Limited Transfer of Newly Acquired Movement Patterns across Walking and Running in Humans

The two major modes of locomotion in humans, walking and running, may be regarded as a function of different speed (walking as slower and running as faster). Recent results using motor learning tasks in humans, as well as more direct evidence from animal models, advocate for independence in the neural control mechanisms underlying different locomotion tasks. In the current study, we investigated the possible independence of the neural mechanisms underlying human walking and running. Subjects were tested on a split-belt treadmill and adapted to walking or running on an asymmetrically driven treadmill surface. Despite the acquisition of asymmetrical movement patterns in the respective modes, the emergence of asymmetrical movement patterns in the subsequent trials was evident only within the same modes (walking after learning to walk and running after learning to run) and only partial in the opposite modes (walking after learning to run and running after learning to walk) (thus transferred only limitedly across the modes). Further, the storage of the acquired movement pattern in each mode was maintained independently of the opposite mode. Combined, these results provide indirect evidence for independence in the neural control mechanisms underlying the two locomotive modes.     

Oxidative Stress Induced Inflammation Initiates Functional Decline of Tear Production

Oxidative damage and inflammation are proposed to be involved in an age-related functional decline of exocrine glands. However, the molecular mechanism of how oxidative stress affects the secretory function of exocrine glands is unclear. We developed a novel mev-1 conditional transgenic mouse model (Tet-mev-1) using a modified tetracycline system (Tet-On/Off system). This mouse model demonstrated decreased tear production with morphological changes including leukocytic infiltration and fibrosis. We found that the mev-1 gene encodes Cyt-1, which is the cytochrome b₅₆₀ large subunit of succinate-ubiquinone oxidoreductase in complex II of mitochondria (homologous to succinate dehydrogenase C subunit (SDHC) in humans). The mev-1 gene induced excessive oxidative stress associated with ocular surface epithelial damage and a decrease in protein and aqueous secretory function. This new model provides evidence that mitochondrial oxidative damage in the lacrimal gland induces lacrimal dysfunction resulting in dry eye disease. Tear volume in Tet-mev-1 mice was lower than in wild type mice and histopathological analyses showed the hallmarks of lacrimal gland inflammation by intense mononuclear leukocytic infiltration and fibrosis in the lacrimal gland of Tet-mev-1 mice. These findings strongly suggest that oxidative stress can be a causative factor for the development of dry eye disease.     

Content-based image retrieval system using neural networks

An effective image retrieval system is developed based on the use of neural networks (NNs). It takes advantages of association ability of multilayer NNs as matching engines which calculate similarities between a user's drawn sketch and the stored images. The NNs memorize pixel information of every size-reduced image (thumbnail) in the learning phase. In the retrieval phase, pixel information of a user's drawn rough sketch is inputted to the learned NNs and they estimate the candidates. Thus the system can retrieve candidates quickly and correctly by utilizing the parallelism and association ability of NNs. In addition, the system has learning capability: it can automatically extract features of a user's drawn sketch during the retrieval phase and can store them as additional information to improve the performance. The software for querying, including efficient graphical user interfaces, has been implemented and tested. The effectiveness of the proposed system has been investigated through various experimental tests.     

Bone matrix proteins and extracellular acidification: Potential co‐regulators of osteoclast morphology

Osteoclasts are signaled by the bone matrix proteins fibronectin (FN), vitronectin (VN), and osteopontin (OPN) via integrins. To perform their resorptive function, osteoclasts cycle between compact (polarized), spread (non‐resorbing) and migratory morphologies. Here we investigate the effects of matrix proteins on osteoclast morphology and how those effects are mediated using RAW 264.7 cells differentiated into osteoclasts on FN, VN, and OPN‐coated culture dishes. After 96 h, 80% of osteoclasts on FN were compact while 25% and 16% on VN were in compact and migratory states respectively. In contrast, OPN induced osteoclast spreading. Furthermore, osteoclasts formed on VN and FN were two‐ to fourfold smaller than those formed on OPN in the 21–30 nuclei/osteoclast group. These effects were not due to defects in cytoskeletal reorganization of osteoclasts on VN and FN, demonstrated by the ability of these cells to spread in response to 35 ng/ml macrophage colony stimulating factor (M‐CSF). Conversely, osteoclasts on OPN failed to spread when induced by M‐CSF. Moreover, the extracellular pH on FN and VN (7.25 and 7.3, respectively) was significantly lower than that on OPN (～7.4). We further investigated the role of extracellular pH and found that at pH 7.5 the duration of an osteoclast's compact phase was 25.6 min and that of the spread phase was 62.5 min. Reducing the pH to 7.0 increased the frequency of osteoclast cycling by threefold. These results show that matrix proteins play a role in regulating osteoclast morphology, possibly via altering extracellular and intracellular pH. J. Cell. Biochem. 111: 350–361, 2010. © 2010 Wiley‐Liss, Inc.     

Eremophilane sesquiterpenes from the endophyte Microdiplodia sp. KS 75-1 and revision of the stereochemistries of phomadecalins C and D

Two new eremophilane sesquiterpenes, compounds 1 and 2, were isolated from the endophytic fungus Microdiplodia sp. KS 75-1, together with the known compounds phomadecalins C (3) and D (4). Their structures were determined by extensive 1D– and 2D–NMR and MS spectral analyses. The previously reported stereochemistry at C-8 of 3 and 4 were revised on the basis of NOEs experiments. Compounds 1 and 2 showed antimicrobial activity against Pseudomonas aeruginosa.     

HJURP is involved in the expansion of centromeric chromatin

The CENP-A–specific chaperone HJURP mediates CENP-A deposition at centromeres. The N-terminal region of HJURP is responsible for binding to soluble CENP-A. However, it is unclear whether other regions of HJURP have additional functions for centromere formation and maintenance. In this study, we generated chicken DT40 knockout cell lines and gene replacement constructs for HJURP to assess the additional functions of HJURP in vivo. Our analysis revealed that the middle region of HJURP associates with the Mis18 complex protein M18BP1/KNL2 and that the HJURP-M18BP1 association is required for HJURP function. In addition, on the basis of the analysis of artificial centromeres induced by ectopic HJURP localization, we demonstrate that HJURP exhibits a centromere expansion activity that is separable from its CENP-A–binding activity. We also observed centromere expansion surrounding natural centromeres after HJURP overexpression. We propose that this centromere expansion activity reflects the functional properties of HJURP, which uses this activity to contribute to the plastic establishment of a centromeric chromatin structure.     

Radical Prostatectomy versus External Beam Radiotherapy for cT1-4N0M0 Prostate Cancer: Comparison of Patient Outcomes Including Mortality

Background

Although radical prostatectomy (RP) and external beam radiotherapy (EBRT) have been considered as comparable treatments for localized prostate cancer (PC), it is controversial which treatment is better. The present study aimed to compare outcomes, including mortality, of RP and EBRT for localized PC.

Methods

We retrospectively analyzed 891 patients with cT1-4N0M0 PC who underwent either RP (n = 569) or EBRT (n = 322) with curative intent at our single institution between 2005 and 2012. Of the EBRT patients, 302 (93.8%) underwent intensity-modulated radiotherapy. Primary endpoints were overall survival (OS) and cancer-specific survival (CSS). Related to these, other-cause mortality (OCM) was also calculated. Biochemical recurrence-free survival was assessed as a secondary endpoint. Cox proportional hazards model was used for multivariate analysis.

Results

Median follow-up durations were 53 and 45 months, and median ages were 66 and 70 years (P <0.0001), in the RP and EBRT groups, respectively. As a whole, significantly better prognoses of the RP group than the EBRT group were observed for both OS and CSS, although OCM was significantly higher in the EBRT group. There was no death from PC in men with low and intermediate D’Amico risks, except one with intermediate-risk in the EBRT group. In high-risk patients, significantly more patients died from PC in the EBRT group than the RP group. Multivariate analysis demonstrated the RP group to be an independent prognostic factor for better CSS. On the other hand, the EBRT group had a significantly longer biochemical recurrence-free survival than the RP group.

Conclusions

Mortality outcomes of both RP and EBRT were generally favorable in low and intermediate risk patients. Improvement of CSS in high risk patients was seen in patients receiving RP over those receiving EBRT.     

Effect of Lactacidosis on Pyridine Nucleotide Stability During Ischemia in Mouse Brain

Brain levels of NADH and NAD+ were measured in three models of cerebral ischemia to determine whether degradation of the pyridine nucleotides is enhanced in models that generate high concentrations of lactic acid. Complete ischemia (decapitation), in which lactate increased to 14 mmol/kg, caused a gradual decrease in the NAD pool to 50% of control by 2 h. During focal ischemia (occlusion of the middle cerebral artery), the decrease in the NAD pool was less pronounced (82% of control at 2 h) despite the accentuated accumulation of lactate to 33 mmol/kg. In a third model (unilateral hypoxia-ischemia), pretreatment of animals with glucose augmented the ischemic elevation of lactate from 30 mmol/kg to 40 mmol/kg and greatly impaired restoration of energy metabolites during recirculation. However, glucose pretreatment had no effect on the size of the NAD pool during ischemia or early recovery. These results, therefore, demonstrate that the pyridine nucleotide pool is not rapidly degraded during ischemic insults that accumulate high concentrations of lactic acid. The stability of the NAD pool may have been enhanced by the limited increase in brain levels of NADH that occurred in these models of incomplete ischemia.     

KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates

Chromosome segregation during mitosis requires the assembly of a large proteinaceous structure termed the kinetochore. In Caenorhabditis elegans, KNL-1 is required to target multiple outer kinetochore proteins. Here, we demonstrate that the vertebrate KNL1 counterpart is essential for chromosome segregation and is required to localize a subset of outer kinetochore proteins. However, unlike in C. elegans, depletion of vertebrate KNL1 does not abolish kinetochore localization of the microtubule-binding Ndc80 complex. Instead, we show that KNL1 and CENP-K, a subunit of a constitutively centromere-associated complex that is missing from C. elegans, coordinately direct Ndc80 complex localization. Simultaneously reducing both hKNL1 and CENP-K function abolishes all aspects of kinetochore assembly downstream of centromeric chromatin and causes catastrophic chromosome segregation defects. These findings explain discrepancies in kinetochore assembly pathways between different organisms and reveal a surprising plasticity in the assembly mechanism of an essential cell division organelle.     

Genome-wide comparison of the His-to-Asp phosphorelay signaling components of three symbiotic genera of Rhizobia.

Histidine-to-aspartate (His-Asp) phosphorelay (or two-component) systems are very common signal transduction mechanisms that are implicated in a wide variety of cellular responses to environmental stimuli. The His-Asp phosphorelay components include "sensor histidine kinase (HK)", "phosphotransfer intermediate (HPt)", and "response regulator (RR)". With special reference to three bacterial species (Mesorhizobium loti, Bradyrhizobium japonicum, Sinorhizobium meliloti), each of which belongs to a different genera of Rhizobia, here we attempted to compile all of the His-Asp phosphorelay components in order to reveal a comparative genome-wide overview as to the His-Asp phosphorelay. It was revealed that M. loti has 47 HKs, 1 HPts, and 58 RRs; B. japonicum has 80 HKs, 3 HPts, and 91 RRs; whereas S. meliloti has 40 HKs, 1 HPt, and 58 RRs. These His-Asp phosphorelay components were extensively compiled and characterized. The resulting overview as to the His-Asp phosphorelay of Rhizobia will provide us with a basis for understanding of the fundamental mechanisms underlying interactions between plants and microorganisms (including symbiosis), as well as nitrogen fixation.