Synthesizing and Salvaging NAD+: Lessons Learned from Chlamydomonas reinhardtii

The essential coenzyme nicotinamide adenine dinucleotide (NAD+) plays important roles in metabolic reactions and cell regulation in all organisms. Bacteria, fungi, plants, and animals use different pathways to synthesize NAD+. Our molecular and genetic data demonstrate that in the unicellular green alga Chlamydomonas NAD+ is synthesized from aspartate (de novo synthesis), as in plants, or nicotinamide, as in mammals (salvage synthesis). The de novo pathway requires five different enzymes: L-aspartate oxidase (ASO), quinolinate synthetase (QS), quinolate phosphoribosyltransferase (QPT), nicotinate/nicotinamide mononucleotide adenylyltransferase (NMNAT), and NAD+ synthetase (NS). Sequence similarity searches, gene isolation and sequencing of mutant loci indicate that mutations in each enzyme result in a nicotinamide-requiring mutant phenotype in the previously isolated nic mutants. We rescued the mutant phenotype by the introduction of BAC DNA (nic2-1 and nic13-1) or plasmids with cloned genes (nic1-1 and nic15-1) into the mutants. NMNAT, which is also in the de novo pathway, and nicotinamide phosphoribosyltransferase (NAMPT) constitute the nicotinamide-dependent salvage pathway. A mutation in NAMPT (npt1-1) has no obvious growth defect and is not nicotinamide-dependent. However, double mutant strains with the npt1-1 mutation and any of the nic mutations are inviable. When the de novo pathway is inactive, the salvage pathway is essential to Chlamydomonas for the synthesis of NAD+. A homolog of the human SIRT6-like gene, SRT2, is upregulated in the NS mutant, which shows a longer vegetative life span than wild-type cells. Our results suggest that Chlamydomonas is an excellent model system to study NAD+ metabolism and cell longevity

Applications of satellite technology to broadband ISDN networks

Two satellite architectures for delivering broadband integrated services digital network (B-ISDN) service are evaluated. The first is assumed integral to an existing terrestrial network, and provides complementary services such as interconnects to remote nodes as well as high-rate multicast and broadcast service. The interconnects are at a 155 Mbs rate and are shown as being met with a nonregenerative multibeam satellite having 10-1.5 degree spots. The second satellite architecture focuses on providing private B-ISDN networks as well as acting as a gateway to the public network. This is conceived as being provided by a regenerative multibeam satellite with on-board ATM (asynchronous transfer mode) processing payload. With up to 800 Mbs offered, higher satellite EIRP is required. This is accomplished with 12-0.4 degree hopping beams, covering a total of 110 dwell positions. It is estimated the space segment capital cost for architecture one would be about $190M whereas the second architecture would be about$250M. The net user cost is given for a variety of scenarios, but the cost for 155 Mbs services is shown to be about $15-22/minute for 25 percent system utilization

Crack analysis of concrete beams based on pseudo-discrete crack model

Crack widths are important considerations in both serviceability and durability design of concrete structures and should be evaluated to ensure compliance with design limits. However, existing empirical formulas for maximum crack width prediction are discrepant with each other, and they cannot reveal key information such as crack number and crack spacing. To obtain such information, finite element analysis has to be adopted. However, conventional finite element analysis has its limits in carrying out crack analysis. Particularly, the common smeared crack models, which do not realistically reflect bond-slip of reinforcing bars, would not give correct crack widths. In contrast, the discrete crack models are difficult to apply because of the need to adaptively generate discrete crack elements according to the cracks formed during the loading process. In this paper, a pseudo-discrete crack model is developed for finite element implementation. The conventional smeared crack model is transformed and reformulated, and a novel crack queuing algorithm is introduced for crack analysis. The method has been applied to analyse concrete beams in the literature. It is demonstrated that the computational results of crack number, spacing and widths agree closely with the measured results

He I λ10830 as a Probe of Winds in Accreting Young Stars

He I 10830 profiles acquired with Keck\u27s NIRSPEC for six young low-mass stars with high disk accretion rates (AS 353A, DG Tau, DL Tau, DR Tau, HL Tau, and SVS 13) provide new insight into accretion-driven winds. In four of the stars, the profiles have the signature of resonance scattering, and they possess a deep and broad blueshifted absorption that penetrates more than 50% into the 1 m continuum over a continuous range of velocities from near the stellar rest velocity to the terminal velocity of the wind, unlike inner wind signatures seen in other spectral features. This deep and broad absorption provides the first observational tracer of the acceleration region of the inner wind and suggests that this acceleration region is situated such that it occults a significant portion of the stellar disk. The remaining two stars also have blue absorption extending below the continuum, although here the profiles are dominated by emission, requiring an additional source of helium excitation beyond resonant scattering. This is likely the same process that produces the emission profiles seen at He I 5876 Å

Galantamine Attenuates Type 1 Diabetes and Inhibits Anti-Insulin Antibodies in Non-Obese Diabetic Mice

Type 1 diabetes in mice is characterized by autoimmune destruction of insulin-producing pancreatic beta cells. Disease pathogenesis involves invasion of pancreatic islets by immune cells, including macrophages and T cells, and production of antibodies to self-antigens, including insulin. Activation of the inflammatory reflex, the neural circuit that inhibits inflammation, culminates on cholinergic receptor signals on immune cells to attenuate cytokine release and inhibit B cell antibody production. Here, we show that galantamine, a centrally acting acetylcholinesterase inhibitor and an activator of the inflammatory reflex, attenuates murine experimental type 1 diabetes. Administration of galantamine to animals immunized with keyhole limpet hemocyanin (KLH) significantly suppressed splenocyte release of immunoglobulin G (IgG), interleukin-4 and -6 (IL-4 and IL-6) during KLH-challenge ex vivo. Administration of galantamine beginning at one month of age in non-obese diabetic (NOD) mice significantly delayed the onset of hyperglycemia, attenuated immune cell infiltration in pancreatic islets and decreased anti-insulin antibodies in serum. These observations indicate that galantamine attenuates experimental type 1 diabetes in mice and suggest that activation of the inflammatory reflex should be further studied as a potential therapeutic approach

Space-charge-limited flows in the quantum regime

This paper reviews the recent developments of space-charge-limited (SCL) flow or Child-Langmuir (CL) law in the quantum regime. According to the classical CL law for planar diodes, the current density scales as 3/23∕2’s power of gap voltage and to the inverse squared power of gap spacing. When the electron de Broglie wavelength is comparable or larger than the gap spacing, the classical SCL current density is enhanced by a large factor due to electron tunneling and exchange-correlation effects, and there is a new quantum scaling for the current density, which is proportional to the 1/21∕2’s power of gap voltage, and to the inverse fourth-power of gap spacing. It is also found that the classical concepts of the SCL flow such as bipolar flow, transit time, beam-loaded capacitance, emitted charge density, and magnetic insulation are no longer valid in quantum regime. In the quantum regime, there exists a minimum transit time of the SCL flows, in contrast to the classical solution. By including the surface properties of the emitting surface, there is a threshold voltage that is required to obtain the quantum CL law. The implications of the Fowler-Nordheim-like field emission in the presence of intense space charge over the nanometer scale is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87757/2/056701_1.pd

Measurement of Cosmic-ray Muons and Muon-induced Neutrons in the Aberdeen Tunnel Underground Laboratory

We have measured the muon flux and production rate of muon-induced neutrons at a depth of 611 m water equivalent. Our apparatus comprises three layers of crossed plastic scintillator hodoscopes for tracking the incident cosmic-ray muons and 760 L of gadolinium-doped liquid scintillator for producing and detecting neutrons. The vertical muon intensity was measured to be $I_{\mu} = (5.7 \pm 0.6) \times 10^{-6}$ cm$^{-2}$s$^{-1}$sr$^{-1}$. The yield of muon-induced neutrons in the liquid scintillator was determined to be $Y_{n} = (1.19 \pm 0.08 (stat) \pm 0.21 (syst)) \times 10^{-4}$ neutrons/($\mu\cdot$g$\cdot$cm$^{-2}$). A fit to the recently measured neutron yields at different depths gave a mean muon energy dependence of $\left\langle E_{\mu} \right\rangle^{0.76 \pm 0.03}$ for liquid-scintillator targets.Comment: 14 pages, 17 figures, 3 table