3D hollow hybrid composites with ultrafine cobalt sulfide nanoparticles uniformly embedded within the well‐graphitized porous carbon polyhedra/carbon nanotubes framework are rationally fabricated ...using a green and one‐step method involving the simultaneous pyrolysis and sulfidation of ZIF‐67. Because of the synergistic coupling effects favored by the unique nanohybridization, these composites exhibit high specific capacity, excellent cycle stability, and superior rate capability when evaluated as electrodes in lithium‐ion batteries.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cerebral autoregulation describes a mechanism that maintains cerebral blood flow stable despite fluctuating perfusion pressure. Multiple nonperfusion pressure processes also regulate cerebral ...perfusion. These mechanisms are integrated. The effect of the interplay between carbon dioxide and perfusion pressure on cerebral circulation has not been specifically reviewed. On the basis of the published data and speculation on the aspects that are without supportive data, the authors offer a conceptualization delineating the regulation of cerebral autoregulation by carbon dioxide. The authors conclude that hypercapnia causes the plateau to progressively ascend, a rightward shift of the lower limit, and a leftward shift of the upper limit. Conversely, hypocapnia results in the plateau shifting to lower cerebral blood flows, unremarkable change of the lower limit, and unclear change of the upper limit. It is emphasized that a sound understanding of both the limitations and the dynamic and integrated nature of cerebral autoregulation fosters a safer clinical practice.
Members of the Prdm family are characterized by an N-terminal PR domain that is related to the SET methyltransferase domain, and multiple zinc fingers that mediate sequence-specific DNA binding and ...protein-protein interactions. Prdm factors either act as direct histone methyltransferases or recruit a suite of histone-modifying enzymes to target promoters. In this way, they function in many developmental contexts to drive and maintain cell state transitions and to modify the activity of developmental signalling pathways. Here, we provide an overview of the structure and function of Prdm family members and discuss the roles played by these proteins in stem cells and throughout development.
Highlights • We highlight a novel memory network, using evidence from multiple MRI methods. • We term this network the parietal memory network (PMN). • PMN regions deactivate to novel, but activate ...to familiar, stimuli. • This network sits adjacent to, but is distinct from, the default mode network.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina ...propria CD11b+ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24+CD64− DCs and contaminating CSF-1R-dependent CD24−CD64+ macrophages. Functionally, loss of CD24+CD11b+ DCs abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state and after Aspergillus fumigatus challenge. Human CD1c+ DCs, the equivalent of murine CD24+CD11b+ DCs, also expressed IRF4, secreted IL-23, and promoted T helper 17 cell responses. Our data revealed heterogeneity in the mouse CD11b+ DC compartment and identifed mucosal tissues IRF4-expressing DCs specialized in instructing IL-17 responses in both mouse and human. The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in vivo findings to advance DC-based clinical therapies.
•Mucosal CD11b+ DCs consist of CD24+CD64− DCs and CD24−CD64+ macrophages•Mucosal CD24+CD11b+ DCs are IRF4-dependent•IRF4-dependent CD24+CD11b+ DCs secrete IL-23α and control mucosal IL-17 responses•Human CD1c+CD11b+ DCs are functional homologs of murine CD24+CD11b+ DCs
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cerebral blood flow (CBF) is rigorously regulated by various powerful mechanisms to safeguard the match between cerebral metabolic demand and supply. The question of how a change in cardiac output ...(CO) affects CBF is fundamental, because CBF is dependent on constantly receiving a significant proportion of CO. The authors reviewed the studies that investigated the association between CO and CBF in healthy volunteers and patients with chronic heart failure. The overall evidence shows that an alteration in CO, either acutely or chronically, leads to a change in CBF that is independent of other CBF-regulating parameters including blood pressure and carbon dioxide. However, studies on the association between CO and CBF in patients with varying neurologic, medical, and surgical conditions were confounded by methodologic limitations. Given that CBF regulation is multifactorial but the various processes must exert their effects on the cerebral circulation simultaneously, the authors propose a conceptual framework that integrates the various CBF-regulating processes at the level of cerebral arteries/arterioles while still maintaining autoregulation. The clinical implications pertinent to the effect of CO on CBF are discussed. Outcome research relating to the management of CO and CBF in high-risk patients or during high-risk surgeries is needed.
Resting state functional MRI (fMRI) has enabled description of group-level functional brain organization at multiple spatial scales. However, cross-subject averaging may obscure patterns of brain ...organization specific to each individual. Here, we characterized the brain organization of a single individual repeatedly measured over more than a year. We report a reproducible and internally valid subject-specific areal-level parcellation that corresponds with subject-specific task activations. Highly convergent correlation network estimates can be derived from this parcellation if sufficient data are collected—considerably more than typically acquired. Notably, within-subject correlation variability across sessions exhibited a heterogeneous distribution across the cortex concentrated in visual and somato-motor regions, distinct from the pattern of intersubject variability. Further, although the individual’s systems-level organization is broadly similar to the group, it demonstrates distinct topological features. These results provide a foundation for studies of individual differences in cortical organization and function, especially for special or rare individuals.
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•Single-subject areal parcellation is reproducible, valid, and convergent with task•Highly reliable correlation estimates require considerable data•Within-subject correlation is most variable in visual and somatosensory cortex•Individuals exhibit topological features distinct from group system organization
Resting state functional MRI allows non-invasive analysis of functional brain organization at multiple spatial scales. Laumann et al. report areal and system organization in a highly sampled human and demonstrate that an individual exhibits topological features distinct from group-level system organization.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A novel, efficient and green MOFs-templated sulfidation route has been developed to synthesize Cu(1.96)S-C hybrid composites, in which ultrafine Cu(1.96)S nanoparticles are embedded uniformly within ...porous carbon octahedra. The as-synthesized composites exhibit high specific capacitance and good cycling performance in supercapacitors.
In recent years, there has been a surge in the research and development of novel molecules as potential therapeutic alternatives to traditional treatments (such as intravenous immunoglobulins) for ...autoimmune disorders. The aim of this review is to describe different drug development strategies and evaluate how various molecules have performed in clinical trials to date. Broadly, three main approaches have been pursued. Recombinant fragment crystallisable (rFc) multimers primarily target Fcγ receptors (FcγRs) but may also affect the complement system. These include PF-06755347 (GL-2045), CSL730 (M230), CSL777 and Pan Fc Receptor Interacting Molecule (PRIM). Neonatal Fc receptor (FcRn)-targeting therapeutics block the FcRn receptor and are represented by candidate drugs such as the Fc fragment efgartigimod and the monoclonal antibodies rozanolixizumab (UCB7665), M281 and SYNT001. Finally, Fc and FcγR-targeting therapeutics, comprise molecules that target the Fc of IgG, such as the recombinant soluble FcγIIb receptor valziflocept (SM101/SHP652) and various monoclonal antibodies directed against the receptors. The developmental status of these three classes of molecules ranges from preclinical to ongoing phase 3 clinical studies. Efgartigimod and rozanolixizumab are the most advanced and have demonstrated encouraging results from phase 2 trials in immune thrombocytopenia and myasthenia gravis. Although initial results are promising, further long-term data and a better understanding of the unique mechanisms of action of the different molecules are needed. The efficacy, safety, convenience of administration, duration of effects, and cost will all contribute to determining which of the molecules will be successful in the clinic.
•Next-generation treatments for immune-complex mediated autoimmune diseases are on the horizon.•Approaches include recombinant molecules targeting the Fcγ and neonatal Fc receptor.•Results from clinical trials have been encouraging, but more data are needed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
One of the most controversial practices in resting-state fMRI functional connectivity studies is whether or not to regress out the global average brain signal (GS) during artifact removal. Some ...groups have argued that it is absolutely essential to regress out the GS in order to fully remove head motion, respiration, and other global imaging artifacts. Others have argued that removing the GS distorts the resulting correlation matrices and inappropriately alters the results of group comparisons and relationships to behavior. At the core of this argument is the assessment of dimensionality in terms of the number of brain networks with uncorrelated time series. If the dimensionality is high, then the distortions due to GS removal could be effectively negligible. In the current paper, we examine the dimensionality of resting-state fMRI data using principal component analyses (PCA) and network clustering analyses. In two independent datasets (Set 1: N = 62, Set 2: N = 32), scree plots of the eigenvalues level off at or prior to 10 principal components, with prominent elbows at 3 and 7 components. While network clustering analyses have previously demonstrated that numerous networks can be distinguished with high thresholding of the voxel-wise correlation matrices, lower thresholding reveals a lower-dimensional hierarchical structure, with the first prominent branch at 2 networks (corresponding to the previously described “task-positive"/"task-negative” distinction) and further stable subdivisions at 4, 7 and 17. Since inter-correlated time series within these larger branches do not cancel to zero when averaged, the hierarchical nature of the correlation structure results in low effective dimensionality. Consistent with this, partial correlation analyses revealed that network-specific variance remains present in the GS at each level of the hierarchy, accounting for at least 14–18% of the overall GS variance in each dataset. These results demonstrate that GS regression is expected to remove substantial portions of network-specific brain signals along with artifacts, not simply whole-brain signals corresponding to arousal levels. We highlight alternative means of controlling for residual global artifacts when not removing the GS.
•Dimensionality of resting-state fMRI data is quantified using PCA.•Dimensionality is found to be low (<10), despite many distinguishable networks.•Networks are organized in low-order hierarchy with “task-positive/negative” at top.•As a result, network-specific sources remain in global signal at ~14–18% of variance.•We highlight alternative, covariate-based approaches to residual global artifacts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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