Monocytes, Macrophages, and Their Potential Niches in Synovial Joints – Therapeutic Targets in Post-Traumatic Osteoarthritis?

Synovial joints are complex structures that enable normal locomotion. Following injury, they undergo a series of changes, including a prevalent inflammatory response. This increases the risk for development of osteoarthritis (OA), the most common joint disorder. In healthy joints, macrophages are the predominant immune cells. They regulate bone turnover, constantly scavenge debris from the joint cavity and, together with synovial fibroblasts, form a protective barrier. Macrophages thus work in concert with the non-hematopoietic stroma. In turn, the stroma provides a scaffold as well as molecular signals for macrophage survival and functional imprinting: “a macrophage niche”. These intricate cellular interactions are susceptible to perturbations like those induced by joint injury. With this review, we explore how the concepts of local tissue niches apply to synovial joints. We introduce the joint micro-anatomy and cellular players, and discuss their potential interactions in healthy joints, with an emphasis on molecular cues underlying their crosstalk and relevance to joint functionality. We then consider how these interactions are perturbed by joint injury and how they may contribute to OA pathogenesis. We conclude by discussing how understanding these changes might help identify novel therapeutic avenues with the potential of restoring joint function and reducing post-traumatic OA risk.

The Tongue in Three Species of Lemurs: Flower and Nectar Feeding Adaptations

The mobility of the primate tongue allows for the manipulation of food, but, in addition, houses both general sensory afferents and special sensory end organs. Taste buds can be found across the tongue, but the ones found within the fungiform papillae on the anterior two thirds of the tongue are the first gustatory structures to come into contact with food, and are critical in making food ingestion decisions. Comparative studies of both the macro and micro anatomy in primates are sparse and incomplete, yet there is evidence that gustatory adaptation exists in several primate taxa. One is the distally feathered tongues observed in non-destructive nectar feeders, such as Eulemur rubriventer. We compare both the macro and micro anatomy of three lemurid species who died of natural causes in captivity. We included the following two non-destructive nectar feeders: Varecia variegata and Eulemur macaco, and the following destructive flower feeder: Lemur catta. Strepsirrhines and tarsiers are unique among primates, because they possess a sublingua, which is an anatomical structure that is located below the tongue. We include a microanatomical description of both the tongue and sublingua, which were accomplished using hematoxylin–eosin and Masson trichrome stains, and scanning electron microscopy. We found differences in the size, shape, and distribution of fungiform papillae, and differences in the morphology of conical papillae surrounding the circumvallate ones in all three species. Most notably, large distinct papillae were present at the tip of the tongue in nectar-feeding species. In addition, histological images of the ventro-apical portion of the tongue displayed that it houses an encapsulated structure, but only in Lemur catta case such structure presents cartilage inside. The presence of an encapsulated structure, coupled with the shared morphological traits associated with the sublingua and the tongue tip in Varecia variegata and Eulemur macaco, point to possible feeding adaptations that facilitate non-destructive flower feeding in these two lemurids.

Micro-Anatomical Characterization of African Native Monotypic Genera - Anogeissus (DC.) Guill and Quisqualis Linn (Combretaceae)

This study was designed to explore the micro-anatomical characteristics of leaf and petiole of two unstudied West African native monotypic genera - Anogeissus and Qusqualis in Combretaceae with a view to characterizing the taxa, providing useful research-based information for identification. The samples were prepared following standard procedures. The light microscopic study of the transverse sections of the leaves in A. leiocarpus revealed a thick upper and lower cuticle while the cuticle on both leaf surfaces in Q. indica remain thin. The midrib vascular bundle of the leaf in Q. indica is characterized by arc-shape and starch grains were observed in the parenchyma cells of the ground tissue. The uniseriate rows of lamina epidermis were oval, squared, rectangular or polygonal in Q. indica while it was rectangular or slightly oval in A. leiocarpus. Vascular bundle in the leaves and petioles of both taxa were collateral. Simple, slender and short unicellular non-glandular trichomes were also observed in the leaf and petiole micro-anatomy of both taxa. It was concluded that the micro-anatomical features of the leaves and petioles are important parameters of characterization, used in the identification of the studied taxa.

Morphological, anatomical and antibacterial characteristics of Leonotis nepetifolia plants growing in Binh Thuan Province, Vietnam

Lion's ear [Leonotis nepetifolia (L.) R. Br.] is a Vietnamese medicinal plant that has been described in basic morphology and isolated for a number of chemical compounds. This study aims to supplement a database of morphology, micro-anatomy and antibacterial abilities of this species. Micro-anatomical analysis was based on a double staining method microscopic dimensional measurement of plant. The antibacterial capacity was based on the diameter of the inhibitory zone. The results showed that the plant had the characteristics of adapting to the dry and light conditions of the region. Leaf extract at the content of 4.8 to 8.0 mg had the best inhibitory ability on 5 strains of bacteria B. cereus, S. aureus, E. faecalis, P. aeruginosa, and E. coli. The inhibition zone diameters were 0.27, 10.33, 5.00, 3.80 and 2.23 mm, respectively.

40 The orion™ platform from rarecyte® enables same-day 21-plex fluorescence tissue analysis

BackgroundTissue consists of heterogenous cell types, each with diverse functions and functional states, arranged spatially in a way that impacts patient health status. Resolving this complexity at the subcellular level has historically been challenged by fluorescence overlap, autofluorescence, a limited number of targets that can be simultaneously assessed, and low throughput. Orion technology breaks these barriers, providing rapid, straightforward, highly multiplexed whole slide tissue analysis. The recently announced Orion platform rapidly generates high resolution 21-channel images to enable comprehensive phenotypic profiling and characterization of tissue architecture including micro-anatomy, analysis of tumor heterogeneity and the complex tissue microenvironment.MethodsFFPE tissue samples are stained with TissuePlex™ reagents and whole slides are imaged on the Orion Instrument. Resulting 21-channel datasets are reviewed by a pathologist to verify staining specificity. The TissuePlex core panel includes antibodies against CD45, CD4, FoxP3, CD8A, CD11b, LAG-3, PD-L1, CD11c, CD163, CD68, PD-1, Ki-67, CD3d, and CD20. Single marker IHC is used as the gold standard to evaluate TissuePlex reagents and instrument spectral isolation performance is evaluated using fluorescent microspheres.ResultsWe will present the novel Orion spatial biology platform, provide a technology and workflow overview, demonstrate instrument validation results, and present sample datasets.ConclusionsThe Orion platform enables rapid and deep phenotypic analysis of tissue samples for high resolution, whole slide sample analysis.

Improving a probabilistic cytoarchitectonic atlas of auditory cortex using a novel method for inter-individual alignment

The human superior temporal plane, the site of the auditory cortex, displays high inter-individual macro-anatomical variation. This questions the validity of curvature-based alignment (CBA) methods for in vivo imaging data. Here, we have addressed this issue by developing CBA+, which is a cortical surface registration method that uses prior macro-anatomical knowledge. We validate this method by using cytoarchitectonic areas on 10 individual brains (which we make publicly available). Compared to volumetric and standard surface registration, CBA+ results in a more accurate cytoarchitectonic auditory atlas. The improved correspondence of micro-anatomy following the improved alignment of macro-anatomy validates the superiority of CBA+ compared to CBA. In addition, we use CBA+ to align in vivo and postmortem data. This allows projection of functional and anatomical information collected in vivo onto the cytoarchitectonic areas, which has the potential to contribute to the ongoing debate on the parcellation of the human auditory cortex.

Optoacoustic skin mesoscopy opens a window to systemic effects of diabetes

Diabetes mellitus affects the microvasculature of several organs, including the eyes, heart, brain, kidneys and skin. The skin is the most accessible organ and could offer a window for detecting diabetes-related systemic effects on the microvasculature. However, assessment of skin microvasculature is typically performed based on invasive histological analysis, which is a method that is not well suited for disease monitoring and application to large populations. We introduce ultra-wide band raster-scan optoacoustic mesoscopy (RSOM) for precise, non-invasive assessment of diabetes-related changes in the dermal microvasculature and skin micro-anatomy, resolved with unprecedented sensitivity and detail without the need of contrast agents. Based on this novel contrast, we investigated whether RSOM could impart a new concept in diabetes healthcare, offering characterization of systemic effects of the disease. We applied pretibial RSOM to 72 patients with diabetes, grouped according to disease complications, and 20 age-matched healthy volunteers. We extracted six label-free optoacoustic biomarkers, including dermal microvasculature density, total dermal blood volume and epidermal parameters. We study the effects of diabetes on these parameters as a function of disease severity and find strong statistically significant differences between microvasculature parameters and diabetes progression. We discuss how RSOM label-free biomarkers can lead to a quantitative assessment of the systemic effects of diabetes, complementing the qualitative assessment allowed by current clinical metrics and possibly, in the future, enable a more precise scoring system capturing the gradual evolution of disease.