Uninterrupted translation through putative 12-nucleotide coding gap in sequence of carA: business as usual

Previous work of others reported an untranslated stretch of 12 nucleotides in the 5' coding sequence of carA from Pseudomonas aeruginosa. However, N-terminal protein sequencing of carA-lacZ translational fusions shows that these 12 nucleotides are normally translated in a continuous triplet manner, both in P. aeruginosa and in Escherichia coli.     

Forward telescoping: the question matters

This study examines the effect of pulse repetition rate (PRR), pulse intensity, and bicuculline on the minimum threshold (MT) and latency of inferior collicular neurons of the big brown bat, Eptesicus fuscus, under free-field stimulation conditions. It tests the hypothesis that changes in MT and latency of collicular neurons are co-dependent on PRR. The number of impulses in inferior collicular neurons (n = 245) increased either monotonically (25%) or non-monotonically (75%) with pulse intensity. Latencies either decreased to a plateau (72%), fluctuated unpredictably within 3 ms (21%) or changed very little (7%) with increasing pulse intensity. Latencies and MTs of most collicular neurons increased by 1.5-24 ms (mean +/- SD = 4.8 +/- 3.3 ms) and 4-75 dB (mean +/- SD = 22.1 +/- 16.2 dB) with increasing PRR. In most neurons (94%), the latency increase was completely (42%) or partially (52%) eliminated when pulse intensity was compensated for the MT increase with PRR. Complete elimination of latency was achieved by bicuculline application. In a few neurons (6%), the latency increase with PRR was not affected by compensated pulse intensity or bicuculline application.     

Input and central processing expressed in ERP and heart rate changes to rare target and rare nontarget stimuli

Whether late positive components of event-related potentials (ERPs) parallel changes in heart rate (HR) indicative of attention/orienting to rare stimuli has been debated. In the present study, a three-stimulus design was used, with rare target, rare nontarget, and frequent standard stimuli delivered under identical conditions except that instructions to subjects described the targets to which subjects should respond but did not describe the nontargets. In Experiment 1, stimuli varied among modalities; in Experiment 2, auditory stimuli were employed. Both ERPs and HR were consistent with automatic processing preceding two stages of controlled processing. Rare stimuli evoked larger parietal P300 and initial HR deceleration than standards. Presumably because of load-reducing effects of long interstimulus intervals, targets and nontargets were not distinguished before a late slow wave and a late phase of HR acceleration. Neither rare stimulus elicited a recognizable frontal P3a.     

Hinge bending within the cytokine receptor superfamily revealed by the 2.4 A crystal structure of the extracellular domain of rabbit tissue factor

Tissue factor (TF), a member of the cytokine receptor superfamily, is the obligate cofactor of coagulation factor VIIa (FVIIa), and has a pivotal role in initiating the extrinsic pathway of blood coagulation through formation of the TF x FVIIa complex. The crystal structure of the extracellular portion of rabbit TF has been solved at 2.35 A resolution and refined to a crystallographic R-value of 19.1% (free R-value, 27.7%). Like the human homologue, the extracellular portion consists of two fibronectin type III domains connected by a short alpha-helical segment. Unexpectedly, the two molecules in the crystallographic asymmetric unit differ in their relative domain-domain orientation, revealing unsuspected hinge motion consisting of a rotation of about 12.7 degrees around an axis intersecting the linker segment at residue 106. Superposition of rabbit tissue factor with free and bound human tissue factor allows for the detection of an identical, albeit smaller, hinge motion in human TF induced upon binding of FVIIa. This raises the possibility that a very similar hinge axis may be present in other members of the cytokine receptor superfamily.     

Identification and characterization of a novel member of the fibroblast growth factor family

A new member of the fibroblast growth factor (FGF) family, FGF-13, has been molecularly cloned as a result of high throughput sequencing of a human ovarian cancer cell library. The open reading frame of the novel human gene (1419 bp) encodes for a protein of 216 a.a. with a molecular weight of 22 kDa. The FGF-13 sequence contains an amino-terminal hydrophobic region of 23 a.a. characteristic of a signal secretion sequence. FGF-13 is most homologous, 70% similarity at the amino acid level, to FGF-8. Northern hybridization analysis demonstrated prominent expression of FGF-13 in human foetal and adult brain, particularly in the cerebellum and cortex. In proliferation studies with BaF3 cells, FGF-13 preferentially activates cell clones expressing either FGF receptor variant, 3-IIIc or 4. The signal transduction pathways of FGF-13 and FGF-2 were compared in rat hippocampal astrocytes. The two FGFs induce an equivalent level of tyrosine phosphorylation of mitogen-activated protein kinase (MAPK) and c-raf activation. However, FGF-13 is more effective than FGF-2 in inducing the phosphorylation of phospholipase C-gamma (PLC-gamma). Treatment of neuronal cultures from rat embryonic cortex with FGF-13 increases the number of glutamic acid decarboxylase immunopositive neurons, the level of high-affinity gamma-aminobutyric acid (GABA) uptake, and choline acetyltransferase enzyme activity. The GABAergic neuronal response to FGF-13 treatment is rapid with a significant increase occurring within 72 h. We have identified a novel member of the FGF family that is expressed in the central nervous system (CNS) and increases the number as well as the level of phenotypic differentiation of cortical neurons in vitro.     

The dynamics of pAL2-1 homologous linear plasmids in Podospora anserina

We have investigated the properties of the newly synthesized proton-pump inhibitor, 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline (YJA20379-6), on gastric mucosal proton-pump (H+/K+-ATPase) activity, gastric acid secretion and gastroduodenal lesions in experimental rats. YJA20379-6 markedly inhibited H+/K+-ATPase activity in rabbit isolated gastric mucosal microsomes, confirming its classification as a proton-pump inhibitor. The inhibitory efficacy of YJA20379-6 on the proton pump was approximately 14-times higher than that of omeprazole at pH 7.4. YJA20379-6 given intraduodenally had a potent inhibitory effect on gastric secretion in pylorus-ligated rats (ED50 22.9 mg kg(-1)) but was less active than omeprazole. Pretreatment of rats with YJA20379-6 dose-dependently protected the gastric mucosa from damage induced by water-immersion stress, indomethacin and absolute ethanol, and the duodenal mucosa from damage induced by mepirizole. Repeated administration of YJA20379-6 also dose-dependently accelerated the spontaneous healing of acetic acid-induced gastric ulcers. These results suggest that YJA20379-6 has potent anti-secretory and anti-ulcer effects which are exerted by suppression of H+/K+-ATPase activity in gastric parietal cells. YJA20379-6 might be useful for the clinical treatment of peptic ulcer diseases.     

Food for thought: a critique on the hypothesis that endogenous cholecystokinin acts as a physiological satiety factor

This review evaluates the various lines of evidence supporting the hypothesis that cholecystokinin (CCK) released from the small intestine during feeding plays a physiological satiety. Issues considered include, the effects of systemic injection of CCK on consummatory and operant feeding, the role of the vagus nerve, the effects of CCKB receptor antagonists, and the neuroendocrine responses to exogenous CCK. A critical appraisal of this research indicates that while it is clearly demonstratable that exogenous peripheral CCK can alter food intake by acting on CCKA receptors, the mechanism involved may be more closely related to the induction if aversion and nausea, rather than satiety. With regard to peripheral endogenous CCK, the available evidence also does not seem to support a role for the hormone in satiety. In particular, it is doubtful whether plasma concentrations of CCK following a meal are sufficiently high to inhibit feeding. Moreover, CCKA receptor antagonist which do not cross the blood brain barrier fail to increase meal size, as would be expected if peripheral CCK was an effective satiety factor. In addition, the recent literature concerned with the possibility that CCK may have a direct action within the brain in the control of food intake has been reviewed. These studies show that CCK administered intracerebroventicularly, or by micoinjection into discrete brain regions, also inhibits feeding via a CCKA receptor mechanism. However, the physiological relevance of these findings have yet to be determined.     

Recipient and provider perspectives of barriers to rural prenatal care

Barriers to prenatal care have been linked to inappropriate service usage and poor health outcomes of mothers and infants. This study describes barriers to prenatal care, as identified by low-income recipients and providers of prenatal care in a small rural county in the Midwest. A prospective survey design and focus group were used. An unexpected finding occurred. Almost half of the recipients identified no barriers to prenatal care; however, these women still received less than adequate prenatal care. Providers identified the attitudinal barrier of women as not valuing prenatal care, but the women did not. Some women were found to need information about availability and eligibility for Medicaid and other services. Issues surrounding prenatal care for rural women are complex and subtle. Community health nursing can inform and influence community leaders and members about prenatal care services for rural low-income women.     

Analysis of major histocompatibility complex class I, TAP expression, and LMP2 epitope sequence in Epstein-Barr virus-positive Hodgkin's disease

The Epstein-Barr virus (EBV)-encoded latent membrane proteins, LMP1 and LMP2, are consistently expressed by the malignant Hodgkin/Reed-Sternberg (HRS) cells of EBV-associated Hodgkin's disease (HD). Cytotoxic T lymphocyte (CTL) responses to both of these proteins have been shown in the blood of EBV-seropositive individuals, yet in HD the apparent failure of the CTL response to eliminate HRS cells expressing LMP1 and LMP2 in vivo has given rise to the suggestion that HD may be characterized by the presence of defects in antigen processing/presentation or in CTL function. This study has used immunohistochemistry to show high-level expression of major histocompatibility complex (MHC) class I molecules by the HRS cells of EBV-associated HD and either low level or absence of expression of MHC class I molecules on HRS cells of EBV-negative tumors. In addition, HRS cells expressed high levels of transporter-associated proteins (TAP-1, -2), irrespective of the presence of latent EBV infection. These results suggest that global downregulation of MHC class I molecules does not account for the apparent ability of EBV-infected HRS cells to evade CTL responses, but may be important in the understanding of EBV-negative disease. We have also sequenced an epitope in LMP2A (CLGGLLTMV) that is restricted through HLA A2.1, a relatively common allele in Caucasian populations, and showed that this epitope is wild type in a small group of EBV-associated HLA A2.1-positive HD tumors. This result may be relevant to proposed immunotherapeutic approaches for EBV-positive HD patients that target CTL epitopes.