Forecasting age-related changes in breast cancer mortality among white and black US women: a functional data approach

Background: The disparity in breast cancer mortality rates among white and black US women is widening, with higher mortality rates among black women. We apply functional time series models on age-specific breast cancer mortality rates for each group of women, and forecast their mortality curves using exponential smoothing state-space models with damping. Materials and Methods: The data were obtained from the Surveillance, Epidemiology and End Results (SEER) program of the US [1]. Mortality data were obtained from the National Centre for Health Statistics (NCHS) available on the SEER*Stat database. We use annual unadjusted breast cancer mortality rates from 1969 to 2004 in 5-year age groups (45–49, 50–54, 55–59, 60–64, 65–69, 70–74, 75–79, 80–84). Age-specific mortality curves were obtained using nonparametric smoothing methods. The curves are then decomposed using functional principal components and we fit functional time series models with four basis functions for each population separately. The curves from each population are forecast and prediction intervals are calculated. Results: Twenty-year forecasts indicate an overall decline in future breast cancer mortality rates for both groups of women. This decline appears to be steeper among white women aged 55–73 and black women aged 60–84. For black women under 55 years of age, the forecast rates are relatively stable indicating there is no significant change in future breast cancer mortality rates among young black women in the next 20 years. Conclusion: White women have smooth and consistent patterns in breast cancer mortality rates for all age-groups whereas the mortality rates for black women are much more variable. The projections suggest, for some age groups, black American women may not benefit equally from the overall decline in breast cancer mortality in the United States.     

Bmp4 and Noggin expression during early thymus and parathyroid organogenesis

The thymus and parathyroids originate from the third pharyngeal pouches, which form as endodermal outpocketings in the pharyngeal region beginning on embryonic day 9 (E9.0) of mouse development. Using organ-specific markers, we have previously shown that thymus and parathyroid-specific organ domains are established within the primordium prior to formation of the organs proper: Gcm2 expression defines the prospective parathyroid cells in the dorsal pouch from E9.5, while Foxn1 is expressed in the thymus domain from E11.25. Bmp (bone morphogenetic protein) signaling has been implicated in thymic epithelial cell differentiation and thymus organogenesis. In the present study, we report expression patterns of Bmp4 and Noggin, a Bmp4 antagonist, in the third pharyngeal pouch using two lacZ transgenic mouse strains. Results from this gene expression study revealed localization of Bmp4 expression to the ventral region of the third pharyngeal pouch endoderm at E10.5 and E11.5, in those cells that will express Foxn1 and form the thymus. Conversely, the expression of Noggin was confined to the dorsal region of the pouch and primordium at these stages, and thus appeared to be co-expressed with Gcm2 in the parathyroid domain. This represents the first detailed study of Bmp4 and Noggin expression during the early stages of thymus and parathyroid organogenesis.     

Diversity of filamentous fungi associated with Hypothenemus hampei (Ferrari) (Coleoptera: Scolytidae) and its galleries in berries of Coffea canephora (Pierre)

Field sampling was carried out in Ouro Preto d'Oeste - Rond?nia (10 degrees 45'S and 62 degrees 15'W) to evaluate the mycobiota associated with Hypothenemus hampei Ferrari [cuticle, mouth, prothorax (mycangia), gut and feces] and its galleries on berries of Coffea canephora Pierre. Ten genera (201 isolates) were directly related with the insect while five genera (20 isolates) were related with galleries on berries. All the genera identified in the insects were also present in their galleries, what indicates that boring may be an active way of fungi inoculation by H. hampei. The fungi genera were more diverse in the mouth and prothorax of borers, and lower in feces. Fusarium, Penicillium and Geotrichum, with abundance of 55.7, 24.3 and 10.8%, respectively, were dominant genera. In the galleries Fusarium, Geotrichum, Trichoderma and Aspergillus with abundance of 33.3, 29.6, 18.5 and 14.8%, respectively, were dominant genera. The overall presence of Fusarium in coffee berry borer and its galleries) reinforces previous indications of a close interaction between H. hampei-Fusarium. The presence of Aspergillus and Penicillium emphasizes the possibility of "ochratoxin dispersion" by the borer. This work provides the first record of the mycobiota associated with H. hampei in C. canephora. Among the identified genera, Cephalosporium, Geotrichum and Oidiodendrum were recorded for the first time in association with H. hampei and its galleries in C. canephora.     

Both the 5' and 3' LTRs of FIV contain minor RNA encapsidation determinants compared to the two core packaging determinants within the 5' untranslated region and gag

This study was undertaken to address the role of feline immunodeficiency virus (FIV) long terminal repeats (LTR) as potential packaging determinants. A number of studies in the recent past have clearly demonstrated that the core packaging determinants of FIV reside within at least two distinct regions at the 5' end of the viral genome, from R in the 5' LTR to approximately 150 bp within the 5' untranslated region (5' UTR) and within the first 100 bp of gag; however, there have been conflicting observations as to the role of the LTR regions in packaging and whether they contain the principal packaging determinants of FIV. Using a semi-quantitative RT-PCR approach on heterologous non-viral vector RNAs in an in vivo packaging assay, this study demonstrates that the principal packaging determinants of FIV reside within the first 150 bp of 5' UTR and 100 bp of gag (the two core regions) and not the viral 5' LTR. Furthermore, it shows that in addition to the 5' LTR, the 3' LTR also contains packaging determinants, but of a less significant nature compared to the core packaging determinants. This study defines the relative contribution of the various regions implicated in FIV genomic RNA packaging, and reveals that like other primate lentiviruses, the packaging determinants of FIV are multipartite and spread out, an observation that has implications for safer and more streamlined design of FIV-based gene transfer vectors.     

Isolates of Candida albicans that differ in virulence for mice elicit strain-specific antibody-mediated protective responses

Three distinct isolates of Candida albicans were used to establish systemic and oral infections in inbred mice that are genetically resistant or susceptible to tissue damage. Patterns of infection differed significantly between both yeasts and mouse strains. Systemic infection conferred significant protection against re-challenge with the homologous, but not the heterologous yeast; however, the protective effect was more evident in the tissue-susceptible CBA/CaH mice than in the resistant BALB/c strain. In contrast, oral infection induced protection against both homologous and heterologous oral challenge, although this was significant only in the CBA/CaH mice. CBA/CaH mice produced antibodies of both IgG1 and IgG2a subclasses, whereas BALB/c mice produced predominantly IgG1. Western blotting demonstrated considerable differences between epitopes recognised by serum antibodies from mice of both strains after immunisation with each of the three yeasts. Thus, different strains of yeast show considerable specificity in antibody responses elicited by either systemic or oral infection.     

Ca2+-induced rolling of tropomyosin in muscle thin filaments: the alpha- and beta-band hypothesis revisited

Tropomyosin is a filamentous coiled-coil protein directly involved in the regulation of the actomyosin interaction responsible for muscle contraction: it transmits the local calcium-induced conformational change in troponin to the helical array of myosin-binding sites on the surface of the actin filament. McLachlan and Stewart (McLachlan, A. D., and Stewart, M. (1976) J. Mol. Biol. 103, 271-298) proposed that the tropomyosin coiled-coil structure can be divided into 14 alternating 19- to 20-residue "alpha- and beta-bands," which could act as alternate 7-fold sets of sites for specific binding to actin in the different conformational states of the regulated thin filament. Here we present the first direct experimental evidence in support of the alpha- and beta-band hypothesis: we analyze the acrylamide quenching of the fluorescence of mutant tropomyosins containing 5-hydroxytryptophan residues at different positions along the coiled-coil structure under a variety of conditions (alone, complexed with actin, and complexed with actin and troponin with or without Ca(2+)). We show that fluorescent probes placed in the alpha-bands become less solvent-exposed in the absence of calcium, whereas those in the beta-bands become less solvent-exposed in the presence of calcium. A model in which the tropomyosin coiled-coil rolls across the actin surface in response to Ca(2+)-binding to troponin most easily explains these observations.     

Actions or hand-object interactions? Human inferior frontal cortex and action observation

Cells in macaque ventral premotor cortex (area F5c) respond to observation or production of specific hand-object interactions. Studies in humans associate the left inferior frontal gyrus, including putative F5 homolog pars opercularis, with observing hand actions. Are these responses related to the realized goal of a prehensile action or to the observation of dynamic hand movements? Rapid, event-related fMRI was used to address this question. Subjects watched static pictures of the same objects being grasped or touched while performing a 1-back orienting task. In all 17 subjects, bilateral inferior frontal cortex was differentially activated in response to realized goals of observed prehensile actions. Bilaterally, precentral gyrus was most frequently activated (82%) followed by pars triangularis (73%) and pars opercularis (65%).     

Enhanced heart rate variability and baroreflex index after stress and cholinesterase inhibition in mice

Experiments tested the effect of stress coupled with cholinesterase inhibition on blood pressure, heart rate, baroreflex index, and variability in time and frequency domain in conscious mice. The objective was to determine whether cholinergic systems interact with stress to alter cardiovascular responses. Male C57BL/6J mice with arterial catheters were exposed to 3-day treatments: 1) intermittent shaker stress, 2) pyridostigmine (10 mg.kg(-1).day(-1)); or 3) combined pyridostigmine and stress. Pyridostigmine reduced blood cholinesterase (-33%) with no added effects of stress. Twenty-four-hour blood pressure recordings showed that there were no differences in blood pressure and heart rate with the treatments. Pulse interval standard deviation was greatly increased in the pyridostigmine/stress group compared with stress or pyridostigmine groups (11.0 +/- 1.4, 5.0 +/- 0.9, and 7.5 +/- 0.9 ms, respectively). Spectral analysis showed two distinct components for pulse interval variability (low and high frequency). Variability in the low-frequency range was greatly enhanced in the pyridostigmine/stress group, seen as a doubling of the power (9.5 +/- 1.7, 3.3 +/- 0.9, and 5.0 +/- 0.6 ms for pyridostigmine/stress, stress and pyridostigmine groups, respectively). Baroreflex sensitivity was also increased in the pyridostigmine/stress group (3.6 +/- 0.5 compared with 1.8 +/- 0.3 and 1.7 +/- 0.5 ms/mmHg in the stress and pyridostigmine groups, respectively). There was no difference in blood pressure variability or its spectral components. Results demonstrate that there are potent interactions between a mild stressor and cholinesterase inhibition seen as an accentuation of low-frequency variability in pulse interval time series, probably associated with baroreflex input and autonomic drive.