CA1 pyramidal cells (PCs) are not homogeneous but rather can be grouped by molecular, morphological, and functional properties. However, less is known about synaptic sources differentiating PCs. ...Using paired recordings in vitro, two-photon Ca2+ imaging in vivo, and computational modeling, we found that parvalbumin-expressing basket cells (PVBCs) evoked greater inhibition in CA1 PCs located in the deep compared to superficial layer of stratum pyramidale. In turn, analysis of reciprocal connectivity revealed more frequent excitatory inputs to PVBCs by superficial PCs, demonstrating bias in target selection by both the excitatory and inhibitory local connections in CA1. Additionally, PVBCs further segregated among deep PCs, preferentially innervating the amygdala-projecting PCs but receiving preferential excitation from the prefrontal cortex-projecting PCs, thus revealing distinct perisomatic inhibitory interactions between separate output channels. These results demonstrate the presence of heterogeneous PVBC-PC microcircuits, potentially contributing to the sparse and distributed structure of hippocampal network activity.
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•Nonuniform inhibition of pyramidal cells by parvalbumin-expressing basket cells•Biased excitation of PV basket cells by functionally distinct pyramidal cells•Routing of perisomatic inhibition by specialized network motifs•Specialized connectivity as basis for interactions between distinct output channels
The CA1 region consists of heterogeneous pyramidal cells. Lee et al. find that GABAergic, parvalbumin-expressing basket cells preferentially target specific subsets of pyramidal cells, while being selectively excited by other subsets, demonstrating nonuniform perisomatic inhibition of hippocampal output channels.
The Roles of Autophagy in Cancer Yun, Chul Won; Lee, Sang Hun
International journal of molecular sciences,
11/2018, Letnik:
19, Številka:
11
Journal Article
Recenzirano
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Autophagy is an intracellular degradative process that occurs under several stressful conditions, including organelle damage, the presence of abnormal proteins, and nutrient deprivation. The ...mechanism of autophagy initiates the formation of autophagosomes that capture degraded components and then fuse with lysosomes to recycle these components. The modulation of autophagy plays dual roles in tumor suppression and promotion in many cancers. In addition, autophagy regulates the properties of cancer stem-cells by contributing to the maintenance of stemness, the induction of recurrence, and the development of resistance to anticancer reagents. Although some autophagy modulators, such as rapamycin and chloroquine, are used to regulate autophagy in anticancer therapy, since this process also plays roles in both tumor suppression and promotion, the precise mechanism of autophagy in cancer requires further study. In this review, we will summarize the mechanism of autophagy under stressful conditions and its roles in tumor suppression and promotion in cancer and in cancer stem-cells. Furthermore, we discuss how autophagy is a promising potential therapeutic target in cancer treatment.
Over the past few decades, metal nanoparticles less than 100 nm in diameter have made a substantial impact across diverse biomedical applications, such as diagnostic and medical devices, for ...personalized healthcare practice. In particular, silver nanoparticles (AgNPs) have great potential in a broad range of applications as antimicrobial agents, biomedical device coatings, drug-delivery carriers, imaging probes, and diagnostic and optoelectronic platforms, since they have discrete physical and optical properties and biochemical functionality tailored by diverse size- and shape-controlled AgNPs. In this review, we aimed to present major routes of synthesis of AgNPs, including physical, chemical, and biological synthesis processes, along with discrete physiochemical characteristics of AgNPs. We also discuss the underlying intricate molecular mechanisms behind their plasmonic properties on mono/bimetallic structures, potential cellular/microbial cytotoxicity, and optoelectronic property. Lastly, we conclude this review with a summary of current applications of AgNPs in nanoscience and nanomedicine and discuss their future perspectives in these areas.
Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease in the elderly and the patients suffer from uncontrolled movement disorders due to loss of dopaminergic (DA) ...neurons on substantia nigra pars compacta (SNpc). We previously reported that transplantation of human fetal midbrain-derived neural precursor cells restored the functional deficits of a 6-hydroxy dopamine (6-OHDA)-treated rodent model of PD but its low viability and ethical issues still remain to be solved. Albeit immune privilege and neural differentiation potentials suggest mesenchymal stem cells (MSCs) from various tissues including human placenta MSCs (hpMSCs) for an alternative source, our understanding of their therapeutic mechanisms is still limited. To expand our knowledge on the MSC-mediated PD treatment, we here investigated the therapeutic mechanism of hpMSCs and hpMSC-derived neural phenotype cells (hpNPCs) using a PD rat model. Whereas both hpMSCs and hpNPCs protected DA neurons in the SNpc at comparable levels, the hpNPC transplantation into 6-OHDA treated rats exhibited longer lasting recovery in motor deficits than either the saline or the hpMSC treated rats. The injected hpNPCs induced delta-like ligand (DLL)1 and neurotrophic factors, and influenced environments prone to neuroprotection. Compared with hpMSCs, co-cultured hpNPCs more efficiently protected primary neural precursor cells from midbrain against 6-OHDA as well as induced their differentiation into DA neurons. Further experiments with conditioned media from hpNPCs revealed that the secreted factors from hpNPCs modulated immune responses and neural protection. Taken together, both DLL1-mediated contact signals and paracrine factors play critical roles in hpNPC-mediated improvement. First showing here that hpMSCs and their neural derivative hpNPCs were able to restore the PD-associated deficits via dual mechanisms, neuroprotection and immunosuppression, this study expanded our knowledge of therapeutic mechanisms in PD and other age-related diseases.
Video-based eye tracking relies on locating pupil center to measure gaze positions. Although widely used, the technique is known to generate spurious gaze position shifts up to several degrees in ...visual angle because pupil centration can change without eye movement during pupil constriction or dilation. Since pupil size can fluctuate markedly from moment to moment, reflecting arousal state and cognitive processing during human behavioral and neuroimaging experiments, the pupil size artifact is prevalent and thus weakens the quality of the video-based eye tracking measurements reliant on small fixational eye movements. Moreover, the artifact may lead to erroneous conclusions if the spurious signal is taken as an actual eye movement. Here, we measured pupil size and gaze position from 23 human observers performing a fixation task and examined the relationship between these two measures. Results disclosed that the pupils contracted as fixation was prolonged, at both small (<16s) and large (∼4min) time scales, and these pupil contractions were accompanied by systematic errors in gaze position estimation, in both the ellipse and the centroid methods of pupil tracking. When pupil size was regressed out, the accuracy and reliability of gaze position measurements were substantially improved, enabling differentiation of 0.1° difference in eye position. We confirmed the presence of systematic changes in pupil size, again at both small and large scales, and its tight relationship with gaze position estimates when observers were engaged in a demanding visual discrimination task.
Abstract
Our perception is often attracted to what we have seen before, a phenomenon called ‘serial dependence.’ Serial dependence can help maintain a stable perception of the world, given the ...statistical regularity in the environment. If serial dependence serves this presumed utility, it should be pronounced when consecutive elements share the same identity when multiple elements spatially shift across successive views. However, such preferential serial dependence between identity-matching elements in dynamic situations has never been empirically tested. Here, we hypothesized that serial dependence between consecutive elements is modulated more effectively by the spatial correspondence in relative space than by that in absolute space because spatial correspondence in relative coordinates can warrant identity matching invariantly to changes in absolute coordinates. To test this hypothesis, we developed a task where two targets change positions in unison between successive views. We found that serial dependence was substantially modulated by the correspondence in relative coordinates, but not by that in absolute coordinates. Moreover, such selective modulation by the correspondence in relative space was also observed even for the serial dependence defined by previous non-target elements. Our findings are consistent with the view that serial dependence subserves object-based perceptual stabilization over time in dynamic situations.
Discrimination and quantification of trace amounts of steroid hormones in biological specimens are needed to elucidate their changing expression because their biological functions are responsible for ...the development and prevention of endocrine disorders. Although mass-spectrometry-based assays are most commonly recommended, development of a new type of highly sensitive and selective detection methods in clinical practices is needed. Here, we introduce a label-free type of terahertz molecule sensor capable of sensing and identifying progesterone and 17α-OH-progesterone selectively. Nanoslot-array-based sensing chips were used as launching pads for absorption cross-section enhancement of molecules at a reliable terahertz frequency. With use of nanoslots with resonances at 1.17 THz corresponding to intrinsic THz absorption resonance mode for progesterone and at 1.51 THz for 17α-OH-progesterone, respectively, each steroid shows prominent transmittance change in terms of its amount. In particular, the sensing performance has been much improved by controlling evaporation speed, in turn resulting in an efficient, homogeneous distribution of the molecules onto a sensing hot spot.
With the growing demand for the use of thin perforator flaps, obtaining knowledge on the superficial anatomy of perforators is imperative for stable flap elevation. Conventional modalities for ...perforator mapping fall short in providing such information. High-frequency ultrasound (HFUS), known for visualizing the superficially located anatomic structures, may potentially fill this void. This study aimed to evaluate the effectiveness of HFUS in the outcome of anterolateral thigh (ALT) and superficial circumflex iliac artery perforator (SCIP) flap-based reconstructions.
Consecutive patients who underwent free ALT or SCIP flap-based reconstruction from January 2021 to November 2022 were retrospectively reviewed. Perforator mapping was conducted using a handheld Doppler during the first year, while HFUS was used in the latter part. The two techniques were compared in terms of flap harvesting time and perfusion-related complication rates while considering the flap elevation plane.
In total, 123 cases were analyzed, including 82 ALT flaps (41 in each group) and 41 SCIP flaps (16 in the Doppler and 25 in the HFUS group). The time required for flap elevation exhibited a tendency to decrease in the HFUS group, with a significant difference observed in cases involving thin flap elevation (super-thin ALT flaps and pure-skin-perforator SCIP flaps). Compared with the Doppler group, the HFUS group demonstrated significantly lower rates of PRCs, particularly partial flap necrosis. This difference remained significant in multivariable analyses.
Our results suggest that HFUS might be an appealing modality for perforator mapping in cases requiring thin ALT and SCIP flap.
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•Struvite precipitation under changing ionic concentrations was investigated.•More than 90% struvite precipitation was observed for 300mg-NL−1 and 100mg-PL−1.•Ca2+ reduced the purity ...of the precipitated struvite crystals.•High nitrogen concentrations was effective for more P recovery.•Developed computation model well explained struvite precipitation.
A computational model was developed and applied to investigate struvite precipitation under different pH levels and ionic concentrations. Ionic species, including ammonium (NH4+), hydrogen phosphate (HPO42−), magnesium (Mg2+), calcium (Ca2+), and struvite, were incorporated into the proposed model. The unknown kinetic coefficients of struvite were identified from the experimental data. In this study, the kinetics of struvite precipitation, which combined the ionic reactions (NH4+/NH3 and HPO42−/H2PO4−) on the basis of pseudo-equilibrium conditions was parameterized. The experiments for model verification were conducted at a constant initial Mg/P ratio with changing ionic concentrations at pH levels of 8.7 and 9.7. The batch experiments showed high struvite precipitation (>90% for 300mg-NL−1 and 100mg-PL−1). The presence of Ca2+ (Ca2+/Mg2+ >0.5) in the reactors interfered with the formation and growth of struvite. The decrease in the pH level with the struvite precipitation verified the simulation data. The model also confirmed the optimal ionic conditions in order to maximize the struvite precipitation (300mg-PL−1, and N/P molar ratio >7). The model responding to the ionic conditions provided good prediction of the decrease in the pH levels and the positive role of the nitrogen levels for struvite precipitation. High nitrogen concentrations provided high P removal due to pH buffering and crystal purity.
Organoid techniques provide unique platforms to model brain development and neurological disorders. Whereas several methods for recapitulating corticogenesis have been described, a system modeling ...human medial ganglionic eminence (MGE) development, a critical ventral brain domain producing cortical interneurons and related lineages, has been lacking until recently. Here, we describe the generation of MGE and cortex-specific organoids from human pluripotent stem cells that recapitulate the development of MGE and cortex domains, respectively. Population and single-cell RNA sequencing (RNA-seq) profiling combined with bulk assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) analyses revealed transcriptional and chromatin accessibility dynamics and lineage relationships during MGE and cortical organoid development. Furthermore, MGE and cortical organoids generated physiologically functional neurons and neuronal networks. Finally, fusing region-specific organoids followed by live imaging enabled analysis of human interneuron migration and integration. Together, our study provides a platform for generating domain-specific brain organoids and modeling human interneuron migration and offers deeper insight into molecular dynamics during human brain development.
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•hMGEOs and hCOs recapitulate human brain organization and fetal brain transcriptomes•Transcriptome and chromatin accessibility distinguish hMGEOs and hCOs•hMGEOs and hCOs display activity-dependent and synchronized calcium oscillations•Interneurons migrate from hMGEOs and functionally integrate in hCOs
Xiang and colleagues report a method for generating human medial ganglionic eminence (MGE)-like organoids (hMGEOs) and cortical-like organoids (hCOs), which resemble the developing human MGE and cortex, respectively. By fusing hMGEOs and hCOs, they establish a 3D model to investigate human interneuron migration.
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