Dilated Cardiomyopathy with Increased SR Ca2+ Loading Preceded by a Hypercontractile State and Diastolic Failure in the α1CTG Mouse

Mice over-expressing the α₁₋subunit (pore) of the L-type Ca²⁺ channel (α_1CTG) by 4months (mo) of age exhibit an enlarged heart, hypertrophied myocytes, increased Ca²⁺ current and Ca²⁺ transient amplitude, but a normal SR Ca²⁺ load. With advancing age (8–11 mo), some mice demonstrate advanced hypertrophy but are not in congestive heart failure (NFTG), while others evolve to frank dilated congestive heart failure (FTG). We demonstrate that older NFTG myocytes exhibit a hypercontractile state over a wide range of stimulation frequencies, but maintain a normal SR Ca²⁺ load compared to age matched non-transgenic (NTG) myocytes. However, at high stimulation rates (2–4 Hz) signs of diastolic contractile failure appear in NFTG cells. The evolution of frank congestive failure in FTG is accompanied by a further increase in heart mass and myocyte size, and phospholamban and ryanodine receptor protein levels and phosphorylation become reduced. In FTG, the SR Ca²⁺ load increases and Ca²⁺ release following excitation, increases further. An enhanced NCX function in FTG, as reflected by an accelerated relaxation of the caffeine-induced Ca²⁺ transient, is insufficient to maintain a normal diastolic Ca²⁺ during high rates of stimulation. Although a high SR Ca²⁺ release following excitation is maintained, the hypercontractile state is not maintained at high rates of stimulation, and signs of both systolic and diastolic contractile failure appear. Thus, the dilated cardiomyopathy that evolves in this mouse model exhibits signs of both systolic and diastolic failure, but not a deficient SR Ca²⁺ loading or release, as occurs in some other cardiomyopathic models.     

Zooplankton in the Schelde estuary, Belgium and The Netherlands. Spatial and temporal patterns

The zooplankton fauna of the Zeeschelde estuary (Belgium) wasinvestigated over 10 months by means of monthly sampling. CanonicalCorrespondence Analysis (CCA) was used to relate the speciesdistribution to environmental factors. The variation in thespecies data was significantly (P < 0.05) related to a setof 10 environmental variables (chlorinity, NH₄⁺, temperature,PO₄-P^-, DW, Chl a and Chl b, NO₂-N, NO₃-N and pH). The mainspatial and seasonal gradients were associated with chlorinityand temperature respectively. The brackish water zone was dominatedby the calanoid Eurytemora affinis in spring, succeeded by Acartiatonsa and mysid species during summer. In the freshwater transect,cyclopoids dominated, together with several cladoceran species.Thermophilic cyclopoid species (Thermocyclops oithonoides, Th.crassus and Mesocyclops leuckarti) occurred during periods ofmaximal temperature. The cyclopoids Acanthocyclops robustus,Paracyclops poppei and Cyclops vicinus, the cladocerans Daphnialongispina, Chydorus sphaericus and Bosmina longirostris togetherwith the numerically dominant rotifers, oligochaetes, nematodesand juvenile copepods seemed little affected by environmentalgradients.     

Effects of allogeneic contact on life-history traits of the colonial ascidian Botryllus schlosseri in Monterey Bay

The formation of chimeric colonies following allogeneic contact between benthic invertebrates may strongly affect colony fitness. Here we show that, in a field population of the colonial ascidian Botryllus schlosseri in Monterey Bay, California, more than 20% of all colonies occur in allogeneic contact with conspecifics. We experimentally assessed the effects of allogeneic contact on the following life-history traits under natural field conditions: growth, age and size at first reproduction, and egg production (fecundity). When compared with isolated colonies, and in some cohorts also with colonies that rejected allogeneic neighbors, colonies that fused with neighbors incurred reduced fitness in terms of most life-history traits measured. We propose that one of the benefits of precise allorecognition is that, in fused colonies, it limits the unit of selection to chimeric individuals composed of closely related kin.     

Life on the edge – to which degree does phreatic water sustain vegetation in the periphery of the Taklamakan Desert?

Questions: Do the vegetation‐specific patterns in the forelands of river oases of the Taklamakan Desert provide clues to the degree to which a vegetation type depends on unsaturated soil moisture, brought about by extensive floodings, or phreatic water? Location: Foreland of the Qira oasis on the southern rim of the Taklamakan Desert, Xinjiang Uygur Autonomous Region, China. Methods: A vegetation map was prepared using a SPOT satellite image and ground truthing. Measurements of soil water contents were obtained from a flooding experiment and transformed into water potentials. Sum excedance values were calculated as the percentage of days on which different thresholds of soil water potentials were transgressed. Groundwater depth was mapped by drilling 30 groundwater holes and extrapolating the distances to the whole study area. Results: The vegetation was characterized by only six dominant or codominant species: Alhagi sparsifolia, Karelinia caspia, Populus euphratica, Tamarix ramosissima, Calligonum caput‐medusae and Phragmites australis. The vegetation patterns encountered lacked any linear features typical of phreatophytes, thus not allowing direct conclusions on the type of the sustaining water sources. Soil water potentials never transgressed a threshold of pF 5 (?10 MPa) in horizons above the capillary fringe during periods without inundation, thus representing water not accessible for plants. Depth to the groundwater ranged between 2.3 and 17.5 m among plots and varied between 1.7 and 8.0 m within a plot owing to dune relief. The seven main vegetation types showed distinct niches of groundwater depths, corresponding to the observed concentric arrangement of vegetation types around the oasis. Conclusions: Inundation by flooding and unsaturated soil moisture are irrelevant for the foreland vegetation water supply. Although distances to the groundwater table can reach about 20 m, which is exceptionally large for phreatophytes, groundwater is the only water source for all vegetation types in the oasis foreland. In consequence, successful maintenance of oasis foreland vegetation will crucially depend on providing non‐declining ground water tables.     

Heterogeneity in SDF-1 expression defines the vasculogenic potential of adult cardiac progenitor cells

Rationale

The adult myocardium has been reported to harbor several classes of multipotent progenitor cells (CPCs) with tri-lineage differentiation potential. It is not clear whether c-kit+CPCs represent a uniform precursor population or a more complex mixture of cell types.

Objective

To characterize and understand vasculogenic heterogeneity within c-kit+presumptive cardiac progenitor cell populations.

Methods and Results

c-kit+, sca-1+ CPCs obtained from adult mouse left ventricle expressed stem cell-associated genes, including Oct-4 and Myc, and were self-renewing, pluripotent and clonogenic. Detailed single cell clonal analysis of 17 clones revealed that most (14/17) exhibited trilineage differentiation potential. However, striking morphological differences were observed among clones that were heritable and stable in long-term culture. 3 major groups were identified: round (7/17), flat or spindle-shaped (5/17) and stellate (5/17). Stellate morphology was predictive of vasculogenic differentiation in Matrigel. Genome-wide expression studies and bioinformatic analysis revealed clonally stable, heritable differences in stromal cell-derived factor-1 (SDF-1) expression that correlated strongly with stellate morphology and vasculogenic capacity. Endogenous SDF-1 production contributed directly to vasculogenic differentiation: both shRNA-mediated knockdown of SDF-1 and AMD3100, an antagonist of the SDF-1 receptor CXC chemokine Receptor-4 (CXCR4), reduced tube-forming capacity, while exogenous SDF-1 induced tube formation by 2 non-vasculogenic clones. CPCs producing SDF-1 were able to vascularize Matrigel dermal implants in vivo, while CPCs with low SDF-1 production were not.

Conclusions

Clonogenic c-kit+, sca-1+ CPCs are heterogeneous in morphology, gene expression patterns and differentiation potential. Clone-specific levels of SDF-1 expression both predict and promote development of a vasculogenic phenotype via a previously unreported autocrine mechanism.     

Exploring the Functional Complementation between Grp94 and Hsp90

Grp94 and Hsp90 are the ER and cytoplasmic paralog members, respectively, of the hsp90 family of molecular chaperones. The structural and biochemical differences between Hsp90 and Grp94 that allow each paralog to efficiently chaperone its particular set of clients are poorly understood. The two paralogs exhibit a high degree of sequence similarity, yet also display significant differences in their quaternary conformations and ATPase activity. In order to identify the structural elements that distinguish Grp94 from Hsp90, we characterized the similarities and differences between the two proteins by testing the ability of Hsp90/Grp94 chimeras to functionally substitute for the wild-type chaperones in vivo. We show that the N-terminal domain or the combination of the second lobe of the Middle domain plus the C-terminal domain of Grp94 can functionally substitute for their yeast Hsp90 counterparts but that the equivalent Hsp90 domains cannot functionally replace their counterparts in Grp94. These results also identify the interface between the Middle and C-terminal domains as an important structural unit within the Hsp90 family.     

A blend of formic acid,benzoic acid,and aliphatic alkanes mediates alarm recruitment responses in western carpenter ants,Camponotus modoc

Formicine ants in distress spray alarm pheromone which typically recruits nestmates for help. Studying the western carpenter ant, Camponotus modoc Wheeler (Hymenoptera: Formicidae), our objectives were to (1) determine the exocrine glands that contain alarm recruitment pheromone, (2) identify the key alarm recruitment pheromone components, and (3) ascertain the pheromone components that are discharged by distressed ants. In Y-tube olfactometer experiments, extracts of poison glands, but not of Dufour’s glands, elicited anemotactic responses from worker ants. Gas chromatographic-mass spectrometric analyses of poison gland extracts revealed the presence of (1) aliphatic alkanes (undecane, tridecane, pentadecane, heptadecane), (2) aliphatic alkenes [(Z)-7-pentadecene, (Z)-7- and (Z)-8-heptadecene], (3) two acids (formic, benzoic), and (4) other oxygenated compounds (hexadecan-1-ol, hexadecyl formate, hexadecyl acetate). Testing the responses of worker ants in Y-tube olfactometers to complete and partial synthetic blends of these compounds revealed that the acids and the alkanes are essential alarm pheromone components. In two-choice arena bioassays, micro-locations treated with synthetic alarm pheromone recruited worker ants. Acids and alkanes were abundant in the poison gland and the Dufour’s gland, respectively, suggesting that the alarm pheromone components originate from both glands. Moreover, alarm pheromone sprays of ants differed in that all sprays contained formic acid but only some also contained alkanes, implying that ants can independently discharge the content of either one or both glands in accordance with the type of distress incident they experience.     

Cluster analysis of the national weight control registry to identify distinct subgroups maintaining successful weight loss

The National Weight Control Registry (NWCR) is the largest ongoing study of individuals successful at maintaining weight loss; the registry enrolls individuals maintaining a weight loss of at least 13.6 kg (30 lb) for a minimum of 1 year. The current report uses multivariate latent class cluster analysis to identify unique clusters of individuals within the NWCR that have distinct experiences, strategies, and attitudes with respect to weight loss and weight loss maintenance. The cluster analysis considers weight and health history, weight control behaviors and strategies, effort and satisfaction with maintaining weight, and psychological and demographic characteristics. The analysis includes 2,228 participants enrolled between 1998 and 2002. Cluster 1 (50.5%) represents a weight-stable, healthy, exercise conscious group who are very satisfied with their current weight. Cluster 2 (26.9%) has continuously struggled with weight since childhood; they rely on the greatest number of resources and strategies to lose and maintain weight, and report higher levels of stress and depression. Cluster 3 (12.7%) represents a group successful at weight reduction on the first attempt; they were least likely to be overweight as children, are maintaining the longest duration of weight loss, and report the least difficulty maintaining weight. Cluster 4 (9.9%) represents a group less likely to use exercise to control weight; they tend to be older, eat fewer meals, and report more health problems. Further exploration of the unique characteristics of these clusters could be useful for tailoring future weight loss and weight maintenance programs to the specific characteristics of an individual.     

Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity

Alpha/beta interferon immune defenses are essential for resistance to viruses and can be triggered through the actions of the cytoplasmic helicases retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). Signaling by each is initiated by the recognition of viral products such as RNA and occurs through downstream interaction with the IPS-1 adaptor protein. We directly compared the innate immune signaling requirements of representative viruses of the Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Reoviridae for RIG-I, MDA5, and interferon promoter-stimulating factor 1 (IPS-1). In cultured fibroblasts, IPS-1 was essential for innate immune signaling of downstream interferon regulatory factor 3 activation and interferon-stimulated gene expression, but the requirements for RIG-I and MDA5 were variable. Each was individually dispensable for signaling triggered by reovirus and dengue virus, whereas RIG-I was essential for signaling by influenza A virus, influenza B virus, and human respiratory syncytial virus. Functional genomics analyses identified cellular genes triggered during influenza A virus infection whose expression was strictly dependent on RIG-I and which are involved in processes of innate or adaptive immunity, apoptosis, cytokine signaling, and inflammation associated with the host response to contemporary and pandemic strains of influenza virus. These results define IPS-1-dependent signaling as an essential feature of host immunity to RNA virus infection. Our observations further demonstrate differential and redundant roles for RIG-I and MDA5 in pathogen recognition and innate immune signaling that may reflect unique and shared biologic properties of RNA viruses whose differential triggering and control of gene expression may impact pathogenesis and infection.     

Female German cockroaches join conspecific groups based on the incidence of auditory cues

Insects deciding whether to approach and join a group of conspecifics may utilize olfactory and auditory signals, or cues, from that group as indicators of its size or the suitability of its shelter. Here we show (1) that German cockroaches, Blattella germanica L. (Dictyoptera: Blattellidae), in groups wing‐fan; (2) that the incidence of wing‐fanning (WF) increases proportionately to group size; and (3) that gravid females utilize auditory cues associated with WF behaviour when they decide whether or not to enter a shelter. In binary choice arena bioassays, proportionately more gravid females avoided shelters associated with play‐back of high‐incidence male‐ or female‐produced WF sound, indicating a high‐density group of conspecifics, but sought shelters associated with play‐back of low‐incidence WF sound, indicating a low‐density group of conspecifics. These auditory cues seem to convey information on group size or density, avoid sensory fatigue in enclosed environments, and allow sonotactic orientation to the group's location.