The Effect of Calcium Ions on Mechanosensation and Neuronal Activity in Proprioceptive Neurons

Proprioception of all animals is important in being able to have coordinated locomotion. Stretch activated ion channels (SACs) transduce the mechanical force into electrical signals in the proprioceptive sensory endings. The types of SACs vary among sensory neurons in animals as defined by pharmacological, physiological and molecular identification. The chordotonal organs within insects and crustaceans offer a unique ability to investigate proprioceptive function. The effects of the extracellular environment on neuronal activity, as well as the function of associated SACs are easily accessible and viable in minimal saline for ease in experimentation. The effect of extracellular [Ca2+] on membrane properties which affect voltage-sensitivity of ion channels, threshold of action potentials and SACs can be readily addressed in the chordotonal organ in crab limbs. It is of interest to understand how low extracellular [Ca2+] enhances neural activity considering the SACs in the sensory endings could possibly be Ca2+ channels and that all neural activity is blocked with Mn2+. It is suggested that axonal excitability might be affected independent from the SAC activity due to potential presence of calcium activated potassium channels (K(Ca)) and the ability of Ca2+ to block voltage gated Na+ channels in the axons. Separating the role of Ca2+ on the function of the SACs and the excitability of the axons in the nerves associated with chordotonal organs is addressed. These experiments may aid in understanding the mechanisms of neuronal hyperexcitability during hypocalcemia within mammals

Prognostic value of hematogenous dissemination and biological profile of the tumor in early breast cancer patients: A prospective observational study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate the incidence and prognostic value of disseminated tumor cells in bone marrow of breast carcinoma patients with early disease, and to analyze this finding in relation to lymph node involvement, determined by sentinel lymph node (SLN) biopsy analysis, and to prognostic factors of interest.</p> <p>Methods</p> <p>104 patients with operable (T < 3 cm) breast cancer and clinically- and sonographically-negative axillary lymph nodes were scheduled for SLN biopsy. Bone marrow aspirates were collected before the start of surgery from both iliac crests, and mononuclear cell layers were separated by density centrifugation (Lymphoprep). Slide preparations were then examined for the presence of disseminated tumor cells by immunocytochemistry with anti-cytokeratin antibodies (A45-B/B3). Lymphoscintigraphy was performed 2 hours after intratumor administration of 2 mCi (74 MBq) of 99mTc colloidal albumin. The SLN was evaluated for the presence of tumor cells by hematoxylin-eosin staining and, when negative, by immunocytochemistry using anti-cytokeratin antibody (CAM 5.2). Survival analyses and comparative analyses were performed on the results of bone marrow determinations, SLN biopsy, and known prognostic factors, including breast cancer subtypes according to the simplified classification based on ER, PR and HER2.</p> <p>Results</p> <p>Lymph node and hematogenous dissemination occur in one-third of patients with early-stage breast cancer, although not necessarily simultaneously. In our study, disseminated tumor cells were identified in 22% of bone marrow aspirates, whereas 28% of patients had axillary lymph node involvement. Simultaneous lymph node and bone marrow involvement was found in only 5 patients (nonsignificant). In the survival study (60 months), a higher, although nonsignificant rate of disease-related events (13%) was seen in patients with disseminated tumor cells in bone marrow, and a significant association of events was documented with the known, more aggressive tumor subtypes: triple negative receptor status (21%) and positive ERBB2 status (29%).</p> <p>Conclusions</p> <p>Tumor cell detection in bone marrow can be considered a valid prognostic parameter in patients with early disease. However, the classic prognostic factors remain highly relevant, and the newer breast cancer subtypes are also useful for this purpose.</p

The effect of extreme spring weather on body condition and stress physiology in Lapland longspurs and white-crowned sparrows breeding in the Arctic

AbstractClimate change is causing rapid shifts in temperature while also increasing the frequency, duration, and intensity of extreme weather. In the northern hemisphere, the spring of 2013 was characterized as extreme due to record high snow cover and low temperatures. Studies that describe the effects of extreme weather on phenology across taxa are limited while morphological and physiological responses remain poorly understood. Stress physiology, as measured through baseline and stress-induced concentrations of cortisol or corticosterone, has often been studied to understand how organisms respond to environmental stressors. We compared body condition and stress physiology of two long-distance migrants breeding in low arctic Alaska – the white-crowned sparrow (Zonotrichia leucophrys) and Lapland longspur (Calcarius lapponicus) – in 2013, an extreme weather year, with three more typical years (2011, 2012, and 2014). The extended snow cover in spring 2013 caused measureable changes in phenology, body condition and physiology. Arrival timing for both species was delayed 4–5days compared to the other three years. Lapland longspurs had reduced fat stores, pectoralis muscle profiles, body mass, and hematocrit levels, while stress-induced concentrations of corticosterone were increased. Similarly, white-crowned sparrows had reduced pectoralis muscle profiles and hematocrit levels, but in contrast to Lapland longspurs, had elevated fat stores and no difference in mass or stress physiology relative to other study years. An understanding of physiological mechanisms that regulate coping strategies is of critical importance for predicting how species will respond to the occurrence of extreme events in the future due to global climate change

Fecal Glucocorticoid Metabolites as Biomarkers in Equids: Assay Choice Matters

From Wiley via Jisc Publications RouterHistory: received 2020-05-06, rev-recd 2021-03-29, accepted 2021-04-09, pub-electronic 2021-06-01Article version: VoRPublication status: PublishedFunder: Royal Society; Id: http://dx.doi.org/10.13039/501100000288; Grant(s): UF110641Funder: Chester Zoo; Id: http://dx.doi.org/10.13039/501100005359; Grant(s): Conservation FellowshipABSTRACT: Free ranging animals are exposed to environmental, demographic, and ecological challenges over time, which can affect their health and fitness. Non‐invasive biomarkers can provide insight into how animals cope with these challenges and assess the effectiveness of conservation management strategies. We evaluated how free ranging ponies (Equus ferus caballus) on the Carneddau Mountain range, North Wales respond to 2 stimuli: an acute stressor of an annual roundup event in November 2014, and spatial and temporal variation in ecological factors in 2018. We evaluated fecal glucocorticoid metabolites using 2 enzyme immunoassays (EIAs): an 11‐oxoetiocholanolone EIA (measuring 11,17‐dioxoandrostanes [11,17‐DOAs]) and a corticosterone EIA. The former assay has been validated in equids, whereas there is limited evidence for the suitability of the latter. We used an additional parent testosterone EIA to measure fecal androgen metabolites in response to the ecological challenges. Following the roundup, the metabolite concentrations measured by the 2 glucocorticoid EIAs were not correlated. The 11,17‐DOAs were elevated from the second day following the roundup and then slowly returned to pre‐round levels over the next 2 weeks. In contrast, the metabolites measured by the corticosterone assay showed no response to the roundup. For the ecological data, all 3 assays detected a positive correlation between metabolites and social group size in males but not in females. The metabolite concentrations measured by the testosterone and corticosterone assays were highly correlated and were temporally associated with the onset of the breeding season, whereas the 11,17‐DOAs were not. The co‐variance of metabolites measured by the corticosterone and testosterone assays, and the lack of an acute response in the corticosterone assay to the roundup, suggests that metabolites detected by the corticosterone assay were not primarily associated with increased glucocorticoid production. We recommend using well‐validated fecal biomarker assays of hypothalamus‐pituitary‐adrenal axis activity to evaluate and compare the effect of different management interventions and environmental change. © 2021 The Authors. The Journal of Wildlife Management published by Wiley Periodicals LLC on behalf of The Wildlife Society

Breeding on the leading edge of a northward range expansion: differences in morphology and the stress response in the arctic Gambel's white-crowned sparrow

Individuals at the forefront of a range shift are likely to exhibit phenotypic traits that distinguish them from the population breeding within the historic range. Recent studies have examined morphological, physiological and behavioral phenotypes of individuals at the edge of their range. Several studies have found differences in the hypothalamic-pituitary-adrenal (HPA) axis activity in response to acute restraint stress in individuals at the range limits. HPA axis activation leads to elevations in glucocorticoids that regulate physiology and behavior. Here we compare the hormonal profiles and morphometrics from Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) breeding at the northern limit of the population's range to those birds breeding within the historic population range. Birds breeding at the northern limit experienced a harsher environment with colder temperatures; however, we found no differences in arthropod prey biomass between the northern limit and more southern (historic) sites. Males at the northern limit had higher body condition scores (mass corrected for body size) compared to individuals within the historic range, but no differences were found in beak and tarsus lengths, wing chord, muscle profile or fat stores. In males during the pre-parental stage, before breeding commenced, HPA axis activity was elevated in birds at the northern limit of the range, but no differences were found during the parental or molt stages. Females showed no differences in HPA axis activity during the parental stage. This study suggests that "pioneering" individuals at the limits of their breeding range exhibit physiology and morphology that are distinct from individuals within the historic range