CRIM1 Complexes with ?-catenin and Cadherins,Stabilizes Cell-Cell Junctions and Is Critical for Neural Morphogenesis

In multicellular organisms, morphogenesis is a highly coordinated process that requires dynamically regulated adhesion between cells. An excellent example of cellular morphogenesis is the formation of the neural tube from the flattened epithelium of the neural plate. Cysteine-rich motor neuron protein 1 (CRIM1) is a single-pass (type 1) transmembrane protein that is expressed in neural structures beginning at the neural plate stage. In the frog Xenopus laevis, loss of function studies using CRIM1 antisense morpholino oligonucleotides resulted in a failure of neural development. The CRIM1 knockdown phenotype was, in some cases, mild and resulted in perturbed neural fold morphogenesis. In severely affected embryos there was a dramatic failure of cell adhesion in the neural plate and complete absence of neural structures subsequently. Investigation of the mechanism of CRIM1 function revealed that it can form complexes with ß-catenin and cadherins, albeit indirectly, via the cytosolic domain. Consistent with this, CRIM1 knockdown resulted in diminished levels of cadherins and ß-catenin in junctional complexes in the neural plate. We conclude that CRIM1 is critical for cell-cell adhesion during neural development because it is required for the function of cadherin-dependent junctions.     

CRIM1 complexes with ß-catenin and cadherins, stabilizes cell-cell junctions and is critical for neural morphogenesis

In multicellular organisms, morphogenesis is a highly coordinated process that requires dynamically regulated adhesion between cells. An excellent example of cellular morphogenesis is the formation of the neural tube from the flattened epithelium of the neural plate. Cysteine-rich motor neuron protein 1 (CRIM1) is a single-pass (type 1) transmembrane protein that is expressed in neural structures beginning at the neural plate stage. In the frog Xenopus laevis, loss of function studies using CRIM1 antisense morpholino oligonucleotides resulted in a failure of neural development. The CRIM1 knockdown phenotype was, in some cases, mild and resulted in perturbed neural fold morphogenesis. In severely affected embryos there was a dramatic failure of cell adhesion in the neural plate and complete absence of neural structures subsequently. Investigation of the mechanism of CRIM1 function revealed that it can form complexes with ?-catenin and cadherins, albeit indirectly, via the cytosolic domain. Consistent with this, CRIM1 knockdown resulted in diminished levels of cadherins and ?-catenin in junctional complexes in the neural plate. We conclude that CRIM1 is critical for cell-cell adhesion during neural development because it is required for the function of cadherin-dependent junctions.     

Synthesis and antiviral activity of certain second generation methylenecyclopropane nucleosides

A second-generation series of substituted methylenecyclopropane nucleosides (MCPNs) has been synthesized and evaluated for antiviral activity against a panel of human herpesviruses, and for cytotoxicity. Although alkylated 2,6-diaminopurine analogs showed little antiviral activity, the compounds containing ether and thioether substituents at the 6-position of the purine did demonstrate potent and selective antiviral activity against several different human herpesviruses. In the 6-alkoxy series, antiviral activity depended on the length of the ether carbon chain, with the optimum chain length being about four carbon units long. For the corresponding thioethers, compounds containing secondary thioethers were more potent than those with primary thioethers.     

Clinical features and predictors for disease natural progression in adults with Pompe disease: a nationwide prospective observational study

Background

Due partly to physicians’ unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression.

Methods

We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry), muscle function (quick motor function test), and pulmonary function (forced vital capacity in sitting and supine positions) were assessed every 3–6 months and analyzed using repeated-measures ANOVA.

Results

Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were included in the study. Although skeletal muscle weakness was typically distributed in a limb-girdle pattern, many patients had unfamiliar features such as ptosis (23%), bulbar weakness (28%), and scapular winging (33%). During follow-up (average 1.6 years, range 0.5-4.2 years), skeletal muscle strength deteriorated significantly (mean declines of ?1.3% point/year for manual muscle testing and of ?2.6% points/year for hand-held dynamometry; both p<0.001). Longer disease duration (>15 years) and pulmonary involvement (forced vital capacity in sitting position <80%) at study entry predicted faster decline. On average, forced vital capacity in supine position deteriorated by 1.3% points per year (p=0.02). Decline in pulmonary function was consistent across subgroups. Ten percent of patients declined unexpectedly fast.

Conclusions

Recognizing patterns of common and less familiar characteristics in adults with Pompe disease facilitates timely diagnosis. Longer disease duration and reduced pulmonary function stand out as predictors of rapid disease progression, and aid in deciding whether to initiate enzyme replacement therapy, or when.

     

Rodent Plasmodium: population dynamics of early sporogony within Anopheles stephensi mosquitoes

Early sporogony of Plasmodium parasites involves 2 major developmental transitions within the insect vector, i.e., gametocyte-to-ookinete and ookinete-to-oocyst. This study compared the population dynamics of early sporogony among murine rodent Plasmodium (Plasmodium berghei, Plasmodium chabaudi, Plasmodium vinckei, and Plasmodium yoelii) developing within Anopheles stephensi mosquitoes. Estimates of absolute densities were determined for gametocytes, ookinetes, and oocysts for 108 experimental infections. Total losses throughout early sporogony were greatest in P. vinckei (ca. 250,000-fold loss), followed by P. yoelii (ca. 70,000-fold loss), P. berghei (ca. 45,000-fold loss), and P. chabaudi (ca. 15,000-fold loss). The gametocyte-to-ookinete transition represented the most severe population bottleneck. Numerical losses during this transition (ca. 3,000- to 30,000-fold, depending on species) were orders of magnitude greater than losses incurred during the ookinete-to-oocyst transition (3- to 14-fold). There were no significant correlations between gametocyte and ookinete densities. Significant correlations between ookinete and oocyst densities existed for P. berghei, P. chabaudi, and P. yoelii (but not for P. vinckei), and were best described by nonlinear functions (P. berghei = sigmoid, P. chabaudi = hyperbolic, P. yoelii = sigmoid), indicating that conversion of ookinetes to oocysts in these species is density dependent. The upper theoretical limit for oocyst density on the mosquito midgut for P. chabaudi and P. yoelii (ca. 300 oocysts per midgut) was higher than for P. berghei (ca. 30 oocysts per midgut). This study provides basic information about population processes that occur during the early sporogonic development of some common laboratory model systems of malaria.     

Using amplified fragment length polymorphism analysis to differentiate isolates of Pasteurella multocida serotype 1

Avian cholera, an infectious disease caused by the bacterium Pasteurella multocida, kills thousands of North American wild waterfowl annually. Pasteurella multocida serotype 1 isolates cultured during a laboratory challenge study of Mallards (Anas platyrhynchos) and collected from wild birds and environmental samples during avian cholera outbreaks were characterized using amplified fragment length polymorphism (AFLP) analysis, a whole-genome DNA fingerprinting technique. Comparison of the AFLP profiles of 53 isolates from the laboratory challenge demonstrated that P. multocida underwent genetic changes during a 3-mo period. Analysis of 120 P. multocida serotype 1 isolates collected from wild birds and environmental samples revealed that isolates were distinguishable from one another based on regional and temporal genetic characteristics. Thus, AFLP analysis had the ability to distinguish P. multocida isolates of the same serotype by detecting spatiotemporal genetic changes and provides a tool to advance the study of avian cholera epidemiology. Further application of AFLP technology to the examination of wild bird avian cholera outbreaks may facilitate more effective management of this disease by providing the potential to investigate correlations between virulence and P. multocida genotypes, to identify affiliations between bird species and bacterial genotypes, and to elucidate the role of specific bird species in disease transmission.     

Meal-related changes in ghrelin, peptide YY, and appetite in normal weight and overweight children

Objective: Ghrelin and peptide YY (PYY) are two gut hormones that have effects on appetite. Our objectives were to characterize the patterns of secretion of these hormones in response to feeding in school‐age children and determine whether there were differences between normal weight (NW) and overweight (OW) subjects. Methods and Procedures: This was a cross‐sectional study at one tertiary care center. Subjects were 7‐ to 11‐year‐old healthy NW and OW volunteers recruited from local advertisements. Following an overnight fast, the subjects were given a standardized breakfast and lunch and had nine hourly blood samples for total ghrelin and total PYY. We assessed whether ghrelin and PYY levels changed from the preprandial to postprandial state and corresponded to reported hunger/satiety. Results: Hunger ratings were similar between the two groups throughout the study period. Ghrelin was not suppressed after eating, did not rise prior to the next meal, and did not correspond to hunger ratings in either group. PYY increased postprandially and decreased preprandially in the NW group, but OW children exhibited this pattern for only part of the day. PYY levels incompletely corresponded to reported satiety in the OW group. Discussion: Mixed meal consumption had little effect on ghrelin secretion and a variable effect on PYY secretion in young children in our study. Differences that were observed between the groups do not suggest that an abnormality in their secretion contributes to the development of obesity.     

A study of the microbial quality of grey water and an evaluation of treatment technologies for reuse

The reuse of grey water for non-potable water applications is a potential solution for water-deprived regions worldwide. Adequate treatment of grey water prior to reuse is important to reduce the risks of pathogen transmission and to improve the efficacy of subsequent disinfection. This study investigated the presence of common pathogens in grey water and compared the pathogen removal performance of leading contender treatment technologies. The opportunistic pathogens Pseudomonas aeruginosa and Staphylococcus aureus were detected in the grey water tested. Three configurations of constructed wetland, a membrane bioreactor (MBR), and a membrane chemical reactor (MCR) were evaluated for indicator bacteria (total coliforms, Escherichia coli, Enterococci, Clostridia, and heterotrophs) removal over a period of 2 years under conditions of low and high strength grey water influent. Total coliforms were found to be good indicators for P. aeruginosa, showing strong and significant Spearman's rank correlations in the influent grey water (r_s = 0.77, P = 0.005) and treated effluents (r_s = 0.81, P ≤ 0.001). The MBR provided the highest quality treated effluent and was the most robust treatment technology, remaining unaffected by an increase in influent grey water strength. Of the three constructed wetlands, the VFRB was the most reliable performer under low and high strength influent conditions, indicating aerobic unsaturated wetland to be the most suitable form of the technology for pathogen removal.     

Revision of the neotropical species of Triplophyllum (Tectariaceae)

This paper re-examines the species of Triplophyllum in the neotropics. The indument of the laminae (hairs and glands) provides many characteristics for distinguishing the species. Nine species are recognized, including three new ones: T. boliviense, T. chocoense, and T. glabrum. New combinations are made for T. hirsutum and T. perpilosum . A key is provided to distinguish the species, and all species are described and illustrated. The spores of the neotropical species are like those from African and Madagascan species. As such, they offer no evidence to determine whether the neotropical species form a monophyletic clade within the genus.