We investigated how the microstructure of relevant white matter connections is associated with cortical responsivity and working memory (WM) performance by collecting diffusion tensor imaging and ...verbal WM functional magnetic resonance imaging data from 29 young adults. We measured cortical responsivity within the frontoparietal WM network as the difference in blood oxygenation level-dependent (BOLD) signal between 3-back and 1-back conditions. Fractional anisotropy served as an index of the integrity of the superior longitudinal fasciculi (SLF), which connect frontal and posterior regions. We found that SLF integrity is associated with better 3-back performance and greater task-related BOLD responsivity. In addition, BOLD responsivity in right premotor cortex reliably mediated the effects of SLF integrity on 3-back performance but did not uniquely predict 3-back performance after controlling for individual differences in SLF integrity. Our results suggest that task-related adjustments of local gray matter processing are conditioned by the properties of anatomical connections between relevant cortical regions. We suggest that the microarchitecture of white matter tracts influences the speed of signal transduction along axons. This in turn may affect signal summation at neural dendrites, action potential firing, and the resulting BOLD signal change and responsivity.
Src homology 2 (SH2) domains are the largest family of interaction modules encoded by the human genome to recognize tyrosine-phosphorylated sequences and thereby play pivotal roles in transducing and ...controlling cellular signals emanating from protein-tyrosine kinases. Different SH2 domains select for distinct phosphopeptides, and the function of a given SH2 domain is often dictated by the specific motifs that it recognizes. Therefore, deciphering the phosphotyrosyl peptide motif recognized by an SH2 domain is the key to understanding its cellular function. Here we cloned all 120 SH2 domains identified in the human genome and determined the phosphotyrosyl peptide binding properties of 76 SH2 domains by screening an oriented peptide array library. Of these 76, we defined the selectivity for 43 SH2 domains and refined the binding motifs for another 33 SH2 domains. We identified a number of novel binding motifs, which are exemplified by the BRDG1 SH2 domain that selects specifically for a bulky, hydrophobic residue at P + 4 relative to the Tyr(P) residue. Based on the oriented peptide array library data, we developed scoring matrix-assisted ligand identification (or SMALI), a Web-based program for predicting binding partners for SH2-containing proteins. When applied to SH2D1A/SAP (SLAM-associated protein), a protein whose mutation or deletion underlies the X-linked lymphoproliferative syndrome, SMALI not only recapitulated known interactions but also identified a number of novel interacting proteins for this disease-associated protein. SMALI also identified a number of potential interactors for BRDG1, a protein whose function is largely unknown. Peptide in-solution binding analysis demonstrated that a SMALI score correlates well with the binding energy of a peptide to a given SH2 domain. The definition of the specificity space of the human SH2 domain provides both the necessary molecular basis and a platform for future exploration of the functions for SH2-containing proteins in cells.
Abstract
Previous research has demonstrated reduction in cortical and subcortical, including basal ganglia (BG), gray matter volumes (GMV) in individuals with attention deficit hyperactivity disorder ...(ADHD), a neurodevelopmental condition that is more prevalent in males than in females. However, the volumetric deficits vary across studies. Whether volumetric reductions are more significant in males than females; to what extent these neural markers are heritable and relate to cognitive dysfunction in ADHD remain unclear. To address these questions, we followed published routines and performed voxel-based morphometry analysis of a data set (n = 11,502; 5,464 girls, 9–10 years) curated from the Adolescent Brain Cognition Development project, a population-based study of typically developing children. Of the sample, 634 and 2,826 were identified as monozygotic twins and dizygotic twins/siblings, respectively. In linear regressions, a cluster in the hypothalamus showed larger GMV, and bilateral caudate and putamen, lateral orbitofrontal and occipital cortex showed smaller GMVs, in correlation with higher ADHD scores in girls and boys combined. When examined separately, boys relative to girls showed more widespread (including BG) and stronger associations between GMV deficits and ADHD scores. ADHD traits and the volumetric correlates demonstrated heritability estimates (
a
2
) between 0.59 and 0.79, replicating prior findings of the genetic basis of ADHD. Further, ADHD traits and the volumetric correlates (except for the hypothalamus) were each negatively and positively correlated with N-back performance. Together, these findings confirm volumetric deficits in children with more prominent ADHD traits. Highly heritable in both girls and boys and potentially more significant in boys than in girls, the structural deficits underlie diminished capacity in working memory and potentially other cognitive deficits in ADHD.
Energy harvesting devices based on the triboelectric and piezoelectric principles have been widely developed to scavenge wasteful and tiny mechanical energy into usable electrical energy. In ...particular, triboelectric energy harvesting generators with relatively simpler structure and piezoelectric fiber-based counterpart with extremely light weight compositions showed a very promising application in the self-powered sensors. In this paper, a novel hybridization of graphenebased piezoelectric generator (GBPG) and graphene-PET triboelectric generator (GPTG) were simultaneously packaged. The integrated structure, graphene-based hybridized self-powered sensor (GHSPS), was demonstrated to be optically transparent and mechanically robust. For the piezoelectrically harvesting device, an in-situ poling and direct-write near-field electrospinning (NFES) Poly(vinylidene fluoride) (PVDF) piezoelectric fibers were fabricated and integrated with a single layer chemical vapor deposition (CVD) grown graphene. On the other hand for GPTG counterpart, two composite layers of a single layer graphene/PET simultaneously served as triboelectrically rubbing layers as well as bottom/top electrode. This GHSPS successfully superimposed both piezoelectric and triboelectric electricity and the synergistically higher output voltage/current/power were measured as ~6 V/280 nA/172 nW in one press-and-release cycle of finger induced motion. The proposed GHSPS showed a promising application in the field of self-powered sensors to be ubiquitously implemented in the future Industry 4.0 scenarios.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In vitro models are available as alternatives for the Draize eye irritation test. However, most of the alternative models are not quantitative nor designed to evaluate the effects of chemicals on the ...corneal barrier such as those encountered in pharmaceutical and cosmetic products. The objective of the present study was to investigate tissue electrical resistance to provide sensitive in vitro testing of tissue alteration caused by chemicals in pharmaceutical and cosmetic formulations as a potential eye irritation testing approach. The experimental protocols for effective tissue resistance measurements were examined using two in vitro eye models: porcine cornea and EpiCorneal. In these models, a test chemical was applied to the cornea or EpiCorneal tissue for 1 min, and tissue resistances/conductances were measured at 1–60 min after the application. The changes in conductance of the tissues after exposure to the chemicals were shown to provide quantitative evaluations to the influence of the chemicals. A correlation was found between the two in vitro models. The results suggest that these models can provide quantitative in vitro assessments of eye-irritating chemicals.
•Tissue electrical resistance can provide quantitative assessment of cornea alteration.•A reasonable correlation was observed between porcine cornea and EpiCorneal models.•The models can identify chemical solutions that affect the corneal barrier.•The models can differentiate cornea alteration caused by different chemical concentration.
Plasmodium vivax remains an important cause of malaria in South America and the Asia-Pacific. Naturally acquired antibody responses against multiple P. vivax proteins have been described in numerous ...countries, however, direct comparison of these responses has been difficult with different methodologies employed. We measured antibody responses against 307 P. vivax proteins at the time of P. vivax infection, and at 2-3 later time-points in three countries. We observed that seropositivity rates at the time of infection were highest in Thailand, followed by Brazil then PNG, reflecting the level of antigenic input. The majority of sero-reactive antigens in all sites induced short-lived antibody responses with estimated half-lives of less than 6 months, although there was a trend towards longer-lived responses in PNG children. Despite these differences, IgG seropositivity rates, magnitude and longevity were highly and significantly rank-correlated between the different regions, suggesting such features are reflective of the individual protein.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study investigated the effects of placement of N at different soil depths on CH
4
emissions and related microbial communities in no-tillage paddy soil. Five fertilizing treatments, including no ...N fertilizer, N surface broadcasting, and N deep placement at the soil depths of 5 cm, 10 cm, and 20 cm were applied in the paddy field. The composition of main microbial groups were determined using phospholipid fatty acid (PLFA) analysis. The absolute real-time quantitative PCR was applied to determine the abundance of the methanogenic and methanotrophic populations with
mcrA
,
pmoA
,
mmoX
, and
mxaF
as the functional gene markers. Compared with N surface broadcasting, the deep placement of N (i) significantly increased the microbial biomass carbon (C) and dissolved organic C by 7–90% and 6–75%, respectively; (ii) significantly enhanced the amount of the total PLFAs by 12–70% and the bacterial PLFAs by 15–82%; (iii) significantly mitigated the CH
4
emissions by 6–39%; and (iv) significantly enhanced the abundance of the methanogenic and methanotrophic populations by 16–55% and 13–210%, respectively. The percent changes varied over a wide range due to different N placement depths as well as the seasonal variations. Moreover, structural equation modeling revealed that N deep placement directly or indirectly affected the CH
4
-related microbial communities through the increased labile soil organic C fractions by activating plant growth and soil microbial abundance, thereby mitigating the CH
4
emissions in no-tillage paddy soil.
Mutations in isocitrate dehydrogenases (IDHs) have a gain‐of‐function effect leading to R(−)‐2‐hydroxyglutarate (R‐2HG) accumulation. By using biochemical, structural and cellular assays, we show ...that either or both R‐ and S‐2HG inhibit 2‐oxoglutarate (2OG)‐dependent oxygenases with varying potencies. Half‐maximal inhibitory concentration (IC50) values for the R‐form of 2HG varied from approximately 25 μM for the histone Nε‐lysine demethylase JMJD2A to more than 5 mM for the hypoxia‐inducible factor (HIF) prolyl hydroxylase. The results indicate that candidate oncogenic pathways in IDH‐associated malignancy should include those that are regulated by other 2OG oxygenases than HIF hydroxylases, in particular those involving the regulation of histone methylation.
The oncometabolite 2‐hydroxyglutarate (2‐HG) inhibits chromatin‐modifying oxygenases (as histone lysine demethylases) with greater potency than HIF hydroxylases. This suggests that 2‐HG‐associated oncogenic pathways involve the regulation of histone methylation, rather than an elevated HIF response.
PDF
