Relational Ecology: A Theoretical Framework for Understanding the Human-Animal Bond

This qualitative study investigated the perceived impact of companion animals on the psychological well-being of lesbian women over age 65. Twelve women, ranging in age from 65-80, were interviewed with a semi-structured interview guide. Four thematic findings are highlighted: love and attachment, animals in transitional spaces, challenges and rewards of caregiving, and preparation for death. The author offers the term relational ecology to explain how animals contribute to well-being. This integrates the growth task model of human development, object relations theory, liminality, and deep ecology

Lifesaving in Every Way: The Role of Companion Animals in the Lives of Older Lesbian, Gay, Bisexual, and Transgender Adults Age 50 and Over

This study uses mixed-methods data and a life-course perspective to explore the role of pets in the lives of lesbian, gay, bisexual, and transgender (LGBT) adults age 50 and over and addresses the following research questions: (1) How does having a pet relate to perceived social support and social network size? and (2) how do LGBT older adults describe the meaning of pets in their lives? The qualitative data (N = 59) were collected from face-to-face interviews, and the quantitative data (N = 2,560) were collected via surveys from a sample across the United States. Qualitative findings show that pets are characterized as kin and companions and provide support; we also explore why participants do not have pets. The quantitative findings show that LGBT older adults with a pet had higher perceived social support; those with a disability and limited social network size, who had a pet had significantly higher perceived social support than those without a pet

Phase-Locked Signals Elucidate Circuit Architecture of an Oscillatory Pathway

This paper introduces the concept of phase-locking analysis of oscillatory cellular signaling systems to elucidate biochemical circuit architecture. Phase-locking is a physical phenomenon that refers to a response mode in which system output is synchronized to a periodic stimulus; in some instances, the number of responses can be fewer than the number of inputs, indicative of skipped beats. While the observation of phase-locking alone is largely independent of detailed mechanism, we find that the properties of phase-locking are useful for discriminating circuit architectures because they reflect not only the activation but also the recovery characteristics of biochemical circuits. Here, this principle is demonstrated for analysis of a G-protein coupled receptor system, the M3 muscarinic receptor-calcium signaling pathway, using microfluidic-mediated periodic chemical stimulation of the M3 receptor with carbachol and real-time imaging of resulting calcium transients. Using this approach we uncovered the potential importance of basal IP3 production, a finding that has important implications on calcium response fidelity to periodic stimulation. Based upon our analysis, we also negated the notion that the Gq-PLC interaction is switch-like, which has a strong influence upon how extracellular signals are filtered and interpreted downstream. Phase-locking analysis is a new and useful tool for model revision and mechanism elucidation; the method complements conventional genetic and chemical tools for analysis of cellular signaling circuitry and should be broadly applicable to other oscillatory pathways

Attenuation of Canonical Transient Receptor Potential-Like Channel 6 Expression Specifically Reduces the Diacylglycerol-Mediated Increase in Intracellular Calcium in Human Myometrial Cells

An increase in intracellular Ca2+ ([Ca2+]i) as a result of release of Ca2+ from intracellular stores or influx of extracellular Ca2+ contributes to the regulation of smooth muscle contractile activity. Human uterine smooth muscle cells exhibit receptor-, store-, and diacylglycerol (OAG)-mediated extracellular Ca2+-dependent increases in [Ca2+]i (SRCE) and express canonical transient receptor potential-like channels (TRPC) mRNAs (predominantly TRPC1, -4, and -6) that have been implicated in SRCE. To determine the role of TRPC6 in human myometrial SRCE, short hairpin RNA constructs were designed that effectively targeted a TRPC6 mRNA reporter for degradation. One sequence was used to produce an adenovirus construct (TC6sh1). TC6sh1 reduced TRPC6 mRNA but not TRPC1, -3, -4, -5, or -7 mRNAs in PHM1-41 myometrial cells. Compared with uninfected cells or cells infected with empty vector, the increase in [Ca2+]i in response to OAG was specifically inhibited by TC6sh1, whereas SRCE responses elicited by either oxytocin or thapsigargin were not changed. Similar findings were observed in primary pregnant human myometrial cells. When PHM1-41 cells were activated by OAG in the absence of extracellular Na+, the increase in [Ca2+]i was partially reduced. Furthermore, pretreatment with nifedipine, an L-type calcium channel blocker, also partially reduced the OAG-induced [Ca2+]i increase. Similar effects were observed in primary human myometrial cells. These findings suggest that OAG activates channels containing TRPC6 in myometrial cells and that these channels act via both enhanced Na+ entry coupled to activation of voltage-dependent Ca2+ entry channels and a nifedipine-independent Ca2+ entry mechanism to promote elevation of intracellular Ca2+

2-APB-potentiated channels amplify CatSper-induced Ca signals in human sperm

Ca(2+)(i) signalling is pivotal to sperm function. Progesterone, the best-characterized agonist of human sperm Ca(2+)(i) signalling, stimulates a biphasic [Ca(2+)](i) rise, comprising a transient and subsequent sustained phase. In accordance with recent reports that progesterone directly activates CatSper, the [Ca(2+)](i) transient was detectable in the anterior flagellum (where CatSper is expressed) 1–2 s before responses in the head and neck. Pre-treatment with 5 μM 2-APB (2-aminoethoxydiphenyl borate), which enhances activity of store-operated channel proteins (Orai) by facilitating interaction with their activator [STIM (stromal interaction molecule)] ‘amplified’ progesterone-induced [Ca(2+)](i) transients at the sperm neck/midpiece without modifying kinetics. The flagellar [Ca(2+)](i) response was unchanged. 2-APB (5 μM) also enhanced the sustained response in the midpiece, possibly reflecting mitochondrial Ca(2+) accumulation downstream of the potentiated [Ca(2+)](i) transient. Pre-treatment with 50–100 μM 2-APB failed to potentiate the transient and suppressed sustained [Ca(2+)](i) elevation. When applied during the [Ca(2+)](i) plateau, 50–100 μM 2-APB caused a transient fall in [Ca(2+)](i), which then recovered despite the continued presence of 2-APB. Loperamide (a chemically different store-operated channel agonist) enhanced the progesterone-induced [Ca(2+)](i) signal and potentiated progesterone-induced hyperactivated motility. Neither 2-APB nor loperamide raised pH(i) (which would activate CatSper) and both compounds inhibited CatSper currents. STIM and Orai were detected and localized primarily to the neck/midpiece and acrosome where Ca(2+) stores are present and the effects of 2-APB are focussed, but store-operated currents could not be detected in human sperm. We propose that 2-APB-sensitive channels amplify [Ca(2+)](i) elevation induced by progesterone (and other CatSper agonists), amplifying, propagating and providing spatio-temporal complexity in [Ca(2+)](i) signals of human sperm