Far-Infrared Laser Stark Spectroscopy of CH3OD

The high resolution Stark spectra of the singly deuterated methanol isotope, CH₃OD, have been studied using the HCN laser with Stark fields up to approximately 60 000 V/cm. Numerous families of absorption lines have been observed in both parallel and perpendicular polarizations, resulting in the following assignments: with the 311 μm line – J _K = 18₁ ← 18₀ E ₂, υ _t = 1; and with the 337 μm line – J _k = 6₄ ← 5₃ E ₂, υ _t = 0 and J _K = 14₆ ← 13₅ A, υ _t = 1. Zero-field frequencies for the assigned transitions are in agreement with Fourier transform measurements and those calculated from the available molecular constants.     

Transgene expression of bcl-xL permits anti-immunoglobulin (Ig)-induced proliferation in xid B cells

Mutations in the tyrosine kinase, Btk, result in a mild immunodeficiency in mice (xid). While B lymphocytes from xid mice do not proliferate to anti-immunoglobulin (Ig), we show here induction of the complete complement of cell cycle regulatory molecules, though the level of induction is about half that detected in normal B cells. Cell cycle analysis reveals that anti-Ig stimulated xid B cells enter S phase, but fail to complete the cell cycle, exhibiting a high rate of apoptosis. This correlated with a decreased ability to induce the anti-apoptosis regulatory protein, Bcl-xL. Ectopic expression of Bcl-xL in xid B cells permitted anti-Ig induced cell cycle progression demonstrating dual requirements for induction of anti-apoptotic proteins plus cell cycle regulatory proteins during antigen receptor mediated proliferation. Furthermore, our results link one of the immunodeficient traits caused by mutant Btk with the failure to properly regulate Bcl-xL.     

Plant sources of vitamin A and human nutrition: red palm oil does the job

Studies in India demonstrate that the beta-carotene in red palm oil is as effective as high-dose retinyl palmitate as a supplement to restore and preserve vitamin A nutriture in schoolchildren and may be an effective food-based strategy to combat hypovitaminosis A.     

Dental pain and suffering prior to the advent of modern dentistry

In Prehistoric and Mediaeval times few dentitions in this country remained intact much after the age of 40-45 years. The point is made that dental caries and periodontal disease played little part in this early disintegration and it is unlikely that the population of this time suffered severely with their teeth. A change in dietary habits in the late seventeenth and early eighteenth century measurably increased the lifespan of the dentition, but also radically altered the prevalence of caries. This change is likely to have been responsible for a vast increase in dentally-related pain and suffering which was only capable of being tackled as a social problem by the advent of modern dentistry.     

Conjugates of catecholamines with cysteine and GSH in Parkinson's disease: possible mechanisms of formation involving reactive oxygen species

Oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine (DA) to generate semiquinones/quinones, oxygen radicals, and other reactive oxygen species may play a role in neuronal cell death in Parkinson's disease (PD). In particular, semiquinones/quinones can form conjugates with thiol compounds such as GSH and cysteine. Exposure of L-DOPA, DA, and other catecholamines to a system generating O2.- radical led to O2(.-)-dependent depletion of added GSH (or cysteine), accompanied by the formation of thiol-DA or -DOPA adducts as detected by HPLC. Superoxide could additionally cause destruction of these adducts. Iron or copper ions could also promote conjugate formation between GSH or cysteine and DA and L-DOPA, especially if H2O2 was present. We applied HPLC to measure glutathionyl and cysteinyl conjugates of L-DOPA, DA, and 3,4-dihydroxyphenylacetic acid (DOPAC) in postmortem brain samples from PD patients and normal control subjects. Conjugates were detected in most brain areas examined, but levels were highest in the substantia nigra and putamen. In most regions, adduct levels were lower in PD, but there were significant increases in cysteinyl adducts of L-DOPA, DA, and DOPAC in PD substantia nigra, suggesting that acceleration of L-DOPA/DA oxidation occurs in PD, although we cannot say if this is a primary feature of the disease or if it is related to therapy with L-DOPA. In vitro, conjugate formation could be inhibited by the dithiol dihydrolipoate but not by its oxidised form, lipoic acid.     

Apoprotein structure in the LH2 complex from Rhodopseudomonas acidophila strain 10050: modular assembly and protein pigment interactions

The refined structure of the peripheral light-harvesting complex from Rhodopseudomonas acidophila strain 10050 reveals a membrane protein with protein-protein interactions in the trans-membrane region exclusively of a van der Waals nature. The dominant factors in the formation of the complex appear to be extramembranous hydrogen bonds (suggesting that each apoprotein must achieve a fold close to its final structure in order to oligomerize), protein-pigment and pigment-pigment interactions within the membrane-spanning region. The pigment molecules are known to play an important role in the formation of bacterial light-harvesters, and their extensive mediation of structural contacts within the membrane bears this out. Amino acid residues determining the secondary structure of the apoproteins influence the oligomeric state of the complex. The assembly of the pigment array is governed by the apoproteins of LH2. The particular environment of each of the pigment molecules is, however, influenced directly by few protein contacts. These contacts produce functional effects that are not attributable to a single cause, e.g. the arrangement of an overlapping cycle of chromophores not only provides energy delocalisation and storage properties, but also has consequences for oligomer size, pigment distortion modes and pigment chemical environment, all of which modify the precise function of the complex. The evaluation of site energies for the pigment array requires the consideration of a number of effects, including heterogeneous pigment distortions, charge distributions in the local environment and mechanical interactions.     

Fas (APO-1, CD95)-mediated apoptosis in thyroid cells is regulated by a labile protein inhibitor

To determine whether thyroid cell apoptosis observed in autoimmune thyroid disease could be related to activation of the Fas pathway, we examined the expression and function of Fas on thyroid follicular cells in vitro. Fas messenger RNA was found to be present using two different techniques and was expressed at equal levels in thyrocytes cultured either in the presence or absence of TSH. Fas antigen protein expression was demonstrated by Western blot of thyroid cell lysates and by immunohistochemical staining of thyrocytes, and the amount of Fas protein present did not appear to vary regardless of culture conditions. Despite expressing substantial amounts of Fas protein, thyrocytes treated with anti-Fas monoclonal antibody failed to undergo apoptosis. The addition of either interferon-gamma or interleukin-1beta to the anti-Fas-treated cell cultures also did not promote apoptotic signaling through this pathway. In contrast, the concomitant administration of cycloheximide allowed the induction of apoptosis through the activation of Fas in thyrocytes. These results suggest that Fas is constitutively expressed in thyrocytes, but that the induction of apoptosis through the Fas pathway is blocked by a labile protein inhibitor.