It is well known that bone loss accompanies aging in both men and women and contributes to skeletal fragility in the older population, but changes that occur to the bone tissue matrix itself are less ...well known. These changes in bone quality aggravate the skeletal fragility associated with loss of bone mass. Bone tissue quality is affected by age-related changes in bone mineral, collagen and its cross-linking profiles, water compartments and even non-collagenous proteins. It is commonly assumed that greater tissue mineralization accompanies aging as bone turnover slows down in elderly individuals, but the data for this are weak. However, there may be changes in the quality of the mineral crystals, and the substitutions found within the crystal. Both enzymatically-mediated and non-enzymatically-mediated collagen cross-links multiply with age. The former tend to make the bone stiffer and stronger, but the latter, while making the bone stiffer can also make it more brittle and more likely to fracture. Bone pore water that is not bound to collagen or mineral increases with age as bone mass is lost, but water that is bound to collagen and mineral declines with age. These changes contribute to skeletal fragility by reducing the amount that bone can deform before fracturing. Finally, non-collagenous proteins have physical properties that can alter matrix mechanical properties and can also have molecular signaling functions that regulate bone remodeling. Whether these change with age, how they change, and how this affects skeletal fragility with aging is still largely a black box, and requires much more investigation. The roles of any of these factors in skeletal fragility are difficult to assess clinically as there is no easy or economical way to evaluate them, but a picture of fragility in the aging skeleton is incomplete without them.
•The material properties of bone matrix contribute to bone's strength, and can contribute to the increased fracture risk caused by a loss of bone.•Bone quality is affected by age-related changes in mineral, collagen and its cross-linking, water, and non-collagenous proteins.•The increased brittleness that occurs with age is related to changes to the collagen, and the interface between collagen and mineral.•The decline in loosely bound water at the collagen-mineral interface reduces the capacity of older bone to dissipate energy and resist fracture.
Perceptual experience is influenced both by incoming sensory information and prior knowledge about the world, a concept recently formalised within Bayesian decision theory. We propose that Bayesian ...models can be applied to autism – a neurodevelopmental condition with atypicalities in sensation and perception – to pinpoint fundamental differences in perceptual mechanisms. We suggest specifically that attenuated Bayesian priors – ‘hypo-priors’ – may be responsible for the unique perceptual experience of autistic people, leading to a tendency to perceive the world more accurately rather than modulated by prior experience. In this account, we consider how hypo-priors might explain key features of autism – the broad range of sensory and other non-social atypicalities – in addition to the phenomenological differences in autistic perception.
The functional role of serial dependence Cicchini, Guido Marco; Mikellidou, Kyriaki; Burr, David C
Proceedings of the Royal Society. B, Biological sciences,
10/2018, Letnik:
285, Številka:
1890
Journal Article
Recenzirano
Odprti dostop
The world tends to be stable from moment to moment, leading to strong serial correlations in natural scenes. As similar stimuli usually require similar behavioural responses, it is highly likely that ...the brain has developed strategies to leverage these regularities. A good deal of recent psychophysical evidence is beginning to show that the brain is sensitive to serial correlations, causing strong drifts in observer responses towards previously seen stimuli. However, it is still not clear that this tendency leads to a functional advantage. Here, we test a formal model of optimal serial dependence and show that as predicted, serial dependence in an orientation reproduction task is dependent on current stimulus reliability, with less precise stimuli, such as low spatial frequency oblique Gabors, exhibiting the strongest effects. We also show that serial dependence depends on the similarity between two successive stimuli, again consistent with the behaviour of an ideal observer aiming at minimizing reproduction errors. Lastly, we show that serial dependence leads to faster response times, indicating that the benefits of serial integration go beyond reproduction error. Overall our data show that serial dependence has a beneficial role at various levels of perception, consistent with the idea that the brain exploits the temporal redundancy of the visual scene as an optimization strategy.
The microarchitecture of bone tissue presents many features that could act as stress concentrators for the initiation of bone microdamage. This was first identified by John Currey in a seminal paper ...in 1962 in which he presented the mechanical and biological evidence for stress concentrations at the bone surface, within the bone through the action of stiffness differentials between architectural features including between lamellae, and at the level of the lacunar and canalicular walls. Those early observations set the stage to consider how microscopic damage to bone tissue might affect the properties of bone at a time when most in the scientific community dismissed microcracks in bone as artifact. Evidence collected in the nearly 60 years since those important initial observations suggest that some of these architectural features in bone tissue are more effective as crack arrestors than as crack initiators. Sites of higher mineralization in the bone matrix, particularly interstitial sites in both cortical and trabecular bone, may serve preferentially as locations for crack initiation, whereas those boundaries identified by Currey as both stress concentrators and stress arrestors are more effective at stopping cracks than at initiating them.
•John Currey identified stress concentrators and stress arrestors in bone nearly 60 years ago.•Evidence collected since indicate some of these architectural features are more effective crack arrestors than initiators.•Highly mineralized bone matrix, rather than stress concentration per se, may be effective stress concentrators.
One function of perceptual systems is to construct and maintain a reliable representation of the environment. A useful strategy intrinsic to modern “Bayesian” theories of perception1–6 is to take ...advantage of the relative stability of the input and use perceptual history (priors) to predict current perception. This strategy is efficient1–7 but can lead to stimuli being biased toward perceptual history, clearly revealed in a phenomenon known as serial dependence.8–14 However, it is still unclear whether serial dependence biases sensory encoding or only perceptual decisions.15,16 We leveraged on the “surround tilt illusion”—where tilted flanking stimuli strongly bias perceived orientation—to measure its influence on the pattern of serial dependence, which is typically maximal for similar orientations of past and present stimuli.7,10 Maximal serial dependence for a neutral stimulus preceded by an illusory one occurred when the perceived, not the physical, orientations of the two stimuli matched, suggesting that the priors biasing current perception incorporate the effect of the illusion. However, maximal serial dependence of illusory stimuli induced by neutral stimuli occurred when their physical (not perceived) orientations were matched, suggesting that priors interact with incoming sensory signals before they are biased by flanking stimuli. The evidence suggests that priors are high-level constructs incorporating contextual information, which interact directly with early sensory signals, not with highly processed perceptual representations.
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•Perception is heavily biased by perceptual history and expectations•Perceptual history includes illusory effects driven by spatial context•This representation propagates back to sensory areas preceding context effects•The results point to a neural architecture consistent with predictive coding
Perception can be strongly biased by expectations, which are in part shaped by perceptual history. Cicchini et al. demonstrate that the bias is driven by signals from high levels of analysis propagating down to interact at relatively low levels, implicating a recurrent network in sensory analysis.
Humans, including infants, and many other species have a capacity for rapid, nonverbal estimation of numerosity. However, the mechanisms for number perception are still not clear; some maintain that ...the system calculates numerosity via density estimates-similar to those involved in texture-while others maintain that more direct, dedicated mechanisms are involved. Here we show that provided that items are not packed too densely, human subjects are far more sensitive to numerosity than to either density or area. In a two-dimensional space spanning density, area and numerosity, subjects spontaneously react with far greater sensitivity to changes in numerosity, than either area or density. Even in tasks where they were explicitly instructed to make density or area judgments, they responded spontaneously to number. We conclude, that humans extract number information, directly and spontaneously, via dedicated mechanisms.
After fifty years of experience with several generations of bisphosphonates (BPs), and 25 years after these drugs were approved for use in humans, their mechanical effects on bone are still not fully ...understood. Certainly, these drugs have transformed the treatment of osteoporosis in both men and women. There is no question that they do prevent fractures related to low bone mass, and there is widespread agreement that they increase strength and stiffness of the vertebrae. There is less consensus, however, about their effects on cortical bone, or on bone tissue properties in either trabecular or cortical bone, or their effects with longer periods of treatment. The consensus of most studies, both those based on ovariectomized and intact animal models and on testing of human bone, is that long-term treatment and/or high doses with certain BPs make the bone tissue more brittle and less tough. This translates into reduced energy to fracture and potentially a shorter bone fatigue life. Many studies have been done, but Interpretation of the results of these studies is complicated by variations in which BP is used, the animal model used, dose, duration, and methods of testing. Duration effects and effects on impact properties of bone are gaps that should be filled with additional testing.
•Bisphosphonate treatment for up to 3 years increases bone strength and stiffness, but reduces toughness.•Bisphosphonate treatment appears to have little effect on diaphyseal bone.•Computational models differ about whether some mechanical properties begin to decline after 7 years of treatment.•Cyclic loading studies suggest that bone fatigue life may be shorter following bisphosphonate treatment.•Different bisphosphonates may have different effects on tissue properties of bone tissue.
The mapping of number onto space is fundamental to measurement and mathematics. However, the mapping of young children, unschooled adults, and adults under attentional load shows strong compressive ...nonlinearities, thought to reflect intrinsic logarithmic encoding mechanisms, which are later “linearized” by education. Here we advance and test an alternative explanation: that the nonlinearity results from adaptive mechanisms incorporating the statistics of recent stimuli. This theory predicts that the response to the current trial should depend on the magnitude of the previous trial, whereas a static logarithmic nonlinearity predicts trialwise independence. We found a strong and highly significant relationship between numberline mapping of the current trial and the magnitude of the previous trial, in both adults and school children, with the current response influenced by up to 15% of the previous trial value. The dependency is sufficient to account for the shape of the numberline, without requiring logarithmic transform. We show that this dynamic strategy results in a reduction of reproduction error, and hence improvement in accuracy.
Although humans are the only species to possess language-driven abstract mathematical capacities, we share with many other animals a nonverbal capacity for estimating quantities or numerosity. For ...some time, researchers have clearly differentiated between small numbers of items—less than about four—referred to as the subitizing range, and larger numbers, where counting or estimation is required. In this review, we examine more recent evidence suggesting a further division, between sets of items greater than the subitizing range, but sparse enough to be individuated as single items; and densely packed stimuli, where they crowd each other into what is better considered as a texture. These two different regimes are psychophysically discriminable in that they follow distinct psychophysical laws and show different dependencies on eccentricity and on luminance levels. But provided the elements are not too crowded (less than about two items per square degree in central vision, less in the periphery), there is little evidence that estimation of numerosity depends on mechanisms responsive to texture. The distinction is important, as the ability to discriminate numerosity, but not texture, correlates with formal maths skills.
Bone remodelling in osteoarthritis Burr, David B; Gallant, Maxime A
Nature reviews. Rheumatology,
11/2012, Letnik:
8, Številka:
11
Journal Article
Recenzirano
The classical view of the pathogenesis of osteoarthritis (OA) is that subchondral sclerosis is associated with, and perhaps causes, age-related joint degeneration. Recent observations have ...demonstrated that OA is associated with early loss of bone owing to increased bone remodelling, followed by slow turnover leading to densification of the subchondral plate and complete loss of cartilage. Subchondral densification is a late event in OA that involves only the subchondral plate and calcified cartilage; the subchondral cancellous bone beneath the subchondral plate may remain osteopenic. In experimental models, inducing subchondral sclerosis without allowing the prior stage of increased bone remodelling to occur does not lead to progressive OA. Therefore, both early-stage increased remodelling and bone loss, and the late-stage slow remodelling and subchondral densification are important components of the pathogenetic process that leads to OA. The apparent paradoxical observations that OA is associated with both increased remodelling and osteopenia, as well as decreased remodelling and sclerosis, are consistent with the spatial and temporal separation of these processes during joint degeneration. This Review provides an overview of current knowledge on OA and discusses the role of subchondral bone in the initiation and progression of OA. A hypothetical model of OA pathogenesis is proposed.
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