FAM69C functions as a kinase for eIF2α and promotes stress granule assembly.

Stress granules are dynamic cytoplasmic ribonucleoprotein granules that assemble in response to cellular stress. Aberrant formation of stress granules has been linked to neurodegenerative diseases. However, the molecular mechanisms underlying the initiation of stress granules remain elusive. Here we report that the brain-enriched protein kinase FAM69C promotes stress granule assembly through phosphorylation of eukaryotic translation initiation factor 2 (eIF2α). FAM69C physically interacts with eIF2α and functions as a stress-specific kinase for eIF2α, leading to stress-induced protein translation arrest and stress granule assembly. Primary microglia derived from Fam69c knockout mice exhibit aberrant stress granule assembly in response to oxidative stress and ATP. Defective stress granule assembly in microglia correlates with the formation of ASC specks and NLRP3 inflammasome activation, whereas induction of stress granule precludes inflammasome formation. Consistently, increased NLRP3 levels, caspase-1 cleavage and Il18 expression corroborate microglia-associated neuroinflammation in aged Fam69c knockout mice. Our study demonstrates that FAM69C is critical for stress granule assembly and suggests its role in the regulation of microglia function.

FAM69C, a kinase critical for synaptic function and memory, is defective in neurodegenerative dementia.

Synapse loss and memory decline are the primary features of neurodegenerative dementia. However, the molecular underpinnings that drive memory loss remain largely unknown. Here, we report that FAM69C is a kinase critically involved in neurodegenerative dementia. Biochemical analyses uncover that FAM69C is a serine/threonine kinase. We generate the Fam69c knockout mice and show by single-cell RNA sequencing that FAM69C deficiency drives cell-type-specific transcriptional changes relevant to synapse dysfunction. Electrophysiological, morphological, and behavioral experiments demonstrate impairments in synaptic plasticity, dendritic spine density, and memory in Fam69c knockout mice, as well as stress-induced neuronal death. Phosphoproteomic characterizations reveal that FAM69C substrates are involved in synaptic structure and function. Finally, reduced levels of FAM69C are found in postmortem brains of Alzheimer's disease patients. Our study demonstrates that FAM69C is a protective regulator of memory and suggests FAM69C as a potential therapeutic target for memory loss in neurodegenerative dementia.

Distance makes a difference in crystalline photoluminescence.

Crystallization-induced photoluminescence weakening was recently revealed in ultrasmall metal nanoparticles. However, the fundamentals of the phenomenon are not understood yet. By obtaining conformational isomer crystals of gold nanoclusters, we investigate crystallization-induced photoluminescence weakening and reveal that the shortening of interparticle distance decreases photoluminescence, which is further supported by high-pressure photoluminescence experiments. To interpret this, we propose a distance-dependent non-radiative transfer model of excitation electrons and support it with additional theoretical and experimental results. This model can also explain both aggregation-induced quenching and aggregation-induced emission phenomena. This work improves our understanding of aggregated-state photoluminescence, contributes to the concept of conformational isomerism in nanoclusters, and demonstrates the utility of high pressure studies in nanochemistry.

Study on anterior and posterior approaches for spinal tuberculosis: a meta-analysis.

BACKGROUND: Timely and appropriate surgical intervention can enhance the stability of spine, eliminate the compression on spinal cord and prevent the further development the complications that may follow. However, there is no optimum surgical approach that has been agreed by surgeons. OBJECTIVE: Incidence rate of spinal tuberculosis is still high in many developing countries. Except from chemotherapy, some patients require surgical treatment at certain phases of disease development. However, there is still not a standard operative procedure for spinal tuberculosis in the current research, and we studied the differences of anterior and posterior approach for spinal tuberculosis, to provide guidance for the further operative treatments. METHODS: We searched "Pubmed" (2000.1-2014.7), "Medline" (2000.1-2014.7), "Elseveir" (2000.1-2014.7), Cochrane library (2008.1-2014.7), Wanfang (2000.1-2014.7), and CNKI (2000.1-2014.7) databases with the key words of "thoracolumbar tuberculosis", "controlled randomized trial", "RCT", "anterior" "posterior", and searched for randomized controlled trials for spinal tuberculosis. We compared the operative time, total blood loss, correction of Cobb angle, loss of Cobb angle at final follow-up, fusion time of allograft, time of total hospital stay, and the effectiveness of operative treatment between the anterior and posterior surgical approaches by Revman5.3 software. RESULTS: From 1,523 papers found, we chose eight randomized controlled trials comparing different surgical approaches for the treatment of spinal tuberculosis. The total number of patients was 754, in which 377 were treated with anterior approach and 377 were treated with posterior approach correction of Cobb angle (P < 0.05), and no significant differences were found regarding operation time, loss of correction of Cobb angle in the last follow-up, time of total hospital stay, and fusion time of bone graft (P > 0.05). CONCLUSIONS: There are significant differences between the two operative approaches regarding the correction of Cobb angle, but no significant differences regarding operation time, blood loss, loss of Cobb angle at the last follow-up, total fusion time, and length of total stay in the hospital.

Comparison of the short- and long-term treatment effect of cervical disk replacement and anterior cervical disk fusion: a meta-analysis.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) has been used as a gold standard for the treatment of cervical spondylosis, but it may cause complications such as pseudarthrosis and junctional degeneration. Cervical disk arthroplasty (CDA) may help overcome such problems, but there are inconsistencies among the published literature on its effectiveness comparing with ACDF. METHODOLOGY: We searched "PubMed" (2000.1-2013.10), "Medline" (2000.1-2013.10), "Elsevier" (2000.1-2013.10), Cochrane library (2008.1-2013.10) databases with the key words of "cervical disk arthroplasy", "CDA", "anterior cervical disk fusion", "ACDF", "cervical", "randomized controlled study", "RCT" and searched for randomized controlled trials comparing the efficacy of ACDF and CDA for the treatment of cervical spondylosis. Neck disability index (NDI), VAS arm pain score, VAS neck pain score, ROM of the adjacent level, SF36-PCS score, SF36-MCS score and patient satisfaction were calculated by Revman5.2 software. RESULTS: From 1,400 papers found, we chose 18 randomized controlled trials and cohorts evaluating the efficacy of CDA and ACDF on symptomatic cerebral spondylosis. The total number of patients is 3,056, in which 1,576 were in the CDA group and 1,480 were in the ACDF group. The CDA group demonstrated better results than the ACDF group concerning VAS arm pain score 1, 2, 4 years after the surgery, VAS neck pain score 1, 2, 4 years after the surgery, ROM of the adjacent level 1 and 2 years after the surgery, patient satisfaction 1, 2, 4 years after the surgery, NDI scores 1, 2, 4 years after the surgery, SF36-PCS score 1 and 2 years after the surgery and SF36-MCS score at 1 and 4 years after the surgery. There are no significant differences between the groups concerning SF36-PCS score 4 years after the surgery and SF36-MCS score at 2 years after the surgery. CONCLUSIONS: CDA can be an effective alternative method to ACDF for the treatment of cervical spondylosis.

Association of apolipoprotein A5 genetic polymorphisms with steroid-induced osteonecrosis of femoral head in a Chinese Han population.

BACKGROUND: Previous studies suggested that apolipoprotein A5 (ApoA5) genetic polymorphisms (SNPs) may result in lipid metabolism disorders. Therefore, genetic polymorphisms in ApoA5 may be associated with the occurrence of osteonecrosis of femoral head (ONFH). METHODS: We designed a case-control study including 223 patients of osteonecrosis and 201 age- and sex-matched control subjects to analyze the association between ApoA5 polymorphisms and susceptibility of steroid-induced ONFH. We utilized polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to genotype two SNPs (rs662799 and rs3135506) in ApoA5 gene. RESULTS: We found both rs662799 and rs3135506 were associated with the risk of ONFH in codominant, dominant, and recessive model, respectively. Haplotype analyses suggested that T-C haplotype was associated with decreased risk of ONFH, whereas the haplotype C-C was significantly associated with an increased risk of ONFH. CONCLUSION: Our study suggested that ApoA5 genetic polymorphisms were associated with susceptibility to ONFH in Chinese population. However, our results need further investigation with large sample size and various populations. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_229.