CRMP/UNC-33 organizes microtubule bundles for KIF5-mediated mitochondrial distribution to axon.

Neurons are highly specialized cells with polarized cellular processes and subcellular domains. As vital organelles for neuronal functions, mitochondria are distributed by microtubule-based transport systems. Although the essential components of mitochondrial transport including motors and cargo adaptors are identified, it is less clear how mitochondrial distribution among somato-dendritic and axonal compartment is regulated. Here, we systematically study mitochondrial motors, including four kinesins, KIF5, KIF17, KIF1, KLP-6, and dynein, and transport regulators in C. elegans PVD neurons. Among all these motors, we found that mitochondrial export from soma to neurites is mainly mediated by KIF5/UNC-116. Interestingly, UNC-116 is especially important for axonal mitochondria, while dynein removes mitochondria from all plus-end dendrites and the axon. We surprisingly found one mitochondrial transport regulator for minus-end dendritic compartment, TRAK-1, and two mitochondrial transport regulators for axonal compartment, CRMP/UNC-33 and JIP3/UNC-16. While JIP3/UNC-16 suppresses axonal mitochondria, CRMP/UNC-33 is critical for axonal mitochondria; nearly no axonal mitochondria present in unc-33 mutants. We showed that UNC-33 is essential for organizing the population of UNC-116-associated microtubule bundles, which are tracks for mitochondrial trafficking. Disarrangement of these tracks impedes mitochondrial transport to the axon. In summary, we identified a compartment-specific transport regulation of mitochondria by UNC-33 through organizing microtubule tracks for different kinesin motors other than microtubule polarity.

Application of microRNA in Human Osteoporosis and Fragility Fracture: A Systemic Review of Literatures.

MicroRNAs (miRNAs) could serve as ideal entry points to the deregulated pathways in osteoporosis due to their relatively simple upstream and downstream relationships with other molecules in the signaling cascades. Our study aimed to give a comprehensive review of the already identified miRNAs in osteoporosis from human blood samples and provide useful information for their clinical application. A systematic literature search for relevant studies was conducted in the Pubmed database from inception to December 2020. We set two essential inclusion criteria: human blood sampling and design of controlled studies. We sorted the results of analysis on human blood samples according to the study settings and compiled the most promising miRNAs with analyzed diagnostic values. Furthermore, in vitro and in vivo evidence for the mechanisms of the identified miRNAs was also illustrated. Based on both diagnostic value and evidence of mechanism from in vitro and in vivo experiments, miR-23b-3p, miR-140-3p, miR-300, miR-155-5p, miR-208a-3p, and miR-637 were preferred candidates in diagnostic panels and as therapeutic agents. Further studies are needed to build sound foundations for the clinical usage of miRNAs in osteoporosis.

Ultrasonography has high positive predictive value for medial epicondyle lesions among adolescent baseball players.

PURPOSE: Only few studies have investigated medial epicondyle (MEC) lesions, particularly in the 12-18 age group. To the best of our knowledge, no study has compared ultrasonography (US), radiography and magnetic resonance imaging (MRI) in detecting MEC lesions. The aims of this study were to examine the value of US for detecting MEC lesions and to investigate correlations among diagnostic tools. METHODS: A prospective, comparative study was performed. Young baseball players from southern Taiwan were recruited, and basic characteristics, as well as passive range of motion (pROM) of the upper extremities, were recorded. Screening US was performed to identify MEC lesions, and players with MEC lesions received follow-up plain radiography and MRI. RESULTS: A total of 299 young baseball players were screened using US, and 28 of 299 players with possible MEC lesions were identified with a positive predictive value (PPV) of 88% according to MRI findings. The MEC lesions were primarily comprised of unfused ossicles and bony fragmentation. Other diagnoses, including UCL strain and medial epicondylitis, were also found by MRI in players with abnormal US screening results. The pROM of shoulder external rotation (ER) of the throwing hand was significantly reduced in players with MEC lesions (p = 0.006). CONCLUSIONS: Bony cortical discontinuity or fragmentation over the MEC warrants further research, and US provides good PPV for types of MEC lesions. Decreased shoulder ER may relate to MEC lesions and should be taken into consideration. The use of US may facilitate early detection and intervention. LEVEL OF EVIDENCE: IV, Cross-sectional study.

Effectiveness of ultrasonography screening and risk factor analysis of capitellar osteochondritis dissecans in adolescent baseball players.

BACKGROUND: Capitellar osteochondritis dissecans (COCD) is a common elbow injury in young baseball athletes. It may be asymptomatic at the early stage and may progress if left untreated. This study investigated the effectiveness of ultrasonography (US) screening for COCD in adolescent baseball players and identified risk factors of COCD. METHODS: A cross-sectional analysis study was conducted among baseball athletes aged 12 to 18 years. US screening of the throwing elbow was performed in all participants, and additional magnetic resonance imaging (MRI) was arranged for those with abnormal screening results. The prevalence of COCD was calculated according to MRI results. The US findings were compared with MRI findings. Data for characteristics, joint range of motion, and quality of pain were collected and analyzed using a logistic regression model to identify the risk factors of COCD. RESULTS: A total of 299 adolescent baseball players were screened, and 17 were found to have COCD according to US findings. MRI was performed in 15 of these 17 players, and the MRI findings further confirmed COCD in 10 players (66.7%). The presence of elbow pain while at rest, body height, and age at introduction to baseball were predictors of COCD. CONCLUSIONS: Although the effectiveness of diagnosing stage 1 COCD is satisfactory, US is a helpful tool for detecting stage 2 and higher-stage COCD. Elbow resting pain, lower body height, and introduction to baseball at a younger age are risk factors for COCD.