Myosin 1a Regulates Osteoblast Differentiation Independent of Intestinal Calcium Transport.

Myosin 1A (Myo1a) is a mechanoenzyme previously thought to be located exclusively in the intestinal epithelium. It is the principle calmodulin-binding protein of the brush border. Based on earlier studies in chickens, we hypothesized that Myo1a facilitates calcium transport across the brush border membrane of the intestinal epithelium, perhaps in association with the calcium channel Trpv6. Working with C2Bbe1 cells, a human intestinal epithelial cell line, we observed that overexpression of Myo1a increased, whereas the antisense construct blocked calcium transport. To further test this hypothesis, we examined mice in which either or both Myo1a and Trpv6 had been deleted. Although the Trpv6-null mice had decreased intestinal calcium transport, the Myo1a-null mouse did not, disproving our original hypothesis, at least in mice. Expecting that a reduction in intestinal calcium transport would result in decreased bone, we examined the skeletons of these mice. To our surprise, we found no decrease in bone in the Trpv6-null mouse, but a substantial decrease in the Myo1a-null mouse. Double deletions were comparable to the Myo1a null. Moreover, Myo1a but not Trpv6 was expressed in osteoblasts. In vitro, the bone marrow stromal cells from the Myo1a-null mice showed normal numbers of colony-forming units but marked decrements in the formation of alkaline phosphatase-positive colonies and mineralized nodules. We conclude that Myo1a regulates osteoblast differentiation independent of its role, if any, in intestinal calcium transport, whereas Trpv6 functions primarily to promote intestinal calcium transport with little influence in osteoblast function

Multi-Scale Information, Network, Causality, and Dynamics: Mathematical Computation and Bayesian Inference to Cognitive Neuroscience and Aging

The human brain is estimated to contain 100 billion or so neurons and 10 thousand times as many connections. Neurons never function in isolation: each of them is connected to 10, 000 others and they interact extensively every millisecond. Brain cells are organized into neural circuits often in a dynamic way, processing specific types of information and providing th

Vortex signal detection method with stochastic resonance based on adaptive coupled feedback control

The control of stochastic resonance is the key to its application. A feedback method is proposed to control the generation of stochastic resonance with coupling, and then enhance resonance effect with the optimization of control parameters. The method is applied to detect vortex signal. Artificial fish swarm algorithm is used to adjust the control variables adaptively, thus the optimal control of the coupled bistable stochastic resonance is realized. Numerical simulation and experimental results manifest that by this means the resonance effect can be enhanced effectively, the signal-to-noise ratio (SNR) of vortex signal can be improved, and the vortex shedding frequency can be obtained accurately

Group-Based Asynchronous Distributed Alternating Direction Method of Multipliers in Multicore Cluster

The distributed alternating direction method of multipliers (ADMM) algorithm is one of the effective methods to solve the global consensus optimization problem. Considering the differences between the communication of intra-nodes and inter-nodes in multicore cluster, we propose a group-based asynchronous distributed ADMM (GAD-ADMM) algorithm: based on the traditional star topology network, the grouping layer is added. The workers are grouped according to the process allocation in nodes and model similarity of datasets, and the group local variables are used to replace the local variables to compute the global variable. The algorithm improves the communication efficiency of the system by reducing communication between nodes and accelerates the convergence speed by relaxing the global consistency constraint. Finally, the algorithm is used to solve the logistic regression problem in a multicore cluster. The experiments on the Ziqiang 4000 showed that the GAD-ADMM reduces the system time cost by 35 % compared with the AD-ADMM

Rapid onset of hypercalcemia from high-grade lymphoma in the setting of HIV-related immune reconstitution inflammatory syndrome.

Hypercalcemia in HIV patients has been previously reported, but 1,25-(OH)2 vitamin D-mediated hypercalcemia, due to increased activity of extrarenal 1-alpha hydroxylase, is rarely described with HIV-related infections or malignancies. We describe a case of 1,25-(OH)2 vitamin D-mediated hypercalcemia in a patient presenting with progressive cognitive decline and weakness. Initial evaluation revealed a new diagnosis of HIV, for which he was started on antiretroviral therapy (ART). He was also noted to have mild asymptomatic hypocalcemia, likely from his acute illness and malnutrition, which was not further investigated at the time. While the patient's mental status initially improved with ART, he became progressively delirious and was found to be hypercalcemic approximately 4 weeks after the initiation of ART. Possible etiologies for hypercalcemia were vigorously evaluated, including granulomatous disease, infection, and malignancy, in the setting of suspected immune reconstitution inflammatory syndrome (IRIS), due to recent initiation of ART. Infectious workup was unrevealing, but computed tomography (CT) of the chest, abdomen, and pelvis revealed new extensive diffuse lymphadenopathy and hepatomegaly, not present on admission studies. Cytology and flow cytometry of a liver biopsy specimen revealed CD10 positive high-grade B-cell lymphoma. Chemotherapy was not pursued due to poor performance status. Over the next week, spontaneous tumor lysis developed, and the patient expired. Postmortem, his 1,25-(OH)2 vitamin D level returned as markedly elevated. Immunohistochemical staining of his liver biopsy tissue showed strong expression of CYP27B1. 1,25-(OH)2 vitamin D-mediated hypercalcemia is uncommon in a patient with newly diagnosed HIV and, in this case, was likely due to IRIS unmasking an underlying high-grade lymphoma and restoration of immune function (including T-cells and cytokine production). This case emphasizes the importance of including aggressive lymphomas, capable of progressing over days to weeks, in the evaluation of hypercalcemia in HIV patients at risk for developing IRIS and the rapid dynamic changes in mineral homeostasis that can occur with such an aggressive tumor in an immunocompromised host