Diffusion Tensor Imaging Evaluation of Corticospinal Tract Hyperintensity in Upper Motor Neuron-Predominant ALS Patients

Amyotrophic lateral sclerosis (ALS) patients with predominant upper motor neuron (UMN) signs occasionally have hyperintensity of corticospinal tract (CST) on T2- and proton-density-(PD-) weighted brain images. Diffusion tensor imaging (DTI) was used to assess whether diffusion parameters along intracranial CST differ in presence or absence of hyperintensity and correspond to UMN dysfunction. DTI brain scans were acquired in 47 UMN-predominant ALS patients with (n = 21) or without (n = 26) CST hyperintensity and in 10 control subjects. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured in four regions of interests (ROIs) along CST. Abnormalities (P < 0.05) were observed in FA, AD, or RD in CST primarily at internal capsule (IC) level in ALS patients, especially those with CST hyperintensity. Clinical measures corresponded well with DTI changes at IC level. The IC abnormalities suggest a prominent axonopathy in UMN-predominant ALS and that tissue changes underlying CST hyperintensity have specific DTI changes, suggestive of unique axonal pathology

Bilateral transfer of motor performance as a function of motor imagery training: a systematic review and meta-analysis

ObjectiveThe objective of this review was to evaluate the efficacy of mental imagery training (MIT) in promoting bilateral transfer (BT) of motor performance for healthy subjects.Data sourcesWe searched 6 online-databases (Jul-Dec 2022) using terms: “mental practice,” “motor imagery training,” “motor imagery practice,” “mental training,” “movement imagery,” “cognitive training,” “bilateral transfer,” “interlimb transfer,” “cross education,” “motor learning,” “strength,” “force” and “motor performance.”Study selection and data extractionWe selected randomized-controlled studies that examined the effect of MIT on BT. Two reviewers independently determined if each study met the inclusion criteria for the review. Disagreements were resolved through discussion and, if necessary, by a third reviewer. A total of 9 articles out of 728 initially identified studies were chosen for the meta-analysis.Data synthesisThe meta-analysis included 14 studies for the comparison between MIT and no-exercise control (CTR) and 15 studies for the comparison between MIT and physical training (PT).ResultsMIT showed significant benefit in inducing BT compared to CTR (ES = 0.78, 95% CI = 0.57–0.98). The effect of MIT on BT was similar to that of PT (ES = –0.02, 95% CI = –0.15–0.17). Subgroup analyses showed that internal MIT (IMIT) was more effective (ES = 2.17, 95% CI = 1.57–2.76) than external MIT (EMIT) (ES = 0.95, 95% CI = 0.74–1.17), and mixed-task (ES = 1.68, 95% CI = 1.26–2.11) was more effective than mirror-task (ES = 0.46, 95% CI = 0.14–0.78) and normal-task (ES = 0.56, 95% CI = 0.23–0.90). No significant difference was found between transfer from dominant limb (DL) to non-dominant limb (NDL) (ES = 0.67, 95% CI = 0.37–0.97) and NDL to DL (ES = 0.87, 95% CI = 0.59–1.15).ConclusionThis review concludes that MIT can serve as a valuable alternative or supplement to PT in facilitating BT effects. Notably, IMIT is preferable to EMIT, and interventions incorporating tasks that have access to both intrinsic and extrinsic coordinates (mixed-task) are preferred over those that involve only one of the two coordinates (mirror-task or normal-task). These findings have implications for rehabilitation of patients such as stroke survivors

Effect of non-phytate phosphorus levels and phytase sources on the growth performance, serum biochemical and tibial parameters of broiler chickens

A 3×3 fattorial arrangement with dietary non-phytate phosphorus (NPP) levels and phytase sources (3- and 6-phytase) was conducted to evaluate the effects of NPP levels, phytase sources and their possible interactions on growth performance, serum biochemical and tibia parameters of broiler chickens from hatch to 42 days of age. A total of 540 1-day-old Arbor Acres male broiler chicks were randomly allocated into nine dietary treatments, each containing 5 replicates pens with 12 birds per pen. Interaction was statistically significant in the performance till day 21 of trial, supplementation of low NPP diet decreased body weight (BW) (P<0.001), depressed average daily gain (ADG) (P<0.001) and deteriorated average daily feed intake (ADFI) (P<0.001) over day 42. During the 8-to-21-day period, even if interaction between NPP levels and phytase sources was significant (P<0.01), BW, ADG and ADFI always increased due to dietary supplementation of phytase, with source not differing. Dietary high NPP enhanced serum calcium and P concentrations on day 21 and 42 (linear contrast, P<0.01), while decreased alkaline phosphatase (AKP) activity on day 42 (linear contrast, P<0.001), and interaction was not significant. Both dietary sources of phytase decreased serum AKP activities on day 42 (P<0.001), and urea nitrogen content on day 21 (P<0.01) and 42 (P<0.001). Both phytase improved ash percentage on day 21 and P content in tibia at 21 and 42 days of age (P<0.001). The results confirmed that dietary supplementation of phytase may enhance P availability during the 8-to-21-day period. Nevertheless, no difference between the two phytase sources was observed

SO(3) Gauge Symmetry and Neutrino-Lepton Flavor Physics

Based on the SO(3) gauge symmetry for three family leptons and general see-saw mechanism, we present a simple scheme that allows three nearly degenerate Majorana neutrino masses needed for hot dark matter. The vacuum structure of the spontaneous SO(3) symmetry breaking can automatically lead to a maximal CP-violating phase. Thus the current neutrino data on both the atmospheric neutrino anomaly and solar neutrino deficit can be accounted for via maximal mixings without conflict with the current data on the neutrinoless double beta decay. The model also allows rich interesting phenomena on lepton flavor violations.Comment: 10 pages, Revtex, no figures, minor changes and references added, the version to appear in Phys. Rev.

Establishment of a canine model of cardiac memory using endocardial pacing via internal jugular vein

<p>Abstract</p> <p>Background</p> <p>Development of experimental animal models has played an important role in understanding the mechanisms of cardiac memory. The purpose of this study was to evaluate a new canine model of cardiac memory using endocardial ventricular pacing via internal jugular vein.</p> <p>Methods</p> <p>Twelve Beagle dogs underwent placement of a permanent ventricular pacemaker mimicking the use of pacemakers in humans and induction of cardiac memory by endocardial ventricular pacing.</p> <p>Results</p> <p>Cardiac memory was achieved in 11 of 12 attempts overall. Procedural mortality due to cardiac tamponade (n = 1) occurred in the first attempt. The T-wave memory persisted for 96 ± 17 minutes and 31 ± 6 days in the short-term and long-term cardiac memory groups, respectively. There were no significant differences in the heart rate, blood pressure and echocardiographic parameters in the animals between before and after ventricular pacing in the short-term and long-term cardiac memory groups. No significant pathologic changes with the light microscopy were found in the present study in all dogs.</p> <p>Conclusion</p> <p>The model does require surgery but is not as invasive as an open-chest model. This canine model can serve as a useful tool for studying mechanisms of cardiac memory.</p

Dihydroartemisinin Enhances Apo2L/TRAIL-Mediated Apoptosis in Pancreatic Cancer Cells via ROS-Mediated Up-Regulation of Death Receptor 5

BACKGROUND: Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells. Apo2 ligand or tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is regarded as a promising anticancer agent, but chemoresistance affects its efficacy as a treatment strategy. Apoptosis induced by the combination of DHA and Apo2L/TRAIL has not been well documented, and the mechanisms involved remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that DHA enhances the efficacy of Apo2L/TRAIL for the treatment of pancreatic cancer. We found that combined therapy using DHA and Apo2L/TRAIL significantly enhanced apoptosis in BxPC-3 and PANC-1 cells compared with single-agent treatment in vitro. The effect of DHA was mediated through the generation of reactive oxygen species, the induction of death receptor 5 (DR5) and the modulation of apoptosis-related proteins. However, N-acetyl cysteine significantly reduced the enhanced apoptosis observed with the combination of DHA and Apo2L/TRAIL. In addition, knockdown of DR5 by small interfering RNA also significantly reduced the amount of apoptosis induced by DHA and Apo2L/TRAIL. CONCLUSIONS/SIGNIFICANCE: These results suggest that DHA enhances Apo2L/TRAIL-mediated apoptosis in human pancreatic cancer cells through reactive oxygen species-mediated up-regulation of DR5

Deep Sequencing of Human Nuclear and Cytoplasmic Small RNAs Reveals an Unexpectedly Complex Subcellular Distribution of miRNAs and tRNA 3′ Trailers

MicroRNAs (miRNAs) are ∼22-nt small non-coding regulatory RNAs that have generally been considered to regulate gene expression at the post-transcriptional level in the cytoplasm. However, recent studies have reported that some miRNAs localize to and function in the nucleus.To determine the number of miRNAs localized to the nucleus, we systematically investigated the subcellular distribution of small RNAs (sRNAs) by independent deep sequencing sequenced of the nuclear and cytoplasmic pools of 18- to 30-nucleotide sRNAs from human cells. We identified 339 nuclear and 324 cytoplasmic known miRNAs, 300 of which overlap, suggesting that the majority of miRNAs are imported into the nucleus. With the exception of a few miRNAs evidently enriched in the nuclear pool, such as the mir-29b, the ratio of miRNA abundances in the nuclear fraction versus in the cytoplasmic fraction vary to some extent. Moreover, our results revealed that a large number of tRNA 3′trailers are exported from the nucleus and accumulate in the cytoplasm. These tRNA 3′ trailers accumulate in a variety of cell types, implying that the biogenesis of tRNA 3′ trailers is conserved and that they have a potential functional role in vertebrate cells.Our results provide the first comprehensive view of the subcellular distribution of diverse sRNAs and new insights into the roles of miRNAs and tRNA 3′ trailers in the cell

Microtubular Stability Affects pVHL-Mediated Regulation of HIF-1alpha via the p38/MAPK Pathway in Hypoxic Cardiomyocytes

BACKGROUND: Our previous research found that structural changes of the microtubule network influence glycolysis in cardiomyocytes by regulating the hypoxia-inducible factor (HIF)-1α during the early stages of hypoxia. However, little is known about the underlying regulatory mechanism of the changes of HIF-1α caused by microtubule network alternation. The von Hippel-Lindau tumor suppressor protein (pVHL), as a ubiquitin ligase, is best understood as a negative regulator of HIF-1α. METHODOLOGY/PRINCIPAL FINDINGS: In primary rat cardiomyocytes and H9c2 cardiac cells, microtubule-stabilization was achieved by pretreating with paclitaxel or transfection of microtubule-associated protein 4 (MAP4) overexpression plasmids and microtubule-depolymerization was achieved by pretreating with colchicine or transfection of MAP4 siRNA before hypoxia treatment. Recombinant adenovirus vectors for overexpressing pVHL or silencing of pVHL expression were constructed and transfected in primary rat cardiomyocytes and H9c2 cells. With different microtubule-stabilizing and -depolymerizing treaments, we demonstrated that the protein levels of HIF-1α were down-regulated through overexpression of pVHL and were up-regulated through knockdown of pVHL in hypoxic cardiomyocytes. Importantly, microtubular structure breakdown activated p38/MAPK pathway, accompanied with the upregulation of pVHL. In coincidence, we found that SB203580, a p38/MAPK inhibitor decreased pVHL while MKK6 (Glu) overexpression increased pVHL in the microtubule network altered-hypoxic cardiomyocytes and H9c2 cells. CONCLUSIONS/SIGNIFICANCE: This study suggests that pVHL plays an important role in the regulation of HIF-1α caused by the changes of microtubular structure and the p38/MAPK pathway participates in the process of pVHL change following microtubule network alteration in hypoxic cardiomyocytes