with Prognosis in Colorectal Cancer Patients: Analysis of Two Independent Cohorts from Newfoundland

Introduction

In this study, 27 genetic polymorphisms that were previously reported to be associated with clinical outcomes in colorectal cancer patients were investigated in relation to overall survival (OS) and disease free survival (DFS) in colorectal cancer patients from Newfoundland.

Methods

The discovery and validation cohorts comprised of 532 and 252 patients, respectively. Genotypes of 27 polymorphisms were first obtained in the discovery cohort and survival analyses were performed assuming the co-dominant genetic model. Polymorphisms associated with disease outcomes in the discovery cohort were then investigated in the validation cohort.

Results

When adjusted for sex, age, tumor stage and microsatellite instability (MSI) status, four polymorphisms were independent predictors of OS in the discovery cohort MTHFR Glu429Ala (HR: 1.72, 95%CI: 1.04–2.84, p = 0.036), ERCC5 His46His (HR: 1.78, 95%CI: 1.15–2.76, p = 0.01), SERPINE1 −675indelG (HR: 0.52, 95%CI: 0.32–0.84, p = 0.008), and the homozygous deletion of GSTM1 gene (HR: 1.4, 95%CI: 1.03–1.92, p = 0.033). In the validation cohort, the MTHFR Glu429Ala polymorphism was associated with shorter OS (HR: 1.71, 95%CI: 1.18–2.49, p = 0.005), although with a different genotype than the discovery cohort (CC genotype in the discovery cohort and AC genotype in the validation cohort). When stratified based on treatment with 5-Fluorouracil (5-FU)-based regimens, this polymorphism was associated with reduced OS only in patients not treated with 5-FU. In the DFS analysis, when adjusted for other variables, the TT genotype of the ERCC5 His46His polymorphism was associated with shorter DFS in both cohorts (discovery cohort: HR: 1.54, 95%CI: 1.04–2.29, p = 0.032 and replication cohort: HR: 1.81, 95%CI: 1.11–2.94, p = 0.018).

Conclusions

In this study, associations of the MTHFR Glu429Ala polymorphism with OS and the ERCC5 His46His polymorphism with DFS were identified in two colorectal cancer patient cohorts. Our results also suggest that the MTHFR Glu429Ala polymorphism may be an adverse prognostic marker in patients not treated with 5-FU.     

Saturation transfer EPR spectroscopy on spin-labeled muscle fibers using a loop-gap resonator.

Previously, saturation transfer (ST-EPR) studies of biomolecular dynamics have involved the use of a resonant cavity and the V'2 display (absorption, second harmonic, out of phase). In the present study, we replaced the resonant cavity with a loop-gap resonator and used the U'1 display (dispersion, first harmonic, out of phase) to study spin-labeled muscle fibers. The new resonator and display showed several advantages over those previously used. It produced virtually noiseless U'1 spectra on a 0.4 microliter sample using a 4 min scan; previous U'1 experiments on spin-labeled muscle, using a conventional rectangular cavity, resulted in an unacceptably low signal-to-noise ratio. The high filling factor of the resonator facilitated the study of these extremely small fiber bundles and permitted high microwave field intensities to be achieved at much lower incident microwave power levels, thus greatly enhancing the signal-to-noise ratio in U'1 experiments. This reduction in the noise level made it possible to benefit from the other advantages of U'1 over V'2, such as stronger signals, simpler line shapes, and simpler data analysis. For these muscle fiber samples, the resulting sensitivity (signal/noise/sample volume) of the U'1 signals was greater than 100 times that of V'2 signals obtained in a conventional cavity. Another advantage of the U'1 display is that signals from weakly immobilized probes, i.e., probes that have nanosecond rotational mobility relative to the labeled protein (myosin), are greatly suppressed relative to strongly immobilized probes. This reduces the ambiguity of spectral analysis, and eliminates the need for chemical treatments [e.g., using K3Fe(CN)6] that were previously required in muscle fibers and other systems. Further suppression of this weakly immobilized component was achieved in U'1 spectra by increasing the microwave power and decreasing the field modulation frequency.     

The genusSavoryella from freshwater habitats,includingS. grandispora sp. nov.

The species ofSavoryella from freshwater are discussed and a key is provided.Savoryella grandispora sp. nov. from Malaysia is described and illustrated with interference contrast micrographs.     

Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view

The mitochondrial life cycle consists of frequent fusion and fission events. Ample experimental and clinical data demonstrate that inhibition of either fusion or fission results in deterioration of mitochondrial bioenergetics. While fusion may benefit mitochondrial function by allowing the spreading of metabolites, protein and DNA throughout the network, the functional benefit of fission is not as intuitive. Remarkably, studies that track individual mitochondria through fusion and fission found that the two events are paired and that fusion triggers fission. On average each mitochondrion would go though ~5 fusion:fission cycles every hour. Measurement of Deltapsi(m) during single fusion and fission events demonstrates that fission may yield uneven daughter mitochondria where the depolarized daughter is less likely to become involved in a subsequent fusion and is more likely to be targeted by autophagy. Based on these observations we propose a mechanism by which the integration of mitochondrial fusion, fission and autophagy forms a quality maintenance mechanism. According to this hypothesis pairs of fusion and fission allow for the reorganization and sequestration of damaged mitochondrial components into daughter mitochondria that are segregated from the networking pool and then becoming eliminated by autophagy.     

Phylogenetics and evolution of nematode-trapping fungi (Orbiliales) estimated from nuclear and protein coding genes

The systematic classification of nematode-trapping fungi is redefined based on phylogenies inferred from sequence analyses of 28S rDNA, 5.8S rDNA and beta-tubulin genes. Molecular data were analyzed with maximum parsimony, maximum likelihood and Bayesian analysis. An emended generic concept of nematode-trapping fungi is provided. Arthrobotrys is characterized by adhesive networks, Dactylellina by adhesive knobs, and Drechslerella by constricting-rings. Phylogenetic placement of taxa characterized by stalked adhesive knobs and non-constricting rings also is confirmed in Dactylellina. Species that produce unstalked adhesive knobs that grow out to form loops are transferred from Gamsylella to Dactylellina, and those that produce unstalked adhesive knobs that grow out to form networks are transferred from Gamsylella to Arthrobotrys. Gamsylella as currently circumscribed cannot be treated as a valid genus. A hypothesis for the evolution of trapping-devices is presented based on multiple gene data and morphological studies. Predatory and nonpredatory fungi appear to have been derived from nonpredatory members of Orbilia. The adhesive knob is considered to be the ancestral type of trapping device from which constricting rings and networks were derived via two pathways. In the first pathway adhesive knobs retained their adhesive material forming simple two-dimension networks, eventually forming complex three-dimension networks. In the second pathway adhesive knobs lost their adhesive materials, with their ends meeting to form nonconstricting rings and they in turn formed constricting rings with three inflated-cells.     

EVIDENCE OF RELATIONSHIP BETWEEN EXTRA DIMINUTIVE CHROMOSOMES IN GEOGRAPHICALLY REMOTE RACES OF OENOTHERA

Cleland , R. E. (Indiana U., Bloomington), and B. B. Hyde . Evidence of relationship between extra diminutive chromosomes in geographically remote races of Oenothera. Amer. Jour. Bot. 50(2): 179–185. Illus. 1963.—Two California races of O. hookeri, Mono (from Mono Co.) and Mataguey (from San Diego Co.), have extra diminutive chromosomes. These diminutives do not associate with any of the normal chromosomes present. The extras from the 2 races, however, are able to synapse with each other and to form chiasmata, although the extras in Mono are distinctly larger than these in Mataguey. This suggests that they are at least partially homologous and that they have come from a common source. Two alternative hypotheses for their origin are suggested: (1) they have resulted from the loss of pairing ends through deletion, having descended from the same chromosome; (2) they represent normal chromosomes derived from another subgenus, through an inter-subgeneric cross followed by a backcross to hookeri. The facts tend to favor the latter hypothesis.