Real-world memories are formed in a particular context and are often not acquired or recalled in isolation
. Time is a key variable in the organization of memories, as events that are experienced ...close in time are more likely to be meaningfully associated, whereas those that are experienced with a longer interval are not
. How the brain segregates events that are temporally distinct is unclear. Here we show that a delayed (12-24 h) increase in the expression of C-C chemokine receptor type 5 (CCR5)-an immune receptor that is well known as a co-receptor for HIV infection
-after the formation of a contextual memory determines the duration of the temporal window for associating or linking that memory with subsequent memories. This delayed expression of CCR5 in mouse dorsal CA1 neurons results in a decrease in neuronal excitability, which in turn negatively regulates neuronal memory allocation, thus reducing the overlap between dorsal CA1 memory ensembles. Lowering this overlap affects the ability of one memory to trigger the recall of the other, and therefore closes the temporal window for memory linking. Our findings also show that an age-related increase in the neuronal expression of CCR5 and its ligand CCL5 leads to impairments in memory linking in aged mice, which could be reversed with a Ccr5 knockout and a drug approved by the US Food and Drug Administration (FDA) that inhibits this receptor, a result with clinical implications. Altogether, the findings reported here provide insights into the molecular and cellular mechanisms that shape the temporal window for memory linking.
Cell migration is controlled by various Ca2+ signals. Local Ca2+ signals, in particular, have been identified as versatile modulators of cell migration because of their spatiotemporal diversity. ...However, little is known about how local Ca2+ signals coordinate between the front and rear regions in directionally migrating cells. Here, we elucidate the spatial role of local Ca2+ signals in directed cell migration through combinatorial application of an optogenetic toolkit. An optically guided cell migration approach revealed the existence of Ca2+ sparklets mediated by L-type voltage-dependent Ca2+ channels in the rear part of migrating cells. Notably, we found that this locally concentrated Ca2+ influx acts as an essential transducer in establishing a global front-to-rear increasing Ca2+ gradient. This asymmetrical Ca2+ gradient is crucial for maintaining front–rear morphological polarity by restricting spontaneous lamellipodia formation in the rear part of migrating cells. Collectively, our findings demonstrate a clear link between local Ca2+ sparklets and front–rear coordination during directed cell migration.
Cancer is the second leading cause of death worldwide, with 9.6 million people estimated to have died of cancer in 2018. Excess body fat deposition is a risk factor for many types of cancer. Men and ...women exhibit differences in body fat distribution and energy homeostasis regulation. This systematic review aimed to understand why sex disparities in obesity are associated with sex differences in the incidence of gastrointestinal cancers. Cancers of the esophagus, liver, and colon are representative gastrointestinal cancers, and obesity is a convincing risk factor for their development. Numerous epidemiological studies have found sex differences in the incidence of esophageal, liver, and colorectal cancers. We suggest that these sexual disparities are partly explained by the availability of estrogens and other genetic factors regulating inflammation, cell growth, and apoptosis. Sex differences in gut microbiota composition may contribute to differences in the incidence and phenotype of colorectal cancer. To establish successful practices in personalized nutrition and medicine, one should be aware of the sex differences in the pathophysiology and associated mechanisms of cancer development.
Optical diffraction tomography (ODT) provides label-free three-dimensional (3D) refractive index (RI) measurement of biological samples. However, due to the nature of the RI values of biological ...specimens, ODT has limited access to molecular specific information. Here, we present an optical setup combining ODT with three-channel 3D fluorescence microscopy, to enhance the molecular specificity of the 3D RI measurement. The 3D RI distribution and 3D deconvoluted fluorescence images of HeLa cells and NIH-3T3 cells are measured, and the cross-correlative analysis between RI and fluorescence of live cells are presented.
Dimensional analysis of magnetophoresis Heo, Won-Seok; Hetts, Steven W.; Rayz, Vitaliy L.
International journal of engineering science,
12/2023, Letnik:
193
Journal Article
Recenzirano
Magnetophoresis is used in various applications requiring selective collection of magnetic particles. This study is aimed at quantitatively describing magnetophoretic systems via dimensional analysis ...to assess the relative contribution of hydrodynamics, electromagnetism, and particle dynamics. We introduce dimensionless numbers characterizing the transport of magnetic particles in a fluid. Analytical and numerical studies were conducted for magnetophoretic systems where magnetic particles were suspended in a fluid exposed to magnetic fields generated by permanent magnets. The magnetically induced mobility of the magnetic particles was simulated for a range of parameters relevant in biomedical applications, including the particle and fluid properties, flow velocity, and geometries of the particle, flow channel, and magnet. The numerical results obtained in multiphysics modeling of magnetophoretic systems were analyzed based on the proposed dimensionless numbers, resulting in a functional relationship for the particle capture efficiency (CE), defined as the ratio of captured particles to all particles injected in the flow. The performance of magnetophoretic systems predicted with the dimensional analysis was verified in comparison with published experimental data. Using dimensional analysis, 12 input parameters determining the particle CE were reduced to 3 dimensionless numbers characterizing the ratios of magnetophoretic and hydrodynamic forces, cross-sectional areas of the magnet and the flow channel, and length and diameter of the magnet. A set of curves predicting particle CE was obtained using these dimensionless numbers. A close agreement was found between the CEs predicted by the curves and those obtained in both numerical simulations and experiments where cylindrical magnets were placed in a flow through a cylindrical pipe. This study provides a promising framework for analyzing and predicting performance of various magnetophoretic systems for a range of applications.
Background:
Few studies to date have compared clinical outcomes in patients who have undergone medial patellofemoral ligament (MPFL) reconstruction using the suture anchor and double transpatellar ...tunnel fixation methods. This meta-analysis therefore compared the clinical results, including the patellar redislocation rate and improvement in functional scores, of suture anchor and double transpatellar tunnel fixation.
Hypothesis:
The recurrence rate and improvement in functional outcomes after surgery would be similar using the suture anchor and double transpatellar tunnel fixation methods.
Study Design:
Meta-analysis.
Methods:
Studies evaluating MPFL reconstruction using either the suture anchor or double transpatellar tunnel technique for patellar site fixation were included if they reported the patellar redislocation rate after surgery and/or validated patient-reported outcomes such as the Kujala and Lysholm scores.
Results:
Twenty-one studies were included in this meta-analysis. The mean patellar redislocation rates were similar using the suture anchor (3.2% 95% CI, 1.6%-6.2%) and double transpatellar tunnel (3.4% 95% CI, 2.1%-5.4%) techniques (P = .879). The mean improvement in the Kujala score from before to after MPFL reconstruction was greater using the suture anchor (37.2 95% CI, 31.1-43.4) method than the double transpatellar tunnel method (28.7 95% CI, 21.2-36.1) (P = .018). However, the mean improvement in the Lysholm score did not differ significantly using the 2 techniques.
Conclusion:
The patellar redislocation rate did not differ significantly in patients who underwent MPFL reconstruction using the suture anchor and double transpatellar tunnel fixation methods. The suture anchor fixation method, however, resulted in a greater degree of improvement in patient-reported outcomes.
A diselenide-based BODIPY probe was prepared; it was found to be sensitive and selective for superoxide in giving -Se(O)Se(O)- oxidation. Probing was reversible through the use of biothiols; 77Se NMR ...and other types of spectroscopy were employed. Practical medicinal utility was demonstrated in MCF-7/ADR cancer cells.
Background:
Given the superiority of meniscal repair over partial meniscectomy according to biomechanical data, the clinical outcomes of meniscal repair are likely to be better than those of partial ...meniscectomy for a medial meniscus root tear (MMRT).
Purpose/Hypothesis:
This review was designed to compare the clinical and radiological results between meniscal repair and partial meniscectomy for MMRTs. It was hypothesized that meniscal repair would result in better clinical and radiological results compared with partial meniscectomy.
Study Design:
Systematic review; Level of evidence, 4.
Methods:
Studies were included in the review if they (1) included patients with MMRTs who underwent primary arthroscopic meniscal repair or partial meniscectomy and (2) analyzed validated patient-reported outcomes and/or radiological evaluations. Summary odds ratios (ORs) with 95% CIs were calculated to compare partial meniscectomy with meniscal repair for each outcome.
Results:
A total of 13 studies were included. The mean duration of follow-up was 33.5 and 47.2 months in the meniscal repair group and partial meniscectomy group, respectively. The change in the Lysholm score from preoperatively to postoperatively was statistically significantly in favor of meniscal repair (OR, 2.20 95% CI, 1.55-3.12), while no difference was found with respect to the change in the Tegner score between the 2 surgical approaches (OR, 1.21 95% CI, 0.65-2.24). The prevalence of postoperative severe knee osteoarthritis (OR, 0.31 95% CI, 0.17-0.54) as well as that of reoperations (OR, 0.05 95% CI, 0.01-0.19) were significantly in favor of meniscal repair.
Conclusion
Better outcomes were seen after meniscal repair compared with partial meniscectomy for MMRTs, with greater improvements in Lysholm scores, and lower rates of progression to knee osteoarthritis, and lower reoperation rate.
Governments have been investing in extensive operations to minimize economic losses and casualties from natural disasters such as floods and storms. A suitable verification process is required to ...guarantee maximum effectiveness and efficiency of investments while ensuring sustained funding. Active investment can be expected by verifying the effectiveness of disaster prevention spending. However, the results of the budget invested in disaster-safety-related projects are not immediate but evident only over a period of time. Additionally, their effects should be verified in terms of the state or society overall, not from an individualistic perspective because of the nature of public projects. In this study, an economic analysis of the short- and long-term effects of investment in a disaster-safety-related project was performed and the effects of damage reduction before and after project implementation were analyzed to evaluate the short-term effects and a cost–benefit analysis was conducted to assess the long-term effects. The results show that disaster prevention projects reduce damages over both the short and long term. Therefore, investing in preventive projects to cope with disasters effectively is important to maximize the return on investment. This analysis can be used for developing effective disaster prevention projects.
Neurotrophin-3 (NT-3) is a secreted neurotrophic factor that binds neurotrophin receptor tyrosine kinase C (TrkC), which in turn binds to presynaptic protein tyrosine phosphatase σ (PTPσ) to govern ...excitatory synapse development. However, whether and how NT-3 cooperates with the TrkC-PTPσ synaptic adhesion pathway and TrkC-mediated intracellular signaling pathways in rat cultured neurons has remained unclear. Here, we report that NT-3 enhances TrkC binding affinity for PTPσ. Strikingly, NT-3 treatment bidirectionally regulates the synaptogenic activity of TrkC: at concentrations of 10-25 ng/ml, NT-3 further enhanced the increase in synapse density induced by TrkC overexpression, whereas at higher concentrations, NT-3 abrogated TrkC-induced increases in synapse density. Semiquantitative immunoblotting and optogenetics-based imaging showed that 25 ng/ml NT-3 or light stimulation at a power that produced a comparable level of NT-3 (6.25 μW) activated only extracellular signal-regulated kinase (ERK) and Akt, whereas 100 ng/ml NT-3 (light intensity, 25 μW) further triggered the activation of phospholipase C-γ1 and CREB independently of PTPσ. Notably, disruption of TrkC intracellular signaling pathways, extracellular ligand binding, or kinase activity by point mutations compromised TrkC-induced increases in synapse density. Furthermore, only sparse, but not global, TrkC knock-down in cultured rat neurons significantly decreased synapse density, suggesting that intercellular differences in TrkC expression level are critical for its synapse-promoting action. Together, our data demonstrate that NT-3 is a key factor in excitatory synapse development that may direct higher-order assembly of the TrkC/PTPσ complex and activate distinct intracellular signaling cascades in a concentration-dependent manner to promote competition-based synapse development processes.
In this study, we present several lines of experimental evidences to support the conclusion that neurotrophin-3 (NT-3) modulates the synaptic adhesion pathway involving neurotrophin receptor tyrosine kinase C (TrkC) and presynaptic protein tyrosine phosphatase σ (PTPσ) in a bidirectional manner at excitatory synapses. NT-3 acts in concentration-independent manner to facilitate TrkC-mediated presynaptic differentiation, whereas it acts in a concentration-dependent manner to exert differential effects on TrkC-mediated organization of postsynaptic development. We further investigated TrkC extracellular ligand binding, intracellular signaling pathways, and kinase activity in NT-3-induced synapse development. Last, we found that interneuronal differences in TrkC levels regulate the synapse number. Overall, these results suggest that NT-3 functions as a positive modulator of synaptogenesis involving TrkC and PTPσ.