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21.
Niina Airas Anu Näreaho Jere Lindén Erkka Valo Sampsa Hautaniemi Pikka Jokelainen Antti Sukura 《Experimental parasitology》2013
Trichinella spiralis causes a significantly higher parasite burden in rat muscle than Trichinella nativa. To assess whether the difference in infectivity is due to the early intestinal response, we analyzed gene expression changes in the rat jejunum during Trichinella infection with a whole-genome microarray. The rats were euthanized on day five of infection, and their jejunal mucosa was sampled for microarray analysis. In addition, intestinal histology and hematology were examined. Against our expectations, the gene expression changes were similar in both T.nativa- and T. spiralis-infected groups. The two groups were hence pooled, and in the combined Trichinella-infected group, 551 genes were overexpressed and 427 underexpressed when compared to controls (false discovery rate ?0.001 and fold change at least 2 in either direction). Pathway analysis identified seven pathways significantly associated with Trichinella infection (p < 0.05). The microarray data suggested nonspecific damage and an inflammatory response in the jejunal mucosa. Histological findings, including hyperemia, hemorrhage and a marked infiltration of inflammatory cells, supported the microarray data. Trichinella infection caused complex gene expression changes that indicate a host response to tissue damage in the mucosa of the jejunum, but the changes were not notably dependent on the studied species of Trichinella. 相似文献
22.
Kshitij Gupta Hyunbum Jang Kevin Harlen Anu Puri Ruth Nussinov Joel P. Schneider Robert Blumenthal 《Biophysical journal》2013
We have investigated the membrane destabilizing properties of synthetic amphiphilic cationic peptides, MAX1 and MAX35, which have the propensity to form β-hairpin structures under certain conditions, and a control non-β-hairpin-forming peptide MAX8V16E. All three peptides bind to liposomes containing a mixture of zwitterionic POPC and negatively charged POPS lipids as determined by Zeta potential measurements. Circular dichroism measurements indicated folding of MAX1 and MAX35 in the presence of the POPC/POPS liposomes, whereas no such folding was observed with MAX8V16E. There was no binding or folding of these peptides to liposomes containing only POPC. MAX1 and MAX35 induced release of contents from negatively charged liposomes, whereas MAX8V16E failed to promote solute release under identical conditions. Thus, MAX1 and MAX35 bind to, and fold at the surface of negatively charged liposomes adopting a lytic conformation. We ruled out leaky fusion as a mechanism of release by including 2 mol % PEG-PE in the liposomes, which inhibits aggregation/fusion but not folding of MAX or MAX-induced leakage. Using a concentration-dependent quenching probe (calcein), we determined that MAX-induced leakage of liposome contents was an all-or-none process. At MAX1 concentrations, which cause release of ∼50% of the liposomes that contain small (Rh <1.5 nm) markers, only ∼15% of those liposomes release a fluorescent dextran of 40 kDa. A multimeric model of the pore is presented based on these results. Atomistic molecular dynamics simulations show that barrels consisting of 10 β-hairpin MAX1 and MAX35 peptides are relatively more stable than MAX8V16E barrels in the bilayer, suggesting that barrels of this size are responsible for the peptides lytic action. 相似文献
23.
Anu Vehmaa Hedvig Hogfors Elena Gorokhova Andreas Brutemark Towe Holmborn Jonna Engström‐Öst 《Ecology and evolution》2013,3(13):4548-4557
Zooplankton are an important link between primary producers and fish. Therefore, it is crucial to address their responses when predicting effects of climate change on pelagic ecosystems. For realistic community‐level predictions, several biotic and abiotic climate‐related variables should be examined in combination. We studied the combined effects of ocean acidification and global warming predicted for year 2100 with toxic cyanobacteria on the calanoid copepod, Acartia bifilosa. Acidification together with higher temperature reduced copepod antioxidant capacity. Higher temperature also decreased egg viability, nauplii development, and oxidative status. Exposure to cyanobacteria and its toxin had a negative effect on egg production but, a positive effect on oxidative status and egg viability, giving no net effects on viable egg production. Additionally, nauplii development was enhanced by the presence of cyanobacteria, which partially alleviated the otherwise negative effects of increased temperature and decreased pH on the copepod recruitment. The interactive effects of temperature, acidification, and cyanobacteria on copepods highlight the importance of testing combined effects of climate‐related factors when predicting biological responses. 相似文献
24.
Background
Visual cross-modal re-organization is a neurophysiological process that occurs in deafness. The intact sensory modality of vision recruits cortical areas from the deprived sensory modality of audition. Such compensatory plasticity is documented in deaf adults and animals, and is related to deficits in speech perception performance in cochlear-implanted adults. However, it is unclear whether visual cross-modal re-organization takes place in cochlear-implanted children and whether it may be a source of variability contributing to speech and language outcomes. Thus, the aim of this study was to determine if visual cross-modal re-organization occurs in cochlear-implanted children, and whether it is related to deficits in speech perception performance.Methods
Visual evoked potentials (VEPs) were recorded via high-density EEG in 41 normal hearing children and 14 cochlear-implanted children, aged 5–15 years, in response to apparent motion and form change. Comparisons of VEP amplitude and latency, as well as source localization results, were conducted between the groups in order to view evidence of visual cross-modal re-organization. Finally, speech perception in background noise performance was correlated to the visual response in the implanted children.Results
Distinct VEP morphological patterns were observed in both the normal hearing and cochlear-implanted children. However, the cochlear-implanted children demonstrated larger VEP amplitudes and earlier latency, concurrent with activation of right temporal cortex including auditory regions, suggestive of visual cross-modal re-organization. The VEP N1 latency was negatively related to speech perception in background noise for children with cochlear implants.Conclusion
Our results are among the first to describe cross modal re-organization of auditory cortex by the visual modality in deaf children fitted with cochlear implants. Our findings suggest that, as a group, children with cochlear implants show evidence of visual cross-modal recruitment, which may be a contributing source of variability in speech perception outcomes with their implant. 相似文献25.
We briefly introduce the most common lysosomal storage disorder, Gaucher disease, concisely describe the Food and Drug Administration approved strategies to ameliorate Gaucher disease, and then outline the emerging pharmacologic chaperone strategy that offers the promise to remedy this malady. 相似文献
26.
A mixture of 4-chloro-1-butanol and 2,2,2-Trifluoroethanol (TFE) has been used to generate Molten globule (MG) state of structurally
homologous but functionally different proteins bovine α-lactalbumin and hen egg-white lysozyme. The thermal denaturation was
done using UV–Visible spectroscopy. From UV–Visible profile, thermal transition was not observed beyond a particular concentration.
There was an indication of molten globule state in case of α-lactalbumin from circular dichroism experiments. By intrinsic
tryptophan fluorescence, acrylamide and potassium iodide quenching, 8-anilino-naphthalene sulfonic acid (ANS) binding and
energy transfer studies the presence of molten globule state was confirmed. Quantitative characterization of MG state and
determining the binding thermodynamics of ANS to the MG state was done using Isothermal Titration Calorimetry (ITC). Results
show that α-lactalbumin exists in MG state at a particular concentration but lysozyme does not show features of MG state. 相似文献
27.
Anu Manhas Dhaval Patel Mohsin Y. Lone Prakash C. Jha 《Journal of cellular biochemistry》2019,120(9):14531-14543
In the present contribution, multicomplex-based pharmacophore studies were carried out on the structural proteome of Plasmodium falciparum 1-deoxy-D -xylulose-5-phosphate reductoisomerase. Among the constructed models, a representative model with complementary features, accountable for the inhibition was used as a primary filter for the screening of database molecules. Auxiliary evaluations of the screened molecules were performed via drug-likeness and molecular docking studies. Subsequently, the stability of the docked inhibitors was envisioned by molecular dynamics simulations, principle component analysis, and molecular mechanics-Poisson-Boltzmann surface area-based free binding energy calculations. The stability assessment of the hits was done by comparing with the reference (beta-substituted fosmidomycin analog, LC5) to prioritize more potent candidates. All the complexes showed stable dynamic behavior while three of them displayed higher binding free energy compared with the reference. The work resulted in the identification of the compounds with diverse scaffolds, which could be used as initial leads for the design of novel PfDXR inhibitors. 相似文献
28.
Ann-Helen Rosendahl Mia Monnius Anu Laitala Antti Railo Ilkka Miinalainen Ritva Heljasvaara Joni M. Mki Johanna Myllyharju 《The Journal of biological chemistry》2022,298(4)
Hypoxia-inducible factors (HIFs) induce numerous genes regulating oxygen homeostasis. As oxygen sensors of the cells, the HIF prolyl 4-hydroxylases (HIF-P4Hs) regulate the stability of HIFs in an oxygen-dependent manner. During hair follicle (HF) morphogenesis and cycling, the location of dermal papilla (DP) alternates between the dermis and hypodermis and results in varying oxygen levels for the DP cells. These cells are known to express hypoxia-inducible genes, but the role of the hypoxia response pathway in HF development and homeostasis has not been studied. Using conditional gene targeting and analysis of hair morphogenesis, we show here that lack of Hif-p4h-2 in Forkhead box D1 (FoxD1)-lineage mesodermal cells interferes with the normal HF development in mice. FoxD1-lineage cells were found to be mainly mesenchymal cells located in the dermis of truncal skin, including those cells composing the DP of HFs. We found that upon Hif-p4h-2 inactivation, HF development was disturbed during the first catagen leading to formation of epithelial-lined HF cysts filled by unorganized keratins, which eventually manifested as truncal alopecia. Furthermore, the depletion of Hif-p4h-2 led to HIF stabilization and dysregulation of multiple genes involved in keratin formation, HF differentiation, and HIF, transforming growth factor β (TGF-β), and Notch signaling. We hypothesize that the failure of HF cycling is likely to be mechanistically caused by disruption of the interplay of the HIF, TGF-β, and Notch pathways. In summary, we show here for the first time that HIF-P4H-2 function in FoxD1-lineage cells is essential for the normal development and homeostasis of HFs. 相似文献
29.
Impact of hypoglycemia and diabetes on CNS: correlation of mitochondrial oxidative stress with DNA damage 总被引:3,自引:0,他引:3
Oxidative stress plays an important role in tissue damage caused by hypoglycemia and diabetes, which may be the result of deterioration in glucose homeostasis caused by these metabolic disorders. The present study examined the effects of insulin-induced hypoglycemia and streptozotocin induced diabetes on mitochondrial lipid peroxidation and antioxidant enzymes from different brain regions, namely, cerebral hemispheres, cerebellum, brain stem and diencephalon. In situ localization of DNA single strand breaks (SSBs) were also studied by DNA polymerase-I mediated biotin dATP labeled nick translation method after inducing hypoglycemia and diabetes. Significant decrease in mitochondrial catalase, manganese superoxide-dismutase (Mn-SOD) and reduced glutathione (GSH) content and increase in the lipid peroxidation (LPx) and glutathione peroxidase (GPx) activity was observed under these metabolic stress conditions with more pronounced effects in hypoglycemic group. We conclude that during severe energy deprivation following hypoglycemia and diabetes, mitochondrial free radicals scavenger system is down regulated, which leads to reactive oxygen species (ROS) generation. High levels of ROS in turn activate the processes leading to DNA damage. DNA SSBs, which indicates nuclear disintegration is an important feature of neuronal cell death. 相似文献
30.
This study tests whether crown and stem development in Norway spruce could be described using a modified profile theory. 29 trees from three age-groups (25, 67, 86) with different treatments (unthinned, normally and intensively thinned) were destructively sampled. Crown ratio and crown length varied between age groups and treatments. Crown width was positively correlated with crown length, but branch length along the crown depended on tree age and growing space. Foliage mass density peaked at a relative crown height of 50–70% in middle-aged and mature stands, while young crowns were densest and widest at the base. Foliage mass was predictable from branch and stem cross-sectional area, provided the distance from the top was included. The ratio of foliage mass to branch cross-sectional area increased for 2–4 m down from the tip of the crown, then started to decrease. The relationship between cumulative foliage mass and stem cross-sectional area was non-linear along the stem in the upper crown, but the ratio of cumulative branch to stem cross-sectional area was linear. Trees in the mature and unthinned stands had more cross-sectional area in branches relative to stems than in the young and thinned stands. We conclude that the profile theory needs modification regarding (1) crown shape which varies with age and growing space, and (2) the ratio of foliage mass to branch area which varies along the stem. Both aspects emphasise the need to include impacts of disuse of sapwood pipes in models of crown and stem development. 相似文献