Thorium speciation in seawater

Author Posting. © The Authors, 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Marine Chemistry 100 (2006): 250-268, doi:10.1016/j.marchem.2005.10.024.Since the 1960’s, thorium isotopes occupy a special place in the oceanographer’s toolbox as tracers for determining rates and mechanisms of oceanic scavenging, particle dynamics, and carbon fluxes. Due to their unique and constant production rates from soluble parent nuclides of uranium and radium, their disequilibrium can be used to calculate rates and time scales of sinking particles. In addition, by ratio-ing particulate 234Th (as well, in principle, other Thnuclides) to carbon (and other elements), and linking this ratio to the parent-daughter disequilibrium in the water column, it is possible to calculate fluxes of carbon and other elements. Most of these applications are possible with little knowledge of the dissolved chemical properties of thorium, other than its oxidation state (IV) and tendency to strongly sorb to surfaces, i.e., its “particle- or surface-activity”. However, the use of any tracer is hindered by a lack of knowledge of its chemical properties. Recent observations in the variability of carbon to 234Th ratios in different particle types, as well as of associations of Th(IV) with various marine organic biomolecules has led to the need for a review of current knowledge and what future endeavors should be taken to understand the marine chemistry of thorium.The writing of this paper was supported, in parts by NSF (OCE-0351559; OCE-0350758, and OCE 0354757)

Gβγ and the C Terminus of SNAP-25 Are Necessary for Long-Term Depression of Transmitter Release

Short-term presynaptic inhibition mediated by G protein-coupled receptors involves a direct interaction between G proteins and the vesicle release machinery. Recent studies implicate the C terminus of the vesicle-associated protein SNAP-25 as a molecular binding target of Gβγ that transiently reduces vesicular release. However, it is not known whether SNAP-25 is a target for molecular modifications expressing long-term changes in transmitter release probability.This study utilized two-photon laser scanning microscopy for real-time imaging of action potential-evoked [Ca(2+)] increases, in single Schaffer collateral presynaptic release sites in in vitro hippocampal slices, plus simultaneous recording of Schaffer collateral-evoked synaptic potentials. We used electroporation to infuse small peptides through CA3 cell bodies into presynaptic Schaffer collateral terminals to selectively study the presynaptic effect of scavenging the G-protein Gβγ. We demonstrate here that the C terminus of SNAP-25 is necessary for expression of LTD, but not long-term potentiation (LTP), of synaptic strength. Using type A botulinum toxin (BoNT/A) to enzymatically cleave the 9 amino acid C-terminus of SNAP-25 eliminated the ability of low frequency synaptic stimulation to induce LTD, but not LTP, even if release probability was restored to pre-BoNT/A levels by elevating extracellular [Ca(2+)]. Presynaptic electroporation infusion of the 14-amino acid C-terminus of SNAP-25 (Ct-SNAP-25), to scavenge Gβγ, reduced both the transient presynaptic inhibition produced by the group II metabotropic glutamate receptor stimulation, and LTD. Furthermore, presynaptic infusion of mSIRK, a second, structurally distinct Gβγ scavenging peptide, also blocked the induction of LTD. While Gβγ binds directly to and inhibit voltage-dependent Ca(2+) channels, imaging of presynaptic [Ca(2+)] with Mg-Green revealed that low-frequency stimulation only transiently reduced presynaptic Ca(2+) influx, an effect not altered by infusion of Ct-SNAP-25.The C-terminus of SNAP-25, which links synaptotagmin I to the SNARE complex, is a binding target for Gβγ necessary for both transient transmitter-mediated presynaptic inhibition, and the induction of presynaptic LTD

Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases

The syndrome Multiple Congenital Ocular Anomalies (MCOA) is the collective name ascribed to heritable congenital eye defects in horses. Individuals homozygous for the disease allele (MCOA phenotype) have a wide range of eye anomalies, while heterozygous horses (Cyst phenotype) predominantly have cysts that originate from the temporal ciliary body, iris, and/or peripheral retina. MCOA syndrome is highly prevalent in the Rocky Mountain Horse but the disease is not limited to this breed. Affected horses most often have a Silver coat color; however, a pleiotropic link between these phenotypes is yet to be proven. Locating and possibly isolating these traits would provide invaluable knowledge to scientists and breeders. This would favor maintenance of a desirable coat color while addressing the health concerns of the affected breeds, and would also provide insight into the genetic basis of the disease. Identical-by-descent mapping was used to narrow the previous 4.6-Mb region to a 264-kb interval for the MCOA locus. One haplotype common to four breeds showed complete association to the disease (Cyst phenotype, n = 246; MCOA phenotype, n = 83). Candidate genes from the interval, SMARCC2 and IKZF4, were screened for polymorphisms and genotyped, and segregation analysis allowed the MCOA syndrome region to be shortened to 208 kb. This interval also harbors PMEL17, the gene causative for Silver coat color. However, by shortening the MCOA locus by a factor of 20, 176 other genes have been unlinked from the disease and only 15 genes remain

Non-medical prescribing versus medical prescribing for acute and chronic disease management in primary and secondary care.

The aim of this Cochrane review was to find out if prescribing by health professionals other than doctors delivers comparable outcomes to prescribing by doctors. Cochrane researchers collected and analysed all relevant studies to answer this question and found 46 studies. Key messages With appropriate training and support, nurses and pharmacists are able to prescribe medicines as part of managing a range of conditions to achieve comparable health management outcomes to doctors. The majority of studies focus on chronic disease management in higher-income counties where there is generally a moderate-certainty of evidence supporting similar outcomes for the markers of disease in high blood pressure, diabetes, and high cholesterol. Further high-quality studies are needed in poorer countries and to better quantify differences in prescribing outcomes for adverse events, and to determine health economic outcomes. Further studies could also focus more specifically on the prescribing component of care. What was studied in the review? A number of countries allow health professionals other than doctors to prescribe medicines. This shift in roles is thought to provide improved and timely access to medicines for consumers where there are shortages of doctors or the health system is facing pressures in coping with the burden of disease. In addition, this task shift has been supported by a number of governments as a way to more appropriately use the skills of health professionals, such as nurses and pharmacists, in the care of patients. We compared the outcomes of any healthcare workers who were prescribing with a high degree of autonomy with medical prescribers in the hospital or community setting in low-, middle- and high-income countries. What are the main results of the review? This review found 45 studies where nurses and pharmacists with high levels of prescribing autonomy were compared with usual care medical prescribers. A further study compared nurse prescribing with guideline support with usual nurse prescribing care. No studies were found with other health professionals or lay prescribers. Four nurse prescribing studies were undertaken in the low- and middle-income settings of Colombia, South Africa, Uganda, and Thailand. The remainder of studies were undertaken in high-income Western countries. Forty-two studies were based in a community setting, two studies were located in hospitals, one study in the workplace, and one study in an aged care facility. Prescribing was but one part of many health-related interventions, particularly in the management of chronic disease. The review found that the outcomes for non-medical prescribers were comparable to medical prescribers for: high blood pressure (moderate-certainty of evidence); diabetes control (high-certainty of evidence); high cholesterol (moderate-certainty of evidence); adverse events (low-certainty of evidence); patients adhering to their medication regimeans (moderate-certainty of evidence); patient satisfaction with care (moderate-certainty of evidence); and health-related quality of life (moderate-certainty of evidence). Pharmacists and nurses with varying levels of undergraduate, postgraduate, and specific on-the-job training related to the disease or condition were able to deliver comparable prescribing outcomes to doctors. Non-medical prescribers frequently had medical support available to facilitate a collaborative practice model

Therapeutic strategies to improve control of hypertension.

Blood pressure is poorly controlled in most European countries and the control rate is even lower in high-risk patients such as patients with chronic kidney disease, diabetic patients or previous coronary heart disease. Several factors have been associated with poor control, some of which involve the characteristic of the patients themselves, such as socioeconomic factors, or unsuitable life-styles, other factors related to hypertension or to associated comorbidity, but there are also factors directly associated with antihypertensive therapy, mainly involving adherence problems, therapeutic inertia and therapeutic strategies unsuited to difficult-to-control hypertensive patients.It is common knowledge that only 30% of hypertensive patients can be controlled using monotherapy; all the rest require a combination of two or more antihypertensive drugs, and this can be a barrier to good adherence and log-term persistence in patients who also often need to use other drugs, such as antidiabetic agents, statins or antiplatelet agents. The fixed combinations of three antihypertensive agents currently available can facilitate long-term control of these patients in clinical practice. If well tolerated, a long-term therapeutic regimen that includes a diuretic, an ACE inhibitor or an angiotensin receptor blocker, and a calcium channel blocker is the recommended optimal triple therapy