Altered Cerebellar Short-Term Plasticity but No Change in Postsynaptic AMPA-Type Glutamate Receptors in a Mouse Model of Juvenile Batten Disease

Juvenile Batten disease is the most common progressive neurodegenerative disorder of childhood. It is associated with mutations in the CLN3 gene, causing loss of function of CLN3 protein and degeneration of cerebellar and retinal neurons. It has been proposed that changes in granule cell AMPA-type glutamate receptors (AMPARs) contribute to the cerebellar dysfunction. In this study we compared AMPAR properties and synaptic transmission in cerebellar granule cells from wild-type and Cln3 knockout mice. In Cln3Δex1–6 cells the amplitude of AMPA-evoked whole-cell currents was unchanged. Similarly, we found no change in the amplitude, kinetics, or rectification of synaptic currents evoked by individual quanta, or in their underlying single-channel conductance. We found no change in cerebellar expression of GluA2 or GluA4 protein. By contrast, we observed a reduced number of quantal events following mossy-fiber stimulation in Sr2+, altered short-term plasticity in conditions of reduced extracellular Ca2+, and reduced mossy fiber vesicle number. Thus, while our results suggest early presynaptic changes in the Cln3Δex1–6 mouse model of juvenile Batten disease, they reveal no evidence for altered postsynaptic AMPARs

Homomeric Q/R edited AMPA receptors conduct when desensitized

Desensitization is a canonical property of ligand-gated ion channels, causing progressive current decline in the continued presence of agonist. AMPA-type glutamate receptors, which mediate fast excitatory signaling throughout the brain, exhibit profound desensitization. Recent cryo-EM studies of AMPAR assemblies show their ion channels to be closed in the desensitized state. Here we report the surprising finding that homomeric Q/R edited AMPARs still allow ions to flow when the receptors are desensitized. GluA2(R) expressed alone, or with auxiliary subunits (γ-2, γ-8 or GSG1L), generates large steady-state currents and anomalous current-variance relationships. Using fluctuation analysis, single-channel recording, and kinetic modeling we demonstrate that the steady-state current is mediated predominantly by ‘conducting desensitized’ receptors. When combined with crystallography this unique functional readout of a hith-erto silent state enabled us to examine cross-linked cysteine mutants to probe the conformation of the desensitized ligand binding domain of functioning AMPAR complexes within the plasma membrane

Reconstruction of MIS 5 climate in the central Levant using a stalagmite from Kanaan Cave, Lebanon

Lying at the transition between the temperate Mediterranean domain and subtropical deserts, the Levant is a key area to study the palaeoclimatic response over glacial–interglacial cycles. This paper presents a precisely dated last interglacial (MIS 5) stalagmite (129–84 ka) from the Kanaan Cave, Lebanon. Variations in growth rate and isotopic records indicate a warm humid phase at the onset of the last interglacial at ~ 129 ka that lasted until ~ 125 ka. A gradual shift in speleothem isotopic composition (125–122 ka) is driven mainly by the δ18O source effect of the eastern Mediterranean surface waters during sapropel 5 (S5). The onset of glacial inception began after ~ 122 ka, interrupted by a short wet pulse during the sapropel 4 (S4) event. Low growth rates and enriched oxygen and carbon values until ~ 84 ka indicate a transition to drier conditions during Northern Hemisphere glaciation

Physiological and molecular insights into drought tolerance.

Water is a major limiting factor in world agriculture. In general, most crop plants are highly sensitive to even a mild dehydration stress. There are however, a few genera of plants unique to Southern Africa, called "resurrection plants" which can tolerate extreme water loss or desiccation. We have used Xerophyta viscosa, a representative of the monocotyledonous resurrection plants to isolate genes that are associated with osmotic stress tolerance. Several genes that are differentially expressed, and that confer functional sufficiency to osmotically-stressed Escherichia coli are being studied at the molecular and biochemical levels. In this review, we use this as a basis to discuss the physiological and molecular insights into drought tolerance

Scaling in high-temperature superconductors

A Hartree approximation is used to study the interplay of two kinds of scaling which arise in high-temperature superconductors, namely critical-point scaling and that due to the confinement of electron pairs to their lowest Landau level in the presence of an applied magnetic field. In the neighbourhood of the zero-field critical point, thermodynamic functions scale with the scaling variable $(T-T_{c2}(B))/B^{1/2\nu}$, which differs from the variable $(T - T_c(0))/B^{1/2\nu}$ suggested by the gaussian approximation. Lowest-Landau-level (LLL) scaling occurs in a region of high field surrounding the upper critical field line but not in the vicinity of the zero-field transition. For YBaCuO in particular, a field of at least 10 T is needed to observe LLL scaling. These results are consistent with a range of recent experimental measurements of the magnetization, transport properties and, especially, the specific heat of high-$T_c$ materials.Comment: 22 pages + 1 figure appended as postscript fil

Screening Different Zambian Market Classes of Common Beans (Phaseolus vulgaris) for Antioxidant Properties and Total Phenolic Profiles

Abstract Nutraceutical foods are thought to play an important role in the prevention and management of cardiovascular diseases, diabetes, obesity and some cancers. This study was undertaken to screen the commonly grown Zambian market classes of common beans for nutraceutical value based on the antioxidant activities (DPPH and FRAP) and total polyphenolic profiles. Phenolic phytochemical profiles were determined using Folin Ciocalteu assay and aluminium chloride colorimetric method. The total polyphenol content ranged from 37.3 to 123.7 mg GAE / 100 g DW. Red beans consistently displayed the highest total polyphenol contents in both the methanolic and aqueous extracts, followed by grey mottled, brown and white. Tannin concentration ranged from 10.2 to 55.4 mg GAE / 100 g DW for the aqueous and from 3.1 to 53 mg GAE / 100 g DW for the 70% methanol extract. Flavonoid concentration ranged from 42.1 to 62.6 mg quercetin equivalents / 100 g DW (aqueous extraction) and 95.2 to 123.5 mg quercetin equivalents / 100 g DW (70% methanol extraction). The various classes of common beans displayed varying antioxidant activities. The bean extracts exhibited DPPH free radical scavenging activities with pseudo firstorder rate constants (K) ranging between 0.006 min -1 and 0.053 min -1 and FRAP derived antioxidant power between 1.69 and 6.88 Fe 2+ / 100 g DW. The red market class displayed the highest antioxidant activity in the aqueous extract, but showed little difference with the grey mottled beans in the methanolic extract. Ranking the market classes based on the free radical scavenging capacities and the FRAP-derived total antioxidant power, the following order was observed: red beans > grey mottled beans > brown beans > white beans. On a comparative basis, white beans displayed far lower antioxidant activities compared to the others. Keywords: antioxidant, polyphenols, nutraceuticals, common beans Cite This Article

Experimental observation of high field diamagnetic fluctuations in Niobium

We have performed a magnetic study of a bulk metallic sample of Nb with critical temperature $T_{c}=8.5$ K. Magnetization versus temperature (M {\it vs} T) data obtained for fixed magnetic fields above 1 kOe show a superconducting transition which becomes broader as the field is increased. The data are interpreted in terms of the diamagnetic lowest Landau level (LLL) fluctuation theory. The scaling analysis gives values of the superconducting transition temperature $T_{c}(H)$ consistent with $H_{c2}(T)$% . We search for universal 3D LLL behavior by comparing scaling results for Nb and YBaCuO, but obtain no evidence for universality.Comment: 5 pages, 6 figures, Accepted for publication in Phys.Rev.

BGS karst report series. C7, karst in the Chalk of the South Downs.

This report documents the evidence for karst and rapid groundwater flow in the Chalk of the South Downs area in Southern England. It is part of the BGS karst report series on those karst aquifers in England in which cave development is limited – principally the Upper Cretaceous Chalk and the Jurassic and Permian limestones. The series is the main output of the NERC funded Knowledge Exchange fellowship “Karst knowledge exchange to improve protection of groundwater resources”. The term “karst” applies to rocks that are soluble. In classic karst there are extensive caves and large scale surface karst landforms such as dolines, shafts, stream/river sinks, and springs. In the past, the Chalk and the Jurassic and Permian limestones of England were not considered karstic because they have limited cave development, and because karst features are usually small and have not been well documented. However, permeability in these aquifers is determined by their soluble nature and groundwater flow is predominantly through small-scale karstic solutional features. These reports provide data and information on karst in each area. Karst data are compiled from the British Geological Survey databases on karst, springs, and transmissivity; reports and peer reviewed papers; from geological mapping, and through knowledge exchange with the Environment Agency, universities, water companies and consultants. This report shows that in the C7 karst knowledge exchange area, the South Downs area of the Chalk, there is extensive evidence for karst development with dry valleys, caves, stream sinks, dolines, dissolution pipes, and springs present. Short caves have been recorded in the area, and the longest known Chalk cave in England (~350 m) is in this area at Beachy Head. Observations of coastal cliffs have been particularly important in demonstrating that caves and conduits can occur even beneath interfluves and in the absence of obvious surface karst. Coastal sections also provide evidence for pervasive stratigraphical influence on subsurface karst with distinct stratigraphical horizons (particularly sheet and semi-tabular flints, marl seams and hardgrounds) being important for conduit development. In the Beachy Head area, the Seven Sisters Flint, the Belle Tout Marls, the Shoreham Marls, the Navigation Marl, and the Hope Gap sheet flint all host cave and conduit systems. Locally, many stream sinks occur in association with the Chalk-Palaeogene margin, particularly in the west of the area. Stream sinks are less common or absent in the eastern parts of the area where the Palaeogene cover is absent, although major rivers cross the Chalk and their contribution to point recharge via losses to the aquifer was not established during this work. Soakaways and SUDs with high infiltration rates into the Chalk have also not been identified. Dolines also occur in the area, although many recorded surface depressions are likely to be pits of anthropogenic origin. Dissolution pipes are extremely common, especially where the Chalk is overlain by thin unconsolidated superficial deposits, and in some cases can be 10s of metres deep and/or wide. There are many springs in the area, which would have formed the natural outlets for the karstic solutional networks, although little is known about the discharge of most springs and how this has changed in response to groundwater abstraction. Five large springs are identified, the largest being the Bedhampton and Havant complex with a discharge of ~ 600-1900 l.s-1. Evidence from 22 tracer test connections demonstrate very rapid groundwater flow, with velocities ranging from 0.2 to 12.3 km/day over distances of up to 6.6 km; and tracer recoveries ranging from 0.1 to 100 %. Other evidence of karst comes from hydrogeological studies including investigations of transmissivity and pumping tests, water level data from observation boreholes, downhole imaging and borehole logs, groundwater quality, inflows during tunnel construction, saline intrusion, and groundwater flooding. There is considerable evidence for karst and rapid groundwater flow at groundwater abstractions throughout the South Downs area. Karst is clearly important in enabling rapid recharge and providing some rapid flowpaths through the unsaturated zone, especially via stream sinks but also via solutional fissures with no surface expression. However, there appears to be a higher degree of protection from surface pollutants than in highly karstic aquifers, perhaps due to fewer and smaller stream sinks and the potential for more attenuation in the unsaturated zone. Saturated zone networks of solutional fissures and conduits appear to be very common, and there is evidence to suggest that they extend over distances of several kilometres suggesting that karst specific approaches to Source Protection Zone delineation are likely to be useful. Consideration of the karstic processes that result in the enhanced permeability of the aquifer through the development of solutional fissures and conduits is key to understanding the hydrogeology of this area; and improved understanding of rapid flow in both the unsaturated and saturated zones is important for groundwater protection and management of water resources. This report presents an overview of the current conceptual understanding of karst in the Chalk in the South Downs and provides a basis for further investigations of karst in this area to enable improved management and protection of groundwater resources

Synapse-specific expression of calcium-permeable AMPA receptors in neocortical layer 5

In the hippocampus, calcium‐permeable AMPA receptors have been found in a restricted subset of neuronal types that inhibit other neurons, although their localization in the neocortex is less well understood. In the present study, we looked for calcium‐permeable AMPA receptors in two distinct populations of neocortical inhibitory neurons: basket cells and Martinotti cells. We found them in the former but not in the latter. Furthermore, in basket cells, these receptors were associated with particularly fast responses. Computer modelling predicted (and experiments verified) that fast calcium‐permeable AMPA receptors enable basket cells to respond rapidly, such that they promptly inhibit neighbouring cells and shut down activity. The results obtained in the present study help our understanding of pathologies such as stroke and epilepsy that have been associated with disordered regulation of calcium‐permeable AMPA receptors

Alluvial fan records from southeast Arabia reveal multiple windows for human dispersal

The dispersal of human populations out of Africa into Arabia was most likely linked to episodes of climatic amelioration, when increased monsoon rainfall led to the activation of drainage systems, improved freshwater availability, and the development of regional vegetation. Here we present the first dated terrestrial record from southeast Arabia that provides evidence for increased rainfall and the expansion of vegetation during both glacial and interglacial periods. Findings from extensive alluvial fan deposits indicate that drainage system activation occurred during Marine Isotope Stage (MIS) 6 (ca. 160–150 ka), MIS 5 (ca. 130–75 ka), and during early MIS 3 (ca. 55 ka). The development of active freshwater systems during these periods corresponds with monsoon intensity increases during insolation maxima, suggesting that humid periods in Arabia were not confined to eccentricity-paced deglaciations, and providing paleoenvironmental support for multiple windows of opportunity for dispersal out of Africa during the late Pleistocene