In this invited review, we summarize the main results of ongoing research on “in situ” carbon mineralization in ultramafic rocks, including outcrop studies in Oman (e.g., 1, 2), investigation of ...carbon mass transfer in subduction zones from the Oman Drilling Project (e.g., 3-7), laboratory investigations (e.g., 8-12) and numerical modeling (e.g., 13-17) of the pressure of crystallization and reaction-driven cracking, and assessment of the rate, cost and capacity of various proposed methods for engineered carbon mineralization 18, 19.
Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)-rich protein aggregates termed "Lewy bodies" (LBs), is a well-established characteristic of Parkinson's disease ...(PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning-based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneration.
Intermittent or pulsatile dopamine-receptor stimulation is postulated to induce plastic changes in motor systems that are responsible for the development of the motor fluctuations and dyskinesia that ...complicate long-term
l-dopa therapy of Parkinson's disease. As a corollary to this hypothesis, continuous dopamine-receptor stimulation can avoid or reverse these complications. Such continuous stimulation is unlikely to mimic completely the normal function of the dopaminergic system, but should avoid the supra-physiological swings in extracellular dopamine that accompany intermittent
l-dopa dosing. The concern is that this continuous stimulation might induce tolerance rather than sensitization to some effects of
l-dopa. Open clinical trials support the value of continuous dopaminergic stimulation in Parkinson's disease with established motor complications, but rigorous studies, although experimentally difficult, are needed.
We studied anticipatory postural adjustments contributing to gait initiation deficits in patients with Parkinson's disease (PD) to determine if these deficits could be improved by administration of ...levodopa or by external stimuli. Ground reaction forces and body kinematics were recorded for self‐generated and cutaneous cue‐triggered step initiation in normal subjects and in PD subjects when OFF and when ON. The effects of assisting anticipatory postural sway with a surface translation coupled with a cutaneous cue were also examined. Decreased force production, decreased velocity of movement, and slowed execution of the anticipatory postural adjustments for self‐generated step characterized step initiation in PD subjects when OFF. These impairments were significantly less evident when the PD subjects were ON. Both PD and normal subjects increased force and velocity of movement when a cutaneous cue was used as a go signal. When subjects voluntarily initiated a step in response to the surface translation, both PD and normal subjects executed the anticipatory postural adjustments for step more rapidly, but the PD subjects, both ON and OFF, failed to increase force to execute push‐off more rapidly. In conclusion, dopaminergic therapy and an external stimulus similarly improve the deficient force production for the anticipatory postural adjustments associated with step initiation in PD. The findings also suggest that force production during the postural adjustment phase of self‐generated, but not externally triggered, step initiation is influenced by dopaminergic pathways.
Beyond species loss Valiente-Banuet, Alfonso; Aizen, Marcelo A.; Alcántara, Julio M. ...
Functional ecology,
March 2015, Letnik:
29, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Summary
The effects of the present biodiversity crisis have been largely focused on the loss of species. However, a missed component of biodiversity loss that often accompanies or even precedes ...species disappearance is the extinction of ecological interactions.
Here, we propose a novel model that (i) relates the diversity of both species and interactions along a gradient of environmental deterioration and (ii) explores how the rate of loss of ecological functions, and consequently of ecosystem services, can be accelerated or restrained depending on how the rate of species loss covaries with the rate of interactions loss.
We find that the loss of species and interactions are decoupled, such that ecological interactions are often lost at a higher rate. This implies that the loss of ecological interactions may occur well before species disappearance, affecting species functionality and ecosystems services at a faster rate than species extinctions. We provide a number of empirical case studies illustrating these points.
Our approach emphasizes the importance of focusing on species interactions as the major biodiversity component from which the ‘health’ of ecosystems depends.
Lay Summary
Long-term L-dopa treatment is limited by the development of motor complications, such as motor fluctuations and dyskinesias. These motor complications are postulated to arise from a non-physiological ...intermittent or pulsatile stimulation of striatal dopamine (DA) receptors that normally receive tonic stimulation. The concept of continuous dopaminergic stimulation (CDS) proposes that therapies providing more continuous stimulation of brain dopaminergic receptors are associated with a reduced risk of motor complications. One approach to the CDS is to prolong the half-life of L-dopa inhibiting its degradation by means of the administration of catechol-O-methyltransferase (COMT) inhibitors, as entacapone, a potent, selective, and reversible peripherally acting inhibitor. Animal models of L-dopa-induced motor complications can be obtained in monkeys and rats with severe damage in the nigrostriatal dopaminergic pathway induced by 1-methyl-4-phenyl-1-2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA), respectively. The effect of entacapone on L-dopa-induced motor response and complications has been widely investigated in preclinical models. The administration of entacapone is able to potentiate the long-duration response (LDR) to L-dopa and to attenuate L-dopa-induced motor fluctuations and dyskinesias in these preclinical models. These effects, however, are not related with a normalization of the molecular changes induced by L-dopa in the basal ganglia nuclei.
In the late 1980s, a functional and anatomical model of basal ganglia organization was proposed in order to explain the clinical syndrome of Parkinson's disease. According to this model, the ...pathological overactivity observed in the subthalamic nucleus and the output station of the basal ganglia plays a crucial role in the pathophysiology of the motor signs of Parkinson's disease. The hyperactivity of subthalamic neurons in Parkinsonism is viewed as a direct consequence of a pathological hypoactivity of the external segment of the pallidum. This article reviews recent data from different experimental approaches that challenge the established model of basal ganglia organization by reinterpreting the functional interaction between the external segment of the pallidum and the subthalamic nucleus in both the normal and pathological state. Indeed, recent neurobiochemical studies have rather unexpectedly shown that the GABAergic and metabolic activities of the external pallidum are not decreased in human and non-human primates with Parkinsonism. This absence of any decrease in activity might be explained by the functionally antagonistic influences of the striatal and subthalamic afferences within the external pallidum, as suggested by several anatomical studies. In addition, there are clues from electrophysiological studies to suggest that the hyperactivity found in the subthalamic neurons in Parkinsonism may not depend solely on the level of activity in the external pallidum.
In such a framework, the hyperactivity of the subthalamic neurons would have to be explained, at least in part, by other sources of excitation or disinhibition. However, any explanation for the origin of the subthalamic overactivity in Parkinsonism remains speculative.
Cigarette smoke (CS) and chronic hypoxia (CH) can produce pulmonary hypertension. Similarities and differences between both exposures and their interaction have not been explored. The aim of the ...present study was to investigate the effects of CS and CH, as single factors or in combination, on the pulmonary circulation in the guinea pig. 51 guinea pigs were exposed to CS for 12 weeks and 32 were sham-exposed. 50% of the animals in each group were additionally exposed to CH for the final 2 weeks. We measured pulmonary artery pressure (P(pa)), and the weight ratio between the right ventricle (RV) and left ventricle plus the septum. Pulmonary artery contractility in response to noradrenaline (NA), endothelium-dependent vasodilatation and distensibility were evaluated in organ bath chambers. The number of small intrapulmonary vessels showing immunoreactivity to smooth muscle (SM) α-actin and double elastic laminas was assessed microscopically. CS and CH induced similar increases of P(pa) and RV hypertrophy (p<0.05 for both), effects that were further enhanced when both factors were combined. CH increased the contractility to NA (p<0.01) and reduced the distensibility (p<0.05) of pulmonary arteries. Animals exposed to CS showed an increased number of small vessels with positive immunoreactivity to SM α-actin (p<0.01) and those exposed to CH a greater proportion of vessels with double elastic laminas (p<0.05). We conclude that CH amplifies the detrimental effects of CS on the pulmonary circulation by altering the mechanical properties of pulmonary arteries and enhancing the remodelling of pulmonary arterioles.
The precise cause of levodopa-induced dyskinesias is unknown. Current evidence indicates that dyskinesias develop in response to pulsatile stimulation of striatal dopamine receptors. The half-life of ...the dopaminergic agent employed and disease severity are thought to affect the occurrence of pulsatile stimulation. Dyskinesias are not seen or are attenuated with continuous delivery of levodopa or short-acting agonists, or with the use of long-acting agonists. In advanced disease, there are fewer striatal dopamine terminals and reduced buffering capacity; fluctuations in plasma levodopa concentration are more likely to cause fluctuations in striatal dopamine concentration and pulsatile stimulation of dopamine receptors. Pulsatile stimulation is thought to induce postsynaptic gene and protein changes that result in alterations in the patterns of neuronal communication, with the emergence of dyskinetic movements. Thus, strategies preventing pulsatile stimulation may prevent the development of dyskinesias. These could include the use of dopaminergic agents with a relatively long half-life, neuroprotective therapies that prevent the loss of dopamine neurons, and transplantation strategies or trophic factors that increase the number of dopamine terminals capable of buffering fluctuations in striatal dopamine. Alternatively, approaches that interfere with or compensate for postsynaptic molecular and neurophysiologic changes that ensue in downstream neurons might provide antidyskinetic benefits.
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