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At least 145 records · Page 8Linked to original sources
PubMed2001

Actinopolyspora halophila has two separate pathways for betaine synthesis.

The extremely halophilic actinomycete Actinopolyspora halophila is a rare example of a heterotrophic eubacterium producing betaine from simple carbon sources. A. halophila synthesized remarkably high intracellular concentrations of betaine. The highest betaine concentration, determined at 24% (w/v) NaCl, was 33% of the cellular dry weight. Trehalose was synthesized as a compatible solute, accounting for up to 9.7% of the cellular dry weight. The betaine concentration was shown to increase with increasing NaCl concentration, whereas the trehalose concentration was highest at the lowest NaCl concentration used (15% w/v). A. halophila was capable of accumulating betaine from the medium, while at the same time betaine was also excreted back into the medium by the cells. Along with the de novo synthesis of betaine, A. halophila was able to take up choline from the medium and oxidize it to betaine. Some basic characteristics of the choline oxidation system are described. Choline was oxidized to betaine aldehyde in a reaction in which H2O2 generation and oxygen consumption were coupled. Betaine aldehyde was also oxidized, but with lesser efficiency. In addition, betaine aldehyde was oxidized further to betaine in a reaction in which NAD(P)+ was reduced.

Actinomycetales↗
PubMed2006

Nature's green revolution: the remarkable evolutionary rise of C4 plants.

Plants with the C4 photosynthetic pathway dominate today's tropical savannahs and grasslands, and account for some 30% of global terrestrial carbon fixation. Their success stems from a physiological CO2-concentrating pump, which leads to high photosynthetic efficiency in warm climates and low atmospheric CO2 concentrations. Remarkably, their dominance of tropical environments was achieved in only the past 10 million years (Myr), less than 3% of the time that terrestrial plants have existed on Earth. We critically review the proposal that declining atmospheric CO2 triggered this tropical revolution via its effects on the photosynthetic efficiency of leaves. Our synthesis of the latest geological evidence from South Asia and North America suggests that this emphasis is misplaced. Instead, we find important roles for regional climate change and fire in South Asia, but no obvious environmental trigger for C4 success in North America. CO2-starvation is implicated in the origins of C4 plants 25-32 Myr ago, raising the possibility that the pathway evolved under more extreme atmospheric conditions experienced 10 times earlier. However, our geochemical analyses provide no evidence of the C4 mechanism at this time, although possible ancestral components of the C4 pathway are identified in ancient plant lineages. We suggest that future research must redress the substantial imbalance between experimental investigations and analyses of the geological record.

Biological Evolution↗
PubMed1991

Behavioral pathway to evolutionary change.

The extreme malleability or plasticity of cells early in their development is mirrored to a certain, if lesser, degree in the psychological, behavioral, and neural functioning of developing organisms. The early developmental adaptability of organisms has significance for our understanding of evolution. It is the purpose of the present article to make a case for the extra-genetic or, better, the supra-genetic developmental basis of evolutionary change through the genesis of novel behavioral phenotypes. To make things as clear as possible, I contrast this developmental approach to evolution with the population-genetic model of the modern synthesis. I should say at the outset that the present theory can be integrated with the population-genetic model, with the exception of the radically different role ascribed to genes in the two viewpoints.

Adaptation, Biological↗
PubMed2003

Interneuronal projections to identified cilia-activating pedal neurons in Hermissenda.

Neural networks have been shown to support the generation of more than one behavioral motor act. In the nudibranch mollusk Hermissenda, Pavlovian conditioning results in light, the conditioned stimulus (CS), evoking both inhibition of locomotion and foot contraction. The synaptic organization of the eyes and optic ganglion is well documented; however, the characterization of the neural network mediating visually modulated behaviors is incomplete. We have now characterized synaptic connections between identified photoreceptors and a newly identified interneuron (II(b)), identified synaptic projections from type I and type II interneurons to an inhibitory interneuron (III(i)) and to two newly identified pedal neurons, VP1 and VP2. Here we show that VP1 activates ciliary movement on the anterior foot and VP2 innervates the anterior foot and ventral tentacle. Stimulation of the photoreceptors with light produced two effects on the activity of VP1 and VP2. First, light inhibits type I(i) and II(i) interneurons and disinhibits VP1 and VP2. Depolarization of type II(e) interneurons also disinhibits VP1 and VP2. Second, the light-elicited depolarization and increased tonic activity of VP1 and VP2 is produced by excitatory synaptic input from ipsilateral and contralateral type II(b) interneurons. Pedal neurons VP1 and VP2 receive similar synaptic input from type I, II, and III(i) interneurons; this is in agreement with previous research showing that the visual pathway influences both ciliary locomotion and foot movement. The organization of the visual system in Hermissenda provides for the expression of cellular and synaptic plasticity supporting learning without altering the networks ability to carry out the requirements for normal visual processing.

Animals↗
PubMed1999

Identification of extremely reactive gamma-ketoaldehydes (isolevuglandins) as products of the isoprostane pathway and characterization of their lysyl protein adducts.

Isoprostanes are prostaglandin-like compounds produced by non-enzymatic peroxidation of arachidonic acid. The cyclooxygenase-derived endoperoxide, prostaglandin H2, can undergo rearrangement to highly reactive gamma-ketoaldehyde secoprostanoids (levuglandin E2 and D2). We explored whether isoprostane endoperoxide intermediates also rearrange to levuglandin-like compounds (isolevuglandins). Formation of a series of isolevuglandins during oxidation of arachidonic acid in vitro was established utilizing a number of mass spectrometric analyses. However, these compounds could not be detected in free form in protein-containing biological systems, which we hypothesized was due to extremely rapid adduction to amines. This was supported by the finding that >60% of levuglandin E2 adducted to albumin within 20 s, whereas approximately 50% of 4-hydroxynonenal still remained unadducted after 1 h. By utilizing electrospray tandem mass spectrometry, we established that these compounds form oxidized pyrrole adducts (lactams and hydroxylactams) with lysine. Formation of isolevuglandin-lysine adducts on apolipoprotein B was readily detected during oxidation of low density lipoprotein following enzymatic digestion of the protein to single amino acids. These studies identify a novel series of extremely reactive products of the isoprostane pathway that rapidly form covalent adducts with lysine residues on proteins. This provides the basis to explore the formation of isolevuglandins in vivo to investigate the potential biological ramifications of their formation in settings of oxidant injury.

Aldehydes↗
PubMed1990

G protein diversity and the regulation of signaling pathways.

The subunits of the heterotrimeric guanine nucleotide-binding (G) proteins mediate the transfer of information from receptor to effector molecules. Biochemical studies and recent molecular cloning efforts have revealed a rich but largely unexpected diversity in G protein subunit structure and function. Extreme specificity in signaling pathways could be accommodated by the combinatorial association of individual subunits. Alternatively, this wealth of diversity may allow for the simultaneous activation of related G alpha subunits and the modulation of several effector systems. In tissues where the subunits are expressed at different levels, activation of receptors could stimulate distinct effector pathways. Mutations in individual subunits as well as alterations in their level of expression can lead to profound physiological changes. The mechanisms that underlie these changes are being elucidated and will provide insight into the complex regulatory processes associated with the large G protein subunit family.

Animals↗
PubMed1969

A spinocerebellar climbing fibre path activated by the flexor reflex afferents from all four limbs.

1. A pathway ascending in the lateral funiculus of the spinal cord and terminating as climbing fibres in the cerebellar anterior lobe has been investigated in decerebrate cats with the cord partially transected in the third cervical segment sparing only part of the left lateral funiculus. The climbing fibre responses evoked in Purkinje cells were studied by recording from single cells and by recording the mass activity at the cerebellar surface.2. The pathway is activated by the flexor reflex afferents from all four limbs. It ascends in an area of the lateral funiculus which partly overlaps that of the dorsolateral spino-olivocerebellar path (Larson, Miller & Oscarsson, 1969) but also extends more ventrally. The pathway conducts relatively fast in the spinal cord and is considerably delayed in the brain stem suggesting several interneurones at that level. It projects to a narrow sagittal zone in lobule V of the pars intermedia (Fig. 4).3. It is not known if the pathway relays in the inferior olive and it has provisionally been denoted the LF-CF-SCP (lateral funiculus-climbing fibre-spinocerebellar path).4. The Purkinje cells were usually activated by the flexor reflex afferents from all four limbs with equal effectiveness. On natural stimulation responses were obtained on deep pressure of the limbs.5. The pathway and its functional significance are discussed.

Animals↗
PubMed2003

Combined p53/Bax mutation results in extremely poor prognosis in gastric carcinoma with low microsatellite instability.

Gastric cancer is highly refractory to DNA-damaging therapies. We therefore studied both gene mutation and protein expression of p53 and Bax in a cohort of 116 patients with gastric cancer who underwent R0-resection with a curative intent. Bax mutation was independent from severe microsatellite instability (MSI), that is, global mismatch repair deficiency as determined by analysis of BAT-25/BAT-26 microsatellite markers. Thus, Bax-frameshift mutation is a feature of tumors with low MSI. In contrast and as expected, no p53 mutations were observed in the microsatellite instable tumors. p53 Mutation or p53 overexpression did not have an impact on disease prognosis. p53-Inactivation was, however, associated with an extremely poor prognosis in the subgroup of patients with Bax-mutated tumors. Thus, we show for the first time that the combined mutation of p53 and Bax, two key regulators of the mitochondrial apoptosis pathway, results in an extremely aggressive tumor biology and poor clinical prognosis.

Apoptosis↗
PubMed2003

[Clinical pathways -- intervention or surgery for acute ischemia of the extremities].

There is still controversial discussion concerning the therapy of limb-threatening ischaemia. In a retrospective study, we investigated and compared surgical and percutaneous interventional methods in the treatment of both embolic and thrombotic vascular occlusions in patients with pre-existing arteriosclerotic disease and attempted to propose therapy guidelines for these methods in the therapy of acute limb ischaemia. Percutaneous mechanical thrombectomy represents a viable therapeutic alternative to surgical or surgical-interventional modalities, particularly in patients with occlusions consisting of soft, embolic material or located in infrapopliteal vessels. The indication for each respective method should be interdisciplinary and must be based on the individual patients' clinical and angiographic findings. Additional intraoperative endovascular procedures increase the range of therapeutic options and permit optimal revascularisation of vessels both proximal and distal to the site of occlusion.

Acute Disease↗
PubMedDate not supplied

Extrahepatic portal obstruction without hepatopetal pathway associated with congenital arterioportal fistula: a case report.

Extrahepatic portal obstruction is one of the causes of portal hypertension, in which well-developed hepatopetal pathways are commonly recognized. Herein an extremely rare case of extrahepatic portal obstruction without hepatopetal pathway, probably caused by arterioportal fistula, is reported. The patient was a normally matured 16-year-old girl admitted for further evaluation of jaundice, presenting with the clinical manifestations of the portal hypertension associated with hypersplenism and portosystemic venous shunt. Celiac angiography clearly demonstrated an intrahepatic arterial aneurysm fed by the right hepatic artery shunting to the superior mesenteric vein, and portography disclosed complete obstruction of the portal trunk with conspicuous hepatofugal pathway but no hepatopetal collateral veins. The exact mechanism of this phenomenon is not known and whether the extrahepatic portal obstruction was primary or secondary is still obscure. However, this is the first case report in the world literature describing extrahepatic portal obstruction with absence of hepatopetal pathway.

Adolescent↗
PubMed1994

Suppression of activated Let-60 ras protein defines a role of Caenorhabditis elegans Sur-1 MAP kinase in vulval differentiation.

The let-60 ras gene of Caenorhabditis elegans is one of the key players in a signal transduction pathway that controls the choice between vulval and epidermal differentiation in response to extracellular signals. To identify components acting downstream of let-60 ras in the vulval signaling pathway, we have identified a reduction-of-function mutation in the sur-1 gene that completely suppresses the multivulva phenotype of a hyperactive let-60 ras mutation. About 10% of animals homozygous for the sur-1 mutation also display a specific and intriguing vulval cell lineage defect. In addition, the sur-1 mutation results in a cold-sensitive egg-laying defective phenotype and a partial larval lethal phenotype. We have cloned the sur-1 gene by DNA-mediated transformation and have shown that it encodes a protein similar in overall structure to mammalian MAP kinases (ERKs). The functional homology between Sur-1 MAP kinase and mammalian MAP kinases was also demonstrated by the ability of a rat ERK2 kinase to rescue the sur-1 mutant phenotypes. Genetic double-mutant analyses place sur-1 downstream of let-60 ras but upstream of lin-1 in the vulval signaling pathway. Our results provide further evidence for the extreme conservation of Ras-mediated signaling pathway between worms and humans and for the function of MAP kinases in cell signaling processes that control cell differentiation and animal development.

ATP-Binding Cassette Transporters↗
PubMed1985

Evaluation of flecainide acetate in rapid atrial fibrillation complicating Wolff-Parkinson-White syndrome.

Flecainide is reported to be effective in patients with paroxysmal tachycardias, but its effect on rapid ventricular response over accessory atrioventricular pathway during atrial fibrillation is not known. The influence of flecainide on various electrophysiological properties of the accessory pathway with special emphasis on ventricular rate during atrial fibrillation was investigated in 9 patients with severe symptomatic Wolff-Parkinson-White syndrome. The shortest ventricular response during atrial fibrillation increased from 218 (190-270) to 320 (240-block) ms. In 4 patients sustained rapid atrial fibrillation converted to sinus rhythm. The rate of circus movement tachycardia decreased from 166/min to 130/min after flecainide, due to a lengthening of retrograde ventriculoatrial conduction time over the accessory pathway. Flecainide caused a significant prolongation of the effective refractory period of the accessory pathway in our subgroup with extremely fast AV conduction during atrial fibrillation and induced a depressant effect on retrograde accessory pathway conduction. This makes the drug very promising for the emergency treatment of dangerous rapid tachyarrhythias complicating this syndrome.

Adolescent↗
PubMed1993

Molecular cloning and characterization of the Bacillus subtilis spore photoproduct lyase (spl) gene, which is involved in repair of UV radiation-induced DNA damage during spore germination.

Upon UV irradiation, Bacillus subtilis spore DNA accumulates the novel thymine dimer 5-thyminyl-5,6-dihydrothymine. Spores can repair this "spore photoproduct" (SP) upon germination either by the uvr-mediated general excision repair pathway or by the SP-specific spl pathway, which involves in situ monomerization of SP to two thymines by an enzyme named SP lyase. Mutants lacking both repair pathways produce spores that are extremely sensitive to UV. For cloning DNA that can repair a mutation in the spl pathway called spl-1, a library of EcoRI fragments of chromosomal DNA from B. subtilis 168 was constructed in integrative plasmid pJH101 and introduced by transformation into a mutant B. subtilis strain that carries both the uvrA42 and spl-1 mutations, and transformants whose spores exhibited UV resistance were selected by UV irradiation. With a combination of genetic and physical mapping techniques, the DNA responsible for the restoration of UV resistance was shown to be present on a 2.3-kb EcoRI-HindIII fragment that was mapped to a new locus in the metC-pyrD region of the B. subtilis chromosome immediately downstream from the pstI gene. The spl coding sequence was localized on the cloned fragment by analysis of in vitro-generated deletions and by nucleotide sequencing. The spl nucleotide sequence contains an open reading frame capable of encoding a 40-kDa polypeptide that shows regional amino acid sequence homology to DNA photolyases from a number of bacteria and fungi.

Amino Acid Sequence↗
PubMed1981

Hysterosalpingo-radionuclide scintigraphy (HERS).

A radionuclide procedure, hysterosalpingo-radionuclide scintigraphy (HERS), was designed to evaluate the migration of a particulate radioactive tracer from the vagina to the peritoneal cavity and ovaries as well as to image and functionally outline the patency of the pathways between these two extremes of the female reproductive system. Technetium-99m human albumin microspheres (99mTc-HAM) were deposited in the posterior fornices of patients who were divided into two specific groups. Group I consisted of patients who were to undergo different elective gynecologic operations, in which besides obtaining sequential images, radioactivity levels were measured in the removed organs and tissues. Group II consisted of patients referred by the Infertility Clinic for evaluation of their reproductive system pathways patency. In this latter group, HERS was compared with contrast hysterosalpingography (HSG) and peritoneoscopy (PCP). The results obtained from measurements of radioactivity levels on the removed surgical specimens and comparison with other conventional gynecologic diagnostic procedures provide accurate evidence of the migration of 99mTc-HAM from the vagina, through the uterus and tubes, to the peritoneal cavity and ovaries, and show that HERS is a simple noninvasive method for functionally imaging and assessing the patency of the female reproductive system pathways.

Female↗
PubMed2002

Towards a global historical emission inventory for selected PCB congeners--a mass balance approach. 2. Emissions.

Accurate and complete data on the global atmospheric releases (emissions) of individual PCB congeners are essential to study source-receptor relationships and contamination patterns in remote areas, such as the Arctic. Information on the anthropogenic emissions may also be useful for the interpretation of measured levels and patterns of atmospheric PCBs. This study builds upon an accompanying paper, presenting an estimate of the global historical production and consumption of 22 PCB congeners (Breivik K, Sweetman A, Pacyna JM, Jones KC. Towards a global historical emission inventory for selected PCB congeners--a mass balance approach. 1. Global production and consumption. Sci Total Environ, submitted). Here, a dynamic mass balance model is elaborated, parameterised and applied in an attempt to estimate the historical anthropogenic emissions as a direct result of the widespread usage of PCBs for a period of 70 years. This paper presents details of the mass balance approach, along with a discussion of the major uncertainties. It is shown that the diversity of historical usage, disposal and accidental release pathways makes it an extremely difficult task to bridge the gap between consumption and emissions, resulting in an equally complex and diverse true emission pattern. These results may therefore at best represent order-of-magnitude estimates only and the results in absolute terms should be treated with great caution. In spite of these uncertainties, useful information can still be gained. The results suggest that temperature is an extremely important factor controlling both emission amount as well as the emission pattern of PCBs. In particular, the emissions of the more chlorinated (and persistent) PCB congeners appear to be significantly influenced by (uncontrolled) high-temperature sources. As a consequence, it may prove warranted to undertake further measures to avoid that contaminated materials are subject to elevated temperatures and uncontrolled burning. It is furthermore suggested that efforts should be directed towards a better characterisation and quantification of these potentially important release pathways. In addition, alternative approaches to bridge the gap between consumption and emissions in quantitative terms should be considered in order to improve these estimates.

Arctic Regions↗
PubMed2001

Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase.

The Saccharomyces cerevisiae SGS1 gene encodes a RecQ-like DNA helicase, human homologues of which are implicated in the genetic instability disorders, Bloom syndrome (BS), Rothmund-Thomson syndrome (RTS), and Werner syndrome (WS). Telomerase-negative yeast cells can recover from senescence via two recombinational telomere elongation pathways. The "type I" pathway generates telomeres with large blocks of telomeric and subtelomeric sequences and short terminal repeat tracts. The "type II" pathway generates telomeres with extremely long heterogeneous terminal repeat tracts, reminiscent of the long telomeres observed in telomerase-deficient human tumors and tumor-derived cell lines. Here, we report that telomerase-negative (est2) yeast cells lacking SGS1 senesced more rapidly, experienced a higher rate of telomere erosion, and were delayed in the generation of survivors. The est2 sgs1 survivors that were generated grew poorly, arrested in G(2)/M and possessed exclusively type I telomeres, implying that SGS1 is critical for the type II pathway. The mouse WS gene suppressed the slow growth and G(2)/M arrest phenotype of est2 sgs1 survivors, arguing that the telomeric function of SGS1 is conserved. Reintroduction of SGS1 into est2 sgs1 survivors restored growth rate and extended terminal tracts by approximately 300 bp. Both phenotypes were absolutely dependent on Sgs1 helicase activity. Introduction of an sgs1 carboxyl-terminal truncation allele with helicase activity restored growth rate without extending telomeres in most cases, demonstrating that type II telomeres are not necessary for normal growth in the absence of telomerase.

Animals↗