Polychaetes of the mangrove-fouling community at the Colombian Archipelago of San Andres and Old Providence,Western Caribbean

This study records the polychaetes found on the submerged roots of Rhizophora mangl on San Andres and Providence Islands, ColombianCaribbean. Sampling was done in 1998 during the rainy (July) and dry(November) seasons; each season, 17 roots were collected in threedifferent stations with different kinds of human impact, two in San Andresand one in Providence. At the same time temperature, salinity anddissolved oxygen were measured in situ. Aromatic hydrocarbons weremeasured in the laboratory. The polychaetes were removed from the rootsand identified. The available root area for the organisms was alsomeasured.Five genera and 11 species were newly recorded for the ColombianCaribbean. The most abundant families were Terebellidae in Old ProvidenceMc Bean Lagoon, Syllidae in Honda Bay and Nereididae in Hooker Bayon the San Andres Island. Thelepus `setosus' (Terebellidae) and Amblyosyllis sp. (Syllidae) were highly abundant in less polluted samplingstations such as Old Providence Mc Bean Lagoon and Honda Bay. On theother hand, Neanthes `succinea' (Nereididae) were abundant inHooker Bay which was the most polluted station. Salinity seemed to be the mostimportant parameter for the polychaete populations. The populations ofpolychaetes, as a total group, seemed to be related to the root areaavailable on both islands, independent of the season. However, during therainy season, the populations were independent of root area availability,while during the dry season, the populations were dependent on it.     

Neural crest: facing the facts of head development

The cranial neural crest originates at the dorsal margin of the neural tube and produces migratory cells that populate various locations in the head. They are a crucial factor in the development of the vertebrate head because they give rise to numerous differentiated cell types, including the cartilage, bone and connective tissues of the skull. Thus, the coordinated regulation of crest cell movement and patterning is pivotal to the acquisition of organized head structure. Two recent papers cast light on the molecular mechanisms and tissue interactions employed by an embryo to achieve this goal. Here, we discuss the implications of these findings in view of pre-existing principles of neural crest patterning. Crucially, these new data implicate, for the first time, that head skeletal patterning is controlled by tissue other than the neural crest.     

Safety,Tolerability, and Pharmacokinetics of SMT C1100, a 2-Arylbenzoxazole Utrophin Modulator,following Single- and Multiple-Dose Administration to Pediatric Patients with Duchenne Muscular Dystrophy

PurposeSMT C1100 is a utrophin modulator being evaluated as a treatment for Duchenne muscular dystrophy (DMD). This study, the first in pediatric DMD patients, reports the safety, tolerability and PK parameters of single and multiple doses of SMT C1100, as well as analyze potential biomarkers of muscle damage.MethodsThis multicenter, Phase 1 study enrolled 12 patients, divided equally into three groups (A–C). Group A were given 50 mg/kg on Days 1 and 11, and 50 mg/kg bid on Days 2 to 10. Group B and C received 100 mg/kg on Days 1 and 11; Group B and Group C were given 100 mg/kg bid and 100 mg/kg tid, respectively, on Days 2 to 10. A safety review was performed on all patients following the single dose and there was at least 2 weeks between each dose escalation, for safety and PK review. Adverse events (AEs) were monitored throughout the study.ResultsMost patients experienced mild AEs and there were no serious AEs. Two patients required analgesia for pain (headache, ear pain and toothache). One patient experienced moderate psychiatric AEs (abnormal behaviour and mood swings). Plasma concentrations of SMT C1100 at Days 1 and 11 indicated a high degree of patient variability regardless of dose. Unexpectedly the SMT C1100 levels were significantly lower than similar doses administered to healthy volunteers in an earlier clinical study. In general, individual baseline changes of creatine phosphokinase, alanine aminotransferase, aspartate aminotransferase levels fell with SMT C1100 dosing.ConclusionsSMT C1100 was well tolerated in pediatric DMD patients.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02383511","term_id":"NCT02383511"}}NCT02383511     

Three-base periodicity patterns and self-similarity in whole bacterial chromosomes

It has been reported that in a collection of mRNAs the triplets GhN or RNY had a higher propensity to be separated by either three/six/nine, etc., bases than by two/four/five, etc., bases. This has been called three-base periodicity (TBP). In this work the frequency distribution of distances (FDDs) for all triplets in the Borrelia burgdorferi chromosome and selected triplets in other model sequences were determined. The FDDs produced oscillatory decaying patterns with TBP for most triplets and not only for those encompassed by the above formulas. Furthermore, we also found TBP for di- and mononucleotides. However, TBP was not observed for intergenic regions, sequences with a low content of coding regions or when the coding potential of sequences was disrupted by base shuffling. Excluding closely related species the FDDs between bacterial genomes were different and appeared characteristic of the analyzed genome. FDDs also showed self-similarity, since 1Mb sequences rendered FDDs that were very similar to those for the entire sequence.     

Integrity of developing spinal motor columns is regulated by neural crest derivatives at motor exit points

Spinal motor neurons must extend their axons into the periphery through motor exit points (MEPs), but their cell bodies remain within spinal motor columns. It is not known how this partitioning is established in development. We show here that motor neuron somata are confined to the CNS by interactions with a neural crest subpopulation, boundary cap (BC) cells that prefigure the sites of spinal MEPs. Elimination of BC cells by surgical or targeted genetic ablation does not perturb motor axon outgrowth but results in motor neuron somata migrating out of the spinal cord by translocating along their axons. Heterologous neural crest grafts in crest-ablated embryos stop motor neuron emigration. Thus, before the formation of a mature transitional zone at the MEP, BC cells maintain a cell-tight boundary that allows motor axons to cross but blocks neuron migration.     

Patterns of Treatment Interruption among Patients with Multidrug-Resistant TB (MDR TB) and Association with Interim and Final Treatment Outcomes

Background

The reasons that patients with multidrug-resistant tuberculosis (MDR TB) miss treatment are multi-factorial and complex. Identifying patterns of treatment interruption that predict poor outcomes can be used to target program activities aiming to improve treatment adherence.

Objective

To characterize patterns of treatment interruption among MDR TB patients and determine the association between patterns and treatment outcomes.

Methods

Retrospective analysis of MDR TB patients. A treatment interruption was defined as any time that a patient missed a prescribed dose of treatment for at least 1 day but for a period of less than 2 consecutive months. Patients were characterized by the number, length and variability of interruptions, variability of time between interruptions, and percent of missed doses. Final treatment outcome was dichotomized as a successful (cured or completed) or poor outcome (defaulted, failed, or died). Risk ratios were calculated to determine the association between characteristics of treatment interruption and treatment outcomes. All analyses were conducted in 6 month treatment intervals.

Results

Only 7.0% of 583 patients completed treatment without interruption. Of the remaining 542 patients, the median time to the first interruption was 2 ½ months (70 days). In multivariate analysis, patients who had longer interruptions with sporadic variability during the 6–12 month or the 12–18 month treatment period had a significantly increased risk for poor outcomes compared to patients who had short, regular interruptions (RR_adj 4.37, 95% CI 1.2–15.8;  = 0.03 and RR_adj 3.38, 95% CI 1.6–7.1; p = 0.001, respectively). In addition, missing 10% or more of the prescribed doses during any 6 month period in the initial 18 months of therapy significantly increased the risk for poor outcomes (RR_adj range 1.55–2.35; p-value range 0.01–0.005).

Conclusion

Patients that miss more consecutive days of treatment with sporadic interruption patterns or a greater proportion of treatment are at an increased risk for poor treatment outcomes.     

Observations of marketing on food packaging targeted to youth in retail food stores

There is growing evidence that exposure to food marketing influences dietary preferences among youth. Few studies exploring this association, however, have focused on the retail food store environment where families negotiate the influence of food and beverage marketing on purchasing practices. Consequently, we sought to examine: (i) the extent to which foods marketed on the internet and television to youth are also available and marketed in retail food stores, and (ii) whether differences exist in the marketing practices across store types and by neighborhood racial composition. In 2008, a cross-sectional survey of 118 food stores was conducted in four Midwestern cities in the United States. Results showed that 82% of stores assessed carried items commonly marketed to youth via television or the internet. The items most likely to have some type of marketing technique were noncarbonated drinks (97.7%), fruit and cereal bars (76.9%), and soda (62.2%). Grocery stores were significantly more likely than convenience stores to have marketing for breads and pastries (34.6% vs. 17.9%), breakfast cereals (52.0% vs. 22.9%), cookies and crackers (54.2% vs. 25.3%), dairy (70.8% vs. 42.7%), and ice cream (23.8% vs. 9.8%). Stores located in black neighborhoods were significantly more likely to have marketing, in comparison to white neighborhoods, for breads and pastries (35.7% vs. 17.1%), breakfast cereals (44.4% vs. 25.0%), and cookies and crackers (48.1% vs. 26.3%). Our results highlight the importance of examining food marketing techniques in the retail food store environment, where visual cues from television and the internet may be reinforced.     

Insights into pathological mechanisms and interventions revealed by analyzing a mathematical model for cone metabolism

This work analyzes a mathematical model for the metabolic dynamics of a cone photoreceptor, which is the first model to account for energy generation from fatty acids oxidation of shed photoreceptor outer segments (POS). Multiple parameter bifurcation analysis shows that joint variations in external glucose, the efficiency of glucose transporter 1 (GLUT1), lipid utilization for POS renewal, and oxidation of fatty acids affect the cone’s metabolic vitality and its capability to adapt under glucose-deficient conditions. The analysis further reveals that when glucose is scarce, cone viability cannot be sustained by only fueling energy production in the mitochondria, but it also requires supporting anabolic processes to create lipids necessary for cell maintenance and repair. In silico experiments are used to investigate how the duration of glucose deprivation impacts the cell without and with a potential GLUT1 or oxidation of fatty acids intervention as well as a dual intervention. The results show that for prolonged duration of glucose deprivation, the cone metabolic system does not recover with higher oxidation of fatty acids and requires greater effectiveness of GLUT1 to recover. Finally, time-varying global sensitivity analysis (GSA) is applied to assess the sensitivity of the model outputs of interest to changes and uncertainty in the parameters at specific times. The results reveal a critical temporal window where there would be more flexibility for interventions to rescue a cone cell from the detrimental consequences of glucose shortage.