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991.
Cynthia M. Beall Kingman P. Strohl John Blangero Sarah Williams-Blangero Laura A. Almasy Michael J. Decker Carol M. Worthman Melvyn C. Goldstein Enrique Vargas Mercedes Villena Rudy Soria Ana Maria Alarcon Cristina Gonzales 《American journal of physical anthropology》1997,104(4):427-447
Newcomers acclimatizing to high altitude and adult male Tibetan high altitude natives have increased ventilation relative to sea level natives at sea level. However, Andean and Rocky Mountain high altitude natives have an intermediate level of ventilation lower than that of newcomers and Tibetan high altitude natives although generally higher than that of sea level natives at sea level. Because the reason for the relative hypoventilation of some high altitude native populations was unknown, a study was designed to describe ventilation from adolescence through old age in samples of Tibetan and Andean high altitude natives and to estimate the relative genetic and environmental influences. This paper compares resting ventilation and hypoxic ventilatory response (HVR) of 320 Tibetans 9–82 years of age and 542 Bolivian Aymara 13–94 years of age, native residents at 3,800–4,065 m. Tibetan resting ventilation was roughly 1.5 times higher and Tibetan HVR was roughly double that of Aymara. Greater duration of hypoxia (older age) was not an important source of variation in resting ventilation or HVR in either sample. That is, contrary to previous studies, neither sample acquired hypoventilation in the age ranges under study. Within populations, greater severity of hypoxia (lower percent of oxygen saturation of arterial hemoglobin) was associated with slightly higher resting ventilation among Tibetans and lower resting ventilation and HVR among Aymara women, although the associations accounted for just 2–7% of the variation. Between populations, the Tibetan sample was more hypoxic and had higher resting ventilation and HVR. Other systematic environmental contrasts did not appear to elevate Tibetan or depress Aymara ventilation. There was more intrapopulation genetic variation in these traits in the Tibetan than the Aymara sample. Thirty-five percent of the Tibetan, but none of the Aymara, resting ventilation variance was due to genetic differences among individuals. Thirty-one percent of the Tibetan HVR, but just 21% of the Aymara, HVR variance was due to genetic differences among individuals. Thus there is greater potential for evolutionary change in these traits in the Tibetans. Presently, there are two different ventilation phenotypes among high altitude natives as compared with sea level populations at sea level: lifelong sustained high resting ventilation and a moderate HVR among Tibetans in contrast with a slightly elevated resting ventilation and a low HVR among Aymara. Am J Phys Anthropol 104:427–447, 1997. © 1997 Wiley-Liss, Inc. 相似文献
992.
Simona Graziano Nuria Coll-Bonfill Barbara Teodoro-Castro Sahiti Kuppa Jessica Jackson Elena Shashkova Urvashi Mahajan Alessandro Vindigni Edwin Antony Susana Gonzalo 《The Journal of biological chemistry》2021,297(5)
Lamin A/C provides a nuclear scaffold for compartmentalization of genome function that is important for genome integrity. Lamin A/C dysfunction is associated with cancer, aging, and degenerative diseases. The mechanisms whereby lamin A/C regulates genome stability remain poorly understood. We demonstrate a crucial role for lamin A/C in DNA replication. Lamin A/C binds to nascent DNA, especially during replication stress (RS), ensuring the recruitment of replication fork protective factors RPA and RAD51. These ssDNA-binding proteins, considered the first and second responders to RS respectively, function in the stabilization, remodeling, and repair of the stalled fork to ensure proper restart and genome stability. Reduced recruitment of RPA and RAD51 upon lamin A/C depletion elicits replication fork instability (RFI) characterized by MRE11 nuclease–mediated degradation of nascent DNA, RS-induced DNA damage, and sensitivity to replication inhibitors. Importantly, unlike homologous recombination–deficient cells, RFI in lamin A/C-depleted cells is not linked to replication fork reversal. Thus, the point of entry of nucleases is not the reversed fork but regions of ssDNA generated during RS that are not protected by RPA and RAD51. Consistently, RFI in lamin A/C-depleted cells is rescued by exogenous overexpression of RPA or RAD51. These data unveil involvement of structural nuclear proteins in the protection of ssDNA from nucleases during RS by promoting recruitment of RPA and RAD51 to stalled forks. Supporting this model, we show physical interaction between RPA and lamin A/C. We suggest that RS is a major source of genomic instability in laminopathies and lamin A/C-deficient tumors. 相似文献
993.
994.
Liévin Daugimont Nolwenn Baron Gaëlle Vandermeulen Natasa Pavselj Damijan Miklavcic Marie-Caroline Jullien Gonzalo Cabodevila Lluis M. Mir Véronique Préat 《The Journal of membrane biology》2010,236(1):117-125
The association of microneedles with electric pulses causing electroporation could result in an efficient and less painful
delivery of drugs and DNA into the skin. Hollow conductive microneedles were used for (1) needle-free intradermal injection
and (2) electric pulse application in order to achieve electric field in the superficial layers of the skin sufficient for
electroporation. Microneedle array was used in combination with a vibratory inserter to disrupt the stratum corneum, thus
piercing the skin. Effective injection of proteins into the skin was achieved, resulting in an immune response directed to
the model antigen ovalbumin. However, when used both as microneedles to inject and as electrodes to apply the electric pulses,
the setup showed several limitations for DNA electrotransfer. This could be due to the distribution of the electric field
in the skin as shown by numerical calculations and/or the low dose of DNA injected. Further investigation of these parameters
is needed in order to optimize minimally invasive DNA electrotransfer in the skin. 相似文献
995.
Moreno-Gutiérrez C Barberá GG Nicolás E DE Luis M Castillo VM Martínez-Fernández F Querejeta JI 《Plant, cell & environment》2011,34(6):1009-1019
Silvicultural thinning usually improves the water status of remaining trees in water‐limited forests. We evaluated the usefulness of a dual stable isotope approach (δ13C, δ18O) for comparing the physiological performance of remaining trees between forest stands subjected to two different thinning intensities (moderate versus heavy) in a 60‐year‐old Pinus halepensis Mill. plantation in semiarid southeastern Spain. We measured bulk leaf δ13C and δ18O, foliar elemental concentrations, stem water content, stem water δ18O (δ18Ostem water), tree ring widths and leaf gas exchange rates to assess the influence of forest stand density on tree performance. Remaining trees in low‐density stands (heavily thinned) showed lower leaf δ18O, and higher stomatal conductance (gs), photosynthetic rate and radial growth than those in moderate‐density stands (moderately thinned). By contrast, leaf δ13C, intrinsic water‐use efficiency, foliar elemental concentrations and δ18Ostem water were unaffected by stand density. Lower foliar δ18O in heavily thinned stands reflected higher gs of remaining trees due to decreased inter‐tree competition for water, whereas higher photosynthetic rate was largely attributable to reduced stomatal limitation to CO2 uptake. The dual isotope approach provided insight into the early (12 months) effects of stand density manipulation on the physiological performance of remaining trees. 相似文献
996.
Summary. Nodulins encoding repetitive proline-rich cell wall proteins (PRPs) are induced during early interactions with rhizobia, suggesting
a massive restructuring of the plant extracellular matrix during infection and nodulation. However, the proteins corresponding
to these gene products have not been isolated or characterized, nor have cell wall localizations been confirmed. Posttranslational
modifications, conformation, and interactions with other wall polymers are difficult to predict on the basis of only the deduced
amino acid sequence of PRPs. PsENOD2 is expressed in nodule parenchyma tissue during nodule organogenesis and encodes a protein with distinctive PRP motifs that
are rich in glutamate and basic amino acids. A database search for the ENOD2 signature motifs indicates that similar proteins
may have a limited phylogenetic distribution, as they are presently only known from legumes. To determine the ultrastructural
location of the proteins, antibodies were raised against unique motifs from the predicted ENOD2 sequence. The antibodies recognized
nodule-specific proteins in pea (Pisum sativum), with a major band detected at 110 kDa, representing a subset of PRPs from nodules. The protein was detected specifically
in organelles of the secretory pathway and intercellular spaces in the nodule parenchyma, but it was not abundant in primary
walls. Similar proteins with an analogous distribution were detected in soybean (Glycine max). The use of polyclonal antibodies raised against signature motifs of extracellular matrix proteins thus appears to be an
effective strategy to identify and isolate specific structural proteins for functional analysis.
Correspondence and reprints: Delaware Biotechnology Institute, Newark, DE 19711, U.S.A. 相似文献
997.
Puente XS Quesada V Osorio FG Cabanillas R Cadiñanos J Fraile JM Ordóñez GR Puente DA Gutiérrez-Fernández A Fanjul-Fernández M Lévy N Freije JM López-Otín C 《American journal of human genetics》2011,(5):1683-656
Accelerated aging syndromes represent a valuable source of information about the molecular mechanisms involved in normal aging. Here, we describe a progeroid syndrome that partially phenocopies Hutchinson-Gilford progeria syndrome (HGPS) but also exhibits distinctive features, including the absence of cardiovascular deficiencies characteristic of HGPS, the lack of mutations in LMNA and ZMPSTE24, and a relatively long lifespan of affected individuals. Exome sequencing and molecular analysis in two unrelated families allowed us to identify a homozygous mutation in BANF1 (c.34G>A [p.Ala12Thr]), encoding barrier-to-autointegration factor 1 (BAF), as the molecular abnormality responsible for this Mendelian disorder. Functional analysis showed that fibroblasts from both patients have a dramatic reduction in BAF protein levels, indicating that the p.Ala12Thr mutation impairs protein stability. Furthermore, progeroid fibroblasts display profound abnormalities in the nuclear lamina, including blebs and abnormal distribution of emerin, an interaction partner of BAF. These nuclear abnormalities are rescued by ectopic expression of wild-type BANF1, providing evidence for the causal role of this mutation. These data demonstrate the utility of exome sequencing for identifying the cause of rare Mendelian disorders and underscore the importance of nuclear envelope alterations in human aging. 相似文献
998.
999.
1000.
Hsu S Schmid A Sternfeld L Anderie I Solis G Hofer HW Schulz I 《Cellular signalling》2003,15(12):1149-1156
We have studied modulation of “store-operated calcium influx” by tyrosine phosphatases in the pancreatic acinar cell line AR42J and in HEK 293 cells. We show that inhibition of tyrosine phosphatases by bis-(N,N-dimethyl-hydroxamido) hydrooxovanadate (DMHV) leads to an increase in Ca2+ release-activated Ca2+ (CRAC) entry. This effect can be blocked in the presence of 2-aminoethyldiphenyl borate (2-APB). Furthermore, transfection of HEK 293 cells with the human wild-type tyrosine phosphatase PTP1B leads to inhibition of CRAC influx, whereas transfection with the substrate-trapping mutant of PTP1B (D181A) slightly increases Ca2+ influx. It also decreases enzymatic activity of PTP1B as compared to non-transfected cells. Our data suggest that CRAC influx is modulated by tyrosine phosphorylation and dephosphorylation which involves the tyrosine phosphatase PTP1B. 相似文献