Relative expression and regulation by short-term fasting of lysophosphatidic acid receptors and autotaxin in white and brown adipose tissue depots

Lysophosphatidic acid (lysoPtdOH) levels have previously been reported to decrease in rodents with short-term fasting. We investigated whether a 16 h fast would change expression of autotaxin, the predominant phospholipase D responsible for adipose-derived lysoPtdOH synthesis, or any of the lysophosphatidic acid receptors (1–6) in four white adipose tissue (WAT) depots and interscapular brown adipose tissue (BAT) in male C57Bl/6J mice fed ad libitum, or fasted for 16 h. Aside from small inductions of Lpar1 in epididymal WAT and Lpar2 in epididymal and inguinal WAT, no significant changes were observed in expression of the Lpar family members, or autotaxin in perirenal, retroperitoneal, epididymal, or inguinal WAT or BAT with fasting. Comparison of the relative expression of Lpar1-6 in various depots showed that Lpar6 was the predominant Lpar in both WAT and BAT, and suggests that further work on the adipose-specific role of Lpar6 is warranted.     

EXPLORING FOR FAN AND DELTA SANDSTONES IN THE OFFSHORE FALKLANDS BASINS

Four basins surround the Falkland Islands, but only the North Falkland Basin has been drilled; six wells were drilled there in 1998. Although all six wells encountered good quality sandstones, none of them targeted the basin margins, on what are now thought to be the optimum migration pathways associated with the basin's thick lacustrine source rocks. Subsequently, a 3D seismic survey acquired in 2004 was designed to identify potential basin-margin -derived sandstones entering the basin along transfer zones. From this survey, a number of basin-margin -attached fans have been identified; these prograded into lacustrine waters of varying depths. These Early Cretaceous alluvial/fan delta/deep-lacustrine fan systems are interpreted to provide excellent potential reservoir facies as they are intimately associated with thick, mature source rocks. They will provide the focus for the next planned phase of exploration in the North Falkland Basin.
A phase of drilling is also planned for the basins to the south of the Islands, where large deltaic and fan systems, slightly younger than those imaged in the North Falkland Basin, are seen on seismic to prograde from the same Palaeozoic hinterland that produced the older, North Falkland Basin fans.
This paper attempts to show how sedimentary models derived from targeted seismic programmes following initial exploration can be utilised to plan and improve new drilling campaigns in a frontier basin. It presents an analysis of sediment dispersal patterns in basins of marine and lacustrine origin linked to a single hinterland area, and highlights the nature of the relationship between relay ramp/transfer zone development and sediment dispersal patterns in the subsurface.     

Autoimmunity caused by disruption of central T cell tolerance. A murine model of drug-induced lupus

A side effect of therapy with procainamide and numerous other medications is a lupus-like syndrome characterized by autoantibodies directed against denatured DNA and the (H2A-H2B)-DNA subunit of chromatin. We tested the possibility that an effect of lupus-inducing drugs on central T cell tolerance underlies these phenomena. Two intrathymic injections of procainamide-hydroxylamine (PAHA), a reactive metabolite of procainamide, resulted in prompt production of IgM antidenatured DNA antibodies in C57BL/6xDBA/2 F1 mice. Subsequently, IgG antichromatin antibodies began to appear in the serum 3 wk after the second injection and were sustained for several months. Specificity, inhibition and blocking studies demonstrated that the PAHA-induced antibodies showed remarkable specificity to the (H2A-H2B)-DNA complex. No evidence for polyclonal B cell activation could be detected based on enumeration of Ig-secreting B cells and serum Ig levels, suggesting that a clonally restricted autoimmune response was induced by intrathymic PAHA. The IgG isotype of the antichromatin antibodies indicated involvement of T cell help, and proliferative responses of splenocytes to oligonucleosomes increased up to 100-fold. As little as 5 microM PAHA led to a 10-fold T cell proliferative response to chromatin in short term organ culture of neonatal thymi. We suggest that PAHA interferes with self-tolerance mechanisms accompanying T cell maturation in the thymus, resulting in the emergence of chromatin-reactive T cells followed by humoral autoimmunity.     

Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes

Caspases are fundamental components of the mammalian apoptotic machinery, but the precise contribution of individual caspases is controversial. CPP32 (caspase 3) is a prototypical caspase that becomes activated during apoptosis. In this study, we took a comprehensive approach to examining the role of CPP32 in apoptosis using mice, embryonic stem (ES) cells, and mouse embryonic fibroblasts (MEFs) deficient for CPP32. CPP32(ex3-/-) mice have reduced viability and, consistent with an earlier report, display defective neuronal apoptosis and neurological defects. Inactivation of CPP32 dramatically reduces apoptosis in diverse settings, including activation-induced cell death (AICD) of peripheral T cells, as well as chemotherapy-induced apoptosis of oncogenically transformed CPP32(-/-) MEFs. As well, the requirement for CPP32 can be remarkably stimulus-dependent: In ES cells, CPP32 is necessary for efficient apoptosis following UV- but not gamma-irradiation. Conversely, the same stimulus can show a tissue-specific dependence on CPP32: Hence, TNFalpha treatment induces normal levels of apoptosis in CPP32 deficient thymocytes, but defective apoptosis in oncogenically transformed MEFs. Finally, in some settings, CPP32 is required for certain apoptotic events but not others: Select CPP32(ex3-/-) cell types undergoing cell death are incapable of chromatin condensation and DNA degradation, but display other hallmarks of apoptosis. Together, these results indicate that CPP32 is an essential component in apoptotic events that is remarkably system- and stimulus-dependent. Consequently, drugs that inhibit CPP32 may preferentially disrupt specific forms of cell death.     

Arsenic intoxication presenting with macrocytosis and peripheral neuropathy, without anemia

A case of arsenic intoxication associated with macrocytosis and neuropathy, without anemia, is presented. Evaluation of a 68-year-old man with a long history of peripheral neuropathy and persistent macrocytosis revealed exposure to an insecticide. Analysis of urine and hair revealed elevated levels of arsenic. A short course of d-penicillamine failed to promote urinary excretion of arsenic. Removal of the insecticide resulted in resolution of macrocytosis and slight improvement of neuropathy. This case emphasizes that arsenic intoxication should be considered in patients with macrocytosis with peripheral neuropathy, even in the absence of anemia.     

Threshold voltage-minimum gate length trade-off in buried channelPMOS devices for scaled supply voltage CMOS technologies

The trade-off between threshold voltage (V_th) and the minimum gate length (L_min) is discussed for optimizing the performance of buried channel PMOS transistors for low voltage/low power high-speed digital CMOS circuits. In a low supply voltage CMOS technology it is desirable to scale V_th and L_min for improved circuit performance. However, these two parameters cannot be scaled independently due to the channel punch-through effect. Statistical process/device modeling, split lot experiments, circuit simulations, and measurements are performed to optimize the PMOS transistor current drive and CMOS circuit speed. We show that trading PMOS transistor V_th for a smaller L_min results in faster circuits for low supply voltage (3.3 to 1.8 V) n⁺-polysilicon gate CMOS technology, Circuit simulation and measurements are performed in this study. Approximate empirical expressions are given for the optimum buried channel PMOS transistor V _th for minimizing CMOS circuit speed for cases involving: (1) constant capacitive load and (2) load capacitance proportional to MOS gate capacitance. The results of the numerical exercise are applied to the centering of device parameters of a 0.5 μm 3.3 V CMOS technology that (a) matches the speed of our 0.5 μm 5 V CMOS technology, and (b) achieves good performance down to 1.8 V power supply. For this process the optimum PMOS transistor V_th (absolute value) is approximately 0.85-0.90 V