188 research outputs found
Our energy-Ca2+ signaling deficits hypothesis and its explanatory potential for key features of Alzheimer’s disease
No full textAlzheimer’s disease (AD) has not been explained by any current theories, so new hypotheses are urgently needed. We proposed that energy and Ca2+ signaling deficits are perhaps the earliest modifiable defects in brain aging underlying memory decline and tau deposits (by means of inactivating Ca2+-dependent protease calpain). Consistent with this hypothesis, we now notice that at least eight other known calpain substrates have also been reported to accumulate in aging and AD. Thus, protein accumulation or aggregation is not an accidental or random event, but occurs naturally and selectively to a peculiar family of proteins, corroborating the proposed changes of calpain. Why are only calpain substrates accumulated and how can they stay for decades in the brain without being attacked by many other non-specific proteases there? We believe that these long-lasting puzzles can be explained by calpain’s unique properties, especially its unusual specificity and exclusivity in substrate recognition, which can protect the substrates from other proteases’ attacks after calpain inactivation. Interestingly, the energy-Ca2+ deficits model, in essence, may also explain tau phosphorylation (by calcineurin inactivation) and the formation of amyloid plaques. Our studies suggest that α-secretase is an energy-/Ca2+-dual dependent protease and is also the primary determinant for Aβ levels. Finally we discuss why β- and γ-secretases, the current enthusiastic study focuses, are unlikely to be responsible for Aβ genesis or be positively identified by biological laws. Overall, the study suggests that our hypothesis can coherently explain several basic AD features, thus pointing to a new strategy for AD prevention
The maze of APP processing in Alzheimer’s disease: Where did we go wrong in reasoning?
No full textLate onset sporadic Alzheimer’s disease (sAD) has remained a conundrum after vigorous studies today, and the main reason is the stagnation in understanding the mechanism of origins of plaques and tangles. While they are widely thought to be the culprits of the disease or products of the aberrant pathways, we believe that plaques and tangles result from natural aging. From this new perspective we have proposed that age-related inefficiency of α-secretase is the underpinning for Aβ overproduction. This view contrasts sharply with the current doctrine that Aβ overproduction is the product of the overactivated β- and γ-secretases. Following this doctrine it has been claimed that the two secretases are positively identified and that their inhibitors have successfully reduced Aβ levels. But, why have these studies not led to the understanding of the disease? And if so where did they go off course in reasoning? These questions touch the basics of biological science and must be answered. In this paper I dissected several prevailing assumptions and influential reports with an attempt to trace the origins of the conundrum. This work led me to a new model for Aβ overproduction and also to a serious question: given the knowledge that boosting α-secretase reduces Aβ, a straightforward highway for intervention, then why is there such an obsession on inhibiting β- and γ-secretases, a much more costly and twisting road even if possible? This issue requires the attention of policymakers and all researchers. I therefore call for a game change in sAD study
Structure and function of SLC4 family HCO3– transporters
No full textThe SLC4 family contains 10 members, nine of which are HCO3– transporters, including three Na+-independent Cl−/HCO3– exchangers AE1, AE2, and AE3, five Na+-coupled HCO3– transporters NBCe1, NBCe2, NBCn1, NBCn2, and NDCBE, as well as AE4 whose Na+-dependence remains controversial. The SLC4 HCO3– transporters play critical roles in pH regulation and transepithelial movement of electrolytes with a broad range of physiological relevances. Dysfunctions of these transporters are associated with a series of human diseases. During the past decades, tremendous amount of efforts have been undertaken to investigate the topological organization of the SLC4 transporters in the plasma membrane. Based upon the proposed topology models, mutational and functional studies have identified important structural elements likely involved in the ion translocation by the SLC4 transporters. In the present article, we will review the advances during the past decades in understanding the structure and function of the SLC4 transporters
Interfacial Reaction Dependent Performance of Hollow Carbon NanoSphere – Sulfur composite as a cathode for Li-S battery
No full textLithium-sulfur (Li-S) battery is a promising energy storage system due to its high energy density, cost effectiveness and environmental friendliness of sulfur. However, there are still a number of technical challenges, such as low Coulombic efficiency and poor long-term cycle life, impeding the commercialization of Li-S battery. The electrochemical performance of Li-S battery is closely related with the interfacial reactions occurring between hosting substrate and active sulfur species which are poorly conducting at fully oxidized and reduced states. Here, we correlate the relationship between the performance and interfacial reactions in the Li-S battery system, using a hollow carbon nanosphere (HCNS) with highly graphitic character as hosting substrate for sulfur. With an appropriate amount of sulfur loading, HCNS/S composite exhibits excellent electrochemical performance because of the fast interfacial reactions between HCNS and the polysulfides. However, further increase of sulfur loading leads to increased formation of highly resistive insoluble reaction products (Li2S2/Li2S) which limits the reversibility of the interfacial reactions and results in poor electrochemical performances. These findings demonstrate the importance of the interfacial reaction reversibility in the whole electrode system on achieving high capacity and long cycle life of sulfur cathode for Li-S batteries
How many neural oscillators we need on sub- and supra-second intervals processing in the primate brain: comments on Gupta (2014)-Frontiers in psychology: Perception Science
No full textPsychology, MultidisciplinaryPubMedSSCI0EDITORIAL [email protected]
Characterization of a novel zinc transporter ZnuA acquired by Vibrio parahaemolyticus through horizontal gene transfer
No full textVibrio parahaemolyticus is a clinically important foodborne pathogen that causes acute gastroenteritis worldwide. It has been shown that horizontal gene transfer contributes significantly to virulence development of V. parahaemolyticus. In this study, we identified a novel znuA homologue (vpa1307) that belongs to a novel subfamily of ZnuAm, a bacterial zinc transporter. The vpa1307 gene is located upstream of the V. parahaemolyticus pathogenicity island (Vp-PAIs) in both tdh-positive and trh-positive V. parahaemolyticus strains. Phylogenetic analysis revealed the exogenous origin of vpa1307 with 40% of V. parahaemolyticus clinical isolates possessing this gene. The expression of vpa1307 gene in V. parahaemolyticus clinical strain VP3218 is induced under zinc limitation condition. Gene deletion and complementation assays confirmed that vpa1307 contributes to the growth of VP3218 under zinc depletion condition and that conserved histidine residues of Vpa1307 contribute to its activity. Importantly, vpa1307 contributes to the cytotoxicity of VP3218 in HeLa cells and a certain degree of virulence in murine model. These results suggest that the horizontally acquired znuA subfamily gene, vpa1307, contributes to the fitness and virulence of Vibrio species
Perception of visual apparent motion is modulated by a gap within concurrent auditory glides, even when it is illusory
No full textAuditory and visual events often happen concurrently, and how they group together can have a strong effect on what is perceived. We investigated whether/how intra- or cross-modal temporal grouping influenced the perceptual decision of otherwise ambiguous visual apparent motion. To achieve this, we juxtaposed auditory gap transfer illusion with visual Ternus display. The Ternus display involves a multi-element stimulus that can induce either of two different percepts of apparent motion: ‘element motion’ or ‘group motion’. In element motion, the endmost disk is seen as moving back and forth while the middle disk at the central position remains stationary; while in group motion, both disks appear to move laterally as a whole. The gap transfer illusion refers to the illusory subjective transfer of a short gap (around 100 ms) from the long glide to the short continuous glide when the two glides intercede at the temporal middle point. In our experiments, observers were required to make a perceptual discrimination of Ternus motion in the presence of concurrent auditory glides (with or without a gap inside). Results showed that a gap within a short glide imposed a remarkable effect on separating visual events, and led to a dominant perception of group motion as well. The auditory configuration with gap transfer illusion triggered the same auditory capture effect. Further investigations showed that visual interval which coincided with the gap interval (50-230 ms) in the long glide was perceived to be shorter than that within both the short glide and the ‘gap-transfer’ auditory configurations in the same physical intervals (gaps). The results indicated that auditory temporal perceptual grouping takes priority over the cross-modal interaction in determining the final readout of the visual perception, and the mechanism of selective attention on auditory events also plays a role
Transcriptome analysis of differentially expressed genes involved in proanthocyanidin accumulation in the rhizomes of Fagopyrum dibotrys and an irradiation-induced mutant
No full textThe rhizome of Fagopyrum dibotrys is a traditional Chinese medicine that has recently gained attention due to substantial findings regarding its bioactive proanthocyanidin (PA) compounds. However, the molecular mechanism underlying PA accumulation in F.dibotrys remains elusive. We previously obtained an irradiation-induced mutant (RM_R) of F.dibotrys that had a higher PA content compared to that of the wild-type (CK_R). The present study aimed to elucidate the molecular mechanism underlying PA accumulation in F. dibotrys by comparing the rhizome transcriptomes of the irradiation-induced mutant and wild-type using RNA-seq analysis. A total of 53,540 unigenes were obtained, of which 29,901 (55.84%) were annotated based on BLAST searches against public databases, and 501 unique sequences were differentially expressed between the two samples, which consisted of 204 upregulated and 297 down regulated unigenes. Further analysis showed that the expression patterns of some unigenes encoding enzymes involved in PAs biosynthesis in F.dibotrys rhizomes differed between RM_R and CK_R. In addition, we identified transcription factor families and several cytochrome P450s that may be involved in PA regulation in F. dibotrys. Finally, 12 unigenes that encode PA biosynthetic enzymes were confirmed by qRT-PCR analysis. This study sheds light on the molecular mechanism underlying radiation-mediated flavonoid accumulation and regulation in F. dibotrys rhizomes. These results will also provide a platform for further functional genomic research on this particular species
Advanced phenotyping and phenotype data analysis for the plant growth and development study
No full textDue to increase in the consumption of food, feed, fuel and to ensure global food security for rapidly growing human population, there is need to breed high yielding crops that can adapt to future climate. To solve these global issues, novel approaches are required to provide quantitative phenotypes to elucidate the genetic basis of agriculturally import traits and to screen germplasm with super performance in function under resource-limited environment. At present, plant phenomics has offered and integrated suite technologies for understanding the complete set of phenotypes of plants, towards the progression of the full characteristics of plants with whole sequenced genomes. In this aspect, high-throughput phenotyping platforms have been developed that enables to capture extensive and intensive phenotype data from non-destructive imaging over time. These developments advance our view on plant growth and performance with responses to the changing climate and environment. In this paper, we present a brief review on currently developed high-throughput plant phenotyping infrastructures based on imaging techniques and corresponding principles for phenotype data analysis
Predicting individual brain maturity using dynamic functional connectivity
No full textNeuroimaging-based functional connectivity (FC) analyses have revealed significant developmental trends in specific intrinsic connectivity networks linked to cognitive and behavioral maturation. However, knowledge of how brain functional maturation is associated with FC dynamics at rest is limited. Here, we examined age-related differences in the temporal variability of FC dynamics with data publicly released by the Nathan Kline Institute (NKI) (n=183, ages 7-30) and showed that dynamic inter-region interactions can be used to accurately predict individual brain maturity across development. Furthermore, we identified a significant age-dependent trend underlying dynamic inter-network FC, including increasing variability of the connections between the visual network, default mode network (DMN) and cerebellum as well as within the cerebellum and DMN and decreasing variability within the cerebellum and between the cerebellum and DMN as well as the cingulo-opercular network. Overall, the results suggested significant developmental changes in dynamic inter-network interaction, which may shed new light on the functional organization of typical developmental brains
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