Expression and purification of functional human glycogen synthase-1:glycogenin-1 complex in insect cells

We report the successful expression and purification of functional human muscle glycogen synthase (GYS1) in complex with human glycogenin-1 (GN1). Stoichiometric GYS1:GN1 complex was produced by co-expression of GYS1 and GN1 using a bicistronic pFastBac™-Dual expression vector, followed by affinity purification and subsequent size-exclusion chromatography. Mass spectrometry analysis identified that GYS1 is phosphorylated at several well-characterised and uncharacterised Ser/Thr residues. Biochemical analysis, including activity ratio (in the absence relative to that in the presence of glucose-6-phosphate) measurement, covalently attached phosphate estimation as well as phosphatase treatment, revealed that recombinant GYS1 is substantially more heavily phosphorylated than would be observed in intact human or rodent muscle tissues. A large quantity of highly-pure stoichiometric GYS1:GN1 complex will be useful to study its structural and biochemical properties in the future, which would reveal mechanistic insights into its functional role in glycogen biosynthesis

A Simulation of the Policy of Public Pension Finance in Japan

The purpose of this paper is to estimate the total sum of premium payments and benefit payments from 2005 to 2010 and make proposals for future policy. This study has made clear that there is a tendency of a total decrease in premium payments. Moreover, the sum of premiums will be less than the sum of benefit payments to be paid. Therefore, our proposal is benefit cutting, raising of the starting age of benefit payments and raising premium payments. Thus we will be able to save a total of 17.42 trillion yen in finance for the public pension system

An Observation of Worker Duty Recognition at Hospitals and Elder Care Facilities Separately

In this study, we examined measures that could be implemented in personnel affairs and management to insure longer stability in the workforce of hospitals and elder care facilities, by grasping the characteristics of the conditions at both institutions and comparing them. First, we made a factor analysis for 38 question items and set up a duties recognition standard according to hospitals and elder care facilities. As a result, five factors of similar content were obtained for both institutions. Next, we calculated the mean of the duties recognition standard according to each characteristic. The results showed that care workers at hospitals had a lower "sense of purpose." In contrast, in elder care facilities, the lower "sense of purpose" was among nurses. In addition, the over-20-years group of workers had the lowest "stress reactors" at hospitals, but the "work burden" was the highest. Furthermore, an analysis of the relationship between the "duties recognition standard" and "job satisfaction" showed the "continuation awareness" of nurses and care workers at hospitals was lower than other types of jobs. It also showed that the nurses at elder care facilities had a lower "sense of belonging." Finally, in the relevance analysis of the duties recognition standard with job satisfaction, we found that in both hospitals and elder care facilities, "continuation awareness," "sense of belonging" and "office environmental awareness" in common have the strongest equilateral correlation with "human relations in the office.

Regulating the Motor for GLUT4 Vesicle Traffic

Insulin-triggered trafficking of GLUT4 glucose transporter-loaded vesicles and their fusion with the plasma membrane are mechanical processes involving multiprotein complexes that coordinate and facilitate vesicle movement. Now, Yip et al. (2008) link myosin-1c to insulin signaling by demonstrating direct CaMKII-driven phosphorylation of this critical motor protein

Can neap-spring tidal cycles modulate biogeochemical fluxes in the abyssal near-seafloor water column?

Before particulate matter that settles as ‘primary flux’ from the interior ocean is deposited into deep-sea sediments it has to traverse the benthic boundary layer (BBL) that is likely to cover almost all parts of the seafloor in the deep seas. Fluid dynamics in the BBL differ vastly from fluid dynamics in the overlying water column and, consequently, have the potential to lead to quantitative and compositional changes between primary and depositional fluxes. Despite this potential and the likely global relevance very little is known about mechanistic and quantitative aspects of the controlling processes. Here, results are presented for a sediment-trap time-series study that was conducted on the Porcupine Abyssal Plain in the abyssal Northeast Atlantic, with traps deployed at 2, 40 and 569 m above bottom (mab). The two bottommost traps were situated within the BBL-affected part of the water column. The time series captured 3 neap and 4 spring tides and the arrival of fresh settling material originating from a surface-ocean bloom. In the trap-collected material, total particulate matter (TPM), particulate inorganic carbon (PIC), biogenic silica (BSi), particulate organic carbon (POC), particulate nitrogen (PN), total hydrolysable amino acids (AA), hexosamines (HA) and lithogenic material (LM) were determined. The biogeochemical results are presented within the context of time series of measured currents (at 15 mab) and turbidity (at 1 mab). The main outcome is evidence for an effect of neap/spring tidal oscillations on particulate-matter dynamics in BBL-affected waters in the deep sea. Based on the frequency-decomposed current measurements and numerical modelling of BBL fluid dynamics, it is concluded that the neap/spring tidal oscillations of particulate-matter dynamics are less likely due to temporally varying total free-stream current speeds and more likely due to temporally and vertically varying turbulence intensities that result from the temporally varying interplay of different rotational flow components (residual, tidal, near-inertial) within the BBL. Using information from previously published empirical and theoretical relations between fluid and biogeochemical dynamics at the scale of individual particle aggregates, a conceptual and semi-quantitative picture of a mechanism was derived that explains how the neap/spring fluid-dynamic oscillations may translate through particle dynamics into neap/spring oscillations of biogeochemical aggregate decomposition (microbially driven organic-matter breakdown, biomineral dissolution). It is predicted that, during transitions from neap into spring tides, increased aggregation in near-seafloor waters and/or reduced deposition of aggregates at the seafloor coincides with reduced biogeochemical particulate-matter decomposition in near-seafloor waters. By contrast, during transitions from spring into neap tides, enhanced biogeochemical particulate-matter decomposition in near-seafloor waters is predicted to coincide with increased deposition of particulate matter at the seafloor. This study suggests that, in addition to current speed, the specifics and subtleties of the interplay of different rotational flow components can be an important control on how the primary flux from the interior ocean is translated into the depositional flux, with potential implications for sedimentary carbon deposition, benthic food supply and possibly even the sedimentary records of environmental change

Küttner's tumor of the sub-mandibular gland associated with fibrosclerosis and follicular hyperplasia of regional lymph nodes: a case report

<p>Abstract</p> <p>Introduction</p> <p>Küttner's tumor is characterized through histology by peri-ductal fibrosis, dense lymphocytic infiltration with lymphoid follicles, loss of acini, and occasional marked sclerosis of the salivary gland. On occasion, Küttner's tumor can be difficult to distinguish from malignant neoplasm.</p> <p>Case presentation</p> <p>A 58-year-old Japanese man was referred to our hospital with a three-month history of a painless swollen mass in the right sub-mandibular region. Histological findings revealed both lymphoid follicles with reactive germinal centers and variously sized lymphoid follicle-like nodules without definitive germinal centers or mantle zones. B-cells of similar size and shape occupied the lymphoid follicle-like nodules and stained positive for B-cell lymphoma. These cells were detected in the polyclonal B-cells by flow cytometric analysis and tested negative for CD10. Unusual B-cell proliferation was observed, but as there was no definitive evidence of B-cell lymphoma, the lesion was diagnosed as Küttner's tumor.</p> <p>Conclusion</p> <p>We report on a rare case of Küttner's tumor associated with fibrosclerosis and atypical lymphoid hyperplasia in both the sub-mandibular gland and regional lymph nodes. Although more cases need to be investigated, our findings might be helpful to further studies seeking to clarify the etiology of idiopathic sclerosing lesions arising in the organs and regional lymph nodes.</p

Molecular mechanism of action of metformin: old or new insights?

Metformin is the first-line drug treatment for type 2 diabetes. Globally, over 100 million patients are prescribed this drug annually. Metformin was discovered before the era of target-based drug discovery and its molecular mechanism of action remains an area of vigorous diabetes research. An improvement in our understanding of metformin's molecular targets is likely to enable target-based identification of second-generation drugs with similar properties, a development that has been impossible up to now. The notion that 5' AMP-activated protein kinase (AMPK) mediates the anti-hyperglycaemic action of metformin has recently been challenged by genetic loss-of-function studies, thrusting the AMPK-independent effects of the drug into the spotlight for the first time in more than a decade. Key AMPK-independent effects of the drug include the mitochondrial actions that have been known for many years and which are still thought to be the primary site of action of metformin. Coupled with recent evidence of AMPK-independent effects on the counter-regulatory hormone glucagon, new paradigms of AMPK-independent drug action are beginning to take shape. In this review we summarise the recent research developments on the molecular action of metformi