Regulatory mechanisms of long noncoding RNAs in vertebrate central nervous system development and function.

Long noncoding RNAs (lncRNAs) have emerged as an important class of molecules that regulate gene expression at epigenetic, transcriptional, and post-transcriptional levels through a wide array of mechanisms. This regulation is of particular importance in the central nervous system (CNS), where precise modulation of gene expression is required for proper neuronal and glial production, connection and function. There are relatively few functional studies that characterize lncRNA mechanisms, but possible functions can often be inferred based on existing examples and the lncRNA's relative genomic position. In this review, we will discuss mechanisms of lncRNAs as predicted by genomic contexts and the possible impact on CNS development, function, and disease pathogenesis. There is no doubt that investigation of the mechanistic role of lncRNAs will open a new and exciting direction in studying CNS development and function.

Pharmacological characterization of glutamatergic agonists and antagonists at recombinant human homomeric and heteromeric kainate receptors in vitro.

An increasing body of evidence suggests that native kainate receptors form ion channels from homomeric and heteromeric combinations of five receptor subunits: GluR5, GluR6, GluR7, KA1 and KA2. We have examined the activity of agonists and antagonists at recombinant human kainate receptors expressed in HEK293 cells, using both whole-cell electrophysiological recording and 96-well plate fluo-3 based calcium microfluorimetry (FLIPR). Both homomeric (GluR5 and GluR6) and heteromeric (GluR5/6, GluR5/KA2 and GluR6/KA2) receptors were examined. Heteromeric receptor assemblies showed electrophysiological and pharmacological profiles which were distinct from homomeric channels. Several agonists, including AMPA, ATPA and (S)-5-iodowillardiine, and antagonists, including gamma-D-glutamylaminomethylsulphonic acid (GAMS) and the decahydroisoquinoline compounds LY293558, LY377770 and LY382884, were found to act at GluR5-containing channels while having no effect at GluR6 homomers. AMPA, ATPA and (S)-5-iodowillardiine did activate GluR6/KA2 heteromers, but only as partial agonists. Additionally, ATPA was shown to act as an antagonist at homomeric GluR6 receptors at high concentrations (IC50 approximately 2 mM). Kynurenic acid was also found to differentiate between GluR6 and GluR6/KA2 receptors, antagonizing glutamate at GluR6 (IC50 = 0.4 mM), while having no effect at GluR6/KA2 channels. The results of the current study provide a broad pharmacological characterization of both homomeric and heteromeric recombinant human kainate receptors, and identify which compounds are likely to be useful tools for studying these various receptor subtypes.

Medical conditions associated with venous leg ulcers.

BACKGROUND: In patients who have a venous leg ulcer, very little is known about the frequency of their concomitant medical conditions. OBJECTIVES: To evaluate the frequency that other medical conditions are associated with a new venous leg ulcer. METHODS: We studied a 10% random sample of elderly patients registered in the General Practice Research Database between 1988 and 1996. We describe the frequency of medical conditions using simple percentages. In order to assess the associations between medical conditions and the onset of a venous leg ulcer, we used logistic regression models. RESULTS: Several medical conditions occur commonly in patients who develop venous leg ulcers, including anaemia, angina, asthma, cellulitis of the lower extremity, depression, diabetes, limb oedema, hypertension, osteoarthritis, pneumonia and urinary tract infection. After statistical adjustment many medical conditions were significantly associated with those who had recent onset of a venous leg ulcer, including asthma, cellulitis of the lower extremity, congestive heart failure, diabetes, deep venous thrombosis, lower limb oedema, osteoarthritis, peripheral vascular arterial disease of the lower extremity, rheumatoid arthritis, history of hip surgery, and history of venous surgery/ligation. Unexpectedly, some illnesses were inversely associated with those that had recent onset of a venous leg ulcer, including angina, cerebral vascular accident, depression, malignancy, myocardial infarction, pneumonia and urinary tract infection. CONCLUSIONS: Physicians caring for individuals with venous leg ulcers need to be aware that it is likely that these individuals may have one of the comorbid illnesses listed above.

How the law of the sea treaty will affect u.s. Marine science.

The Law of the Sea treaty will clearly affect the way U.S. marine scientists operate in about 40 percent of the ocean. The matter will be made even more complex by the apparent intention of the Reagan Administration to remain outside the treaty.

Marine science and the 1974 law of the sea conference.

More intensive and varied use of the oceans and their resources requires a more comprehensive legal reégime than previously. Three years of preparatory work have been completed leading toward the Law of the Sea Conference that opened on 20 June in Caracas, Venezuela. Although the details of the new reégime are still to be negotiated, it appears certain that the coastal nations will gain some form of jurisdiction over the fisheries and mineral resources off their shores. It is probable that a new "economic zone" will be established between a relatively narrow (12-mile) territorial sea and the international ocean space beyond. If, as seems likely, this economic zone is 200 miles wide, it will encompass some 37 percent of the ocean as shown in Fig. 1. Unless the scientific community can gather more support than it has to date, it seems probable that scientific research within this economic zone will only be possible with the consent of the coastal nation. The United States has proposed a compromise solution which attempts to balance the interests of the scientific community with those of the coastal state. Under the U.S. proposal, a research group abiding by certain specific obligations to the coastal state would be free to carry out its research activities without obtaining explicit consent from the coastal state. To date the U.S. proposal has received little official support from any nation, even from nations with major oceanographic interests.