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1.
The flexibility and self-healing properties of animal cell surface membranes are well known. These properties have been best exploited in various micrurgical studies on living cells (2, 3), especially in amoebae (7, 20). During nuclear transplantation in amoebae, the hole in the membrane through which a nucleus passes can have a diameter of 20-30 μm, and yet such holes are quickly sealed, although some cytoplasm usually escapes during the transfer. While enucleating amoebae in previous studies, we found that if a very small portion of a nucleus was pushed through the membrane and exposed to the external medium, the amoeba expelled such a nucleus on its own accord. When this happened, a new membrane appeared to form around the embedded portion of the nucleus and no visible loss of cytoplasm occurred during nuclear extrusion. In the present study, we examined amoebae that were at different stages of expelling partially exposed nuclei, to follow the sequence of events during the apparent new membrane formation. Unexpectedly, we found that a new membrane is not formed around the nucleus from inside but a hole is sealed primarily by a constriction of the existing membrane, and that cytoplasmic filaments are responsible for the prevention of the loss of cytoplasm. 相似文献
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Ben Mersey Rebecca S. Jabbour Kyle Brudvik Alban Defleur 《American journal of physical anthropology》2013,152(4):516-529
The hand and foot remains from Moula‐Guercy cave (Ardèche, France) comprise 24 specimens of Eemian age (ca. 120 ka). The specimens include primarily complete elements, which are rare among the Moula‐Guercy postcrania. The hand remains have several characteristic Neanderthal traits including a laterally facing (parasagittally oriented) second metacarpal‐capitate articulation, a short styloid process, a wide proximal articular surface on the third metacarpal, and absolutely expanded apical tuberosities on the distal hand phalanges relative to modern humans. The foot remains include several incomplete elements along with an antimeric pair of naviculars, a medial cuneiform and cuboid, and a single complete element from each of the distal segments (one each: metatarsal, proximal foot phalanx, intermediate foot phalanx, distal foot phalanx). Consistent among the specimens are relatively wide diaphyses for length in the metatarsals and phalanges and large and prominent muscle attachments, both consistent with previously published Neanderthal morphology. The hand and foot collection from Moula‐Guercy is an important dataset for future studies of Neanderthal functional morphology, dexterity, and behavior as it represents a previously undersampled time period for European Neanderthals. Am J Phys Anthropol 152:516–529, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
3.
V KW Wong T Li B YK Law E DL Ma N C Yip F Michelangeli C KM Law M M Zhang K YC Lam P L Chan L Liu 《Cell death & disease》2013,4(7):e720
Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump, leading to autophagy induction through the activation of the Ca2+/calmodulin-dependent kinase kinase–AMP-activated protein kinase–mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells. 相似文献
4.
Hagness M Henjum K Landskron J Brudvik KW Bjørnbeth BA Foss A Taskén K Aandahl EM 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(11):5459-5466
Naturally occurring regulatory T cells (Tregs) maintain self tolerance by dominant suppression of potentially self-reactive T cells in peripheral tissues. However, the activation requirements, the temporal aspects of the suppressive activity, and mode of action of human Tregs are subjects of controversy. In this study, we show that Tregs display significant variability in the suppressive activity ex vivo as 54% of healthy blood donors examined had fully suppressive Tregs spontaneously, whereas in the remaining donors, anti-CD3/CD2/CD28 stimulation was required for Treg suppressive activity. Furthermore, anti-CD3/CD2/CD28 stimulation for 6 h and subsequent fixation in paraformaldehyde rendered the Tregs fully suppressive in all donors. The fixation-resistant suppressive activity of Tregs operated in a contact-dependent manner that was not dependent on APCs, but could be fully obliterated by trypsin treatment, indicating that a cell surface protein is directly involved. By add-back of active, fixed Tregs at different time points after activation of responding T cells, the responder cells were susceptible to Treg-mediated immune suppression up to 24 h after stimulation. This defines a time window in which effector T cells are susceptible to Treg-mediated immune suppression. Lastly, we examined the effect of a set of signaling inhibitors that perturb effector T cell activation and found that none of the examined inhibitors affected Treg activation, indicating pathway redundancy or that Treg activation proceeds by signaling mechanisms distinct from those of effector T cells. 相似文献
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M Innes Asher Alistair W Stewart Javier Mallol Stephen Montefort Christopher KW Lai Nadia A?t-Khaled Joseph Odhiambo The ISAAC Phase One Study Group 《Respiratory research》2010,11(1):8
The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here.In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution.Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence.The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit. 相似文献
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The catalytic domains of murine Golgi alpha1,2-mannosidases IA and IB that
are involved in N-glycan processing were expressed as secreted proteins in
P.pastoris . Recombinant mannosidases IA and IB both required divalent
cations for activity, were inhibited by deoxymannojirimycin and
kifunensine, and exhibited similar catalytic constants using
Manalpha1,2Manalpha-O-CH3as substrate. Mannosidase IA was purified as a 50
kDa catalytically active soluble fragment and shown to be an inverting
glycosidase. Recombinant mannosidases IA and IB were used to cleave
Man9GlcNAc and the isomers produced were identified by high performance
liquid chromatography and proton-nuclear magnetic resonance spectroscopy.
Man9GlcNAc was rapidly cleaved by both enzymes to Man6GlcNAc, followed by a
much slower conversion to Man5GlcNAc. The same isomers of Man7GlcNAc and
Man6GlcNAc were produced by both enzymes but different isomers of
Man8GlcNAc were formed. When Man8GlcNAc (Man8B isomer) was used as
substrate, rapid conversion to Man5GlcNAc was observed, and the same
oligosaccharide isomer intermediates were formed by both enzymes. These
results combined with proton-nuclear magnetic resonance spectroscopy data
demonstrate that it is the terminal alpha1, 2-mannose residue missing in
the Man8B isomer that is cleaved from Man9GlcNAc at a much slower rate.
When rat liver endoplasmic reticulum membrane extracts were incubated with
Man9GlcNAc2, Man8GlcNAc2was the major product and Man8B was the major
isomer. In contrast, rat liver Golgi membranes rapidly cleaved
Man9GlcNAc2to Man6GlcNAc2and more slowly to Man5GlcNAc2. In this case all
three isomers of Man8GlcNAc2were formed as intermediates, but a distinctive
isomer, Man8A, was predominant. Antiserum to recombinant mannosidase IA
immunoprecipitated an enzyme from Golgi extracts with the same specificity
as recombinant mannosidase IA. These immunodepleted membranes were enriched
in a Man9GlcNAc2to Man8GlcNAc2- cleaving activity forming predominantly the
Man8B isomer. These results suggest that mannosidases IA and IB in Golgi
membranes prefer the Man8B isomer generated by a complementary mannosidase
that removes a single mannose from Man9GlcNAc2.
相似文献
10.
Ying J Nie Mo Y Mok Godfrey CF Chan Albert W Chan Ou Jin Sushma Kavikondala Albert KW Lie Chak S Lau 《Arthritis research & therapy》2010,12(3):R91