Oxygen inhibition of nitrate uptake is a general regulatory mechanism in nitrate respiration

It has recently been demonstrated that oxygen inhibits nitrate uptake by denitrifying Pseudomonas aeruginosa. The purpose of the present investigation was to determine if this novel mechanism of regulation is universal for the regulation of nitrate respiration in other widely divergent species of bacteria. Nitrate transport by whole cell suspensions was completely and reversibly inhibited in 11 out of 12 species tested, whereas nitrate reduction by cell-free extracts was not affected by oxygen or was only partially inhibited in some cases. These results indicate that oxygen inhibition of nitrate uptake is a general regulatory phenomenon.     

The 30-Base-Pair Deletion in Chinese Variants of the Epstein-Barr Virus LMP1 Gene Is Not the Major Effector of Functional Differences between Variant LMP1 Genes in Human Lymphocytes

One group of sequence variants of Epstein-Barr virus is characterized by a 10-amino-acid deletion within the CTAR-2 functional domain of the latent membrane protein, LMP1. A role for this deletion in enhancing the tumorigenicity of the viral oncogene in rodent fibroblasts was recently demonstrated. We examined the effect of this deletion upon LMP1 function in four human lymphoid cell lines by using three natural variants of LMP1: the prototype B95.8 gene and the CAO and AG876 genes, both of which have codons 343 to 352 of the B95.8-LMP1 deleted. These experiments revealed that LMP1-mediated upregulation of CD40 and CD54 was markedly impaired (by 60 to 90%) with CAO-LMP1 compared with B95.8-LMP1. In contrast, the function of AG876-LMP1 was indistinguishable from that of B95.8-LMP1 in two lines and was only slightly impaired in the other two lines. Activation of NF-κB by CAO-LMP1 was not impaired in any of the lines; rather, activation of an NF-κB reporter by CAO-LMP1 was consistently about twofold greater than the activation with B95.8- or AG876-LMP1. Therefore, while the CAO-LMP1 is functionally distinct from the prototype B95.8-LMP1 in human lymphocytes, the 10-amino-acid deletion appears not to be directly responsible. This conclusion was confirmed by using a B95.8-LMP1 mutant with codons 343 to 352 deleted and chimerae of CAO- and B95.8-LMP1 in which the CTAR-2 domains of these genes were exchanged. Sequences outside the CTAR-2 domain were implicated in the distinct functional characteristics of CAO-LMP1 in human lymphoid cells.     

Diminished Reovirus Capsid Stability Alters Disease Pathogenesis and Littermate Transmission

Reovirus is a nonenveloped mammalian virus that provides a useful model system for studies of viral infections in the young. Following internalization into host cells, the outermost capsid of reovirus virions is removed by endosomal cathepsin proteases. Determinants of capsid disassembly kinetics reside in the viral σ3 protein. However, the contribution of capsid stability to reovirus-induced disease is unknown. In this study, we found that mice inoculated intramuscularly with a serotype 3 reovirus containing σ3-Y354H, a mutation that reduces viral capsid stability, succumbed at a higher rate than those infected with wild-type virus. At early times after inoculation, σ3-Y354H virus reached higher titers than wild-type virus at several sites within the host. Animals inoculated perorally with a serotype 1 reassortant reovirus containing σ3-Y354H developed exaggerated myocarditis accompanied by elaboration of pro-inflammatory cytokines. Surprisingly, unchallenged littermates of mice infected with σ3-Y354H virus displayed higher titers in the intestine, heart, and brain than littermates of mice inoculated with wild-type virus. Together, these findings suggest that diminished capsid stability enhances reovirus replication, dissemination, lethality, and host-to-host spread, establishing a new virulence determinant for nonenveloped viruses.     

Genes for serum amyloid A proteins map to Chromosome 7 in the mouse

Summary Several restriction fragment length variants have been detected among inbred strains using a mouse serum amyloid A cDNA clone. Five variants were shown to segregate as a single genetic unit and were mapped to Chromosome 7 between the glucose phosphate isomerase locus (Gpi-1) and the pink eye dilution locus (p) using recombinant inbred and congenic strains. The finding that no major MspI or BclI restriction fragments were shared between digests of DNAs from a Chromosome 7 congenic strain and its inbred partner, indicate that most, and probably all, sequences detected with the probe are clustered on Chromosome 7. Aneuploid mapping was used to show that the serum amyloid A gene complex (Saa) is proximal to the Chromosome 7 breakpoint in T(7;X)1Ct, a translocation in which the middle third of Chromosome 7 is inserted into the X-chromosome. A survey of inbred strains revealed a single common Saa haplotype and eight rare haplotypes. The complex distribution of 14 different variants suggests that recombination may have played a role in haplotype evolution.This work was supported by grants GM18684 and CA33093 from the National Institute of General Medical Sciences and the National Cancer Institute, respectively.     

Complement Factor H-Related Protein 3 Serum Levels Are Low Compared to Factor H and Mainly Determined by Gene Copy Number Variation in CFHR3

The major human complement regulator in blood, complement factor H (FH), has several closely related proteins, called FH-related (FHR) proteins. As all FHRs lack relevant complement regulatory activity, their physiological role is not well understood. FHR protein 3 (FHR-3) has been suggested to compete with FH for binding to Neisseria meningitidis, thereby affecting complement-mediated clearance. Clearly, the in vivo outcome of such competition greatly depends on the FH and FHR-3 concentrations. While FH levels have been established, accurate FHR-3 levels were never unequivocally reported to date. Moreover, CFHR3 gene copy numbers commonly vary, which may impact the FHR-3 concentration. Hence, we generated five anti-FHR-3 mAbs to specifically measure FHR-3 in human healthy donors of which we determined the gene copy number variation at the CFH/CFHR locus. Finally, we examined the acute-phase response characteristics of FHR-3 in a small sepsis cohort. We determined FHR-3 levels to have a mean of 19 nM and that under normal conditions the copy number of CFHR3 correlates to a very large extent with the FHR-3 serum levels. On average, FHR-3 was 132-fold lower compared to the FH concentration in the same serum samples and FHR-3 did not behave as a major acute phase response protein.     

A Correspondence between Individual Differences in the Brain's Intrinsic Functional Architecture and the Content and Form of Self-Generated Thoughts

Although neural activity often reflects the processing of external inputs, intrinsic fluctuations in activity have been observed throughout the brain. These may relate to patterns of self-generated thought that can occur while not performing goal-driven tasks. To understand the relationship between self-generated mental activity and intrinsic neural fluctuations, we developed the New York Cognition Questionnaire (NYC-Q) to assess the content and form of an individual''s experiences during the acquisition of resting-state fMRI data. The data were collected as a part of the Nathan Kline Rockland Enhanced sample. We decomposed NYC-Q scores using exploratory factor analysis and found that self-reported thoughts clustered into distinct dimensions of content (future related, past related, positive, negative, and social) and form (words, images, and specificity). We used these components to perform an individual difference analysis exploring how differences in the types of self-generated thoughts relate to whole brain measures of intrinsic brain activity (fractional amplitude of low frequency fluctuations, regional homogeneity, and degree centrality). We found patterns of self-generated thoughts related to changes that were distributed across a wide range of cortical areas. For example, individuals who reported greater imagery exhibited greater low frequency fluctuations in a region of perigenual cingulate cortex, a region that is known to participate in the so-called default-mode network. We also found certain forms of thought were associated with other areas, such as primary visual cortex, the insula, and the cerebellum. For example, individuals who reported greater future thought exhibited less homogeneous neural fluctuations in a region of lateral occipital cortex, a result that is consistent with the claim that particular types of self-generated thought depend on processes that are decoupled from sensory processes. These data provide evidence that self-generated thought is a heterogeneous category of experience and that studying its content can be helpful in understanding brain dynamics.     

Influence of the solvent on the conformational-dependent properties of random-coil polypeptides. I. The mean-square of the end-to-end distance and of the dipole moment

Conformational energies for the N-acetyl-N'-methylamides of the 20 natural amino acids were calculated, including the solvent effects, as functions of the angles phi and psi for rotation of the main chain and for six positions chi 1 of the C alpha-C beta bond in the side chain (fixed values for chi 2, chi 3, ...). The computed energies were used to evaluate the mean-square end-to-end distance and mean-square dipole moment of homopolypeptides of the 20 natural amino acids. Ten proteins and three enzymes of current interest were also studied. Slight differences in both properties are found on taking the effects of solvent into consideration. Comparison with other computational and experimental results is made.