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At least 595 records · Page 33Linked to original sources
PubMed1998

DNA minor groove recognition by a tetrahydropyrimidinium analogue of hoechst 33258: NMR and molecular dynamics studies of the complex with d(GGTAATTACC)2.

Hoechst 43254 (H43254), a 2,3,4,5-tetrahydropyrimidin-1-ium analogue of the bis-benzimidazole minor groove binding agent Hoechst 33258 (H33258), has been studied by NMR and restrained molecular dynamics in its complex with d(GGTAATTACC)2. We investigate the origin of the enhanced complex stability afforded by the replacement of the N-methylpiperazine ring of H33258 with the tetrahydropyrimidinium ring of H43254, the latter presenting the opportunity for specific minor groove-directed recognition through a pyrimidinium NH. A set of 25 drug-DNA NOEs define the binding site with some precision and are used as part of the structural analysis using restrained molecular dynamics simulations considering explicit solvation and the treatment of electrostatic interactions using the particle mesh Ewald method within AMBER 4.1. Starting with three different initial structures with the drug located at different sites in the groove (pairwise RMSD 4.3-12.6 A) we arrive at three very similar structures (pairwise RMSD 0.80-1.34 A) representing one converged binding site at the centre of the AATT tract. Two of the three structures show the tetrahydropyrimidinium ring to be suitably positioned for an -NH to adenine N3 hydrogen bond suggesting that electrostatic interactions may play an important role in the enhanced affinity as well as imparting additional A-T specificity. The NMR data show that the pyrimidinium NH interaction is dynamic since signal averaging from the two sides of the ring indicate rapid rotations in the bound form.

Base Sequence↗
PubMed1975

Are we learning what actually goes on when the brain recognizes and controls?

Drawing upon recent advances in neuroscience for examples, the thesis is defended that, in contrast to a Kuhnian view of proress by overturning whole sciences, progress amounting to revolution in our understanding of nervous systems is happening by the accumulation of many discrete discoveries, and that this process may be expected to continue for a long time. Twelve propositions are put forward illustrative of ideas developed during and influenced by C. L. Prosser's career, all in the segment of neuroscience concerned with subsystem organization. They range from the generally accepted to the frankly polemical and the merely heuristic. (1) Ongoing background activity has different forms. (2) Codes, both spike and graded, are several. (3) Integrative variables in neuron function are several. (4) Identifiable cells may be widespread. (5) Neuronal circuits for behavior are known. (6) Redundancy is usually overlap. (7) Reliability can be high. (8) Recognition neurons may be common and complex. (9) Command neurons may be common and complex. (10) Pattern is often central in origin. (11) Hierarchies and switches may be common. (12) Subsystem function is an intellectual challenge. Each of these is briefly elaborated and its logical relation to the others suggested. The role of discrete discovery is thus illustrated--in the generation of new conceptual frameworks that gradually become interrelated and cumulatively change profoundly our picture of what's going on in the brain.

Action Potentials↗
PubMed2002

Innate immunity in plants and animals: emerging parallels between the recognition of general elicitors and pathogen-associated molecular patterns.

Recent findings have highlighted remarkable similarities in the innate pathogen defense systems of plants, animals and insects. Pathogen-associated molecular patterns (PAMP) that are similar to those activating innate immune responses in animals have been shown to mediate the activation of plant defense. Moreover, recognition complexes that are structurally related to animal PAMP receptors are now being discovered in plants, suggesting a common evolutionary origin of pathogen defense systems in higher eukaryotes.

Animals↗
PubMed1989

Auto-tumor recognition following in vitro induction of MHC antigen expression on solid human tumors: stimulation of lymphocytes and generation of cytotoxicity against the original MHC-antigen-negative tumor cells.

Expression of major histocompatibility complex (MHC) class I antigens was induced in eight out of nine freshly prepared tumor cell suspensions by exposure to interferon (IFN gamma) and tumor necrosis factor (TNF alpha) in vitro. The untreated, class-I-antigen-negative, and the treated, antigen-positive, cells of three tumors (one breast carcinoma, one plasmocytoma and one ovarian carcinoma) were compared for the capacity to stimulate autologous and allogeneic blood lymphocytes, to generate auto-tumor cytotoxicity and for sensitivity to the lytic effect induced in autologous mixed lymphocyte tumor cell culture (MLTC). The MHC class I-negative cells did not stimulate, while the cells induced for expression of antigens did. On the other hand, when the autologous cytotoxic cells were generated in the MLTC by the class I antigen-positive tumor cells the class I-negative tumor cells were also damaged. Lysis of the class-I-positive tumor cells was abrogated by the W6/32 monoclonal antibody directed against the monomorphic part of the class I molecules.

Cytotoxicity, Immunologic↗
PubMed1983

Topography of simian virus 40 A protein-DNA complexes: arrangement of protein bound to the origin of replication.

DNA binding regions I, II, and III at the origin of replication have different arrangements of A protein (T antigen) recognition pentanucleotides. The A protein also protects each region from DNase in distinctly different patterns. Footprint and fragment assays led to the following conclusions: (i) in some cases a single recognition pentanucleotide is sufficient to direct the binding and accurate alignment of A protein on DNA; (ii) the A protein binds within isolated region I or II in a sequential process leading to multiple overlapping areas of DNase protection within each region; and (iii) the 23-base pair span of recognition sequences in region II allows binding and protection of a longer length of DNA than the 23-base pair span in region I. We propose a model of protein binding that addresses the problem of variations in the arrangement of pentanucleotides in regions I and II and explains the observed DNase protection patterns. The central feature of the model requires each protomer of A protein to bind to a pentanucleotide in a unique direction. The resulting orientation of protein would protect more DNA at the 5' end of the 5'-GAGGC-3' recognition sequence than at the 3' end. The arrangement of multiple protomers at the origin of simian virus 40 replication is discussed.

Antigens, Viral↗
PubMed1982

Failure to demonstrate a role for line Ib tumor-associated surface antigen in the etiology of age-dependent polioencephalomyelitis.

In the preceding paper [Morris et al. (1982), Molec. Immun. 19, 973-982] we demonstrate an associative interaction between the line Ib tumor-associated surface antigen (Ib-TASA) and the Dk/Kk regions of the major histocompatibility complex, i.e. 'altered-self' antigen. We originally hypothesized that age-dependent polioencephalomyelitis (ADPE) occurred as the result of immune recognition of a 'self'-determinant on the 'altered-self' antigen. In this report we used the non-ionic detergent, NP-40, to solubilize Ib cell surface antigens. Although immunization of immunocompetent C58 mice with the soluble NP-40 Ib cell extract afforded protection to lethal tumor challenge, the extract failed to induce ADPE in immunosuppressed mice. Data presented here demonstrate that Ib-TASA is not involved in the etiology of ADPE. The evidence suggests that lactic dehydrogenase virus, which is a silent virus passaged with line Ib leukemia, is the causative agent of the paralytic disease.

Age Factors↗
PubMed1997

Lossless ECG encoding.

We have studied the lossless encoding of ECG signals. With suitable code we aim to reduce the storage space needed by ECG signals. Several methods designed for ECG compression use lossy, i.e. irreversible techniques, in which the original signal is lost, but the restored approximation is almost equal to the original. We aimed, however, to use reversible methods which are able to restore the original signal exactly. We have examined various methods and developed a new approach based on structural recognition and extraction of ECG complexes. Comparative conclusions are drawn from the compression efficiency of lossless and lossy methods. In this study, the effect of sampling frequency, resolution and filtering is also examined.

Algorithms↗
PubMed2005

Origin recognition and the chromosome cycle.

Prior to the initiation of DNA replication, chromosomes must establish a biochemical mark that permits the recruitment in S phase of the DNA replication machinery that copies DNA. The process of chromosome replication in eukaryotes also must be coordinated with segregation of the duplicated chromosomes to daughter cells during mitosis. Protein complexes that utilize ATP coordinate events at origins of DNA replication and later they participate in the initiation of DNA replication. In eukaryotes, some of these proteins also play a part in later processes that ensure accurate inheritance of chromosomes in mitosis, including spindle attachment of chromosomes, accurate duplication of centrosomes and cytokinesis. A perspective of how ATP-dependent proteins accomplish this task in eukaryotes is discussed.

Archaea↗
PubMed2003

DNA bending by the human damage recognition complex XPC-HR23B.

Genome integrity is maintained, despite constant assault on DNA, due to the action of a variety of DNA repair pathways. Nucleotide excision repair (NER) protects the genome from the deleterious effects of UV irradiation as well as other agents that induce chemical changes in DNA bases. The mechanistic steps required for eukaryotic NER involve the concerted action of at least six proteins or protein complexes. The specificity to incise only the DNA strand including the damage at defined positions is determined by the coordinated assembly of active protein complexes onto damaged DNA. In order to understand the molecular mechanism of the NER reactions and the origin of this specificity and control we analyzed the architecture of functional NER complexes at nanometer resolution by scanning force microscopy (SFM). In the initial step of damage recognition by XPC-HR23B we observe a protein induced change in DNA conformation. XPC-HR23B induces a bend in DNA upon binding and this is stabilized at the site of damage. We discuss the importance of the XPC-HR23B-induced distortion as an architectural feature that can be exploited for subsequent assembly of an active NER complex.

DNA↗
PubMed2005

Molecular recognition of saccharides by proteins. Insights on the origin of the carbohydrate-aromatic interactions.

The existence of stabilizing carbohydrate-aromatic interactions is demonstrated from both the theoretical and experimental viewpoints. The geometry of experimentally based galactose-lectin complexes has been properly accounted for by using a MP2/6-31G(d,p) level of theory and by considering a counterpoise correction during optimization. In this case, the stabilizing interaction energy of the fucose-benzene complex amounts to 3.0 kcal/mol. The theoretical results obtained herein indicate that the carbohydrate-aromatic interactions are stabilizing interactions with an important dispersive component and that electronic density between the sugar hydrogens and the aromatic ring indeed exists, thus giving rise to three so-called nonconventional hydrogen bonds. Experimental evidence of the intrinsic tendency of aromatic moieties to interact with certain sugars has also been shown by simple NMR experiments in water solution. Benzene and phenol specifically interact with the clusters of C-H bonds of the alpha face of methyl beta-galactoside, without requiring the well-defined three-dimensional shape provided by a protein receptor, therefore resembling the molecular recognition features that are frequently observed in many carbohydrate-protein complexes.

Benzene↗
PubMedDate not supplied

Evaluation of free energy landscape for base-amino acid interactions using ab initio force field and extensive sampling.

Structural data of protein-DNA complex show redundancy and flexibility in base-amino acid interactions. To understand the origin of the specificity in protein-DNA recognition, we calculated the interaction free energy, enthalpy, entropy, and minimum energy maps for AT-Asn, GC-Asn, AT-Ser, and GC-Ser by means of a set of ab initio force field with extensive conformational sampling. We found that the most preferable interactions in these pairs are stabilized by hydrogen bonding, and are mainly enthalpy driven. However, minima in the free energy maps are not necessarily the same as those in the minimum energy map or enthalpy maps, due to the entropic effect. The effect of entropy is particularly important in the case of GC-Asn. Experimentally observed structures of base-amino acid interactions are within preferable regions in the calculated free energy maps, where there are many different interaction configurations with similar energy. The full geometry optimization procedure using ab initio molecular orbital method was applied to get the optimal interaction geometries for AT-Asn, GC-Asn, AT-Ser, and GC-Ser. We found that there are various base-amino acid combinations with similar interaction energies. These results suggest that the redundancy and conformational flexibility in the base-amino acid interactions play an important role in the protein-DNA recognition.

Adenine↗
PubMed1994

In vitro binding of the two-finger repressor CreA to several consensus and non-consensus sites at the ipnA upstream region is context dependent.

The two zinc-fingers of the Aspergillus nidulans repressor CreA recognize the consensus hexanucleotide 5'-SYGGRG-3'. We have determined all the CreA binding sites in a approximately 2 kb region upstream the ipnA gene. Our analysis shows that (i) CreA binds to certain consensus sites in a context-dependent manner; (ii) five non-consensus 6-bp sequences are also recognized by CreA; this non-canonical binding correlates with the presence of a second, neighbouring CreA binding site, suggesting that recognition of two linked sites stabilizes CreA binding. Our results suggest that the binding possibilities of CreA might be more complex than originally envisaged.

Aspergillus nidulans↗
PubMed2005

Archaeal cell cycle progress.

The discovery of multiple chromosome replication origins in Sulfolobus species has added yet another eukaryotic trait to the archaea, and brought new levels of complexity to the cell cycle in terms of initiation of chromosome replication, replication termination and chromosome decatenation. Conserved repeated DNA elements--origin recognition boxes--have been identified in the origins of replication, and shown to bind the Orc1/Cdc6 proteins involved in cell cycle control. The origin recognition boxes aid in the identification and characterization of new origins, and their conservation suggests that most archaea have a similar replication initiation mechanism. Cell-cycle-dependent variation in Orc1/Cdc6 levels has been demonstrated, reminiscent of variations in cyclin levels during the eukaryotic cell cycle. Information about archaeal chromosome segregation is also accumulating, including the identification of a protein that binds to short regularly spaced repeats that might constitute centromere-like elements. In addition, studies of cell-cycle-specific gene expression have potential to reveal, in the near future, missing components in crenarchaeal chromosome replication, genome segregation and cell division. Together with an increased number of physiological and cytological investigations of the overall organization of the cell cycle, rapid progress of the archaeal cell cycle field is evident, and archaea, in particular Sulfolobus species, are emerging as simple and powerful models for the eukaryotic cell cycle.

Archaea↗
PubMedDate not supplied

Fracture dislocations of the tarsometatarsal joints: Analysis of interrater reliability in using the modified Hardcastle classification system.

Fracture dislocations/subluxations of the tarsometatarsal joint are complex injuries that are often misdiagnosed. Prompt recognition and treatment of Lisfranc injuries decrease the likelihood of long-term sequelae. The original (1909) classification system was modified in 1982 and again in 1986. The 1986 classification system, developed by Hardcastle et al, is used most widely in clinical practice and is cited most often in the biomedical literature. For this-or any-classification system to be beneficial, however, multiple observers must be able to use it in a consistent manner, and a high level of interrater agreement should exist. This study examined interrater reliability among clinicians using the modified Hardcastle classification system for Lisfranc fracture dislocations. Thirteen Lisfranc injury radiographs were evaluated by 21 independent observers consisting of surgeons and residents (podiatric and orthopedic) as well as musculoskeletal radiologists, who classified radiographs according to the modified Hardcastle classification system. We used kappa statistics to evaluate the degree of interrater reliability for the entire group. A mean weighted kappa value of 0.54 was found for the group. Moderate interrater agreement was observed among clinicians interpreting the modified Hardcastle classification system for Lisfranc fracture dislocations.

Fractures, Bone↗
PubMedDate not supplied

Duplex recognition by oligonucleotides containing 2'-deoxy-2'-fluoro-D-arabinose and 2'-deoxy-2'-fluoro-D-ribose. Intermolecular 2'-OH-phosphate contacts versus sugar puckering in the stabilization of triple-helical complexes.

To gain insight into the origins of the large binding affinity of RNA toward target duplexes, 2'-deoxy-2'-fluororibonucleic acid (2'F-RNA) and 2'-deoxy-2'-fluoroarabinonucleic acid (2'F-ANA) were tested for their ability to recognize duplex DNA, duplex RNA, and RNA-DNA hybrids. 2'F-RNA, 2'F-ANA, and the corresponding control single-stranded (ss) DNA strands were shown to form triple-helical complexes only with duplex DNA and hybrid DNA (Pu)-RNA (Py), but not with duplex RNA and hybrid RNA (Pu)-DNA (Py). In contrast, an RNA third strand recognized all four possible duplexes (DD, DR, RD, and RR) as previously demonstrated by Roberts and Crothers [(1992) Science 258, 1463-1466]. The 2'F-RNA (C3'-endo) strand exhibited significantly reduced affinity for duplexes compared to an unmodified RNA (C3'-endo) strand. These findings are consistent with the intermolecular 2'-OH-phosphate contact mechanism proposed by Escudé et al. [(1993) Nucleic Acids Res. 24, 5547-5553], as a ribo 2'-F atom should not interact with a negatively charged phosphate. In addition, they emphasize the role of the 2'-OH ribose as a general recognition and binding determinant of RNA. The 2'-F arabino modification (2'F-ANA, C2'-endo) led to a considerable increase in the binding affinity for duplex DNA, as compared to those of DNA and 2'F-RNA third strands. This is likely to be the result of a greater population of C2'-endo pucker of the 2'F-ANA compared to DNA. The enhancement observed for 2'F-ANA strands toward duplex DNA is comparable to that observed with 2'-OMe RNA. Since 2'F-ANA has been shown to be more resistant to nuclease degradation than DNA, these results are likely to stimulate experimental work on arabinose derivatives in laboratories concerned with targeting DNA sequences in vivo ("antigene" strategy).

Arabinose↗
PubMed1997

ECG compression and recognition using complete tree representation.

This paper deals with a novel method of Electrocardiogram (ECG) representation, compression and recognition using Complete Tree algorithm. The construction of Complete Tree is like overlaying a ECG waveform on a grid. The waveform is observed through the grid structure with vertical and horizontal grid lines. In addition to nodes created for each interval enclosed by that waveform on a quantisation level, nodes are also created for each point where the waveform cuts the vertical grid line between the current quantisation level and the next quantisation level. A leaf node represents the data sample of ECG at that position. For reconstruction of this ECG waveform, only the leaf nodes are used resulting in ECG compression. This representation is also useful in ECG pattern matching and recognition without reconstructing the original waveform. The ECGs with sampling rate of 500 sps are used. A compression ratio (CR) of 4.8:1 with percent RMS difference (PRD) of 8.45% is obtained. The reconstruction of original ECG waveform from its tree representation shows high fidelity in all its complexes of ECG. The results are compared with all other compression techniques such as AZTEC, TP, FAN, DPCM etc. By using Tree merging and splitting algorithms, the matching and recognition of ECG is implemented.

Algorithms↗
PubMed1997

[Neurocutaneous syndromes with vascular alterations].

There are several syndromes in which neurological and cutaneous alterations of vascular origin, among other symptoms, occur. The key point of this fact is that these cutaneous signs permit early diagnosis, thus helping in further recognition of more complex syndromes and preventing unnecessary, harmful and costly diagnostic procedures or having to wait until the appearance of neurological signs. Therefore, these diseases should be classified attending to the most notorious vascular lesions they show, though they may show other less frequent cutaneous vascular lesions. In this way, these syndromes can be classified as associated with nevus flammeus (Sturge-Weber, Shapiro-Shulman, Bonnet-Dechaume-Blanc, Cobb, Klippel-Trenaunay, Fegeler, Robert), cavernous hemangiomas (Maffucci, blue-rubber-bleb-nevus, Proteus, Bannayan-Zonana, Riley-Smith, familial cavernous angiomatosis, POEMS syndrome), capillary hemangiomas (Rubinstein-Tayabi, Coffin-Siris, PHACE syndrome), telangiectasia (congenital telangiectatic cutis marmorata, Rendu-Osler-Weber, ataxia telangiectasia, Cockayne, De Sanctis-Cacchione), livedo reticularis (Sneddon, Divry-van-Bogaert), angioqueratoma (Fabry disease, Fucosidosis) and hemangioblastoma (Von Hippel-Lindau). Though we have tried that these vascular lesions should be named as angiomas if they are malformations and hemangiomas if they are benign neoplasias, they are called following morphological aspects rather than other criteria, due to their unknown origin.

Brain Neoplasms↗
PubMed1989

Simian virus 40 DNA replication in vitro: identification of multiple stages of initiation.

A cell-free DNA replication system dependent upon five purified cellular proteins, one crude cellular fraction, and the simian virus 40 (SV40)-encoded large tumor antigen (T antigen) initiated and completed replication of plasmids containing the SV40 origin sequence. DNA synthesis initiated at or near the origin sequence after a time lag of approximately 10 min and then proceeded bidirectionally from the origin to yield covalently closed, monomer daughter molecules. The time lag could be completely eliminated by a preincubation of SV40 ori DNA in the presence of T antigen, a eucaryotic single-stranded DNA-binding protein (replication factor A [RF-A]), and topoisomerases I and II. In contrast, if T antigen and the template DNA were incubated alone, the time lag was only partially decreased. Kinetic analyses of origin recognition by T antigen, origin unwinding, and DNA synthesis suggest that the time lag in replication was due to the formation of a complex between T antigen and DNA called the T complex, followed by formation of a second complex called the unwound complex. Formation of the unwound complex required RF-A. When origin unwinding was coupled to DNA replication by the addition of a partially purified cellular fraction (IIA), DNA synthesis initiated at the ori sequence, but the template DNA was not completely replicated. Complete DNA replication in this system required the proliferating-cell nuclear antigen and another cellular replication factor, RF-C, during the elongation stage. In a less fractionated system, another cellular fraction, SSI, was previously shown to be necessary for reconstitution of DNA replication. The SSI fraction was required in the less purified system to antagonize the inhibitory action of another cellular protein(s). This inhibitor specifically blocked the earliest stage of DNA replication, but not the later stages. The implications of these results for the mechanisms of initiation and elongation of DNA replication are discussed.

Antigens, Viral, Tumor↗