Na channel kinetics during the spontaneous heart beat in embryonic chick ventricle cells.

Using cell-attached and whole-cell recording techniques simultaneously allows the measurement of Na currents during action potentials in beating heart cells. In 7-d chick ventricle, the dynamic reversal potential for Na is 30 mV, which is 20 mV less than the reversal potential in nonbeating cells. This result implies that the spontaneous activity of heart cells raises the Na concentration at the internal face of the membrane to nearly 40 mM. Fitting the Na action currents to the Hodgkin and Huxley equations shows that patches may contain from 50 to 700 Na channels, with an average density of 23 +/- 21 per micron2. Only approximately 2% of the available Na channels are open at the peak of the Na action current. This low probability is a consequence of the channels' continual inactivation during the diastolic depolarization phase.     

Ca modulates outward current throughI K1 channels

Summary Inward-rectifier channels in cardiac cells (I _K1) stabilize the resting membrane potential near the K equilibrium potential. Here we investigate the role ofI _K1 in the regulation of action potentials and link this to the influx of Ca during beating. Inward Ca current alters the open-channel probability of outwardI _K1 current. Thus Ca ions depolarize cells not only by carrying an inward current but also by blocking an outward current.     

Ca channel kinetics during the spontaneous heart beat in embryonic chick ventricle cells.

The ability of Ca ions to inhibit Ca channels presents one of the most intriguing problems in membrane biophysics. Because of this negative feedback, Ca channels can regulate the current that flows through them. The kinetics of the channels depend on voltage, and, because the voltage controls the current, a strong interaction exists between voltage dependence and Ca dependence. In addition to this interaction, the proximity of pores and the local concentration of ions also determine how effectively the Ca ions influence channel kinetics. The present article proposes a model that incorporates voltage-dependent kinetics, current-dependent kinetics, and channel clustering. We have based the model on previous voltage-clamp data and on Ca and Ba action currents measured during the action potential in beating heart cells. In general we observe that great variability exists in channel kinetics from patch to patch: Ba or Ca currents have low or high amplitudes and slow or fast kinetics during essentially the same voltage regime, either applied step-protocols or spontaneous cell action potentials. To explain this variability, we have postulated that Ca channels interact through shared ions. The model we propose expands on our previous model for Ba currents. We use the same voltage-dependent rate constants for the Ca currents that we did for the Ba currents. However, we vary the current-dependent rate constants according to the species of the conducting ion. The model reproduces the main features of our data, and we use it to predict Ca channel kinetics under physiological conditions. Preliminary reports of this work have appeared (DeFelice et al., 1991, Biophys. J. 59:551a; Risso et al., 1992, Biophys. J. 61:248a).     

BENTHIC MARINE DIATOM ASSOCIATIONS: UPPER FLORIDA BAY (FLORIDA) AND ASSOCIATED SOUNDS1

Models of the diatom associations found in upper Florida Bay and adjoining sounds have been constructed utilizing Q modal factor-vector analysis and ecologic diversity indices (Shannon index, number of species, evenness). Four distinct associations were defined using Q-mode factor-vector analysis. Two associations were epiphytic, occurring on Thalassia testudinum König—Association I was characterized by Cocconeis placentula Ehr., Association III by Cylindrotheca closterium (Ehr.) Reim. & Lewin and Cocconeis placentula Ehr. The other two associations were epipelic, occurring on the carbonate mud substratum—Association II was characterized by Cyclotella striata (Kütz.) Grun., Rhopalodia gibberula (Ehr.) O. Müller and Surirella fastuosa (Ehr.) Kütz., Association IV by Fragilaria crotonensis Kitton and Cyclotella striata (Kütz.) Grun. The majority of the 161 species identified were present in both the epiphytic and epipelic assemblages. Only 33 species were restricted to the epiphyton, and 18 species restricted to the epipelon. The epipelic assemblage was significantly more diverse than was the epiphytic assemblage. A general trend of increased diversity away from terrestrial environs toward more open areas of water in both the epipelon and epiphyton was also found.     

Deaths and Medical Visits Attributable to Environmental Pollution in the United Arab Emirates

Background

This study estimates the potential health gains achievable in the United Arab Emirates (UAE) with improved controls on environmental pollution. The UAE is an emerging economy in which population health risks have shifted rapidly from infectious diseases to chronic conditions observed in developed nations. The UAE government commissioned this work as part of an environmental health strategic planning project intended to address this shift in the nature of the country’s disease burden.

Methods and Findings

We assessed the burden of disease attributable to six environmental exposure routes outdoor air, indoor air, drinking water, coastal water, occupational environments, and climate change. For every exposure route, we integrated UAE environmental monitoring and public health data in a spatially resolved Monte Carlo simulation model to estimate the annual disease burden attributable to selected pollutants. The assessment included the entire UAE population (4.5 million for the year of analysis). The study found that outdoor air pollution was the leading contributor to mortality, with 651 attributable deaths (95% confidence interval [CI] 143–1,440), or 7.3% of all deaths. Indoor air pollution and occupational exposures were the second and third leading contributors to mortality, with 153 (95% CI 85–216) and 46 attributable deaths (95% CI 26–72), respectively. The leading contributor to health-care facility visits was drinking water pollution, to which 46,600 (95% CI 15,300–61,400) health-care facility visits were attributed (about 15% of the visits for all the diseases considered in this study). Major study limitations included (1) a lack of information needed to translate health-care facility visits to quality-adjusted-life-year estimates and (2) insufficient spatial coverage of environmental data.

Conclusions

Based on international comparisons, the UAE’s environmental disease burden is low for all factors except outdoor air pollution. From a public health perspective, reducing pollutant emissions to outdoor air should be a high priority for the UAE’s environmental agencies.     

K channel kinetics during the spontaneous heart beat in embryonic chick ventricle cells.

By averaging the current that passes through cell-attached patches on beating heart cells, while measuring action potentials with a whole-cell electrode, we were able to study K channels during beating. In 7-d chick ventricle in 1.3 mM K physiological solutions at room temperature, delayed-rectifier channels have three linear conductance states: 60, 30, and 15 pS. The 60 and 15 pS conductances can exist alone, but all three states may appear in the same patch as interconverting conductance levels. The delayed-rectifier conductance states have low densities (less than 10 channels per 10-microns diam cell), and all have a reversal potential near -75 mV and the same average kinetics. Outward K current through delayed-rectifier channels follows the upstroke without appreciable delay and lasts throughout the action potential. No inward current flows through delayed-rectifier channels during beating. The early outward channel has a nonlinear conductance of 18-9 pS depending on the potential. It also turns on immediately after the upstroke of the action potential and lasts on average only 50 ms. The early outward channel has an extrapolated reversal potential near -30 mV; no inward current flows during beating. The inward-rectifier has an extrapolated conductance and reversal potential of 2-3 pS and -80 mV in 1.3 mM K. Channel kinetics are independent of external K between 10 and 120 mM, and the channel conducts current only during the late repolarization and diastolic phases of the action potential. No outward current flows through inward-rectifier channels during beating. This work parallels a previous study of Na channels using similar techniques (Mazzanti, M., and L. J. DeFelice. 1987, Biophys. J. 52:95-100).     

Genomic correlates of recombination rate and its variability across eight recombination maps in the western honey bee (Apis mellifera L.)

Background

Meiotic recombination has traditionally been explained based on the structural requirement to stabilize homologous chromosome pairs to ensure their proper meiotic segregation. Competing hypotheses seek to explain the emerging findings of significant heterogeneity in recombination rates within and between genomes, but intraspecific comparisons of genome-wide recombination patterns are rare. The honey bee (Apis mellifera) exhibits the highest rate of genomic recombination among multicellular animals with about five cross-over events per chromatid.

Results

Here, we present a comparative analysis of recombination rates across eight genetic linkage maps of the honey bee genome to investigate which genomic sequence features are correlated with recombination rate and with its variation across the eight data sets, ranging in average marker spacing ranging from 1 Mbp to 120 kbp. Overall, we found that GC content explained best the variation in local recombination rate along chromosomes at the analyzed 100 kbp scale. In contrast, variation among the different maps was correlated to the abundance of microsatellites and several specific tri- and tetra-nucleotides.

Conclusions

The combined evidence from eight medium-scale recombination maps of the honey bee genome suggests that recombination rate variation in this highly recombining genome might be due to the DNA configuration instead of distinct sequence motifs. However, more fine-scale analyses are needed. The empirical basis of eight differing genetic maps allowed for robust conclusions about the correlates of the local recombination rates and enabled the study of the relation between DNA features and variability in local recombination rates, which is particularly relevant in the honey bee genome with its exceptionally high recombination rate.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1281-2) contains supplementary material, which is available to authorized users.     

An unusual presentation of a malignant jejunal tumor and a different management strategy

BACKGROUND: Malignant small bowel tumors are very rare and leiomyosarcoma accounts for less than 15% of the cases. Management of these tumors is challenging in view of nonspecific symptoms, unusual presentation and high incidence of metastasis. In this case report, an unusual presentation of jejunal sarcoma and management of liver metastasis with radiofrequency ablation (RFA) is discussed. CASE PRESENTATION: A 45-year-old male presented with anemia and features of small bowel obstruction. Operative findings revealed a mass lesion in jejunum with intussusception of proximal loop. Resection of bowel mass was performed. Histopathological findings were suggestive of leiomyosarcoma. After 3-years of follow-up, the patient developed recurrence in infracolic omentum and a liver metastasis. The omental mass was resected and liver lesion was managed with radiofrequency ablation. CONCLUSION: Jejunal leiomyosarcoma is a rare variety of malignant small bowel tumor and a clinical presentation with intussusception is unusual. We suggest that an aggressive management approach using a combination of surgery and a newer technique like RFA can be attempted in patients with limited metastatic spread to liver to prolong the long-term survival in a subset of patients.