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Activation of human hippocampal formation reflects success in both encoding and cued recall of paired associates.

Contemporary theories of hippocampal function suggest that both encoding and retrieval of episodic memories may be accomplished by neural circuitry embedded within the same anatomical structures, but neuroimaging support for this hypothesis has been ambiguous. Recent studies suggest that the best available indicators of hippocampal encoding and retrieval operations are selective activations due to novelty, encoding success, and recall success in a paired associate learning paradigm. In the current study, both encoding and cued recall of paired associate words were conducted during a single session of fMRI scanning. Bilateral activation in the medial temporal lobe was detected for encoding word pairs vs. a fixation baseline and for encoding novel word pairs vs. repeated word pairs. These activations were stronger in subjects who successfully memorized more word pairs. In cued recall, greater responses were seen in higher performing subjects. In lower performing subjects, responses were greater to cue words whose paired associate was correctly recalled than to cue words whose correct associate had been forgotten (or not encoded). The difference between correct and incorrect trials was more pronounced on repeated presentations of the same cue words, but not apparent on their first presentation alone. Overlap of encoding and retrieval effects was maximal in the middle of the longitudinal extent of the right hippocampus, with one additional locus of overlap outside the MTL, in left occipitotemporal cortex. The conjunction of these effects suggests that it is correct to view both encoding and recall of associative memories as functions of an integrated hippocampal system.

Adult↗

The effect of encoding strategies on medial temporal lobe activations during the recognition of words: an event-related fMRI study.

It is known that manipulation of the encoding strategy affects behavioral and activation data during later retrieval. In the present fMRI study, we examined brain activity during the recognition of words encoded using three different strategies formed by the combination of two factors of relational and self-performed processes. The first encoding strategy involved subjects learning words using both relational and self-performed processes (R+S+). In the second, subjects learned words using only a relational process (R+S-). In the third, subjects learned words without using either process (R-S-). During fMRI after encoding, subjects were randomly presented with words encoded previously and with new words (New) and were required to judge whether or not the word presented had been previously encoded. The fMRI experiment was performed with the event-related design. Compared to New, activation of the left medial temporal lobe (MTL) occurred during the recognition of words encoded using R+S+ and R+S-, whereas right MTL activations only occurred with the R+S+ strategy. ROI analysis for the bilateral hippocampus and parahippocampal gyrus showed a linear increase in left MTL activity (hippocampus and parahippocampal gyrus) during the recognition of words encoded with the R-S-, R+S-, to R+S+, whereas right MTL activity (parahippocampal gyrus) was only increased with the R+S+ strategy. The findings suggest that the left and right MTL structures may contribute differentially to the processes involved in the recognition of stimuli and that these differential activities may depend on the encoding strategies formed by the two factors of relational and self-performed processes.

Adult↗

Self-initiated encoding facilitates object working memory in schizophrenia: implications for the etiology of working memory deficit.

BACKGROUND: Working memory (WM) deficit is present in a majority of patients with schizophrenia but it is unclear which components of WM are impaired. Past studies suggest that encoding may be compromised. One important determinant of encoding is the deployment of selective attention to the target stimulus. In addition, attention and encoding are modulated by motivational factors. In this study, we investigated the effects of self-initiated encoding (i.e., voluntary attention) on WM. METHODS: 19 patients with schizophrenia and 19 matched control subjects participated in visual WM and control tasks. Encoding was manipulated by asking subjects to select from two face targets and memorize 1) one of the two identical faces (Non-preference condition), 2) one that is marked (Non-choice condition), and 3) one they prefer (Preference condition). WM accuracy for both location (spatial) and identity (object) was measured. RESULTS: Overall, patients with schizophrenia were less accurate and slower than the control subjects but the deficit was greater for object WM. However, patients were more accurate in object WM when they selected a preferred face as their target during encoding (preference condition) compared with the other two conditions. This effect was not significant for spatial WM. CONCLUSIONS: These results suggest that voluntary, self-initiated attention may facilitate object encoding especially if the selection of the target involves affective choice, and that attention may play different roles in encoding 'what' versus 'where' in WM. Since encoding affects all forms of memory, these results may have a more general implication for memory.

Adult↗

Immunostimulatory effect of IL-18-encoding plasmid in DNA vaccination against murine Schistosoma mansoni infection.

In vivo delivery of DNA encoding antigens is a simple tool to induce immune responses against pathogens. This approach to vaccination also offers the possibility to codeliver plasmids encoding immunomodulatory molecules in order to drive immune responses towards optimal protective effects. In the murine model of Schistosoma mansoni infection, vaccination inducing a Th1 profile has been shown to be protective. In this study, we used a plasmid encoding the Th1-promoting cytokine IL-18, since we observed that percutaneous infection of Balb/c mice strongly induced the production of IL-18 mRNA in the skin. Intradermal injection of the IL-18-encoding plasmid prior to infection did not interfere with parasite migration through the skin although it led to a local and transient cellular infiltration. When the IL-18-encoding plasmid was codelivered with a S. mansoni glutathione S-transferase (Sm28GST)-encoding plasmid, a 30-fold increase of antigen-specific IFN-gamma secretion by spleen cells was observed in comparison to spleen cells from mice that had received only the Sm28GST-encoding plasmid. This immunostimulatory effect was related to a significant protective effect (28% reduction in egg laying and 23% reduction in worm burden) which was attributed to a cooperative effect between both plasmids. Therefore, this study shows that codelivery of an IL-18-encoding plasmid with an antigen-encoding plasmid can stimulate specific cellular responses and induce protective effects against S. mansoni infection.

Animals↗

Fast 3D T(2)-weighted MRI with Hadamard encoding in the slice select direction.

A fast method to obtain 3-dimensional (3D) magnetic resonance imaging with long repetition times is presented. It can be used to obtain fast 3D MRI with for example T(2) or diffusion weighted imaging. The method uses a 3D multiple thin slab sequence with radio frequency encoding, preferably Hadamard encoding, in the slice select direction. The point-spread function of the Hadamard-encoded slices is close to ideal even at low encoding numbers. This allows the acquisition of 3D data volumes with tolerable image quality up to four times faster than is possible using Fourier phase encoding. The scope of the method includes both longitudinal and transverse encoding. Longitudinal encoding provides a better point spread function than transverse encoding, at the expense of having to discard one slice per slab. The method is demonstrated experimentally for 4th order longitudinal Hadamard encoding to obtain 3D T(2)-weighted images.

Animals↗

Encoding of new versus old information by autistic children.

Research and literature on communication problems of autistic individuals have identified specific pragmatic deficiencies. This preliminary study focused upon describing autistic children's verbal performance in regard to the pragmatic ability of encoding new versus old information. Four autistic children with MLUs of 1.96-2.82 were videotaped on two occasions in interactions with their teachers or speech-language pathologists. All of the subjects' referential utterances, including referential echolalic utterances, were categorized as the encoding of new or old information. Two prominent means that speakers used for encoding new versus old information were examined: the encoding of new information through single-word utterances (i.e., a lexicalization strategy) and the use of contrastive stress to highlight new information in multiword utterances. The results revealed that the 4 subjects did encode new information through lexicalization in single-word utterances and through contrastive stress in multiword utterances. However, the subjects encoded old information almost as frequently as they encoded new information. The encoding of a new action or state change was marked relatively infrequently by the subjects, and they consistently produced repetitions of previously encoded information when they failed to offer new information to their listeners. The results are discussed in reference to cognitive processing patterns of autistic individuals.

Adolescent↗

Cue utilization and encoding specificity in picture recognition by older adults.

According to the encoding specificity principle, memory is best when encoding and retrieval conditions are compatible. Some researchers have suggested that older adults encode information in a general fashion and are less sensitive to the specific contextual aspects of a memory situation due to limited processing resources. We investigated the hypothesis that age interacts with encoding specificity. Young and old adults studied target pictures in the presence or absence of pictorial cues factorially varied at encoding and retrieval. If the older adults used the specific cuing information differently from the younger adults, age should have interacted with the encoding and retrieval variables. The results provided no evidence for such an interaction and indicated that both ages showed evidence of encoding specificity. To investigate the role of processing resources in encoding specificity, old and young adults also studied the pictures while simultaneously performing a digit-monitoring task. The divided-attention manipulation also did not interact with age, as both young and old adults showed encoding specificity effects of comparable magnitude in both control and divided-attention conditions.

Adult↗

Equine herpesvirus type 1 unique short fragment encodes glycoproteins with homology to herpes simplex virus type 1 gD, gI and gE.

The nucleotide sequence of a 6.4 kbp portion of the 10.6 kbp BamHI fragment D contained in the unique short region of the equine herpesvirus type 1 (EHV-1) genome has been determined. Analysis of this sequence revealed five open reading frames (ORFs), four complete and one incomplete, which were encoded by the same sense strand. Comparison of the EHV-1 DNA sequence with that encoding glycoproteins of other alphaherpesviruses has revealed no significant homologies. Comparison at the amino acid level, however, has demonstrated regions of significant sequence similarity between the three complete EHV-1 ORFs 2, 3 and 4, and the herpes simplex virus type 1 (HSV-1) glycoprotein gD encoded by the US6 gene, the HSV-1 glycoprotein gI encoded by the US7 gene and the HSV-1 glycoprotein gE encoded by the US8 gene, respectively. The interrupted ORF 5 was found to display partial homology with the HSV-1 US9-encoded protein, but no homology was found between the protein encoded by ORF 1 and other proteins. The three collinear EHV-1 ORFs encoding putative glycoproteins with homology to the HSV-1 glycoproteins were therefore designated EHV-1 gD, gI and gE, respectively. Moreover, further similarities were found between EHV-1 gD and pseudorabies virus (PRV) gp50, between EHV-1 gI and PRV gp63 and varicellazoster virus (VZV) gpIV, and between EHV-1 gE and PRV gI and VZV gpI. It is concluded that EHV-1, PRV, HSV-1 and VZV encode homologous glycoprotein genes in the small unique components of their genomes and that the genetic organization of these regions is conserved.

Amino Acid Sequence↗

Monoclonal antibody E-13 (M-810) to human cytomegalovirus recognizes an epitope encoded by exon 2 of the major immediate early gene.

Monoclonal antibody (MAb) E-13 to human cytomegalovirus is used widely for diagnostic and fundamental studies, and has been shown to be directed against an immediate early (IE) protein(s). To determine which viral antigen is detected by MAb E-13, four subfragments from the open reading frame encoded by exons 2, 3 or 4 of IE-1 were cloned in the bacterial expression vector pROS. The resulting fusion proteins contained amino acids 77 to 491 encoded by mainly exon 4, amino acids 25 to 78 encoded by exon 3, amino acids 1 to 85 encoded by exons 2 and 3, and amino acids 1 to 24 encoded by exon 2. The reactivity of MAb E-13 with the fusion proteins was assayed by Western blotting. MAb E-13 was shown to react exclusively with proteins encoded by exon 2 and therefore recognizes IE proteins which contain the N-terminal amino acid sequence encoded by exon 2, namely the major 72K IE protein, the 82K to 86K IE-2 protein and the 52K to 55K IE-2 protein. MAb E-13 can be used to detect both IE-1- and IE-2-encoded proteins, which share the polypeptide encoded by exon 2.

Antibodies, Monoclonal↗

Functional asymmetry of human prefrontal cortex: encoding and retrieval of verbally and nonverbally coded information.

There are several views about the organization of memory functions in the human prefrontal cortex. One view assumes a process-specific brain lateralization according to different memory subprocesses, that is, encoding and retrieval. An alternative view emphasizes content-specific lateralization of brain systems involved in memory processes. This study addresses this apparent inconsistency between process- and content-specific lateralization of brain activity by investigating the effects of verbal and nonverbal encoding on prefrontal activations during encoding and retrieval of environmental novel sounds using fMRI. An intentional memory task was applied in which subjects were required either to judge the sounds' loudness (nonverbal encoding task) or to indicate whether or not a sound can be verbally described (verbal encoding task). Retrieval processes were examined in a subsequent yes/no recognition test. In the study phase the right posterior dorsolateral prefrontal cortex (PFC) was activated in both tasks. During verbal encoding additional activation of the left dorsolateral PFC was obtained. Retrieval-related fMRI activity varied as a function of encoding task: For the nonverbal task we detected an activation focus in the right posterior dorsolateral PFC whereas an activation in the left dorsolateral PFC was observed for the verbal task. These findings indicate that the right dorsolateral PFC is engaged in encoding of auditory information irrespective of encoding task. The lateralization of PFC activity during retrieval was shown to depend on the availability of verbal codes, with left hemispheric involvement for verbally and right hemispheric activation for nonverbally coded information.

Acoustic Stimulation↗

The novelty effect: support for the Novelty-Encoding Hypothesis.

In two experiments, we examined the "Novelty-Encoding Hypothesis" proposed by Tulving and Kroll (1995), suggesting that the encoding of online information into long-term memory is influenced by its novelty and that novelty increases recognition performance. In Phase 1 (familiarization phase), subjects participated in a standard memory experiment in which different types of materials (verbs and nouns) were studied under different encoding conditions (enactment and non-enactment) and were tested by an expected recognition test. In Phase 2 (critical phase), subjects evaluated the materials (both familiar materials which were encoded earlier in Phase 1, and novel materials which were not presented earlier in Phase 1) in a frequency judgment task and were given an unexpected recognition test. The results of both experiments showed that novel items were recognized better than familiar items. This result held true for both hit rates - false alarms and hit rates. The novelty effect was observed for different subjects (Swedish and Japanese), different materials (verbs and nouns; high frequency and low frequency), and different types of encoding in Phase 1 (enactment and non-enactment). These findings provide support for the "Novelty-Encoding Hypothesis" stating that the effect is based on the encoding of target items at the time of the critical study (Phase 2). A comparison between the present experiments and the Tulving and Kroll (1995), Dobbins, Kroll, Yonelinas & Liu (1998) and Greene (1999) studies suggests that the novelty effect is more pronounced under incidental encoding than under intentional encoding.

Analysis of Variance↗

Prophage induction and expression of prophage-encoded virulence factors in group A Streptococcus serotype M3 strain MGAS315.

The genome of the highly virulent group A Streptococcus (GAS) serotype M3 strain MGAS315 has six prophages that encode six proven or putative virulence factors. We examined prophage induction and expression of prophage-encoded virulence factors by this strain under in vitro conditions inferred to approximate in vivo conditions. Coculture of strain MGAS315 with Detroit 562 (D562) human epithelial pharyngeal cells induced the prophage encoding streptococcal pyrogenic exotoxin K (SpeK) and extracellular phospholipase A(2) (Sla) and the prophage encoding streptodornase (Sdn). Increased gene copy numbers after induction correlated with increased speK, sla, and sdn transcript levels. Although speK and sla are located contiguously in prophage Phi315.4, these genes were transcribed independently. Whereas production of immunoreactive SpeK was either absent or minimal during coculture of GAS with D562 cells, production of immunoreactive Sla increased substantially. In contrast, despite a lack of induction of the prophage encoding speA during coculture of GAS with D562 cells, the speA transcript level and production of immunoreactive streptococcal pyrogenic exotoxin A (SpeA) increased. Exposure of strain MGAS315 to hydrogen peroxide, an oxidative stressor, induced the prophage encoding mitogenic factor 4 (MF4), and there was a concomitant increase in the mf4 transcript. All prophages of strain MGAS315 that encode virulence factors were induced during culture with mitomycin C, a DNA-damaging agent. However, the virulence factor gene transcript levels and production of the encoded proteins decreased after mitomycin C treatment. Taken together, the results indicate that a complex relationship exists among environmental culture conditions, prophage induction, and production of prophage-encoded virulence factors.

Bacterial Proteins↗

Influence of cyclic AMP, agmatine, and a novel protein encoded by a flanking gene on speB (agmatine ureohydrolase) in Escherichia coli.

The speB gene of Escherichia coli encodes agmatine ureohydrolase (AUH), a putrescine biosynthetic enzyme. The speB gene is transcribed either from its own promoter or as a polycistronic message from the promoter of the speA gene encoding arginine decarboxylase. Two open reading frames (ORF1 and ORF2) are present on the strand complementary to speB; approximately 90% of ORF2 overlaps the speB coding region. Analysis of transcriptional and translational fusions of ORF1 or ORF2 to lacZ revealed that ORF1 encoded a novel protein while ORF2 was not transcribed. Deletion of ORF1 from a plasmid containing ORF1, ORF2, and speB reduced the activity of AUH by 83%. In contrast, the presence of plasmid-encoded ORF1 caused an 86% increase in chromosomally encoded AUH activity. ORF1 did not stimulate alkaline phosphatase expressed from a phi(speB-phoA) transcriptional fusion encoded on the same plasmid. Western analysis (immunoblot) of a phi(ORF1-lacZ) translational fusion revealed that ORF1 encodes a 25.3-kDa protein. Agmatine induced transcription of phi(speB-phoA) but not phi(speA-phoA) fusions. Consequently, agmatine affects selection between the monocistronic and the polycistronic modes of speB transcription. In contrast, cyclic AMP (cAMP) repressed AUH activity of chromosomally encoded AUH but had no effect on plasmid-borne speB nor phi(speB-phoA). It is concluded that ORF1 encodes a protein which is a posttranscriptional regulator of speB, agmatine induces speB independent of speA, and cAMP regulates speB indirectly.

Agmatine↗

p-Cymene catabolic pathway in Pseudomonas putida F1: cloning and characterization of DNA encoding conversion of p-cymene to p-cumate.

Pseudomonas putida F1 utilizes p-cymene (p-isopropyltoluene) by an 11-step pathway through p-cumate (p-isopropylbenzoate) to isobutyrate, pyruvate, and acetyl coenzyme A. The cym operon, encoding the conversion of p-cymene to p-cumate, is located just upstream of the cmt operon, which encodes the further catabolism of p-cumate and is located, in turn, upstream of the tod (toluene catabolism) operon in P. putida F1. The sequences of an 11,236-bp DNA segment carrying the cym operon and a 915-bp DNA segment completing the sequence of the 2,673-bp DNA segment separating the cmt and tod operons have been determined and are discussed here. The cym operon contains six genes in the order cymBCAaAbDE. The gene products have been identified both by functional assays and by comparing deduced amino acid sequences to published sequences. Thus, cymAa and cymAb encode the two components of p-cymene monooxygenase, a hydroxylase and a reductase, respectively; cymB encodes p-cumic alcohol dehydrogenase; cymC encodes p-cumic aldehyde dehydrogenase; cymD encodes a putative outer membrane protein related to gene products of other aromatic hydrocarbon catabolic operons, but having an unknown function in p-cymene catabolism; and cymE encodes an acetyl coenzyme A synthetase whose role in this pathway is also unknown. Upstream of the cym operon is a regulatory gene, cymR. By using recombinant bacteria carrying either the operator-promoter region of the cym operon or the cmt operon upstream of genes encoding readily assayed enzymes, in the presence or absence of cymR, it was demonstrated that cymR encodes a repressor which controls expression of both the cym and cmt operons and is inducible by p-cumate but not p-cymene. Short (less than 350 bp) homologous DNA segments that are located upstream of cymR and between the cmt and tod operons may have been involved in recombination events that led to the current arrangement of cym, cmt, and tod genes in P. putida F1.

Acetate-CoA Ligase↗

A second and unusual pucBA operon of Rhodobacter sphaeroides 2.4.1: genetics and function of the encoded polypeptides.

A new operon (designated the puc2BA operon) displaying a high degree of similarity to the original pucBA genes of Rhodobacter sphaeroides 2.4.1 (designated puc1) was identified and studied genetically and biochemically. The puc2B-encoded polypeptide is predicted to exhibit 94% identity with the original beta-apoprotein. The puc2A-encoded polypeptide is predicted to be much larger (263 amino acids) than the 54-amino-acid puc1A-encoded polypeptide. In the first 48 amino acids of the puc2A-encoded polypeptide there is 58% amino acid sequence identity to the original puc1A-encoded polypeptide. We found that puc2BA is expressed, and DNA sequence data suggested that puc2BA is regulated by the PpsR/AppA repressor-antirepressor and FnrL. Employing genetic and biochemical approaches, we obtained evidence that the puc2B-encoded polypeptide is able to enter into LH2 complex formation, but neither the full-length puc2A-encoded polypeptide nor its N-terminal 48-amino-acid derivative is able to enter into LH2 complex formation. Thus, the sole source of alpha-polypeptides for the LH2 complex is puc1A. The role of the puc1C-encoded polypeptide was also determined. We found that the presence of this polypeptide is essential for normal levels of transcription and translation of the puc1 operon but not for transcription and translation of the puc2 operon. Thus, the puc1C gene product appears to have both transcriptional and posttranscriptional roles in LH2 formation. Finally, the absence of any LH2 complex when puc1B was deleted in frame was surprising since we know that in the presence of functional puc2BA, approximately 30% of the LH2 complexes normally observed contain a puc2B-encoded beta-polypeptide.

Amino Acid Sequence↗

Information theoretic analysis of dynamical encoding by four identified primary sensory interneurons in the cricket cercal system.

1. The stimulus/response properties of four identified primary sensory interneurons in the cricket cercal sensory system were studied using electrophysiological techniques. These four cells are thought to represent a functionally discrete subunit of the cercal system: they are the only cells that encode information about stimulus direction to higher centers for low intensity stimuli. Previous studies characterized the quantity of information encoded by these cells about the direction of air currents in the horizontal plane. In the experiments reported here, we characterized the quantity and quality of information encoded in the cells' elicited responses about the dynamics of air current waveforms presented at their optimal stimulus directions. The total sample set included 22 cells. 2. This characterization was achieved by determining the cells' frequency sensitivities and encoding accuracy using the methods of stochastic systems analysis and information theory. The specific approach used for the analysis was the "stimulus reconstruction" technique in which a functional expansion was derived to transform the observed spike train responses into the optimal estimate (i.e., "reconstruction") of the actual stimulus. A novel derivation of the crucial equations is presented. The reverse approach is compared with the more traditional forward analysis, in which an expansion is derived that transforms the stimulus to a prediction of the spike train response. Important aspects of the application of these analytical approaches are considered. 3. All four interneurons were found to have identical frequency tuning, as assessed by the accuracy with which different frequency components of stimulus waveforms could be reconstructed with a linear expansion. The interneurons encoded significant information about stimulus frequencies between 5 and 80 Hz, which peak sensitivities at approximately 15 Hz. 4. All four interneurons were found to have identical stimulus/response latencies. The mean latency between a stimulus component and the corresponding elicited spike was 17 ms. All four interneurons also had identical integration times. The integration time, measured by the duration of stimulus, which could affect the probability of spiking, was approximately 50 ms. 5. The accuracy of the encoding can be expressed as a signal-to-noise ratio, where the noise is a scaled difference between the original signal and the best estimate of the signal. Peak signal-to-noise ratios of approximately 1 were obtained for the cells across all stimulus power levels, using only the linear expansion term. Analysis of the data indicated that the consideration of second-order nonlinear transformations of the stimulus would not have increased the calculated encoding accuracy. 6. The encoding accuracy also can be expressed in the information theoretic units of bits/second, which characterizes the information transmission rate of the cell. Bits/second values varied between 10 and 80 for the 22 different cells in our experimental set. The information rate values were highly correlated with the mean spike rates of the interneurons, but were not correlated with the stimulus power levels. However, normalizing the absolute information rates by the mean spike rate in each case yielded a measure of bits/spike that was remarkably invariant across all experiments. The measured bits/spike rate was approximately 1 for all experiments. This result is discussed in the context of recent theoretical studies on optimal encoding. 7. Although the dynamic sensitivities of the four interneurons were identical, their directional sensitivities are known to be orthogonal. Thus the cells are complementary to one another from a functional standpoint: whereas a particular cell will be insensitive to air currents from some directions, one or more of the other three cells will be sensitive to stimuli from those directions...

Action Potentials↗

Expression of mRNAs encoding for alpha and beta integrin subunits, MMPs, and TIMPs in stretched human periodontal ligament and gingival fibroblasts.

The biological mechanisms of tooth movement result from the cellular responses of connective tissues to exogenous mechanical forces. Among these responses, the degradation of the extracellular matrix takes place, but the identification of the molecular basis as well as the components implicated in this degradation are poorly understood. To contribute to this identification, we subjected human fibroblasts obtained from the periodontal ligament (PDLs) and from the gingiva (HGFs) to a continuous stretch to quantify the mRNAs encoding for various metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and alpha and beta integrin subunits. Both cell lines reacted by inducing the expression of the mRNAs encoding for MMP-1, MMP-2, TIMP-1, and TIMP-2, while other mRNAs did not vary (MT1-MMP, TIMP-3) or were not expressed (MMP-9). PDLs expressed selectively the mRNAs encoding for alpha4 and alphav, with no difference measurable under stretching, while the mRNAs encoding for alpha6 and beta1 were increased and the one encoding for alpha5 was decreased. HGFs increased the mRNAs encoding for alpha2, alpha6, beta1, and beta3 and decreased the one encoding for alpha3. Analysis of our data indicated that stretched HGFs and PDLs induced the same pattern of mRNAs encoding for MMPs and TIMPs but differed for those encoding various integrin subunits, known to act as protein receptors in mechanotransduction.

Cells, Cultured↗

Virally encoded G protein-coupled receptors: targets for potentially innovative anti-viral drug development.

Various herpes- and poxviruses contain DNA sequences encoding proteins with homology to cellular chemokine receptors, which belong to the family of G protein-coupled receptors (GPCRs). Since GPCRs play a crucial role in cellular communication and chemokine receptors play a prominent role in the immune system, the virally encoded GPCRs may be crucial determinants of viral action. The Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus 8), implicated in the pathogenesis of Kaposi's sarcoma (KS), a highly vascularized tumor, encodes a GPCR, referred to as ORF74. This virally encoded receptor was found to induce tumorigenesis and transgenic expression of ORF74 induces an angioproliferative disease resembling KS. Cytomegalovirus (CMV), suggested to play a role in atherosclerosis, encodes four GPCRs, among which US28. This virally encoded GPCR is able to induce migration of smooth muscle cells, a feature essential for the development of atherosclerosis. Remarkably, the KSHV and some CMV-encoded GPCRs display constitutive activity, while their cellular homologs do not. It remains to be determined whether this phenomenon contributes to the pathogenesis of viral action. Also, the family of poxviruses encodes GPCRs of which the function is not clear yet. In this review we will give an overview of the different virally encoded GPCRs, and discuss their putative role in viral action and potential as drug target.

Antiviral Agents↗