The E‐vergent Northern Apennines formed by Oligocene‐Miocene convergence and westward subduction of Adria beneath Europe. Extension ensued in the Mid‐Late Miocene reflecting lower plate roll‐back and ...causing opening of the back‐arc Northern Tyrrhenian Sea. Post‐orogenic extension is commonly advocated as the main driver of the exhumation of the belt's inner domain high‐pressure/low‐temperature (HP‐LT) rock units. The Acquadolce Subunit of the Eastern Elba nappe stack contains HP‐LT rocks recording peak blueschist conditions of 1.5–1.8 GPa at 320°C–370°C loosely dated to the Oligocene‐Early Miocene. It is sandwiched by two Late Miocene, out‐of‐sequence top‐to‐the E thrusts between Jurassic LP serpentinites on top and HT–LP contact metamorphosed marbles at its base. We document widespread W‐verging ductile asymmetries within the Acquadolce Subunit, which correspond to top‐to‐the W extensional shearing for the nappe stack current orientation. This allowed for early syn‐orogenic exhumation from blueschist‐ to greenschist‐facies conditions, wherein coeval W‐directed extension at the top of the exhuming units acted synchronously with E‐directed thrusting at their base causing exhumation by extrusion in an overall contractional setting. The basal, E‐vergent thrusting is, however, challenging to document as the wedge has since been reworked by Late Miocene, E‐verging compressive tectonics, contact metamorphism, and later extension, obliterating much of the evidence supporting exhumation by extrusion during the early stages of wedge build‐up. Syn‐orogenic exhumation by extrusion from deep structural levels within the orogenic wedge is a viable mechanism to account for other exhumed HP‐LT units in the inner part of the belt.
Key Points
Syn‐orogenic extrusion is proposed as a viable mechanism for the exhumation of HP‐LT rock units of the Northern Apennines;
The Acquadolce Subunit of the Eastern Elba nappe stack was exhumed by upward extrusion within an actively shortening orogenic wedge;
Middle Miocene extension shaped the upper Northern Apennines orogenic wedge but did not contribute to the early exhumation of HP rocks.
Osteoarthritis (OA) is a common musculoskeletal disorder characterized by slow progression and joint tissue degeneration. Aging is one of the most prominent risk factors for the development and ...progression of OA. OA is not, however, an inevitable consequence of aging and age‐related changes in the joint can be distinguished from those that are the result of joint injury or inflammatory disease. The question that remains is whether OA can be prevented by undertaking regular physical activity. Would moderate physical activity in the elderly cartilage (and lubricin expression) comparable to a sedentary healthy adult? In this study we used physical exercise in healthy young, adult, and aged rats to evaluate the expression of lubricin as a novel biomarker of chondrocyte senescence. Immunohistochemistry and western blotting were used to evaluate the expression of lubricin in articular cartilage, while enzyme‐linked immunosorbent assay was used to quantify lubricin in synovial fluid. Morphological evaluation was done by histology to monitor possible tissue alterations. Our data suggest that moderate physical activity and normal mechanical joint loading in elderly rats improve tribology and lubricative properties of articular cartilage, promoting lubricin synthesis and its elevation in synovial fluid, thus preventing cartilage degradation compared with unexercised adult rats.
Repetitive transcranial magnetic stimulation (rTMS) of human motor cortex can produce long-lasting changes in the excitability of excitatory and inhibitory neuronal networks. The effects of rTMS ...depend critically on stimulus frequency. The aim of our present study was to compare the effects of different rTMS protocols. We compared the aftereffects of 6 different rTMS protocols paired associative stimulation at interstimulus intervals of 25 (PAS(25)) and 10 ms (PAS(10)); theta burst stimulation delivered as continuous (cTBS) or intermittent delivery pattern (iTBS); 1- and 5-Hz rTMS on the excitability of stimulated and contralateral motor cortex in 10 healthy subjects. A pronounced increase of cortical excitability, evaluated by measuring the amplitude of motor evoked potentials (MEPs), was produced by iTBS (+56%) and PAS(25) (+45%). Five-hertz rTMS did not produce a significant increase of MEPs. A pronounced decrease of cortical excitability was produced by PAS(10) (-31%), cTBS (-29%), and 1-Hz rTMS (-20%). Short-interval intracortical inhibition was suppressed by PAS(10). Cortical silent period duration was increased by 1-Hz stimulation. No significant effect was observed in the contralateral hemisphere. Head-to-head comparison of the different protocols enabled us to identify the most effective paradigms for modulating the excitatory and inhibitory circuits activated by TMS.
The Zuccale Fault, central‐eastern Elba Island, has been regarded since the 1990s as a low‐angle normal fault that records Neogene crustal extension in the inner (Tyrrhenian side) portion of the ...northern Apennines. The flat‐lying attitude of the fault zone and the strong excision of thick nappes were the main reasons for this interpretation. Previous structural and petrographic studies have focused primarily on the fault rocks themselves without map‐scale investigation of the structural setting and deformation structures in the hanging wall and footwall blocks. Furthermore, despite the complex history proposed for the Zuccale Fault, the timing of deformation has not yet been constrained by radiometric age data. We present the findings of recent geological studies on eastern Elba Island that provide significant new insight on the nature and tectonic significance of the Zuccale Fault. We document in detail the architecture of breccias and cataclasites that comprise the Zuccale Fault. Our new observations are consistent with a purely brittle deformation zone that crosscuts older early‐middle and late Miocene regional and local tectonic structures. The activity on the fault postdates emplacement of the late Miocene Porto Azzurro pluton, and it displaces a previously formed nappe stack ~6 km eastward without any footwall exhumation or hanging wall block rotation. These new data raise questions about the development of misoriented faults in the upper crust.
Key Points
Zuccale Fault architecture is consistent with brittle deformation
Radiometric data bracket fault activity between 6.3 and 5.3 Ma
Slip was enhanced by cyclic presence of high pore fluid pressures
Experimental studies have demonstrated that the GABAergic system modulates acetylcholine release and, through GABA A receptors, tonically inhibits cholinergic activity. Little is known about the ...effects of GABA on the cholinergic activity
in the human central nervous system. In vivo evaluation of some cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation
(TMS) protocol based on coupling peripheral nerve stimulation with TMS of the motor cortex. Peripheral nerve inputs have an
inhibitory effect on motor cortex excitability at short intervals (short latency afferent inhibition, SAI). We investigated
whether GABA A activity enhancement by lorazepam modifies SAI. We also evaluated the effects produced by lorazepam on a different TMS protocol
of cortical inhibition, the short interval intracortical inhibition (SICI), which is believed to be directly related to GABA A activity. In 10 healthy volunteers, the effects of lorazepam were compared with those produced by quetiapine, a psychotropic
drug with sedative effects with no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors, and with those
of a placebo using a randomized double-blind study design. Administration of lorazepam produced a significant increase in
SICI ( F 3,9
= 3.19, P
= 0.039). In contrast to SICI, SAI was significantly reduced by lorazepam ( F 3,9
= 9.39, P
= 0.0002). Our findings demonstrate that GABA A activity enhancement determines a suppression of SAI and an increase of SICI.
Multiple sclerosis (MS) is characterized by auto-reactive T cells that respond to central nervous system (CNS)-based antigens and affect motor, sensory as well as behavioral and cognitive functions. ...Cognitive deficits are now considered an early manifestation of the disease in MS patients. However, the pathophysiology responsible for the cognitive symptoms in MS remains unclear. Increasing evidence from a mouse model of MS, the experimental autoimmune encephalomyelitis (EAE), suggests a correlation between the synaptopathy induced by microglia activation in the early phase of the disease and cognitive dysfunction. In particular, EAE causes deficits in hippocampal-dependent learning and memory that are associated with early microglial activation, synaptic loss and neurodegeneration. Interestingly, inflammatory cytokines released from infiltrating lymphocytes or activated microglia are able to alter synaptic transmission. Increased glutamate-mediated transmission and loss of GABAergic inputs were observed in EAE. They may thus underlie cognitive dysfunction in this model and in MS.
In this review article, we describe benefits and disadvantages of the established histochemical methods for studying articular cartilage tissue under normal, pathological and experimental conditions. ...We illustrate the current knowledge on cartilage tissue based on histological and immunohistochemical aspects, and in conclusion we provide a short overview on the degeneration of cartilage, such as osteoarthritis. Adult articular cartilage has low capacity to repair itself, and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. Numerous efforts have been made to implement the knowledge in the study of cartilage in the last years, and histochemistry proved to be an especially powerful tool to this aim.
Abstract Osteoarthritis (OA) is the most common form of joint disease. This review aimed to consolidate the current evidence that implicates the inflammatory process in the attenuation of synovial ...lubrication and joint tissue homeostasis in OA. Moreover, with these findings, we propose some evidence for novel therapeutic strategies for preventing and/or treating this complex disorder. The studies reviewed support that inflammatory mediators participate in the onset and progression of OA after joint injury. The flow of pro-inflammatory cytokines following an acute injury seems to be directly associated with altered lubricating ability in the joint tissue. The latter is associated with reduced level of lubricin, one of the major joint lubricants. Future research should focus on the development of new therapies that attenuate the inflammatory process and restore lubricin synthesis and function. This approach could support joint tribology and synovial lubrication leading to improved joint function and pain relief.
Osteoarthritis is a degenerative joint disease, which affects millions of people around the world. It occurs when the protective cartilage at the end of bones wears over time, leading to loss of ...flexibility of the joint, pain and stiffness. The cause of osteoarthritis is unknown, but its development is associated with different factors, such as metabolic, genetic, mechanical and inflammatory ones. In recent years the biological role of chitinases has been studied in relation to different inflammatory diseases and more in particular the elevated levels of human cartilage glycoprotein 39 (CHI3L1) and chitotriosidase (CHIT1) have been reported in a variety of diseases including chronic inflammation and degenerative disorders. The aim of this study was to investigate, by immunohistochemistry, the distribution of CHI3L1 and CHIT1 in osteoarthritic and normal rat articular cartilage, to discover their potential role in the development of this disease. The hypothesis was that the expression of chitinases could increase in OA disease. Immunohistochemical analysis showed that CHI3L1 and CHIT1 staining was very strong in osteoarthritic cartilage, especially in the superficial areas of the cartilage most exposed to mechanical load, while it was weak or absent in normal cartilage. These findings suggest that these two chitinases could be functionally associated with the development of osteoarthritis and could be used as markers, so in the future they could have a role in the daily clinical practice to stage the severity of the disease. However, the longer-term in vivo and in vitro studies are needed to understand the exact mechanism of these molecules, their receptors and activities on cartilage tissue.
Internal derangement (ID) is among the most common disorders of the temporomandibular joint (TMJ). Previous research by our group highlighted a correlation between apoptosis and TMJ ID. ...Metalloproteinases (MMP)-7 and -9 have been shown to play an important role in extracellular matrix ECM) homeostasis and, through it, in joint disc remodelling. The immunohistochemical expression of MMP-7 and -9 was investigated in discs from patients with TMJ ID and from healthy donors and compared with the degree of histological tissue degeneration. The collagen fibre arrangement in pathological discs exhibited varying degrees of disruption. New vessels were consistently detected; endothelial cells from these vessels were immunolabelled with both MMP-7 and MMP-9. More or less intense MMP-7 and MMP-9 immunolabelling was detected in the cytoplasm of disc cells from all patients. MMP-7 and MMP-9 immunostaining was significantly different between pathological and normal discs and correlated with the extent of histopathological degeneration. MMP-7 and MMP-9 upregulation in discs from patients with TMJ ID demonstrates their involvement in disc damage in this disorder. A greater understanding of these processes could help identify ways to curb MMP overproduction without affecting their tissue remodelling action. The design of specific inhibitors for these MMPs would not only help to gain insights into the biological roles of MMPs, but would also aid in developing therapeutic interventions for diseases associated with abnormal ECM degradation.
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