• Mccarthy Jespersen posted an update 13 hours, 8 minutes ago

    The receptor deleted in colorectal cancer (DCC) and its ligand netrin-1 are essential for axon guidance during development and are expressed by neurons in the mature brain. Netrin-1 recruits GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and is critical for long-term potentiation (LTP) at CA3-CA1 hippocampal Schaffer collateral synapses, while conditional DCC deletion from glutamatergic neurons impairs hippocampal-dependent spatial memory and severely disrupts LTP induction. DCC co-fractionates with the detergent-resistant component of postsynaptic density, yet is enriched in axonal growth cones that differentiate into presynaptic terminals during development. Specific presynaptic and postsynaptic contributions of DCC to the function of mature neural circuits have yet to be identified. Employing hippocampal subregion-specific conditional deletion of DCC, we show that DCC loss from CA1 hippocampal pyramidal neurons resulted in deficits in spatial memory, increased resting membrane potential, abnormal dendritic spine morphology, weaker spontaneous excitatory postsynaptic activity, and reduced levels of postsynaptic adaptor and signaling proteins; however, the capacity to induce LTP remained intact. In contrast, deletion of DCC from CA3 neurons did not induce detectable changes in the intrinsic electrophysiological properties of CA1 pyramidal neurons, but impaired performance on the novel object place recognition task as well as compromised excitatory synaptic transmission and LTP at Schaffer collateral synapses. Together, these findings reveal specific pre- and post-synaptic contributions of DCC to hippocampal synaptic plasticity underlying spatial memory.BACKGROUND Numerous reports regarding sarcopenia have focused on the quantity of skeletal muscle. In contrast, the impact of the quality of skeletal muscle has not been well investigated. METHODS A retrospective analysis of 115 patients who underwent initial hepatectomy for colorectal liver metastasis between January 2009 and December 2016 in our hospital was performed. Intramuscular adipose tissue content (IMAC) was used to evaluate the quality of skeletal muscle by analysing computed tomography (CT) images at the level of the umbilicus. The impact of poor skeletal muscle quality on short-term and long-term outcomes after hepatectomy for colorectal liver metastasis was analysed. RESULTS Patients were divided into two groups (high IMAC and normal IMAC) according to their IMAC values, and their backgrounds were compared. There were no significant differences in most factors between the two groups. However, both body mass index (P = 0.030) and the incidence of postoperative complications of Clavien-Dindo grade 3 or worse (P = 0.008) were significantly higher in the high-IMAC group. In multivariate analyses, an operative blood loss > 600 ml (P = 0.006) and high IMAC (P = 0.008) were associated with postoperative complications of Clavien-Dindo grade 3 or worse. Stem Cells inhibitor Overall survival and recurrence-free survival were significantly lower (P less then 0.001 and P = 0.045, respectively) in the high-IMAC group than in the normal IMAC group. In multivariate analyses for poor overall survival, high IMAC was associated with poor overall survival (P less then 0.001). CONCLUSIONS IMAC is a prognostic factor for poor short- and long-term outcomes in patients with colorectal liver metastasis.Communicating and challenging ideas through written scholarly dialogue is a cornerstone of scientific progress. In the current social and political climate, it is important to reflect upon what constitutes appropriate ways to engage in scholarly dialogues and consider the ramifications of failing to create an environment where individuals are willing to share ideas openly. In this commentary, we provide examples of scholarly dialogues representing antagonistic and collegial tones and discuss the consequences of failing to communicate appropriately in the areas of gatekeeping, mentoring, and most importantly, the silencing of ideas.Metagenomics studies leverage genomic reference databases to generate discoveries in basic science and translational research. However, current microbial studies use disparate reference databases that lack consistent standards of specimen inclusion, data preparation, taxon labelling and accessibility, hindering their quality and comprehensiveness, and calling for the establishment of recommendations for reference genome database assembly. Here, we analyze existing fungal and bacterial databases and discuss guidelines for the development of a master reference database that promises to improve the quality and quantity of omics research.PURPOSE To compare the effect of conventional pedicle screw (CPS) and cement-augmented pedicle screw instrumentation (CAPSI) on adjacent segment degeneration (ASD). METHODS A normal male volunteer without a history of spinal disease was selected, lumbar CT data was collected, an intact L3-S1 three-dimensional finite element model was created by software including Mimics, Geomagic, and SolidWorks, and the fixation methods were performed accordingly. A common pedicle screw model and a cement-augmented pedicle screw model of L4-L5 with fusion and internal fixation were constructed. With ANSYS Workbench 17.0, a 500 N load was applied to the upper surface of L3 to simulate the weight of a human body, and a 7.5 N m moment was applied at the neutral point to simulate flexion, extension, left/right bending, left/right rotation of the spine. The peak von Mises stress of intervertebral disc and the range of motion (ROM) on the adjacent segments (L3-4 and L5-S1) were compared. RESULTS The validity of the intact model shows that the ROM of the model is similar to that of a cadaveric study. Compared with the intact model, CPS model and CAPSI model in all motion patterns increased the ROM of adjacent segments. The intervertebral disc stress and the ROM of adjacent segments were found to be higher in the CAPSI model than in the CPS model, especially in L3-4. CONCLUSION In general, the biomechanical analysis of an osteoporotic lumbar spine showed that both CPS and CAPSI can increase the ROM and disc stresses of osteoporotic lumbar models, and compared with CPS, CAPSI is more likely to increase the potential risk of adjacent segment degeneration.