β1-Integrin-Mediated Uptake of Chondrocyte Extracellular Vesicles Regulates Chondrocyte Homeostasis.

Osteoarthritis (OA) is the most prevalent age-related degenerative disorder, which severely reduces the quality of life of those affected. Whilst management strategies exist, no cures are currently available. Virtually all joint resident cells generate extracellular vesicles (EVs), and alterations in chondrocyte EVs during OA have previously been reported. Herein, we investigated factors influencing chondrocyte EV release and the functional role that these EVs exhibit. Both 2D and 3D models of culturing C28I/2 chondrocytes were used for generating chondrocyte EVs. We assessed the effect of these EVs on chondrogenic gene expression as well as their uptake by chondrocytes. Collectively, the data demonstrated that chondrocyte EVs are sequestered within the cartilage ECM and that a bi-directional relationship exists between chondrocyte EV release and changes in chondrogenic differentiation. Finally, we demonstrated that the uptake of chondrocyte EVs is at least partially dependent on β1-integrin. These results indicate that chondrocyte EVs have an autocrine homeostatic role that maintains chondrocyte phenotype. How this role is perturbed under OA conditions remains the subject of future work

A multidisciplinary study of the final episode of the Manda Hararo dyke sequence, Ethiopia, and implications for trends in volcanism during the rifting cycle

The sequence of dyke intrusions between 2005 and 2010 in the Manda Hararo rift segment, Ethiopia, provided an opportunity to test conceptual models of continental rifting. Based on trends up to dyke 13 in the sequence, it was anticipated that, should magma supply continue, dykes would shorten in length and eruptions would increase in size and decrease in distance from the segment centre as extensional stress was progressively released. In this paper we revisit these predictions by presenting a comprehensive overview of the May 2010 dyke and fissure eruption, the 14th and last in the sequence, from InSAR, seismicity, satellite thermal data, ultra violet SO2 retrievals, and multiple LiDAR surveys. We find the dyke is longer than other eruptive dykes in the sequence, propagating in two directions from the segment centre, but otherwise fairly typical in terms of opening, propagation speed and geodetic and seismic moment. However, though the eruption is located closer to the segment centre, it is much smaller than previous events. We interpret this as indicating that either the Manda Hararo rifting event was magma limited, or that extensional stress varies north and south of the segment centre

Passive phloem loading and long-distance transport in a synthetic tree-on-a-chip

Vascular plants rely on differences of osmotic pressure to export sugars from regions of synthesis (mature leaves) to sugar sinks (roots, fruits). In this process, known as M\"unch pressure flow, the loading of sugars from photosynthetic cells to the export conduit (the phloem) is crucial, as it sets the pressure head necessary to power long-distance transport. Whereas most herbaceous plants use active mechanisms to increase phloem concentration above that of the photosynthetic cells, in most tree species, for which transport distances are largest, loading seems to occur via passive symplastic diffusion from the mesophyll to the phloem. Here, we use a synthetic microfluidic model of a passive loader to explore the nonlinear dynamics that arise during export and determine the ability of passive loading to drive long-distance transport. We first demonstrate that in our device, phloem concentration is set by the balance between the resistances to diffusive loading from the source and convective export through the phloem. Convection-limited export corresponds to classical models of M\"unch transport, where phloem concentration is close to that of the source; in contrast, diffusion-limited export leads to small phloem concentrations and weak scaling of flow rates with the hydraulic resistance. We then show that the effective regime of convection-limited export is predominant in plants with large transport resistances and low xylem pressures. Moreover, hydrostatic pressures developed in our synthetic passive loader can reach botanically relevant values as high as 10 bars. We conclude that passive loading is sufficient to drive long-distance transport in large plants, and that trees are well suited to take full advantage of passive phloem loading strategies

Stretchable liquid-crystal blue-phase gels

Liquid crystalline polymers are materials of considerable scientific interest and technological value to society [1-3]. An important subset of such materials exhibit rubber-like elasticity; these can combine the remarkable optical properties of liquid crystals with the favourable mechanical properties of rubber and, further, exhibit behaviour not seen in either type of material independently [2]. Many of their properties depend crucially on the particular mesophase employed. Stretchable liquid crystalline polymers have previously been demonstrated in the nematic, chiral nematic, and smectic mesophases [2,4]. Here were report the fabrication of a stretchable gel of blue phase I, which forms a self-assembled, three-dimensional photonic crystal that may have its optical properties manipulated by an applied strain and, further, remains electro-optically switchable under a moderate applied voltage. We find that, unlike its undistorted counterpart, a mechanically deformed blue phase exhibits a Pockels electro-optic effect, which sets out new theoretical challenges and new possibilities for low-voltage electro-optic devices.Comment: 15 pages, 6 figures, additional data and discussion included. Supplementary videos available from F. Castles on reques

In vivo operating lengths of the gastrocnemius muscle during gait in children who idiopathically toe-walk

DATA AVAILABILITY STATEMENT: The data that support the findings of this study are available from the corresponding author upon reasonable request.Children who idiopathically toe-walk (ITW) habitually operate at greater plantarflexion angles than typically developing (TD) children, which might result in shorter, sub-optimal gastrocnemius fascicle lengths. However, currently no experimental evidence exists to substantiate this notion. Five children who ITW and 14 TD children completed a gait analysis, whilst gastrocnemius fascicle behaviour was simultaneously quantified using ultrasound. The moment–angle (hip, knee and ankle) and moment–length (gastrocnemius) relationships were determined from isometric maximum voluntary contractions (MVC) on an isokinetic dynamometer combined with ultrasound. During gait, children who ITW operated at more plantarflexed angles (Δ = 20°; P = 0.013) and longer muscle fascicle lengths (Δ = 12 mm; P = 0.008) than TD children. During MVC, no differences in the peak moment of any joint were found. However, peak plantarflexor moment occurred at significantly more plantarflexed angles (−16 vs. 1°; P = 0.010) and at longer muscle fascicle lengths (44 vs. 37 mm; P = 0.001) in children who ITW than TD children. Observed alterations in the moment–angle and moment–length relationships of children who ITW coincided with the ranges used during gait. Therefore, the gastrocnemius muscle in children who ITW operates close to the peak of the force–length relationship, similarly to TD children. Thus, this study indicates that idiopathic toe-walking is truly an ankle joint pathology, and children who ITW present with substantial alterations in the gastrocnemius muscle functional properties, which appear well adapted to the characteristic demands of equinus gait. These findings should be considered when prescribing clinical treatments to restore typical gait

Are bisphosphonates effective in the treatment of osteoarthritis pain? A meta-analysis and systematic review.

Osteoarthritis (OA) is the most common form of arthritis worldwide. Pain and reduced function are the main symptoms in this prevalent disease. There are currently no treatments for OA that modify disease progression; therefore analgesic drugs and joint replacement for larger joints are the standard of care. In light of several recent studies reporting the use of bisphosphonates for OA treatment, our work aimed to evaluate published literature to assess the effectiveness of bisphosphonates in OA treatment

A.N. Kolmogorov’s defence of Mendelism

In 1939 N.I. Ermolaeva published the results of an experiment which repeated parts of Mendel’s classical experiments. On the basis of her experiment she concluded that Mendel’s principle that self-pollination of hybrid plants gave rise to segregation proportions 3:1 was false. The great probability theorist A.N. Kolmogorov reviewed Ermolaeva’s data using a test, now referred to as Kolmogorov’s, or Kolmogorov-Smirnov, test, which he had proposed in 1933. He found, contrary to Ermolaeva, that her results clearly confirmed Mendel’s principle. This paper shows that there were methodological flaws in Kolmogorov’s statistical analysis and presents a substantially adjusted approach, which confirms his conclusions. Some historical commentary on the Lysenko-era background is given, to illuminate the relationship of the disciplines of genetics and statistics in the struggle against the prevailing politically-correct pseudoscience in the Soviet Union. There is a Brazilian connection through the person of Th. Dobzhansky

Muscle architecture and passive lengthening properties of the gastrocnemius medialis and Achilles tendon in children who idiopathically toe-walk

Children who idiopathically toe-walk (ITW) habitually operate at greater plantarflexion angles and thus, at shorter muscle-tendon unit (MTU) lengths than typically developing (TD) children. Therefore, it is often assumed that habitual use of the gastrocnemius muscle in this way will cause remodelling of the muscle-tendon architecture compared to TD children. However, the gastrocnemius muscle architecture of children who ITW has never been measured. It is essential that we gain a better understanding of these muscle-tendon properties, to ensure that appropriate clinical interventions can be provided for these children. Five children who ITW (age 8 ± 2 years) and 14 TD children (age 10 ± 2 years) participated in this study. Ultrasound was combined with isokinetic dynamometry and surface electromyography, to measure muscle architecture at common positions and passive lengthening properties of the gastrocnemius muscle and tendon across full range of motion. Regardless of which common condition groups were compared under, both the absolute and normalised to MTU muscle belly and fascicle lengths were always longer, and the Achilles tendon length was always shorter in children who ITW than TD children (p 0.05); however, passive joint stiffness was greater in children who ITW at maximum dorsiflexion (p = 0.001) and at a joint moment common to all participants (p = 0.029). Consequently, the findings of this pilot study indicate a remodelling of the relative MTU that does not support the concept that children who ITW commonly experience muscle shortening. Therefore, greater consideration of the muscle and tendon properties are required when prescribing clinical interventions that aim to lengthen the MTU, and treatments may be better targeted at the Achilles tendon in children who ITW.This study was funded by a Liverpool John Moores University PhD scholarship

Highly Absorbing Lead-Free Semiconductor Cu₂AgBiI₆ for Photovoltaic Applications from the Quaternary CuI-AgI-BiI₃ Phase Space

Since the emergence of lead halide perovskites for photovoltaic research, there has been mounting effort in the search for alternative compounds with improved or complementary physical, chemical, or optoelectronic properties. Here, we report the discovery of Cu_{2}AgBiI_{6}: a stable, inorganic, lead-free wide-band-gap semiconductor, well suited for use in lead-free tandem photovoltaics. We measure a very high absorption coefficient of 1.0 × 10^{5} cm^{–1} near the absorption onset, several times that of CH_{3}NH_{3}PbI_{3}. Solution-processed Cu2AgBiI6 thin films show a direct band gap of 2.06(1) eV, an exciton binding energy of 25 meV, a substantial charge-carrier mobility (1.7 cm^{2} V^{–1} s^{–1}), a long photoluminescence lifetime (33 ns), and a relatively small Stokes shift between absorption and emission. Crucially, we solve the structure of the first quaternary compound in the phase space among CuI, AgI and BiI_{3}. The structure includes both tetrahedral and octahedral species which are open to compositional tuning and chemical substitution to further enhance properties. Since the proposed double-perovskite Cs2AgBiI6 thin films have not been synthesized to date, Cu_{2}AgBiI_{6} is a valuable example of a stable Ag^{+}/Bi^{3+} octahedral motif in a close-packed iodide sublattice that is accessed via the enhanced chemical diversity of the quaternary phase space