Effects of the vitamin D3 analog 1α,25-dihydroxyvitamin D3-3β-bromoacetate on rat osteosarcoma cells: Comparison with 1α,25-dihydroxyvitamin D3

The actions of the hormonal form of vitamin D, 1α,25-dihydroxyvitamin D₃ [1α,25-(OH)₂D₃], are mediated by both genomic and nongenomic mechanisms. Several vitamin D synthetic analogs have been developed in order to identify and characterize the site(s) of action of 1α,25-(OH)₂D₃ in many cell types including osteoblastic cells. We have compared the effects of 1α,25-(OH)₂D₃ and a novel 1α,25-(OH)₂D₃ bromoester analog (1,25-(OH)₂-BE) that covalently binds to vitamin D receptors. Rat osteosarcoma cells that possess (ROS 17/2.8) or lack (ROS 24/1) the classic intracellular vitamin D receptor were studied to investigate genomic and nongenomic actions. In ROS 17/2.8 cells plated at low density, the two vitamin D compounds (1 × 10⁻⁸ M) caused increased cell proliferation, as assessed by DNA synthesis and total cell counts. Northern blot analysis revealed that the mitogenic effect of both agents was accompanied by an increase in steady-state osteocalcin mRNA levels, but neither agent altered alkaline phosphatase mRNA levels in ROS 17/2.8 cells. ROS 17/2.8 cells responded to 1,25-(OH)₂-BE but not the natural ligand with a significant increase in osteocalcin secretion after 72, 96, 120, and 144 hr of treatment. Treatment of ROS 17/2.8 cells with the bromoester analog also resulted in a significant decrease in alkaline phosphatase-specific activity. To compare the nongenomic effects of 1α,25-(OH)₂D₃ and 1,25-(OH)₂-BE, intracellular calcium was measured in ROS 24/1 cells loaded with the fluorescent calcium indicator Quin 2. At 2 × 10⁻⁸ M, both 1α,25-(OH)₂D₃ and 1,25-(OH)₂-BE increased intracellular calcium within 5 min. Both the genomic and nongenomic actions of 1,25-(OH)₂-BE are similar to those of 1α,25-(OH)₂D₃, and since 1,25-(OH)₂-BE has more potent effects on osteoblast function than the naturally occurring ligand due to more stable binding, this novel vitamin D analog may be useful in elucidating the structure and function of cellular vitamin D receptors. © 1996 Wiley-Liss, Inc.     

Cancer therapy and cardiotoxicity: The need of serial Doppler echocardiography

Morbidity and mortality rates are higher in patients with severe left ventricular (LV) systolic dysfunction and ECG-derived prolonged QRS interval than in those with normal QRS duration. QRS duration is currently used on the grounds that it reflects the presence of ventricular dyssynchrony. However, 30–40% of patients selected on the basis of a prolonged QRS do not receive benefit by cardiac resynchronization therapy (CRT) since they do not show any significant inverse LV remodeling and QRS duration does not accurately distinguish responders to CRT. Consequently, mechanical dyssynchrony (particularly intra-ventricular dyssynchrony) seems to be much more important than electrical dyssinchrony. Pre- and post-echocardiographic assessment should require the combination of conventional and specific applications ranging from M-mode and pulsed/continuous Doppler, to pulsed Tissue Doppler, the off-line analysis of colour Tissue Velocity Imaging, Strain Rate Imaging, and real time three-dimensional reconstruction However, there is not no consensus about the best approach and the best ultrasound parameter for selecting candidates to CRT and ECG representation of abnormal cardiac conduction still remains as the main criterion in guidelines. This review is a practical update of ultrasound methods and measurements of atrio-ventricular, inter-ventricular and intra-ventricular dyssynchrony and describes experiences which used either conventional Doppler echocardiography and more advanced techniques. By these experiences, the global amount of LV dyssynchrony seems to be critical: the greater intra-ventricular dyssynchrony, the higher the possibility of significant LV inverse remodeling. After CRT, it is necessary also to evaluate the optimal atrio-ventricular delay and ventricular-ventricular delay setting that maximizes LV systolic function.     

Hybridization between <Emphasis Type=Italic>Alouatta caraya</Emphasis> and <Emphasis Type=Italic>Alouatta guariba clamitans</Emphasis> in captivity

Hybridization between Alouatta spp. has been suggested at contact zones of A. palliata and A. pigra in Mexico and of A. caraya and A. guariba clamitans in Brazil and Argentina. Whereas genetic data confirmed hybridization between the former pair of species, hybrid individuals of the latter pair have been putatively identified on the basis of a mosaic pelage color. In this paper, we describe the first confirmed cases of hybridization between a female A. guariba clamitans and a male A. caraya. One hybrid male was born in 2007 and one hybrid female was born in 2009 with distinct coat colors. The male resembled the newborn color pattern characteristic of A. guariba clamitans, whereas the female resembled the newborn pattern of A. caraya. The birth and survival of the male hybrid for a year and a half indicated the viability of the heterogametic sex.     

Modelling Co-Infection of the Cystic Fibrosis Lung by Pseudomonas aeruginosa and Burkholderia cenocepacia Reveals Influences on Biofilm Formation and Host Response

The Gram-negative bacteria Pseudomonas aeruginosa and Burkholderia cenocepacia are opportunistic human pathogens that are responsible for severe nosocomial infections in immunocompromised patients and those suffering from cystic fibrosis (CF). These two bacteria have been shown to form biofilms in the airways of CF patients that make such infections more difficult to treat. Only recently have scientists begun to appreciate the complicated interplay between microorganisms during polymicrobial infection of the CF airway and the implications they may have for disease prognosis and response to therapy.To gain insight into the possible role that interaction between strains of P. aeruginosa and B. cenocepacia may play during infection, we characterised co-inoculations of in vivo and in vitro infection models. Co-inoculations were examined in an in vitro biofilm model and in a murine model of chronic infection. Assessment of biofilm formation showed that B. cenocepacia positively influenced P. aeruginosa biofilm development by increasing biomass. Interestingly, co-infection experiments in the mouse model revealed that P. aeruginosa did not change its ability to establish chronic infection in the presence of B. cenocepacia but co-infection did appear to increase host inflammatory response.Taken together, these results indicate that the co-infection of P. aeruginosa and B. cenocepacia leads to increased biofilm formation and increased host inflammatory response in the mouse model of chronic infection. These observations suggest that alteration of bacterial behavior due to interspecies interactions may be important for disease progression and persistent infection.     

Morphological variation over ontogeny and environments in resource polymorphic arctic charr (Salvelinus alpinus)

SUMMARY Natural selection requires genetically based phenotypic variation to facilitate its action and cause adaptive evolution. It has become increasingly recognized that morphological development can become canalized likely as a result of selection. However, it is largely unknown how selection may influence canalization over ontogeny and differing environments. Changes in environments or colonization of a novel one is expected to result in adaptive divergence from the ancestral population when selection favors a new phenotypic optimum. In turn, a novel environment may also expose variation previously hidden from natural selection. We tested for changes in phenotypic variation over ontogeny and environments among ecomorphs of Arctic charr (Salvelinus alpinus) from two Icelandic lakes. Populations represented varying degrees of ecological specialization, with one lake population possessing highly specialized ecomorphs exhibiting a large degree of phenotypic divergence, whereas the other displayed more subtle divergence with more ecological overlap. Here we show that ecomorphs hypothesized to be the most specialized in each lake possess significant reductions in shape variation over ontogeny regardless of environmental treatment suggesting canalized development. However, environments did change the amount of shape variation expressed in these ecomorphs, with novel environments slowing the rate at which variation was reduced over ontogeny. Thus, environmental conditions may play an important role in determining the type and amount of genetically based phenotypic variation exposed to natural selection.     

Of mice and (Viking?) men: phylogeography of British and Irish house mice

The west European subspecies of house mouse (Mus musculus domesticus) has gained much of its current widespread distribution through commensalism with humans. This means that the phylogeography of M. m. domesticus should reflect patterns of human movements. We studied restriction fragment length polymorphism (RFLP) and DNA sequence variations in mouse mitochondrial (mt) DNA throughout the British Isles (328 mice from 105 localities, including previously published data). There is a major mtDNA lineage revealed by both RFLP and sequence analyses, which is restricted to the northern and western peripheries of the British Isles, and also occurs in Norway. This distribution of the 'Orkney' lineage fits well with the sphere of influence of the Norwegian Vikings and was probably generated through inadvertent transport by them. To form viable populations, house mice would have required large human settlements such as the Norwegian Vikings founded. The other parts of the British Isles (essentially most of mainland Britain) are characterized by house mice with different mtDNA sequences, some of which are also found in Germany, and which probably reflect both Iron Age movements of people and mice and earlier development of large human settlements. MtDNA studies on house mice have the potential to reveal novel aspects of human history.     

Unusual partially 3-O-methylated alpha-galactan from mushrooms of the genus Pleurotus

Indistinguishable partially 3-O-methylated galactans were isolated from the edible basidiomycetes Pleurotus eryngii and Pleurotus ostreatoroseus. They were obtained via successive aqueous extraction, freeze-thawing, precipitation with Fehling solution of soluble material, and ultrafiltration. Mono- and bidimensional 13C and 1H-nuclear magnetic resonance spectroscopy (HMBC, HETEROTOCSY, COSY, and HMQC), and methylation analysis were used to determine their structures. They were linear, partially 3-O-methylated, (1-->6)-linked alpha-d-galactans containing Gal and 3-Me-Gal, in a 3:1 molar ratio (GC-MS of alditol acetates).     

QTL associated with Fusarium head blight resistance in the soft red winter wheat Ernie

Fusarium head blight (FHB), mainly caused by Fusarium graminearum Schwabe [telomorph: Gibberella zeae Schw. (Petch)], is an increasingly important disease of wheat (Triticum aestivum L.). Host-plant resistance provides the best hope for reducing economic losses associated with FHB, but new sources of resistance are limited. The moderately resistant winter wheat cultivar, Ernie, may provide a source of resistance that differs from Sumai 3 but these genes have not been mapped. Also hindering resistance breeding may be associations of resistance with agronomic traits such as late maturity that may be undesirable in some production environments. This research was conducted to identify QTL associated with type II FHB resistance (FHB severity, FHBS), and to determine if they are associated with days to anthesis (DTA), number of spikelets (NOS), and the presence/absence of awns. Two hundred and forty-three F₈ recombinant inbred lines from a cross between the resistant cultivar, Ernie and susceptible parent, MO 94-317 were phenotyped for type II FHB resistance using point inoculation in the greenhouse during 2002 and 2003. Genetic linkage maps were constructed using 94 simple sequence repeat (SSR) and 146 amplified fragment length polymorphic (AFLP) markers. Over years four QTL regions on chromosomes 2B, 3B, 4BL and 5A were consistently associated with FHB resistance. These QTL explained 43.3% of the phenotypic variation in FHBS. Major QTL conditioning DTA and NOS were identified on chromosome 2D. Neither the QTL associated with DTA and NOS nor the presence/absence of awns were associated with FHB resistance in Ernie. Our results suggest that the FHB resistance in Ernie appears to differ from that in Sumai 3, thus pyramiding the QTL in Ernie with those from Sumai 3 could result in enhanced levels of FHB resistance in wheat.