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31.
A Sahaboglu O Paquet-Durand J Dietter K Dengler S Bernhard-Kurz P AR Ekstr?m B Hitzmann M Ueffing F Paquet-Durand 《Cell death & disease》2013,4(2):e488
For most neurodegenerative diseases the precise duration of an individual cell''s death is unknown, which is an obstacle when counteractive measures are being considered. To address this, we used the rd1 mouse model for retinal neurodegeneration, characterized by phosphodiesterase-6 (PDE6) dysfunction and photoreceptor death triggered by high cyclic guanosine-mono-phosphate (cGMP) levels. Using cellular data on cGMP accumulation, cell death, and survival, we created mathematical models to simulate the temporal development of the degeneration. We validated model predictions using organotypic retinal explant cultures derived from wild-type animals and exposed to the selective PDE6 inhibitor zaprinast. Together, photoreceptor data and modeling for the first time delineated three major cell death phases in a complex neuronal tissue: (1) initiation, taking up to 36 h, (2) execution, lasting another 40 h, and finally (3) clearance, lasting about 7 h. Surprisingly, photoreceptor neurodegeneration was noticeably slower than necrosis or apoptosis, suggesting a different mechanism of death for these neurons. 相似文献
32.
33.
Influence of phase I duration on phase II VO2 kinetics parameter estimates in older and young adults
Murias JM Spencer MD Kowalchuk JM Paterson DH 《American journal of physiology. Regulatory, integrative and comparative physiology》2011,301(1):R218-R224
Older adults (O) may have a longer phase I pulmonary O(2) uptake kinetics (Vo(2)(p)) than young adults (Y); this may affect parameter estimates of phase II Vo(2)(p). Therefore, we sought to: 1) experimentally estimate the duration of phase I Vo(2)(p) (EE phase I) in O and Y subjects during moderate-intensity exercise transitions; 2) examine the effects of selected phase I durations (i.e., different start times for modeling phase II) on parameter estimates of the phase II Vo(2)(p) response; and 3) thereby determine whether slower phase II kinetics in O subjects represent a physiological difference or a by-product of fitting strategy. Vo(2)(p) was measured breath-by-breath in 19 O (68 ± 6 yr; mean ± SD) and 19 Y (24 ± 5 yr) using a volume turbine and mass spectrometer. Phase I Vo(2)(p) was longer in O (31 ± 4 s) than Y (20 ± 7 s) (P < 0.05). In O, phase II τVo(2)(p) was larger (P < 0.05) when fitting started at 15 s (49 ± 12 s) compared with fits starting at the individual EE phase I (43 ± 12 s), 25 s (42 ± 10 s), 35 s (42 ± 12 s), and 45 s (45 ± 15 s). In Y, τVo(2)(p) was not affected by the time at which phase II Vo(2)(p) fitting started (τVo(2)(p) = 31 ± 7 s, 29 ± 9 s, 30 ± 10 s, 32 ± 11 s, and 30 ± 8 s for fittings starting at 15 s, 25 s, 35 s, 45 s, and EE phase I, respectively). Fitting from EE phase I, 25 s, or 35 s resulted in the smallest CI τVo(2)(p) in both O and Y. Thus, fitting phase II Vo(2)(p) from (but not constrained to) 25 s or 35 s provides consistent estimates of Vo(2)(p) kinetics parameters in Y and O, despite the longer phase I Vo(2)(p) in O. 相似文献
34.
In many cases of interspecific kleptoparasitism, hosts developdefensive behaviors to minimize the impact of kleptoparasites.Because vigilance and defensive behaviors are often costly,selection should favor hosts that adjust the amount of investmentneeded to minimize losses to kleptoparasitism. However, examplesof such facultative responses are rare. Here, we investigatethe response of cooperatively breeding pied babblers (Turdoidesbicolor) to the drongo (Dicrurus adsimilis), an avian kleptoparasitethat regularly follows pied babbler groups, often giving alarmcalls to alert the group to predators but also occasionallygiving false alarm calls in order to steal food items. We showthat pied babbler response to drongos varies markedly accordingto babbler group size. In small groups, where there are fewindividuals available to act as sentinels, babblers sentinelless when a drongo is present and respond strongly to drongoalarm calls. However, in large groups, where there are manyindividuals available to participate in predator vigilance,babblers sentinel more often when a drongo is present, rarelyrespond to drongo alarm calls, and aggressively displace drongos,with a consequent decline in the number of successful kleptoparasitismevents. This behavior represent a facultative response to akleptoparasite according to the costs versus benefits of toleratingtheir presence. 相似文献
35.
N. GARCÍA-MAGALLANES F. LUQUE-ORTEGA E. M. AGUILAR-MEDINA R. RAMOS-PAYÁN C. GALAVIZ-HERNÁNDEZ J. G. ROMERO-QUINTANA L. DEL POZO-YAUNER H. RANGEL-VILLALOBOS E. ARÁMBULA-MERAZ 《Journal of genetics》2014,93(2):325-330
Glucose-6-phosphate dehydrogenase deficiency (G6PD) is the most common enzyme pathology in humans; it is X-linked inherited and causes neonatal hyperbilirubinaemia, chronic nonspherocytic haemolytic anaemia and drug-induced acute haemolytic anaemia. G6PD deficiency has scarcely been studied in the northern region of Mexico, which is important because of the genetic heterogeneity described in Mexican population. Therefore, samples from the northern Mexico were biochemically screened for G6PD-deficiency, and PCR-RFLPs, and DNA sequencing used to identify mutations in positive samples. The frequency of G6PD deficiency in the population was 0.95% (n = 1993); the mutations in 86% of these samples were G6PD A?202A/376G , G6PD A?376G/968C and G6PD Santamaria376G/542T . Contrary to previous reports, we demonstrated that G6PD deficiency distribution is relatively homogenous throughout the country (P = 0.48336), and the unique exception with high frequency of G6PD deficiency does not involve a coastal population (Chihuahua: 2.4%). Analysis of eight polymorphic sites showed only 10 haplotypes. In one individual we identified a new G6PD mutation named Mexico DF193A>G (rs199474830), which probably results in a damaging functional effect, according to PolyPhen analysis. Proteomic impact of the mutation is also described. 相似文献
36.
Spencer MD Murias JM Grey TM Paterson DH 《Journal of applied physiology (Bethesda, Md. : 1985)》2012,112(6):1023-1032
This study examined the separate and combined effects of acute hypoxia (Hypo) and heavy-intensity "priming" exercise (Hvy) on pulmonary O(2) uptake (Vo(2p)) kinetics during moderate-intensity exercise (Mod). Breath-by-breath Vo(2p) and near-infrared spectroscopy-derived muscle deoxygenation {deoxyhemoglobin concentration [HHb]} were monitored continuously in 10 men (23 ± 4 yr) during repetitions of a Mod 1-Hvy-Mod 2 protocol, where each of the 6-min (Mod or Hvy) leg-cycling bouts was separated by 6 min at 20 W. Subjects were exposed to Hypo [fraction of inspired O(2) (Fi(O(2))) = 15%, Mod 2 + Hypo] or "sham" (Fi(O(2)) = 20.9%, Mod 2-N) 2 min following Hvy in half of these repetitions; Mod was also performed in Hypo without Hvy (Mod 1 + Hypo). On-transient Vo(2p) and [HHb] responses were modeled as a monoexponential. Data were scaled to a relative percentage of the response (0-100%), the signals were time-aligned, and the individual [HHb]-to-Vo(2) ratio was calculated. Compared with control (Mod 1), τVo(2p) and the O(2) deficit (26 ± 7 s and 638 ± 144 ml, respectively) were reduced (P < 0.05) in Mod 2-N (20 ± 5 s and 529 ± 196 ml) and increased (P < 0.05) in Mod 1 + Hypo (34 ± 14 s and 783 ± 184 ml); in Mod 2 + Hypo, τVo(2p) was increased (30 ± 8 s, P < 0.05), yet O(2) deficit was unaffected (643 ± 193 ml, P > 0.05). The modest "overshoot" in the [HHb]-to-Vo(2) ratio (reflecting an O(2) delivery-to-utilization mismatch) in Mod 1 (1.06 ± 0.04) was abolished in Mod 2-N (1.00 ± 0.05), persisted in Mod 2 + Hypo (1.09 ± 0.07), and tended to increase in Mod 1 + Hypo (1.10 ± 0.09, P = 0.13). The present data do not support an "O(2) delivery-independent" speeding of τVo(2p) following Hvy (or Hvy + Hypo); rather, this study suggests that local muscle O(2) delivery likely governs the rate of adjustment of Vo(2) at τVo(2p) greater than ~20 s. 相似文献
37.
Lucas Bleicher Ricardo Aparicio Fabio M Nunes Leandro Martinez Sandra M Gomes Dias Carolina Migliorini Ana Figueira Auxiliadora Morim Maria Santos Walter H Venturelli Rosangela da Silva Paulo Marcos Donate Francisco AR Neves Luiz A Simeoni John D Baxter Paul Webb Munir S Skaf Igor Polikarpov 《BMC structural biology》2008,8(1):1-13
Background
Multiple protein templates are commonly used in manual protein structure prediction. However, few automated algorithms of selecting and combining multiple templates are available.Results
Here we develop an effective multi-template combination algorithm for protein comparative modeling. The algorithm selects templates according to the similarity significance of the alignments between template and target proteins. It combines the whole template-target alignments whose similarity significance score is close to that of the top template-target alignment within a threshold, whereas it only takes alignment fragments from a less similar template-target alignment that align with a sizable uncovered region of the target. We compare the algorithm with the traditional method of using a single top template on the 45 comparative modeling targets (i.e. easy template-based modeling targets) used in the seventh edition of Critical Assessment of Techniques for Protein Structure Prediction (CASP7). The multi-template combination algorithm improves the GDT-TS scores of predicted models by 6.8% on average. The statistical analysis shows that the improvement is significant (p-value < 10-4). Compared with the ideal approach that always uses the best template, the multi-template approach yields only slightly better performance. During the CASP7 experiment, the preliminary implementation of the multi-template combination algorithm (FOLDpro) was ranked second among 67 servers in the category of high-accuracy structure prediction in terms of GDT-TS measure.Conclusion
We have developed a novel multi-template algorithm to improve protein comparative modeling. 相似文献38.
Horizontal transmission, vertical inactivation, and stochastic loss of mariner-like transposable elements 总被引:13,自引:5,他引:8
Horizontal transmission has been well documented as a major mechanism for
the dissemination of mariner-like elements (MLEs) among species. Less well
understood are mechanisms that limit vertical transmission of MLEs
resulting in the "spotty" or discontinuous distribution observed in closely
related species. In this article we present evidence that the genome of the
common ancestor of the melanogaster species subgroup of Drosophila
contained an MLE related to the mellifera (honey bee) subfamily. Horizontal
transmission, approximately 3-10 MYA, is strongly suggested by the
observation that the sequence of the MLE in Drosophila erecta is 97%
identical in nucleotide sequence with that of an MLE in the cat flea,
Ctenocephalides felis. The D. erecta MLE has a spotty distribution among
species in the melanogaster subgroup. The element has a high copy number in
D. erecta and D. orena, a moderate copy number in D. teissieri and D.
yakuba, and was apparently lost ("stochastic loss") in the lineage leading
to D. melanogaster, D. simulans, D. mauritiana, and D. sechellia. In D.
erecta, most copies are concentrated in the heterochromatin. Two copies
from D. erecta, denoted De12 and De19, were cloned and sequenced, and they
appear to be nonfunctional ("vertical inactivation"). It therefore appears
that the predominant mode of MLE evolution is vertical inactivation and
stochastic loss balanced against occasional reinvasion of lineages by
horizontal transmission.
相似文献
39.
Yeast-like fungi such as Saccharomyces cerevisiae exhibit a range of cell types differing in cell shape, gene expression and growth pattern. Signal transduction pathways mediate transitions between different cell types. Nutritional signals induce rounded yeast-form cells either to enter invasive growth as elongated filamentous cells or to arrest to prepare for stationary phase, conjugation, or meiosis. An emerging theme is that development critically depends upon differential regulation of vegetative functions, including cytoskeletal organization and cell cycle progression, as much as on the expression of cell type specific gene products. 相似文献
40.
Fine needle aspiration biopsies (FNA) of 47 Warthin's tumours confirmed by histology were re-evaluated for cytomorphological findings. The majority of aspirates (37/47) contained a typical background with proteinaceous substance and cell debris, along with cellular elements represented by oncocytic, lymphoid, and mast cells with degranulated cytoplasm. Uncommon cellular findings were true squamous cells (1/47), atypical cells with vacuoles (1/47), osteoclastic giant cells (1/47), epithelioid cells (1/47), mast cells with preserved granules in cytoplasm (3/47), and siderophages (4/47). Uncommon findings in the background were corpora amylacea-like structures and homogeneous bright red droplets. Squamous cells and atypical cells with vacuoles caused diagnostic difficulties in distinguishing a Warthin's tumour from a squamous cell or mucoepidermoid carcinoma. However, other unusual cellular and background findings were not worrying; therefore, they are merely regarded as a curiosity in the cytomorphological appearance of the tumour. 相似文献