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The GABA neurotransmitter system not only serves as the primary inhibitory system in the adult vertebrate nervous system, but also may play an important role in the the early embryonic development of the nervous system. An essential component of this system is the family of GABA transporters, transmembrane proteins responsible for the reuptake of GABA. In order to investigate the role of the GABA system in neural development in general and the regulation of the GABA transporter more specifically, we have isolated a GABA transporter (GAT1-like) cDNA in Xenopus. Using in situ hybridization and RNase protection analysis we have characterized its developmental expression during embryogenesis and found it to be expressed by neurula stages in a dynamic and spatially restricted pattern. In addition, the putative promoter regions of genomic clones for the GABA transporter in Xenopus laevis and Xenopus tropicalis are currently being analyzed. (Supported by NSF grant IBN-9553176).

The potential of macrocyclic peptides as therapeutics has garnered much attention over the last several years. Unlike their linear counterparts, macrocycles have higher resistance to enzymatic degradation and often display improved bioavailability. However, macrocycles are typically not lipophilic enough for cellular membrane penetration, which prevents them from interacting with intracellular targets. Methods to increase cellular permeability have involved the incorporation of bicyclic scaffolds, d -amino acids and N-methylation of amides. These modifications exert their effect through conformational control of macrocycles and have been well studied in the literature. In contrast, the structural consequences of heterocycle incorporation into macrocyclic rings has not been as exhaustively investigated. In this mini-review we discuss key examples in which heterocycles influence the conformational stability and other properties of macrocycles. [ABSTRACT FROM AUTHOR]

Highlights: [•] We determined pore water helium concentrations from helium in quartz. [•] We compared quartz measurements to previous pore water measurements. [•] Quartz–helium isotherms are linear over two orders of magnitude. [Copyright &y& Elsevier]

Abstract: The successful application of both solid and solution phase library synthesis, combined with tight integration into the medicinal chemistry effort, resulted in the efficient optimization of a novel structural series of selective HDAC1/HDAC2 inhibitors by the MRL-Boston Parallel Medicinal Chemistry group. An initial lead from a small parallel library was found to be potent and selective in biochemical assays. Advanced compounds were the culmination of iterative library design and possess excellent biochemical and cellular potency, as well as acceptable PK and efficacy in animal models. [Copyright &y& Elsevier]

A group of 146 experts representing 29 organizations and professional societies met September 18-19, 2006, in Bethesda, MD, to develop revised evidence-based, consensus guidelines for managing women with abnormal cervical cancer screening tests. Recommendations for managing atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion (LSIL) are essentially unchanged. Changes were made for managing these conditions in adolescents for whom cytological follow-up for 2 years was approved. Recommendations for managing high-grade squamous intraepithelial lesion (HSIL) and atypical glandular cells (AGC) also underwent only minor modifications. More emphasis is placed on immediate screen-and-treat approaches for HSIL. Human papillomavirus (HPV) testing is incorporated into the management of AGC after their initial evaluation with colposcopy and endometrial sampling. The 2004 Interim Guidance for HPV testing as an adjunct to cervical cytology for screening in women 30 years of age and older was formally adopted with only very minor modifications. [ABSTRACT FROM AUTHOR]

A group of 146 experts representing 29 organizations and professional societies met Sept. 18-19, 2006, in Bethesda, MD, to develop revised evidence-based, consensus guidelines for managing women with abnormal cervical cancer screening tests. The management of low-grade cervical intraepithelial neoplasia (CIN) grade 1 has been modified significantly. Previously, management depended on whether colposcopy was satisfactory and treatment using ablative or excisional was acceptable for all women with CIN 1. In the new guidelines, cytological follow-up is the only recommended management option for women with CIN 1 who have low-grade referral cervical cytology, regardless of whether the colposcopic examination is satisfactory. Treatment is particularly discouraged in adolescents. The basic management of women in the general population with CIN 2,3 underwent only minor modifications, but options for the conservative management of adolescents with CIN 2,3 have been expanded. Moreover, management recommendations for women with biopsy-confirmed adenocarcinoma in situ are now included. [ABSTRACT FROM AUTHOR]

OBJECTIVE: At present, clinical management of women referred to colposcopy but found to have

Abstract: Natural tracers (major ions, δ 18O, and O2) were monitored to evaluate groundwater flow and transport to a depth of 20m below the surface in fractured sedimentary (primarily shale and limestone) rocks. Large temporal variations in these tracers were noted in the soil zone and the saprolite, and are driven primarily by individual storm events. During nonstorm periods, an upward flow brings water with high TDS, constant δ 18O, and low dissolved O2 to the water table. During storm events, low TDS, variable δ 18O, and high dissolved O2 water recharges through the unsaturated zone. These oscillating signals are rapidly transmitted along fracture pathways in the saprolite, with changes occurring on spatial scales of several meters and on a time scale of hours. The variations decreased markedly below the boundary between the saprolite and less weathered bedrock. Variations in the bedrock units occurred on time scales of days and spatial scales of at least 20m. The oscillations of chemical conditions in the shallow groundwater are hypothesized to have significant implications for solute transport. Solutes and colloids that adsorb onto aquifer solids can be released into solution by decreases in ionic strength and pH. The decreases in ionic strength also cause thermodynamic undersaturation of the groundwater with respect to some mineral species and may result in mineral dissolution. Redox conditions are also changing and may result in mineral dissolution/precipitation. The net result of these chemical variations is episodic transport of a wide range of dissolved solutes or suspended particles, a phenomenon rarely considered in contaminant transport studies. [Copyright &y& Elsevier]

Mountain-front recharge is a major component of recharge to inter-mountain basin-fill aquifers. The two components of mountain-front recharge are (1) subsurface inflow from the mountain block (subsurface inflow), and (2) infiltration from perennial and ephemeral streams near the mountain front (stream seepage). The magnitude of subsurface inflow is of central importance in source protection planning for basin-fill aquifers and in some water rights disputes, yet existing estimates carry large uncertainties. Stable isotope ratios can indicate the magnitude of mountain-front recharge relative to other components, but are generally incapable of distinguishing subsurface inflow from stream seepage. Noble gases provide an effective tool for determining the relative significance of subsurface inflow, specifically. Dissolved noble gas concentrations allow for the determination of recharge temperature, which is correlated with recharge elevation. The nature of this correlation cannot be assumed, however, and must be derived for the study area. The method is applied to the Salt Lake Valley Principal Aquifer in northern Utah to demonstrate its utility. Samples from 16 springs and mine tunnels in the adjacent Wasatch Mountains indicate that recharge temperature decreases with elevation at about the same rate as the mean annual air temperature, but is on average about 2 °C cooler. Samples from 27 valley production wells yield recharge elevations ranging from the valley elevation (about 1500 m) to mid-mountain elevation (about 2500 m). Only six of the wells have recharge elevations less than 1800 m. Recharge elevations consistently greater than 2000 m in the southeastern part of the basin indicate that subsurface inflow constitutes most of the total recharge in this area. [Copyright &y& Elsevier]

Focuses on the issues concerning the concept of the synapse. Several theories on the organization of the nervous system; Charles Sherrington's introduction of the term synapse in 1897; Origin of the concept of the synapse; Existing confusion regarding the definition of neurotransmitters. INSET: Box I. Sherrington's account of the origin of the term synapse..

The article focuses on the study to find the effect of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in hepatobiliary (HPB) malignancies, and talks of analyzing oncologic outcomes by tumor origin.

Changes in species and diameter class diversity were followed over time in uneven-aged northern hardwood and spruce-fir stands in New England that have been managed to maintain objectives for species composition and residual stand density. Plots in the northern hardwood stands have been treated for 25 years under uneven-age management a harvested to four residual basal area levels (40, 60, 80, and 100 ft2 per acre) while retaining three structural levels (30, 45, an 60% sawtimber). These plots were harvested once in the past 25 years with remeasurements approximately every 5 years. In addition, the spruce-fir stands have been managed under three uneven-age management regimes that vary in residual diameter class distribution and stand density. Over a 40-year period, these stands have been harvested every 5, 10, or 20 years, with remeasurements approximately every 5 years. Diversity profiles were constructed to follow changes in tree species and horizontal diameter class diversity. Criteria for assessing changes in diversity over time need to be based on the major control variable used in the management of the individual stands. Depending on themeasurement used in treatment -- basal area, volume, etc. can provide a more accurate assessment of diversity than number of individuals by species. (c) 1999 Elsevier Science B.V. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) have high mortality following myocardial infarction (MI), but are less likely to undergo coronary angiography than those without CKD. Whether this phenomenon is explained by differences in the presentation of MI or by bias against performing coronary angiography in patients with CKD is unclear. We examined the clinical presentation of 1876 elderly patients who presented with MI and categorized them by estimated glomerular filtration rate: >60 ml/min (no/mild CKD), 30-60 ml/min (CKD Stage 3) or <30 ml/min (CKD Stage 4/5). Compared with patients with no/mild CKD, patients with CKD Stage 3 or Stage 4/5 had more comorbidity, greater prior nursing home use, and higher frequency of conduction abnormalities or anterior infarction. By contrast, peak creatinine kinase-MB fraction (CK-MB) concentrations were lower and ST-elevation MI was less common in patients with CKD Stage 3 or Stage 4/5. In univariate analyses, patients with CKD Stage 4/5 (odds ratio (OR)=0.34, 95% confidence interval (CI): 0.23-0.50) or Stage 3 (OR=0.57, 95% CI: 0.45-0.73) were markedly less likely to undergo angiography than subjects with no/mild CKD. After multivariable adjustment, the association of CKD Stage 3 with the use of coronary angiography was attenuated (OR=0.78, 95% CI: 0.60-1.03), but CKD Stage 4/5 remained strongly associated with lower use (OR=0.52, 95% CI: 0.34-0.80). Clinical features of MI are different in patients with and without CKD and may partly explain the low use of angiography in patients with CKD Stage 3. However, the clinical features of MI do not account for its underuse in MI patients with CKD Stages 4/5. Whether reduced use of angiography in patients with advanced CKD is justified must be evaluated in formal risk-benefit analyses. [ABSTRACT FROM AUTHOR]

Abstract: Sulphur K-edge X-ray absorption near edge structure (XANES) spectroscopy was used to quantify S species in humic substance extracts from ten soils from the UK, China and New Zealand, which differ in land use and agricultural management. XANES spectroscopy showed the presence of most reduced (sulphides, disulphides, thiols and thiophenes), intermediate (sulphoxides and sulphonates) and highly oxidised S (ester sulphates) forms, with the three groups representing 14–32%, 33–50% and 22–53% of the organic S in the humic substance extracts, respectively. Land use had a profound influence on the relative proportions of S species. Well-drained arable soils generally had a higher proportion of organic S present in the most oxidised form than the grassland soils collected nearby, whereas paddy soils showed a more reduced profile due to episodic flooding. In the Broadbalk Classical Experiment at Rothamsted, reversion of an arable system to grassland or woodland in the 1880s resulted in an increase of the most reduced and intermediate S species at the expense of the most oxidised S species. Long-term applications of farmyard manure to an arable plot also shifted S species from the most oxidised to the intermediate and the most reduced species. Sulphur immobilisation and gross mineralisation were determined in seven soils using the 35S isotope dilution method. Gross mineralisation during a 53-day incubation correlated more closely with the amounts of the most reduced and intermediate S species than with the most oxidised S species, suggesting that the former (C-bonded S) were the main source of organic S for mineralisation in the short-term. [Copyright &y& Elsevier]