Progressive Muscular Dystrophy in α-Sarcoglycan–deficient Mice

Limb-girdle muscular dystrophy type 2D (LGMD 2D) is an autosomal recessive disorder caused by mutations in the α-sarcoglycan gene. To determine how α-sarcoglycan deficiency leads to muscle fiber degeneration, we generated and analyzed α-sarcoglycan– deficient mice. Sgca-null mice developed progressive muscular dystrophy and, in contrast to other animal models for muscular dystrophy, showed ongoing muscle necrosis with age, a hallmark of the human disease. Sgca-null mice also revealed loss of sarcolemmal integrity, elevated serum levels of muscle enzymes, increased muscle masses, and changes in the generation of absolute force. Molecular analysis of Sgca-null mice demonstrated that the absence of α-sarcoglycan resulted in the complete loss of the sarcoglycan complex, sarcospan, and a disruption of α-dystroglycan association with membranes. In contrast, no change in the expression of ε-sarcoglycan (α-sarcoglycan homologue) was observed. Recombinant α-sarcoglycan adenovirus injection into Sgca-deficient muscles restored the sarcoglycan complex and sarcospan to the membrane. We propose that the sarcoglycan–sarcospan complex is requisite for stable association of α-dystroglycan with the sarcolemma. The Sgca-deficient mice will be a valuable model for elucidating the pathogenesis of sarcoglycan deficient limb-girdle muscular dystrophies and for the development of therapeutic strategies for this disease.     

The habitat hectares approach to vegetation assessment: An evaluation and suggestions for improvement

Summary The habitat hectares approach is an explicit, quantitative method for assessing the quality of vegetation by adding scores that are assigned to 10 habitat attributes. We believe it will be more repeatable and transparent than other methods that rely on subjective judgement. However, we have four principal criticisms of the method as it is currently proposed: (i) measurement of some of the attributes may be subject to considerable error that varies among assessors; (ii) the comparison of each measure with a single benchmark does not accommodate appropriate disturbance regimes; (iii) the proposed combination of attributes leads to some apparent internal inconsistencies; and (iv) it is not clear how the method will actually be used in practice. We suggest modifications to address these concerns and improve the proposed method. Finally, we make additional suggestions about the method's potential application, including: separate reporting of the extent and quality of different vegetation types to avoid the inappropriate combination of measures of area and quality; valuing appropriate disturbance regimes in natural areas; and considering very carefully the application of compensation or mitigation measures.     

A primer on ankyrin repeat function in TRP channels and beyond

Transient receptor potential (TRP) channels are rapidly gaining attention as important receptors and transducers of diverse sensory and environmental cues. Recent progress in the field has provided new insights into the structure and function of the ankyrin repeat motifs present in the N-terminal cytosolic domain of many TRP channels. The topics addressed in this Highlight include the structural features of canonical ankyrin repeats, new clues into the functions these repeats perform in cells, and how this information can be applied to develop further experiments on TRP channels and other proteins containing ankyrin repeats.     

Discovery and evaluation of single nucleotide polymorphisms (SNPs) for Haliotis midae: a targeted EST approach

In this study, we describe the first set of SNP markers for the South African abalone, Haliotis midae. A cDNA library was constructed from which ESTs were selected for the screening of SNPs. The observed frequency of SNPs in this species was estimated at one every 185 bp. When characterized in wild-caught abalone, the minor allele frequencies and F(ST) estimates for every SNP indicated that these markers may potentially be useful for population analysis, parentage assignment and linkage mapping in Haliotis midae. No linkage disequilibrium was observed between SNPs originating from different EST sequences. These SNPs, together with additional SNPs currently being developed, will provide a useful complementary set of markers to the currently available genetic markers in abalone.     

Effect of creatine phosphate supplementation on anaerobic working capacity and body weight after two and six days of loading in men and women

The purpose of this study was to determine the effects of 2 and 6 days of creatine phosphate loading on anaerobic working capacity (AWC) and body weight (BW) in men and women. Sixty-one men (n = 31) and women (n = 30) randomly received 1 of 3 treatments (4 x 5 g.d(-1) x 6 days) using a double blind design: (a) 18 g dextrose as placebo (PL); (b) 5.0 g Cr + 20 g dextrose (Cr); or (c) 5.0 g Cr + 18 g dextrose + 4 g of sodium and potassium phosphates (CrP). AWC was determined at baseline and following 2 and 6 days of supplementation using the Critical Power Test. BW increased significantly over time, and the mean value for the men was significantly greater compared to that for women, but there were no interactions (p > 0.05). There were gender-specific responses for AWC expressed in both absolute values (kJ) and relative to BW (kJ. kg(-1)), with the women demonstrating no significant interactions. For the men, CrP loading significantly increased AWC following 2 days (23.8%) and 6 days (49.8%) of supplementation vs. PL (kJ and kJ.kg(-1)). Cr supplementation increased AWC 13-15% in both genders compared to PL (1.1%- 3.0% decline); although this result was not statistically significant, it may have some practical significance.     

Response of the microbial community to copper oxychloride in acidic sandy loam soil

AIMS: Determining the response of different microbial parameters to copper oxychloride in acidic sandy loam soil samples using cultivation-dependent and direct microscopic techniques. METHODS AND RESULTS: Culturable microbial populations were monitored for 245 days in a series of soil microcosms spiked with different copper oxychloride concentrations. Microbial populations responded differently to additional Cu. Protistan numbers and soil metabolic potential decreased. Experiments with more soil samples revealed that metabolic potential was not significantly affected by < or =100 mg kg(-1) additional Cu. However, a negative impact on protista was noted in soil containing only 15 mg kg(-1) EDTA-extractable Cu. The negative impact on protistan numbers was less severe in soils with a higher phosphorous and zinc content. CONCLUSIONS: Bacterial populations responded differently, and protista were most sensitive to elevated Cu levels. Protistan numbers in soil from uncultivated land were higher and seemed to be more sensitive to additional Cu than the numbers of these organisms in soil originating from cultivated land. SIGNIFICANCE AND IMPACT OF THE STUDY: Protistan sensitivity to small increases in Cu levels demonstrates the vulnerability of the soil ecosystem to Cu perturbations, especially when the importance of protista as link in the flow of energy between trophic levels is considered.     

Perillyl alcohol as a radio-/chemosensitizer in malignant glioma

The prognosis for patients with malignant glioma has not significantly changed in two decades, despite advances in surgery, radiation, and chemotherapy, emphasizing the growing need for novel approaches to glioma therapy. Perillyl alcohol (POH) is a naturally occurring monoterpene that has been shown to possess chemotherapeutic as well as chemopreventive activity in animal tumor models and is currently in Phase I and Phase II clinical trials. In the present study, we have demonstrated that POH is an effective radiosensitizer at clinically relevant doses of radiation using established glioma cell lines. POH caused a transient arrest in the G2/M phase of the cell cycle and induced apoptosis in glioma cells. POH treatment sensitized glioma cells to Fas-mediated apoptosis, which was further augmented in the presence of ionizing radiation and abrogated in the presence of antagonistic antibody. POH-induced radiosensitization was partially inhibited in glioma cells expressing dominant negative Fas-associated death domain and completely inhibited in glioma cells overexpressing the cytokine response modifier A. In addition, POH treatment resulted in a dose-dependent sensitization to cisplatin and doxorubicin induced cytotoxicity in glioma cells, highlighting its usefulness as a potent radio/chemosensitizer in the treatment of malignant glioma.     

Inter-island movements and population differentiation in a pelagic seabird

We used mark-resight data and amplified fragment length polymorphism (AFLP) markers to assess movements and gene flow between Central Pacific breeding colonies of the great frigatebird, Fregata minor. Of 715 adult frigatebirds marked on Tern Island and Johnston Atoll, 21.3% were resighted at other frigatebird colonies at least 582 km away. Mark-resight data indicated regular movement of males and females between Tern Island and Johnston Atoll (873 km apart), and less frequent movements to other islands; no birds marked on Tern or Johnston were seen on Christmas Island, but one was seen in the Philippines, 7627 km from where it was marked. Despite the regular occurrence of interisland movements, Bayesian analyses of AFLP data showed significant genetic differentiation between Tern Island and Johnston Atoll, and more pronounced differentiation between these two islands and the more distant Christmas Island. The AFLP profiles of three birds breeding on Tern Island fell within the profile-cluster typical for Christmas Island birds, both in a nonmetric multidimensional scaling analysis and in a population assignment test, suggesting dispersal events from Christmas Island to Tern Island. Several factors could explain the persistence of genetic structure despite frequent movements between colonies: many movements occurred during the nonbreeding season, many breeding-season movements did not involve mate-acquisition behaviours and individuals that do disperse may be selected against, as suggested by morphometric differences between colonies. The persistence of genetic structure among breeding colonies despite significant interisland movements suggests limits to the effectiveness of migration as a homogenizing force in this broadly distributed, extremely mobile species.     

Growth kinetics of extremely halophilic archaea (family halobacteriaceae) as revealed by arrhenius plots

Members of the family Halobacteriaceae in the domain Archaea are obligate extreme halophiles. They occupy a variety of hypersaline environments, and their cellular biochemistry functions in a nearly saturated salty milieu. Despite extensive study, a detailed analysis of their growth kinetics is missing. To remedy this, Arrhenius plots for 14 type species of the family were generated. These organisms had maximum growth temperatures ranging from 49 to 58 degrees C. Nine of the organisms exhibited a single temperature optimum, while five grew optimally at more than one temperature. Generation times at these optimal temperatures ranged from 1.5 h (Haloterrigena turkmenica) to 3.0 h (Haloarcula vallismortis and Halorubrum saccharovorum). All shared an inflection point at 31 +/- 4 degrees C, and the temperature characteristics for 12 of the 14 type species were nearly parallel. The other two species (Natronomonas pharaonis and Natronorubrum bangense) had significantly different temperature characteristics, suggesting that the physiology of these strains is different. In addition, these data show that the type species for the family Halobacteriaceae share similar growth kinetics and are capable of much faster growth at higher temperatures than those previously reported.