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At least 271 records · Page 15Linked to original sources
PubMed2003

Temperature adaptation of proteins: engineering mesophilic-like activity and stability in a cold-adapted alpha-amylase.

Two multiple mutants of a psychrophilic alpha-amylase were produced, bearing five mutations (each introducing additional weak interactions found in pig pancreatic alpha-amylase) with or without an extra disulfide bond specific to warm-blooded animals. Both multiple mutants display large modifications of stability and activity arising from synergic effects in comparison with single mutations. Newly introduced weak interactions and the disulfide bond confer mesophilic-like stability parameters, as shown by increases in the melting point t(m), in the calorimetric enthalpy DeltaH(cal) and in protection against heat inactivation, as well as by decreases in cooperativity and reversibility of unfolding. In addition, both kinetic and thermodynamic activation parameters of the catalyzed reaction are shifted close to the values of the porcine enzyme. This study confirms the central role of weak interactions in regulating the balance between stability and activity of an enzyme in order to adapt to the environmental temperature.

Animals↗
PubMed2003

SWAP-70-like adapter of T cells, an adapter protein that regulates early TCR-initiated signaling in Th2 lineage cells.

We describe the isolation of a protein, SWAP-70-like adapter of T cells (SLAT), which is expressed at high levels in thymocytes and differentiated Th2 cells. SLAT expression was upregulated in differentiating Th2 cells and downregulated in Th1 cells. Ectopic SLAT expression exerted positive or negative effects on IL-4 versus IFNgamma induction, respectively. TCR signaling induced translocation of SLAT to the immunological synapse and its association with ZAP-70 kinase. SLAT reduced the association of ZAP-70 with TCR-zeta and interfered with ZAP-70 but not Lck signaling. Consistent with these results, pharmacological inhibition of ZAP-70 also induced Th2 skewing. Thus, SLAT is a protein which plays a role in Th2 development and/or activation, perhaps by interfering with ZAP-70 signaling.

Amino Acid Sequence↗
PubMed2002

The structure of a cold-adapted family 8 xylanase at 1.3 A resolution. Structural adaptations to cold and investgation of the active site.

Enzymes from psychrophilic organisms differ from their mesophilic counterparts in having a lower thermostability and a higher specific activity at low and moderate temperatures. The current consensus is that they have an increased flexibility, enhancing accommodation and transformation of the substrates at low energy costs. Here we describe the structure of the xylanase from the Antarctic bacterium Pseudoalteromonas haloplanktis at 1.3 A resolution. Xylanases are usually grouped into glycosyl hydrolase families 10 and 11, but this enzyme belongs to family 8. The fold differs from that of other known xylanases and can be described as an (alpha/alpha)(6) barrel. Various parameters that may explain the cold-adapted properties were examined and indicated that the protein has a reduced number of salt bridges and an increased exposure of hydrophobic residues. The crystal structures of a complex with xylobiose and of mutant D144N were obtained at 1.2 and 1.5 A resolution, respectively. Analysis of the various substrate binding sites shows that the +3 and -3 subsites are rearranged as compared to those of a family 8 homolog, while the xylobiose complex suggests the existence of a +4 subsite. A decreased acidity of the substrate binding cleft and an increased flexibility of aromatic residues lining the subsites may enhance the rate at which substrate is bound.

Binding Sites↗
PubMed1988

Adaptive mechanisms in perceptual-motor coordination: components of prism adaptation.

Aftereffect measures of visual shift and proprioceptive shift were obtained for prism exposure conditions in which, at the end of a sagittal pointing movement, most of the arm was visible (concurrent exposure) or only the first finger joint was visible (terminal exposure). Intermediate exposure conditions permitted view of the hand or the first two finger joints. Under the concurrent exposure condition, proprioceptive shift was greater than visual shift but, as view of the pointing hand decreased, the relative magnitude of the two components gradually reversed so that, under the terminal exposure condition, visual shift was greater than proprioceptive shift. These results are discussed in terms of a model of perceptual-motor organization (Redding, Clark, & Wallace, 1985) in which the direction of coordinative linkage between eye-head and hand-head systems determines the locus of discordance and adaptive recalibration.

Journal Article↗
PubMed1994

Comparison of ventricular function in atrial rate adaptive versus dual chamber rate adaptive pacing during exercise.

The hemodynamic effects of two different pacing modes--rate adaptive atrial (AAIR) versus dual chamber (DDDR) pacing--were assessed in 12 patients with DDDR pacemakers during upright bicycle exercise first-pass radionuclide angiography using a multiwire gamma camera with tantalum-178 as a tracer. All patients had sinus node disease with intact AV conduction. Patients exercised to the same heart rate in random order in these two different pacing modes, AAIR and DDDR with AV delay (of 100 msec) selected to maintain 100% ventricular capture. Cardiac output increased significantly above baseline values during exercise in both pacing modes: 154 +/- 41% (mean +/- SEM, P = 0.002) with AAIR, versus 95 +/- 24% (P = 0.004) with DDDR (P = NS between the two modes). The peak filling rate, likewise, increased in both pacing modes (2.3 +/- 0.21 end-diastolic volumes/sec to 3.8 +/- 0.31 end-diastolic volumes/sec in AAIR [P = 0.0004] and 2.2 +/- 0.18 end-diastolic volumes/sec to 3.4 +/- 0.27 end-diastolic volumes/sec in DDDR [P = 0.0008]). LV ejection fraction was normal at rest (60 +/- 4%, SEM) and did not significantly change with submaximal exercise in either pacing mode (both 56%, P = NS). No significant changes in end-diastolic volume or stroke volume indexes occurred with exercise in either pacing mode. Our study demonstrates that in patients with normal resting LV function, AAIR and DDDR pacing are equally effective in attaining appropriate increases in cardiac output and LV filling during exercise.

Adult↗
PubMed1981

Evaluation of A/Alaska/6/77 (H3N2) cold-adapted recombinant viruses derived from A/Ann Arbor/6/60 cold-adapted donor virus in adult seronegative volunteers.

The influenza A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) virus was evaluated as a donor of attenuating genes to new variants of influenza A virus. This ca donor virus was mated with the A/Alaska/6/77 (H3N2) wild-type virus, and three A/Alaska/6/77 (H3N2) ca recombinant viruses were produced. The parental origin of the genes in the three ca recombinants had been determined previously (2), and their virulence for adult seronegative volunteers was assessed in the present study to identify the genes present in the ca donor virus that confer attenuation. Each of the recombinants received the hemagglutinin and neuraminidase genes from the A/Alaska/6/77 (H3N2) wild-type parent. One ca recombinant (CR-29) received all six transferable genes from the ca parent and was found to be satisfactorily attenuated in the volunteers. The two other ca recombinants received five of the six transferable genes with a wild-type gene at the M or NS locus. The pattern of infection in humans with these latter two ca recombinants was similar to the CR-29 ca recombinant. These findings demonstrate that inheritance of a gene in ca recombinants at the M or NS locus segregates independently of attenuation and suggest that the M and NS genes present in the ca donor virus are not the major determinants of attenuation conferred by this virus.

Antibodies, Viral↗
PubMed1984

Recombinant cold-adapted attenuated influenza A vaccines for use in children: reactogenicity and antigenic activity of cold-adapted recombinants and analysis of isolates from the vaccinees.

Reactogenicity and antigenic activity of recombinants obtained by crossing cold-adapted donor of attenuation A/Leningrad/134/47/57 with wild-type influenza virus strains A/Leningrad/322/79(H1N1) and A/Bangkok/1/79(H3N2) were studied. The recombinants were areactogenic when administered as an intranasal spray to children aged 3 to 15, including those who lacked or had only low titers of pre-existing anti-hemagglutinin and anti-neuraminidase antibody in their blood. After two administrations of vaccines at a 3-week interval, both strains induced antibody in 75 to 95% of the children. On coinfection of chicken embryos with both recombinants, only weak interference was observed. Administration to children of the bivalent vaccine containing H1N1 and H3N2 recombinants induced efficient production of antibody to H1 and H3 hemagglutinins and N1 and N2 neuraminidases without adverse reactions. The recombinants studied were genetically stable as judged by retention of the temperature-sensitive phenotypes and a lack of reversion of the genes carrying temperature-sensitive mutations in all of the reisolates from vaccinated children.

Adolescent↗
PubMed1999

Neural architecture of the electrosensory lateral line lobe: adaptations for coincidence detection, a sensory searchlight and frequency-dependent adaptive filtering

The electrosensory lateral line lobe (ELL) of weakly electric fish is the only nucleus that receives direct input from peripheral electroreceptor afferents. This review summarises the neurotransmitters, receptors and second messengers identified in the intrinsic circuitry of the ELL and the extrinsic descending direct and indirect feedback pathways, as revealed by recent in vitro and in vivo studies. Several hypotheses of circuitry function are examined on this basis and on the basis of recent functional evidence: (1) fast primary afferent excitatory postsynaptic potentials (EPSPs) and fast granule cell 2 GABAA inhibitory postsynaptic potentials (IPSPs) suggest the involvement of basilar pyramidal cells in coincidence detection; (2) voltage-dependent EPSPs and IPSPs, dendritic spike bursts and frequency-dependent synaptic facilitation support a sensory searchlight role for the direct feedback pathway; and (3) the contributions of distal and proximal inhibition, anti-Hebbian plasticity and beam versus isolated fiber activity patterns are discussed with reference to an adaptive spatio-temporal filtering role for the indirect descending pathway.

Journal Article↗
PubMedDate not supplied

[Spanish adaptation and validation of an anxiety scale derived from the AMDP (AMDP-AT) system. I: Adaptation and convergent validity].

The Spanish translation and adaptation of the 17-item Scale extracted from the francophone extension of the AMPD scales, the AMPD-AT, has been filled out in 120 anxious, depressed and other psychiatric patients along with numerous other rating scales measuring anxiety (Hamilton, Zung, STAI, VAS), depression (Hamilton, VAS), and global psychopathology (AMPD-SY, CGI). The results point to a higher correlation with psychic anxiety than with somatic anxiety and with state anxiety than with trait anxiety. The correlations are lower with depression scales than with anxiety scales. The AMPD-AT shows as an special advantage the possibility to be used into the AMPD-System (in order to extract a score of anxiety in the context of a psychopathological profile) or independently as a scale of psychic anxiety.

Adolescent↗
PubMed1985

[Effects of various anesthesia procedures used in forceps delivery on the cardiopulmonary adaptation of the newborn infant. 1. Modification of cardiac adaptation].

Healthy, spontaneously born infants, delivered at the calculated time shows a postnatal tachycardia combined with harrowing of oscillation. But then there is a normalisation in heart action. This phenomenon is nearly the same both in spontaneous delivery and intubation anesthesia for forceps delivery starting with propanidid. Therefore propanidid is of less risk for the neonate. But after hexobarbital anesthesia our results reveal a lingering cardial adaption of the neonate, which is statistical significant. This points to possible cardiac depressive side effects of this drug. Therefore the usage of hexobarbital anesthesia should be well considered in obstetrics.

Anesthesia, Obstetrical↗
PubMed1998

Adapting residency training. Training adaptable residents.

Graduate medical education has been criticized for failing to adequately prepare young physicians to enter the workforce upon completion of their training. In addressing this criticism, the author makes arguments both for and against this assertion. Broad qualitative changes (graduate medical education training position allocation, subspecialists' role in health care delivery, educational quality, faculty development, and faculty promotion) that graduate medical education has undergone and is undergoing are discussed. Population health management, clinical resource management, teamwork, continuous quality improvement, ethics, and evidence-based medicine are addressed as important curricular elements for residency training. Innovations in graduate medical education that are being introduced as well as those that should be tried are discussed. Finally, the author asserts that although residency education should not be vocationally driven by the needs of managed care organizations, a powerful opportunity exists for collaborative educational research between academic medicine and managed care organizations. In a health care environment undergoing rapid changes, the primary goals of graduate medical education have not significantly changed: to produce compassionate physicians with a passion for lifelong learning who have leadership skills, are critical thinkers, skilled at self-assessment, and able to adapt to the needs of the health care marketplace.

Curriculum↗