SPEG Controls Calcium Re-Uptake into the Sarcoplasmic Reticulum Through Regulating SERCA2a by Its Second Kinase-Domain

Rationale: Striated muscle preferentially expressed protein kinase (SPEG) has two kinase-domains and is critical for cardiac development and function. However, it is not clear how these two kinase-domains function to maintain cardiac performance.Objective: To determine the molecular functions of the two kinase-domains of SPEG. M Methods and Results: A proteomics approach identified sarcoplasmic/endoplasmic reticulum calcium-ATPase 2a (SERCA2a) as a protein interacting with the second kinase-domain but not the first kinase-domain of SPEG. Furthermore, the second kinase-domain of SPEG could phosphorylate Thr484 on SERCA2a, promote its oligomerization and increase calcium re-uptake into the sarcoplasmic/endoplasmic reticulum in culture cells and primary neonatal rat cardiomyocytes. Phosphorylation of SERCA2a by SPEG enhanced its calcium transporting activity without affecting its ATPase activity. Depletion of Speg in neonatal rat cardiomyocytes inhibited SERCA2a Thr484 phosphorylation and SR calcium re-uptake. Moreover, over-expression of SERCA2aThr484Ala mutant protein also slowed SR calcium re-uptake in neonatal rat cardiomyocytes. In contrast, domain-mapping and phosphorylation analysis revealed that the first kinase-domain of SPEG interacted and phosphorylated its recently-identified substrate junctophilin-2 (JPH2). An inducible heart-specific Speg knockout mouse model was generated to further study this SPEG-SERCA2a signal nexus in vivo. Inducible deletion of Speg decreased SERCA2a Thr484 phosphorylation and its oliogomerization in the heart. Importantly, inducible deletion of Speg inhibited SERCA2a calcium transporting activity and impaired calcium re-uptake into the SR in cardiomyocytes, which preceded morphological and functional alterations of the heart and eventually led to heart failure in adult mice.Conclusions: Our data demonstrate that the two kinase-domains of SPEG may play distinct roles to regulate cardiac function. The second kinase-domain of SPEG is a critical regulator for SERCA2a. Our findings suggest that SPEG may serve as a new target to modulate SERCA2a activation for treatment of heart diseases with impaired calcium homeostasis.</p

Multiconsensus of Second-Order Multiagent Systems with Input Delays

The multiconsensus problem of double-integrator dynamic multiagent systems has been investigated. Firstly, the dynamic multiconsensus, the static multiconsensus, and the periodic multiconsensus are considered as three cases of multiconsensus, respectively, in which the final multiconsensus convergence states are established by using matrix analysis. Secondly, as for the multiagent system with input delays, the maximal allowable upper bound of the delays is obtained by employing Hopf bifurcation of delayed networks theory. Finally, simulation results are presented to verify the theoretical analysis

Synchronous Gastric Carcinoma and Nodal Malignant Lymphoma: A Rare Case Report and Literature Review

Synchronous double malignancies of gastric carcinoma (GC) and malignant lymphoma (ML) are rare and very difficult to treat. We report a case of synchronous GC and nodal ML, regarding which clinical and pathological features and treatment are discussed. A 68-year-old woman with a history of inguinal hernia was admitted for abdominal pain and high fever and subsequently underwent herniorrhaphy, but the fever remained. Computerized tomography showed a stomach mass and multiple enlarged lymph nodes in the abdominal cavity and inguinal regions. Gastric adenocarcinoma coexistent with advanced in situ follicular lymphoma was confirmed by endoscopy, biopsy of inguinal lymph nodes and bone marrow examination. Two chemotherapy regimens, R-CHOP (rituximab, cyclophosphamide, perarubicin, vincristine and prednisone) and systemic therapy (5-fluorouracil and calcium folinate) combined with regional perfusion (oxaliplatin and etoposide) through the left gastric artery were performed at intervals against ML and GC, respectively. Partial remission in both tumors was achieved after 4 courses of treatment, but the patient finally died of heart failure. Scrupulous biopsy of non-draining lymph nodes in patients with gastrointestinal carcinomas is supposed to improve the diagnostic rate of simultaneous nodal ML. The interval chemotherapy strategy with two independent regimens is beneficial for such patients, especially for those unable to tolerate major surgery

Rapid Remission in Peripheral T-Cell Lymphoma of the Nasal Type by the Bortezomib plus CHOP Therapy

Peripheral T-cell lymphoma (PTCL) is rare and difficult to treat for its high relapse rate. The authors report a case of PTCL of the skin, regarding which clinical and pathological features, treatment, and prognosis were discussed. A 66-year-old woman was admitted with complaints of enlarging erythematous noduloplaques on the right anterior tibial skin for one year and similar lesions on the left for 6 months. Surgical resection of right leg lesion and biopsy of enlarged inguinal lymph nodes histologically indicated a PTCL of the nasal type. The patient was treated by CHOP plus bortezomib, reached complete remission just after two courses of chemotherapy and then received another two as consolidation. The patient remained in remission for 11 months until local relapse. As for cutaneous lesions, detailed lymph node examination and prompt tissue biopsy are judicious choices prior to any medical management. The chemotherapy consisting of bortezomib and CHOP is safe and efficient in PTCL of the skin

Surface/interface Energy Effect on Electromechanical Responses Around a Nanosized Elliptical Inclusion under Far-field Loading at an Arbitrary Angle

Electro-elastic surface/interface around nano-sized piezoelectric inclusions shows great effect on the response of piezoelectric nano-structures. In this paper, a theoretical model is proposed to examine the surface/interface effect on the electromechanical responses around a nano-sized elliptical piezoelectric inclusion embedded in an infinite piezoelectric matrix under far-field loading with an arbitrary angle, and the effect of loading angle is considered Combining the conformal mapping technique and electro-elastic surface/interface theory, a closed form solution of this problem is obtained and the interactive effect between the surface/interface and the aspect ratio of the elliptical inclusion is examined

The LAMOST Survey of Background Quasars in the Vicinity of the Andromeda and Triangulum Galaxies -- II. Results from the Commissioning Observations and the Pilot Surveys

We present new quasars discovered in the vicinity of the Andromeda and Triangulum galaxies with the LAMOST during the 2010 and 2011 observational seasons. Quasar candidates are selected based on the available SDSS, KPNO 4 m telescope, XSTPS optical, and WISE near infrared photometric data. We present 509 new quasars discovered in a stripe of ~135 sq. deg from M31 to M33 along the Giant Stellar Stream in the 2011 pilot survey datasets, and also 17 new quasars discovered in an area of ~100 sq. deg that covers the central region and the southeastern halo of M31 in the 2010 commissioning datasets. These 526 new quasars have i magnitudes ranging from 15.5 to 20.0, redshifts from 0.1 to 3.2. They represent a significant increase of the number of identified quasars in the vicinity of M31 and M33. There are now 26, 62 and 139 known quasars in this region of the sky with i magnitudes brighter than 17.0, 17.5 and 18.0 respectively, of which 5, 20 and 75 are newly-discovered. These bright quasars provide an invaluable collection with which to probe the kinematics and chemistry of the ISM/IGM in the Local Group of galaxies. A total of 93 quasars are now known with locations within 2.5 deg of M31, of which 73 are newly discovered. Tens of quasars are now known to be located behind the Giant Stellar Stream, and hundreds behind the extended halo and its associated substructures of M31. The much enlarged sample of known quasars in the vicinity of M31 and M33 can potentially be utilized to construct a perfect astrometric reference frame to measure the minute PMs of M31 and M33, along with the PMs of substructures associated with the Local Group of galaxies. Those PMs are some of the most fundamental properties of the Local Group.Comment: 26 pages, 6 figures, AJ accepte