Convergent and parallel activation of low-conductance potassium channels by calcium and cAMP-dependent protein kinase.

K+ channels, which have been linked to regulation of electrogenic solute transport as well as Ca2+ influx, represent a locus in hepatocytes for the concerted actions of hormones that employ Ca2+ and cAMP as intracellular messengers. Despite considerable study, the single-channel basis for synergistic effects of Ca2+ and cAMP on hepatocellular K+ conductance is not well understood. To address this question, patch-clamp recording techniques were applied to a model liver cell line, HTC hepatoma cells. Increasing the cytosolic Ca2+ concentration ([Ca2+]i) in HTC cells, either by activation of purinergic receptors with ATP or by inhibition of intracellular Ca2+ sequestration with thapsigargin, activated low-conductance (9-pS) K+ channels. Studies with excised membrane patches suggested that these channels were directly activated by Ca2+. Exposure of HTC cells to a permeant cAMP analog, 8-(4-chlorophenylthio)-cAMP, also activated 9-pS K+ channels but did not change [Ca2+]i. In excised membrane patches, cAMP-dependent protein kinase (the downstream effector of cAMP) activated K+ channels with conductance and selectivity identical to those of channels activated by Ca2+. In addition, cAMP-dependent protein kinase activated a distinct K+ channel type (5 pS). These data represent the differential regulation of low-conductance K+ channels by signaling pathways mediated by Ca2+ and cAMP. Moreover, since low-conductance Ca(2+)-activated K+ channels have been identified in a variety of cell types, these findings suggest that differential regulation of K+ channels by hormones with distinct signaling pathways may provide a mechanism for hormonal control of solute transport and Ca(2+)-dependent cellular functions in the liver as well as other nonexcitable tissues.

The inositol 1,4,5-trisphosphate receptor is essential for T-cell receptor signaling.

Antigen-specific activation of T lymphocytes, via stimulation of the T-cell antigen receptor (TCR) complex, is marked by a rapid and sustained increase in the concentration of cytoplasmic free Ca2+ ([Ca2+]i). It has been suggested that the second messenger inositol 1,4,5-trisphosphate (IP3) produced after TCR stimulation binds to the IP3 receptor (IP3R), an intracellular Ca(2+)-release channel, and triggers the increase in [Ca2+]i that activates transcription of the gene for T-cell growth factor interleukin 2 (IL-2). However, the role of the IP3R in T-cell signaling and possibly in plasma membrane Ca2+ influx in T cells remains unproven. Stable transfection of T cells (Jurkat) with antisense type 1 IP3R cDNA prevented type 1 IP3R expression, providing a tool for dissecting the role of IP3 signaling during T-cell activation. T cells lacking type 1 IP3R failed to increase [Ca2+]i or produce IL-2 after TCR stimulation. Moreover, depletion of intracellular Ca2+ stores without TCR activation stimulated Ca2+ influx in cells lacking the type 1 IP3R. These results establish that the type 1 IP3R is required for intracellular Ca2+ release that triggers antigen-specific T-cell proliferation but not for plasma membrane Ca2+ influx.

The effect of protein concentration on ion binding.

The concentration of protein in a solution has been found to have a significant effect on ion binding affinity. It is well known that an increase in ionic strength of the solvent medium by addition of salt modulates the ion-binding affinity of a charged protein due to electrostatic screening. In recent Monte Carlo simulations, a similar screening has been detected to arise from an increase in the concentration of the protein itself. Experimental results are presented here that verify the theoretical predictions; high concentrations of the negatively charged proteins calbindin D9k and calmodulin are found to reduce their affinity for divalent cations. The Ca(2+)-binding constant of the C-terminal site in the Asn-56 --> Ala mutant of calbindin D9k has been measured at seven different protein concentrations ranging from 27 microM to 7.35 mM by using 1H NMR. A 94% reduction in affinity is observed when going from the lowest to the highest protein concentration. For calmodulin, we have measured the average Mg(2+)-binding constant of sites I and II at 0.325, 1.08, and 3.25 mM protein and find a 13-fold difference between the two extremes. Monte Carlo calculations have been performed for the two cases described above to provide a direct comparison of the experimental and simulated effects of protein concentration on metal ion affinities. The overall agreement between theory and experiment is good. The results have important implications for all biological systems involving interactions between charged species.

Testimonies of Students, Number 6-10, 1768 April

Handwritten testimonies of students regarding the rebellion. Each student's statement was numbered, and sheets of paper were also assigned a number, as indicated in the list below.

Evidences vs Tudor, [1768 April]

2-page handwritten account of William Tudor's actions on April 2 and 3, 1768.

Evidences against Peabody, [1768 April]

2-page handwritten list of evidence summarizing the testimony provided by individual students against Stephen Peabody.

[Letter from Joseph Thaxter to Revd Charles Lowell], 1820 February 13

2-leaf handwritten letter describing the rebellion. Includes twentieth century typewriten transcription.

Sedimentology on a core from Lonar Lake in India

Concerns about the regional impact of global climate change in a warming scenario have highlighted the gaps in our understanding of the Indian Summer Monsoon (ISM, also referred to as the Indian Ocean summer monsoon) and the absence of long term palaeoclimate data from the central Indian core monsoon zone (CMZ). Here we present the first high resolution, well-dated, multiproxy reconstruction of Holocene palaeoclimate from a 10 m long sediment core raised from the Lonar Lake in central India. We show that while the early Holocene onset of intensified monsoon in the CMZ is similar to that reported from other ISM records, the Lonar data shows two prolonged droughts (PD, multidecadal to centennial periods of weaker monsoon) between 4.6-3.9 and 2-0.6 cal?ka. A comparison of our record with available data from other ISM influenced sites shows that the impact of these PD was observed in varying degrees throughout the ISM realm and coincides with intervals of higher solar irradiance. We demonstrate that (i) the regional warming in the Indo-Pacific Warm Pool (IPWP) plays an important role in causing ISM PD through changes in meridional overturning circulation and position of the anomalous Walker cell; (ii) the long term influence of conditions like El Niño-Southern Oscillation (ENSO) on the ISM began only ca. 2 cal?ka BP and is coincident with the warming of the southern IPWP; (iii) the first settlements in central India coincided with the onset of the first PD and agricultural populations flourished between the two PD, highlighting the significance of natural climate variability and PD as major environmental factors affecting human settlements.

Tolkovyĭ slovarʹ zhivago velikoruskago i͡azyka /

"Pechatano na schet Vsemilostivi͡eĭshe pozhalovannykh sredstv."--T.p., Vol.2-4.

Russkīe pisateli posli︠e︡ Gogoli︠a︡ : chtenīi︠a︡, ri︠e︡chi i statʹi /

t. 1. I.S. Turgenev. Ḟ.M. Dostoevskīĭ. -- t. 2. I.A. Goncharov. A.Ḟ. Pisemskīĭ. M.E. Saltykov. Gr.L.N. Tolstoĭ. -- t. 3. S.T. Aksakov. P.I. Melʹnikov. A.N. Ostrovskīĭ. Izd. 5.

Art Gallery on 3rd floor General Library, Randolph Rogers' statuary, (incl. Lewis Cass, Nydia, etc.) & plaster casts of various antique sculptures

2 scans sharing same hs #, suffix 1of2 for full page, 2of2 for image only

Statues, coins, paintings, etc. in 3rd floor art gallery of General Library building, 1907

2 scans sharing same hs #, suffix 1of2 for full page, 2of2 for image only

View of auditorium stage, University Hall

2 scans sharing same hs #, suffix 1of2 for full page, 2of2 for image only

Picketers protest speech delivered in Oak Park, MI by Y. Rabin, Nov. or Dec. 1968 (Sameer & Nabeel Abraham at center)

2 scans - 1of2=image itself, 2of2=reverse with post-it note

Otechestvovi︠e︡di︠e︡nīe : Rossīi︠a︡ po razskazam puteshestvennikov i uchenym izsli︠e︡dovanīi︠a︡m : uchebnoe posobīe dli︠a︡ uchashchikhsi︠a︡ /

Vol. 3 : Izd. 2.