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The R2R3-MYB transcription factor ScMYB20 negatively regulates drought and salt tolerance through a dual-repression of ScCHALCONE SYNTHASE-1 (ScCHS1)-mediated flavonoid biosynthesis in the desert moss Syntrichia caninervis.

The desert moss Syntrichia caninervis is one of the most desiccation-tolerant land plants known and provides a powerful system for dissecting the molecular foundations of extreme stress adaptation in early-diverging land lineages. The MYB transcription factor superfamily orchestrates secondary metabolism and stress signaling across plants, yet its lineage-specific evolution and mechanistic deployment in bryophytes remain poorly understood. Here, we identified 65 ScMYB genes in the S. caninervis genome and showed that the family expanded predominantly through dispersed duplication, with no detectable synteny to vascular-plant MYBs, indicating bryophyte-specific neo-functionalization. Integrating phylogenetic clustering, cis-element architecture and stress-responsive expression profiling, we pinpointed ScMYB20, a nuclear-localized, S13-subgroup R2R3-MYB that is rapidly and strongly induced by dehydration and salinity. Heterologous overexpression in Arabidopsis, together with overexpression and RNAi in S. caninervis, demonstrated that ScMYB20 negatively regulates drought and salt tolerance by suppressing antioxidant capacity, osmotic adjustment and photosynthetic performance, while concomitantly elevating ROS and MDA accumulation. Mechanistically, ScMYB20 directly binds a TAACCA motif in the ScCHS1 promoter to repress its transcription, and simultaneously sequesters the WD40 protein ScTTG1, a positive transcriptional activator of ScCHS1, thereby antagonising ScTTG1-mediated activation. Transient ScCHS1 overexpression restored flavonoid accumulation, antioxidant capacity and stress tolerance. Together, our findings define a dual-repression module (ScMYB20-ScTTG1-ScCHS1) that fine-tunes flavonoid flux under abiotic stress, and provide evolutionary and mechanistic insights into how R2R3-MYB repressors evolved to balance metabolic investment and stress survival in land plants.

Syntrichia caninervis↗

Morphological evolution of subterranean mammals: integrating structural, functional, and ecological perspectives.

The widely recognized convergence of subterranean mammals offers unique opportunities for the study of patterns, causes and consequences of morphological integration. For example, behavioral and biomechanical observations have revealed a diversity of digging modes among subterranean mammals. In rodents, scratch-digging and chisel-tooth digging, alone or combined, are widespread. This dual nature of the digging apparatus must be understood to avoid erroneous assessments of specializations based on forelimb modifications only. Additionally, bulldozing and disposal of loose soil is performed by head-lifting, by means of the forelimbs, or with the hindlimbs. Insectivores are known to resort to scratch-digging, sand-swimming, or to a unique system known as humeral rotation. Semi-fossorial species among rodents and insectivores are scratch-diggers. In contrast, fully subterranean taxa show further specializations for scratch-digging and/or resort to some of the other digging modes. The ecological correlates of these morphological trends are still poorly known; work in geomyids suggests that scratch-digging specializations are efficient in friable soils, whereas tooth-digging allows the utilization of a much broader spectrum of soil types. This indicates that alternative pathways of morphological specialization are not equivalent in their ecological potentialities. Important morphological features, such as incisor procumbency among tooth-diggers, are shown to be constrained by structural, allometric, and mechanical factors. In geomyids, the same procumbent morphologies may be acquired as a byproduct of size increases, by means of adaptive shifts independent from size, or by a combination of both. Thus, geometric similarity may not be indicative of functional similarity. Further constraints result from the integration of different functions. For instance, it is suggested that mastication imposes limitations upon potential modifications of jaw morphology for tooth-digging. Scratch-digging appears to be less constrained by locomotion, but the effects of integration of various functions in fore- and hind-limbs are largely unexplored. Multiple approaches, combining behavioral, functional, ecological, structural, and phylogenetic data, are necessary for the study of morphological evolution among subterranean mammals.

Animals↗

Evolution of synchronous renal and pancreatic transplantation.

The utilization of pancreatic transplantation as a therapeutic option in type I diabetics is dependent on demonstrating its safety and efficacy. A protocol for synchronous renal and segmental pancreatic transplantation, utilizing pancreaticocystostomy, was initiated in February 1985, and through December 1988, 44 patients (mean age 34.8 years) received dual allografts. At last follow-up, 25 patients had functioning kidneys, and 17 patients were insulin independent 4 to 50 months after transplantation, with a mean fasting blood glucose level of 86 mg/100 ml. As our experience increased, three factors were identified as reducing pancreatic allograft and patient survival: vascular thrombosis, inadequate control of pancreatic secretions, and coronary artery disease. As a result, our protocol was modified to include postoperative heparin, external stenting of the pancreaticocystostomy, and dipyridamole thallium testing to screen for coronary artery disease. With these modifications, technical failures and postoperative morbidity were reduced with a resultant increase in 6-month graft and patient survival. These results provide impetus for considering synchronous renal and pancreatic transplantation as a therapeutic option for type I diabetics with end-stage renal disease.

Adult↗

Longitudinal measurement of regional and whole body bone mass in young healthy adults.

The so-called peak bone mass (PBM) represents the highest amount of bony tissue achieved during life at a given site of the skeleton. It has been suggested that PBM might be achieved as late as the fourth decade, but recent data have indicated that PBM is already achieved by the end of sexual maturation, namely at the end of the second decade. The solving of this apparent controversy is of interest for a better understanding of bone homeostasis and for defining the cohort of normal subjects to be evaluated in order to establish a PBM reference range--necessary for the diagnosis of osteoporosis and evaluation of the fracture risk. To study bone mass evolution in young healthy adults and to determine whether such a cohort can be used to establish PBM reference values, we measured bone mineral density (BMD) in sixty 20- to 35-year-old young healthy adults by dual-energy X-ray absorptiometry at the levels of the lumbar spine (in both anteroposterior and lateral views), femoral neck, trochanter region, total hip and of Ward's triangle, as well as whole-body BMD and bone mineral content (BMC) in cross-sectional and longitudinal studies. In the cross-sectional analysis, none of the bone mass variables was dependent on age using linear regression analysis. The longitudinal study indicated that the mean changes in lumbar spine, proximal femur and whole body BMD or BMC determined after a 1-year interval were not statistically different from zero in either females or males aged 20-35 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Technetium-99m sestamibi brain single-photon emission tomography for detection of recurrent gliomas after radiation therapy.

Technetium-99m sestamibi (MIBI), an alternative radiopharmaceutical for myocardial perfusion imaging, has also been proposed for use as an imaging agent for various tumours, including breast cancer, lung cancer, lymphomas, melanomas and brain tumours. After routine radiation therapy, deteriorating clinical status or treatment failure may be due to either radiation-induced changes or recurrent tumour. Computed tomography and magnetic resonance imaging offer imperfect discrimination of tumour viability and radionecrosis. Against this background we undertook a retrospective study of 35 malignant glioma patients in whom clinical deterioration had occurred, in order to clarify the value of 99mTc-MIBI SPET in identifying tumour recurrence. SPET was performed 15 min after intravenous injection of 1110 MBq with a dual-headed gamma camera using a fan-beam collimator. Transverse, coronal and sagittal views were reconstructed. Intense MIBI uptake was found in 31 patients. This uptake was correlated with tumour recurrence as proved by histology and/or rapid, fatal evolution of these cases. The statistical analysis performed on this population of patients with MIBI uptake revealed a group of patients with a long mean survival and a group with a short mean survival. Two subgroups were found within each of these groups, according to the functional index ratio (tumour uptake/pituitary gland uptake ratio). No MIBI uptake was found in four patients who are still alive and can be considered to be disease-free. In those cases showing MIBI uptake, death occurred an average of 6.69 months following brain SPET. According to our results, the specificity and sensitivity of 99mTc-MIBI brain SPET seem to be high. Moreover, this technique is more accurate than computed tomography or magnetic resonance imaging for discriminating between tumour recurrence and radionecrosis.

Adult↗

The MitoDrome database annotates and compares the OXPHOS nuclear genes of Drosophila melanogaster, Drosophila pseudoobscura and Anopheles gambiae.

The oxidative phosphorylation (OXPHOS) is the primary energy-producing process of all aerobic organisms and the only cellular function under the dual control of both the mitochondrial and the nuclear genomes. Functional characterization and evolutionary study of the OXPHOS system is of great importance for the understanding of many as yet unclear aspects of nucleus-mitochondrion genomic co-evolution and co-regulation gene networks. The MitoDrome database is a web-based database which provides genomic annotations about nuclear genes of Drosophila melanogaster encoding for mitochondrial proteins. Recently, MitoDrome has included a new section annotating genomic information about OXPHOS genes in Drosophila pseudoobscura and Anopheles gambiae and their comparative analysis with their Drosophila melanogaster and human counterparts. The introduction of this new comparative annotation section into MitoDrome is expected to be a useful resource for both functional and structural genomics related to the OXPHOS system.

Animals↗

Glutathione S-transferases and related proteins from pathogenic human parasites behave as immunomodulatory factors.

There is a rapidly expanding interest into the glutathione S-transferases (GSTs) and the structurally related molecules. Many of the latter have been identified as members of conserved protein families sharing structural and some times functional properties being particularly involved in heat-shock response, drug resistance and carcinogenesis. Also, evidence is emerging that members of the GST super family from some pathogens could exert immunomodulatory functions toward the cell of the immune system, involving separate profiles of cytokine gene transcription and different patterns of cell growth, illustrating therefore the 'one gene-dual function' phenomenon. The implication of these biological properties for pathogenesis is discussed.

Adjuvants, Immunologic↗

Primary structure of ribosomal proteins S3 and S7 from Manduca sexta.

We have isolated from Manduca sexta full-length cDNAs encoding proteins homologous to human ribosomal proteins S3 and S7. These are the first ribosomal protein sequences obtained from non-Dipteran insects. M. sexta ribosomal protein S3 has a molecular mass of 26,715 Da. Ribosomal protein S7 has a mass 21,870 Da. Both are basic proteins, with abundant Lys and Arg residues that may interact with ribosomal RNA in the ribosome. Southern blot hybridization suggests the presence of single genes for both ribosomal proteins in the M. sexta genome. Alignments with other S3 and S7 sequences available In the database indicate regions of the ribosomal proteins that have been the most highly conserved in evolution and may point to important functional regions in the proteins. Ribosomal protein S3 appears to be more highly conserved then ribosomal protein S7. This may be due to greater constraints on the structure of S3 because of its dual functions in translation as a ribosomal protein and in DNA repair in the nucleus.

Amino Acid Sequence↗

The sucrase-isomaltase complex: primary structure, membrane-orientation, and evolution of a stalked, intrinsic brush border protein.

The complete primary structure (1827 amino acids) of rabbit intestinal pro-sucrase-isomaltase (pro-SI) was deduced from the sequence of a nearly full-length cDNA. Pro-SI is anchored in the membrane by a single 20 amino acid segment spanning the bilayer only once. The amino-terminal, cytoplasmic domain consists of 12 amino acids and is not preceded by a cleaved leader sequence. This suggests a dual role for the membrane-spanning segment as an uncleaved signal for membrane insertion. This is followed by a 22 residue serine/threonine-rich, probably glycosylated, stretch, presumably forming the stalk on which the globular, catalytic domains are directed into the intestinal lumen. Following this is a high degree of homology between the isomaltase and sucrase portions (41% amino acid identity), indicating that pro-SI evolved by partial gene duplication.

Amino Acid Sequence↗

Genes of the T-cell antigen receptor in normal and malignant T cells.

In this review, the germline genomic and cDNA structures and the evolution of the human TcR-alpha-, TcR-beta-, and Tc gamma-chain genes have been reviewed and discussed. The estimated V-gene segment repertoires established for the human TcR-alpha-, TcR-beta-, and Tc gamma-chain genes have also been summarized. The use of TcR and Tc gamma genes in the evaluation of hematopoietic malignancies and identification of chromosomal translocations has also been presented. It is hoped that such information will serve as a reference point from which the study of TcR genes can further progress. This will almost certainly include the use of TcR and perhaps Tc gamma genes in the study of the dual recognition of antigen and MHC gene products, the role of these genes in thymic education/selection, and the role(s) of these genes in oncogenesis processes and autoimmune settings.

Amino Acid Sequence↗

Fluid flow and reactive transport around potential nuclear waste emplacement tunnels at Yucca Mountain, Nevada.

The evolution of fluid chemistry and mineral alteration around a potential waste emplacement tunnel (drift) is evaluated using numerical modeling. The model considers the flow of water, gas, and heat, plus reactions between minerals, CO(2) gas, and aqueous species, and porosity-permeability-capillary pressure coupling for a dual permeability (fractures and matrix) medium. Two possible operating temperature modes are investigated: a "high-temperature" case with temperatures exceeding the boiling point of water for several hundred years, and a "low-temperature" case with temperatures remaining below boiling for the entire life of the repository. In both cases, possible seepage waters are characterized by dilute to moderate salinities and mildly alkaline pH values. These trends in fluid composition and mineral alteration are controlled by various coupled mechanisms. For example, upon heating and boiling, CO(2) exsolution from pore waters raises pH and causes calcite precipitation. In condensation zones, this CO(2) redissolves, resulting in a decrease in pH that causes calcite dissolution and enhances feldspar alteration to clays. Heat also enhances dissolution of wall rock minerals leading to elevated silica concentrations. Amorphous silica precipitates through evaporative concentration caused by boiling in the high-temperature case, but does not precipitate in the low-temperature case. Some alteration of feldspars to clays and zeolites is predicted in the high-temperature case. In both cases, calcite precipitates when percolating waters are heated near the drift. The predicted porosity decrease around drifts in the high-temperature case (several percent of the fracture volume) is larger by at least one order of magnitude than in the low temperature case. Although there are important differences between the two investigated temperature modes in the predicted evolution of fluid compositions and mineral alteration around drifts, these differences are largely within to the model uncertainty and the variability of water compositions at Yucca Mountain.

Carbon Dioxide↗

Stability of atrial sensing and pacing after dual chamber pulse generator implantation.

The continued efficacy of dual chamber pacing is predicated on the stability of both atrial and ventricular electrodes. The introduction of the tined atrial J lead has decreased the incidence of atrial lead dislodgment, allowing for continued effective sensing and pacing. To study the evolution of atrial pacing and sensing threshold, 54 patients with identical pulse generators and atrial electrodes were evaluated for 58 +/- 29 weeks (mean +/- SD). Immediately after pacemaker implantation in 39 patients, the amplitude of the atrial signal was measured by programming the pulse generator to the lowest sensitivity that assured pacing in the atrial synchronous mode. Three levels of atrial sensing were possible: high (0.5 mV), intermediate (1.3 mV) and low (2.5 mV) sensitivity. Three patients had a high, 16 patients had a medium and 20 patients had a low atrial sensitivity. The P wave amplitude and slew rate measured on a physiologic recorder did not differ significantly between the latter two groups. The atrial charge threshold increased from 1.8 +/- 1.3 microcoulombs (microC) to a maximal value of 2.5 +/- 1.3 microC, 3 days to 1 week after implantation (p = 0.02). This remained elevated for 1 to 3 months (p = 0.05) and then decreased, remaining stable over the ensuing year. The atrial sensitivity for the group with noninvasive measurement did not change significantly, although there was considerable patient variation. For 54% of the patients, atrial sensing remained stable or improved. In 26% of the patients, further programming to higher sensitivity settings ws required. In the remaining 20% of the patients, the atrial sensitivity setting fluctuated.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Is cerebral tomoscintigraphy with 99mTc-MIBI useful in the diagnosis of local recurrence in patients with malignant gliomas?].

PURPOSE: 99mTc-MIBI, an alternative radiopharmaceutical for myocardial perfusion study has been proposed for use as a tumor imaging agent, including breast cancer, lung cancer, lymphomas, melanomas, and brain tumors. After routine radiation therapy, deteriorating clinical status or treatment failure may be due to either radiation changes or recurrent tumor. CT and MRI offer imperfect discrimination of tumor viability and radionecrosis. MATERIALS AND METHODS: Thirty-five malignant glioma patients with clinical deterioration were studied retrospectively. Tomoscintigraphy was performed 15 minutes after intravenous injection of 1110 Mbq 99mTc-MIBI. The images were obtained from a dual headed gamma camera using fan beam collimator. Transverse, coronal and sagittal views were reconstructed. RESULTS: A dramatic MIBI uptake was found in 31 patients. This uptake was correlated to tumor recurrence proven by histological fragments and/or the rapid, fatal evolution of these patients. Death occurred after the brain SPECT had been performed for those cases showing MIBI uptake, an average 5.48 months later. No MIBI uptake was found for these four remaining patients: their evolution can be currently considered to be a disease-free time. CONCLUSIONS: According to our results, the sensibility and specificity of 99mTcMIBI brain SPECT seems to be high. Moreover, this investigation is more accurate for discriminating tumor recurrence from radionecrosis than a CT scan or MRI.

Adult↗

Influence of autothreshold sensing and sinus rate on mode switching algorithm behavior.

Mode switching is beneficial to pacemaker patients with paroxysmal atrial tachyarrhythmias. However, the optimal mode switching algorithm is still in evolution. Mode switching algorithms and atrial sensing circuitry can influence mode switching behavior. This study compared the mode switching behavior of four Medtronic, Inc. implantable devices: Thera DR model 7960 pacemaker, Kappa 700 model KDR701 pacemaker, Gem DR model 7271 dual chamber pacing defibrillator, and Jewel AF model 7250 dual chamber pacemaker atrial and ventricular defibrillator. The Thera and Gem DR use the same mean atrial rate mode switch algorithm. The Kappa and Jewel AF use four of seven short atrial intervals and an atrial fibrillation evidence counter algorithm, respectively. The Thera and Kappa devices use fixed gain sensing and the Gem DR and Jewel AF use autothreshold atrial sensing. Digitally recorded atrial electrograms from 52 episodes of human atrial fibrillation were fed into each device with differing simulated sinus rates before and after the atrial fibrillation. The percent of appropriate mode switching was highest for the Kappa 700 (94%) and lowest for the Thera (85%) (P = 0.046). The time to mode switching was significantly longer for the Thera and Gem DR compared to the Kappa 700 or Jewel AF (all P < 0.05). The time to mode switching was shorter for the Gem DR (9.0 +/- 1.6 s) using autothreshold atrial sensing than for the fixed gain Thera (11.1 +/- 2.1 s, P < 0.05). The mean atrial electrogram amplitude and cycle length were not correlated with the time to mode switching for any device. Faster sinus rates shortened the time to mode switching and prolonged the time to resynchronization in the two devices using the mean atrial interval algorithm. In conclusion, (1) mode switching function among these devices is influenced by algorithms and sensing circuitry, (2) the time to mode switching among these devices is influenced by the algorithm and use of autothreshold atrial sensing, and (3) the sinus rate before and after episodes of atrial fibrillation greatly influences the times to mode switching and resynchronization in devices using the mean atrial interval algorithm.

Algorithms↗

The impact of ICRP/ICRU quantities on high energy neutron dosimetry: a review.

Unlike other fields of toxicology, radiation protection has a dual system of quantities, one set for assessment and the derivation of authorised limits and another set for monitoring radiation performance and compliance. Neutrons are an important or dominant constituent of the radiation field around high energy accelerators and the evolution of the radiation protection quantities used to measure neutrons is described. In 1990 ICRP introduced a new quantity, the effective dose. E. with which to express its protection limits. E represented a radical departure from previous advice of the Commission, particularly in the manner by which it weighted the absorbed dose deposited by high LET radiations. This advice had profound consequences for neutron dosimetry. Over the past decade analyses have revealed logical flaws and inconsistencies in the definition of effective dose. These are briefly discussed with most emphasis being placed on inconsistencies in radiation weighting. Suggestions are made with a view to resolving these inconsistencies.

Neutrons↗

Resolving head rotation for human bipedalism.

Alignment of the body to the gravitational vertical is considered to be the key to human bipedalism. However, changes to the semicircular canals during human evolution suggest that the sense of head rotation that they provide is important for modern human bipedal locomotion. When walking, the canals signal a mix of head rotations associated with path turns, balance perturbations, and other body movements. It is uncertain how the brain uses this information. Here, we show dual roles for the semicircular canals in balance control and navigation control. We electrically evoke a head-fixed virtual rotation signal from semicircular canal nerves as subjects walk in the dark with their head held in different orientations. Depending on head orientation, we can either steer walking by "remote control" or produce balance disturbances. This shows that the brain resolves the canal signal according to head posture into Earth-referenced orthogonal components and uses rotations in vertical planes to control balance and rotations in the horizontal plane to navigate. Because the semicircular canals are concerned with movement rather than detecting vertical alignment, this result shows the importance of movement control and agility rather than precise vertical alignment of the body for human bipedalism.

Adult↗

Regional and welfare perspectives on the public-private hospital dichotomy in New Zealand.

Concern with the social welfare implications of dual (public and private) hospital systems has grown over the last decade as national commitments to welfare state ideals have wavered in the continuing atmosphere of fiscal conservatism that has permeated through western democracies. New Zealand provides an excellent example of a health care system in which private hospitals have survived (and recently flourished) alongside those provided by the state. Following a brief survey of the evolution of the New Zealand hospital system, variations in the 'mix' of public and private hospitals are described at the (regional) Hospital Board District level. It is noted that competition for patients and funding between the public and private sectors occurs almost exclusively in the larger, urban hospital districts, and is invariably to the detriment of public hospitals. Districts with a substantial private hospital presence are found to have fewer resources in the public sector (relative to their population) than those which have few or no private hospitals. The welfare implications of this situation are explored. It is proposed that the maintenance of a dual hospital system in New Zealand has provided, in some parts of the country at least, a 'choice' for those able to afford private hospital charges or insurance coverage, but at the expense of those dependent solely upon a (shrinking) public sector.

Economics, Hospital↗

Detecting Traces of Prehistoric Human Migrations by Geographic Synthetic Maps of Polyomavirus JC.

The polyomavirus JC (JCV) is a double-stranded DNA virus that is ubiquitous in human populations and is excreted in urine by a large percentage of individuals (20-70%). The strong genetic stability, combined with a mechanism of transmission mainly within the family, makes JCV a good marker of human migrations. In this study, the coevolution of JCV with its human host is investigated by using over a thousand nucleotide sequences deposited in the EMBL database; they correspond to the IG region, which is the genomic region with the highest rate of variation. The pattern of genetic diversity in JCV is evaluated by the principal coordinates analysis and the construction of synthetic maps. The first principal coordinate supports the existence of two distinct virus lineages, both arising from the ancestral African type. The first synthetic map suggests a two-migration model of the human dispersal out of Africa, thus implying a more complex picture than that known from human genes. The second principal coordinate points out the distinctiveness of strains coming from Asian/Amerind populations. The picture yielded by the second synthetic map appears to be more consistent with that known from human genes. In fact, it provides evidence of a deep split of the Asian lineage of JCV into two main branches: one diffusing in Japan and Americas, the other in Southeast Asia. The view that JCV, with its peculiar feature of a dual early emergence from Africa, can provide new information about the evolutionary history of our ancestors is discussed.

Databases, Nucleic Acid↗