Biomechanical analysis of the effect of congruence, depth and radius on the stability ratio of a simplistic ‘ball-and-socket’ joint model

Objectives The bony shoulder stability ratio (BSSR) allows for quantification of the bony stabilisers in vivo. We aimed to biomechanically validate the BSSR, determine whether joint incongruence affects the stability ratio (SR) of a shoulder model, and determine the correct parameters (glenoid concavity versus humeral head radius) for calculation of the BSSR in vivo. Methods Four polyethylene balls (radii: 19.1 mm to 38.1 mm) were used to mould four fitting sockets in four different depths (3.2 mm to 19.1mm). The SR was measured in biomechanical congruent and incongruent experimental series. The experimental SR of a congruent system was compared with the calculated SR based on the BSSR approach. Differences in SR between congruent and incongruent experimental conditions were quantified. Finally, the experimental SR was compared with either calculated SR based on the socket concavity or plastic ball radius. Results The experimental SR is comparable with the calculated SR (mean difference 10%, sd 8%; relative values). The experimental incongruence study observed almost no differences (2%, sd 2%). The calculated SR on the basis of the socket concavity radius is superior in predicting the experimental SR (mean difference 10%, sd 9%) compared with the calculated SR based on the plastic ball radius (mean difference 42%, sd 55%). Conclusion The present biomechanical investigation confirmed the validity of the BSSR. Incongruence has no significant effect on the SR of a shoulder model. In the event of an incongruent system, the calculation of the BSSR on the basis of the glenoid concavity radius is recommended

Presynaptic partner selection during retinal circuit reassembly varies with timing of neuronal regeneration in vivo

Whether neurons can restore their original connectivity patterns during circuit repair is unclear. Taking advantage of the regenerative capacity of zebrafish retina, we show here the remarkable specificity by which surviving neurons reassemble their connectivity upon regeneration of their major input. H3 horizontal cells (HCs) normally avoid red and green cones, and prefer ultraviolet over blue cones. Upon ablation of the major (ultraviolet) input, H3 HCs do not immediately increase connectivity with other cone types. Instead, H3 dendrites retract and re-extend to contact new ultraviolet cones. But, if regeneration is delayed or absent, blue-cone synaptogenesis increases and ectopic synapses are made with red and green cones. Thus, cues directing synapse specificity can be maintained following input loss, but only within a limited time period. Further, we postulate that signals from the major input that shape the H3 HC's wiring pattern during development persist to restrict miswiring after damage

Work-Unit Absenteeism: Effects of Satisfaction, Commitment, Labor Market Conditions, and Time

Prior research is limited in explaining absenteeism at the unit level and over time. We developed and tested a model of unit-level absenteeism using five waves of data collected over six years from 115 work units in a large state agency. Unit-level job satisfaction, organizational commitment, and local unemployment were modeled as time-varying predictors of absenteeism. Shared satisfaction and commitment interacted in predicting absenteeism but were not related to the rate of change in absenteeism over time. Unit-level satisfaction and commitment were more strongly related to absenteeism when units were located in areas with plentiful job alternatives

A Positive Feedback Synapse from Retinal Horizontal Cells to Cone Photoreceptors

Cone photoreceptors and horizontal cells (HCs) have a reciprocal synapse that underlies lateral inhibition and establishes the antagonistic center-surround organization of the visual system. Cones transmit to HCs through an excitatory synapse and HCs feed back to cones through an inhibitory synapse. Here we report that HCs also transmit to cone terminals a positive feedback signal that elevates intracellular Ca2+ and accelerates neurotransmitter release. Positive and negative feedback are both initiated by AMPA receptors on HCs, but positive feedback appears to be mediated by a change in HC Ca2+, whereas negative feedback is mediated by a change in HC membrane potential. Local uncaging of AMPA receptor agonists suggests that positive feedback is spatially constrained to active HC-cone synapses, whereas the negative feedback signal spreads through HCs to affect release from surrounding cones. By locally offsetting the effects of negative feedback, positive feedback may amplify photoreceptor synaptic release without sacrificing HC-mediated contrast enhancement

Calcium Homeostasis and Cone Signaling Are Regulated by Interactions between Calcium Stores and Plasma Membrane Ion Channels

Calcium is a messenger ion that controls all aspects of cone photoreceptor function, including synaptic release. The dynamic range of the cone output extends beyond the activation threshold for voltage-operated calcium entry, suggesting another calcium influx mechanism operates in cones hyperpolarized by light. We have used optical imaging and whole-cell voltage clamp to measure the contribution of store-operated Ca2+ entry (SOCE) to Ca2+ homeostasis and its role in regulation of neurotransmission at cone synapses. Mn2+ quenching of Fura-2 revealed sustained divalent cation entry in hyperpolarized cones. Ca2+ influx into cone inner segments was potentiated by hyperpolarization, facilitated by depletion of intracellular Ca2+ stores, unaffected by pharmacological manipulation of voltage-operated or cyclic nucleotide-gated Ca2+ channels and suppressed by lanthanides, 2-APB, MRS 1845 and SKF 96365. However, cation influx through store-operated channels crossed the threshold for activation of voltage-operated Ca2+ entry in a subset of cones, indicating that the operating range of inner segment signals is set by interactions between store- and voltage-operated Ca2+ channels. Exposure to MRS 1845 resulted in ∼40% reduction of light-evoked postsynaptic currents in photopic horizontal cells without affecting the light responses or voltage-operated Ca2+ currents in simultaneously recorded cones. The spatial pattern of store-operated calcium entry in cones matched immunolocalization of the store-operated sensor STIM1. These findings show that store-operated channels regulate spatial and temporal properties of Ca2+ homeostasis in vertebrate cones and demonstrate their role in generation of sustained excitatory signals across the first retinal synapse

Histories of forced sex and health outcomes among Southern African lesbian and bisexual women: a cross-sectional study

BACKGROUND: Experiences of forced sex have been shown to be prevalent in Southern Africa. Negative outcomes of forced sex have been documented in general populations of women and men and include alcohol abuse, drug use, mental health problems, mental distress, sexual health problems and poor overall health. This study is the first to examine experiences of forced sex and associated health problems among lesbian and bisexual women in Southern Africa. METHODS: This study is based on data collected as part of a collaborative endeavor involving various Southern African community-based organizations. Lesbian and bisexual women in four Southern African countries participated in a cross-sectional survey, for a total study sample of 591. RESULTS: Nearly one-third of participants had been forced to have sex at some time in their lives. Thirty-one percent of all women reported to have experienced forced sex at least once in their life: 14.9% reported forced sex by men only; 6.6% reported forced sex by women only; 9.6% had had forced sexual experiences with both men and women. Participants experienced forced sex by men as more serious than forced sex by women; forced sex by women was more likely to involve intimate partners compared to forced sex by men. Participants who experienced forced sex by men were more likely to report drug problems, mental distress and lower sense of belonging. Forced sex by women was associated with drinking problems and mental distress. Having experienced forced sex by both men and women was associated with lower sense of belonging to the LGBT community, drug use problem and mental distress. CONCLUSIONS: The findings indicate that forced sex among Southern African women is a serious issue that needs further exploration. Clinicians should be made aware of the prevalence and possible consequences of forced sex among lesbian and bisexual women. Policies and community interventions should be designed to address this problem

Synaptic Transmission from Horizontal Cells to Cones Is Impaired by Loss of Connexin Hemichannels

In the vertebrate retina, horizontal cells generate the inhibitory surround of bipolar cells, an essential step in contrast enhancement. For the last decades, the mechanism involved in this inhibitory synaptic pathway has been a major controversy in retinal research. One hypothesis suggests that connexin hemichannels mediate this negative feedback signal; another suggests that feedback is mediated by protons. Mutant zebrafish were generated that lack connexin 55.5 hemichannels in horizontal cells. Whole cell voltage clamp recordings were made from isolated horizontal cells and cones in flat mount retinas. Light-induced feedback from horizontal cells to cones was reduced in mutants. A reduction of feedback was also found when horizontal cells were pharmacologically hyperpolarized but was absent when they were pharmacologically depolarized. Hemichannel currents in isolated horizontal cells showed a similar behavior. The hyperpolarization-induced hemichannel current was strongly reduced in the mutants while the depolarization-induced hemichannel current was not. Intracellular recordings were made from horizontal cells. Consistent with impaired feedback in the mutant, spectral opponent responses in horizontal cells were diminished in these animals. A behavioral assay revealed a lower contrast-sensitivity, illustrating the role of the horizontal cell to cone feedback pathway in contrast enhancement. Model simulations showed that the observed modifications of feedback can be accounted for by an ephaptic mechanism. A model for feedback, in which the number of connexin hemichannels is reduced to about 40%, fully predicts the specific asymmetric modification of feedback. To our knowledge, this is the first successful genetic interference in the feedback pathway from horizontal cells to cones. It provides direct evidence for an unconventional role of connexin hemichannels in the inhibitory synapse between horizontal cells and cones. This is an important step in resolving a long-standing debate about the unusual form of (ephaptic) synaptic transmission between horizontal cells and cones in the vertebrate retina

Targeted p120-Catenin Ablation Disrupts Dental Enamel Development

Dental enamel development occurs in stages. The ameloblast cell layer is adjacent to, and is responsible for, enamel formation. When rodent pre-ameloblasts become tall columnar secretory-stage ameloblasts, they secrete enamel matrix proteins, and the ameloblasts start moving in rows that slide by one another. This movement is necessary to form the characteristic decussating enamel prism pattern. Thus, a dynamic system of intercellular interactions is required for proper enamel development. Cadherins are components of the adherens junction (AJ), and they span the cell membrane to mediate attachment to adjacent cells. p120 stabilizes cadherins by preventing their internalization and degradation. So, we asked if p120-mediated cadherin stability is important for dental enamel formation. Targeted p120 ablation in the mouse enamel organ had a striking effect. Secretory stage ameloblasts detached from surrounding tissues, lost polarity, flattened, and ameloblast E- and N-cadherin expression became undetectable by immunostaining. The enamel itself was poorly mineralized and appeared to be composed of a thin layer of merged spheres that abraded from the tooth. Significantly, p120 mosaic mouse teeth were capable of forming normal enamel demonstrating that the enamel defects were not a secondary effect of p120 ablation. Surprisingly, blood-filled sinusoids developed in random locations around the developing teeth. This has not been observed in other p120-ablated tissues and may be due to altered p120-mediated cell signaling. These data reveal a critical role for p120 in tooth and dental enamel development and are consistent with p120 directing the attachment and detachment of the secretory stage ameloblasts as they move in rows