Plasma Membrane Ca ATPase Activity Enables Sustained Store-operated Ca Entry in the Absence of a Bulk Cytosolic Ca Rise.

In many cell types, the rise in cytosolic Ca due to opening of Ca release-activated Ca (CRAC) channels drives a plethora of responses, including secretion, motility, energy production, and gene expression. The amplitude and time course of the cytosolic Ca rise is shaped by the rates of Ca entry into and removal from the cytosol. However, an extended bulk Ca rise is toxic to cells.

AKAP79 Orchestrates a Cyclic AMP Signalosome Adjacent to Orai1 Ca Channels.

To ensure specificity of response, eukaryotic cells often restrict signalling molecules to sub-cellular regions. The Ca nanodomain is a spatially confined signal that arises near open Ca channels. Ca nanodomains near store-operated Orai1 channels stimulate the protein phosphatase calcineurin, which activates the transcription factor NFAT1, and both enzyme and target are initially attached to the plasma membrane through the scaffolding protein AKAP79.

Specific N-cadherin-dependent pathways drive human breast cancer dormancy in bone marrow.

The challenge for treating breast cancer (BC) is partly due to long-term dormancy driven by cancer stem cells (CSCs) capable of evading immune response and resist chemotherapy. BC cells show preference for the BM, resulting in poor prognosis. CSCs use connexin 43 (Cx43) to form gap junctional intercellular communication with BM niche cells, fibroblasts, and mesenchymal stem cells (MSCs).

Mesenchymal Stem Cell-Secreted Extracellular Vesicles Instruct Stepwise Dedifferentiation of Breast Cancer Cells into Dormancy at the Bone Marrow Perivascular Region.

In the bone marrow (BM), breast cancer cells (BCC) can survive in dormancy for decades as cancer stem cells (CSC), resurging as tertiary metastasis. The endosteal region where BCCs exist as CSCs poses a challenge to target them, mostly due to the coexistence of endogenous hematopoietic stem cells. This study addresses the early period of dormancy when BCCs enter BM at the perivascular region to begin the transition into CSCs, which we propose as the final step in dormancy.

Signaling through Ca Microdomains from Store-Operated CRAC Channels.

Calcium (Ca) ion microdomains are subcellular regions of high Ca concentration that develop rapidly near open Ca channels in the plasma membrane or internal stores and generate local regions of high Ca concentration. These microdomains are remarkably versatile in that they activate a range of responses that differ enormously in both their temporal and spatial profile. In this review, we describe how Ca microdomains generated by store-operated calcium channels, a widespread and conserved Ca entry pathway, stimulate different signaling pathways, and how the spatial extent of a Ca microdomain can be influenced by Ca ATPase pumps.

Cost effectiveness of phosphorus removal processes in municipal wastewater treatment.

Meeting stringent phosphorus (P) discharge standards remains one of the major challenges for wastewater utilities due to increased economic burdens associated with advanced (i.e., secondary, tertiary) treatment processes.

Kinesin-dependent mechanism for controlling triglyceride secretion from the liver.

Despite massive fluctuations in its internal triglyceride content, the liver secretes triglyceride under tight homeostatic control. This buffering function is most visible after fasting, when liver triglyceride increases manyfold but circulating serum triglyceride barely fluctuates. How the liver controls triglyceride secretion is unknown, but is fundamentally important for lipid and energy homeostasis in animals.

Reconstitution of microtubule-dependent organelle transport.

Microtubule (MT)-based motor proteins transport many cellular factors to their functionally relevant locations within cells, and defects in transport are linked to human disease. Understanding the mechanism and regulation of this transport process in living cells is difficult because of the complex in vivo environment and limited means to manipulate the system. On the other hand, in vitro motility assays using purified motors attached to beads does not recapitulate the full complexity of cargo transport in vivo.

Teamwork in microtubule motors.

Diverse cellular processes are driven by the collective force from multiple motor proteins. Disease-causing mutations cause aberrant function of motors, but the impact is observed at a cellular level and beyond, therefore necessitating an understanding of cell mechanics at the level of motor molecules. One way to do this is by measuring the force generated by ensembles of motors in vivo at single-motor resolution.

Quantitative optical trapping on single organelles in cell extract.

We have developed an optical trapping method to precisely measure the force generated by motor proteins on single organelles of unknown size in cell extract. This approach, termed VMatch, permits the functional interrogation of native motor complexes. We apply VMatch to measure the force, number and activity of kinesin-1 on motile lipid droplets isolated from the liver of normally fed and food-deprived rats.

Synthesis and detection of oxygen-18 labeled phosphate.

Phosphorus (P) has only one stable isotope and therefore tracking P dynamics in ecosystems and inferring sources of P loading to water bodies have been difficult. Researchers have recently employed the natural abundance of the ratio of (18)O/(16)O of phosphate to elucidate P dynamics. In addition, phosphate highly enriched in oxygen-18 also has potential to be an effective tool for tracking specific sources of P in the environment, but has so far been used sparingly, possibly due to unavailability of oxygen-18 labeled phosphate (OLP) and uncertainty in synthesis and detection.

Tug-of-war between dissimilar teams of microtubule motors regulates transport and fission of endosomes.

Intracellular transport is interspersed with frequent reversals in direction due to the presence of opposing kinesin and dynein motors on organelles that are carried as cargo. The cause and the mechanism of reversals are unknown, but are a key to understanding how cargos are delivered in a regulated manner to specific cellular locations. Unlike established single-motor biophysical assays, this problem requires understanding of the cooperative behavior of multiple interacting motors.

The ICIR--a clinical tool for assessment of critical incidents in various settings.

The assessment of critical incidents (CI) in hospitals and outpatient services has become a crucial issue in the last decade. There is a growing demand by the authorities and insurance companies to implement strategies and tools to deal with it. A new tool for the assessment of the CI in the setting of psychiatric service - both inpatient and outpatient - is introduced.

Cost effectiveness, safety, and satisfaction with video telepsychiatry versus face-to-face care in ambulatory settings.

Videoconference telepsychiatry provides an alternative for the psychiatric treatment of mental health patients who reside in remote communities. The objective of this study was to compare institutional ambulatory and hospitalization costs, treatment adherence, patient and physician satisfaction, and treatment safety between mental healthcare via videoconferencing and care provided in person. Data collected for 1 year of telepsychiatry treatment was compared to that of the preceding year and a matched comparison group.

Serotonin transporter characteristics in lymphocytes and platelets of male aggressive schizophrenia patients compared to non-aggressive schizophrenia patients.

A large body of literature indicates that disturbances of central serotonin (5-HT) function play an important role in aggressive behavior. Results from open-label and placebo-controlled trials as well as the reported inverse relationship between 5-HT function and aggression in human subjects, suggest that reduced 5-HT activity is associated with aggressive behavior. The activity of the 5-HT transporter (5-HTT), as determined by [(3)H]5-HT uptake to blood lymphocytes, was measured in 20 currently aggressive and 20 non-aggressive male schizophrenia patients.

Pindolol augmentation in aggressive schizophrenic patients: a double-blind crossover randomized study.

Treatment of aggression in schizophrenic patients is a major challenge. We sought to examine the efficacy of augmentation of antipsychotic treatment with pindolol in the amelioration of aggression. Thirty male inpatients meeting DSM-IV criteria for schizophrenia, aged 20-65 years involved in four or more aggressive incidents in the two previous months, were enrolled in a double-blind crossover study.

Differences in quality of life domains and psychopathologic and psychosocial factors in psychiatric patients.

Background: Although treatment of severe mental disorders should strive to optimize quality of life (QOL) for the individual patient, little is known about variations in QOL domains and related psychopathologic and psychosocial factors in patients suffering from schizophrenia, schizoaffective disorder, and/or mood disorders. We hypothesized that QOL in severe mental disorder patients would have a more substantial relationship with psychosocial factors than with illness-associated factors.

Method: A case-control, cross-sectional design was used to examine QOL of 210 inpatients who met DSM-IV criteria for a severe mental disorder and who were consecutively admitted to closed, open, and rehabilitation wards.

Homicidal behavior in schizophrenia associated with a genetic polymorphism determining low catechol O-methyltransferase (COMT) activity.

Although aggressive, violent, and dangerous behavior in man has multifactorial causes, genetic factors are estimated by twin and adoption studies to substantially contribute to the development of such conduct. Recently, homozygosity of a low enzyme activity variant of the catechol O-methyltransferase (COMT) gene was reported to be associated with aggressive behavior in a group of schizophrenic patients. We observe a similar tendency in a group of 30 schizophrenic patients who were confined to a maximum-security psychiatric facility for homicide.

The sleeping aviator--aeromedical disposition of Kleine-Levin syndrome.

We present the case of an aviator with Kleine Levin syndrome (KLS). History, physical examination, and special studies presented confirm the diagnosis of this syndrome. Our patient presented as an atypical case of KLS with respect to the presenting symptoms and to frequency of the episodes (6 years apart).

Calcium binding to bile salts.

Calcium binding to bile salt monomers and micelles is an important issue with respect to the possible (but rare) precipitation of calcium bile salts in the gallbladder. In the present work the binding of Ca2+ to six bile salts was measured in solutions containing 2 to 100 mM bile salts by means of a calcium-sensitive dye, murexide, which determines the ionic calcium concentration. In solutions containing bile salt at concentration higher than 20 mM most, if not all, of the bound Ca2+ is associated with micellar surfaces.