Millions of lymphocytes enter and exit mammal lymph nodes (LNs) each day, accessing the parenchyma via high endothelial venules (HEVs) and egressing via lymphatics. Despite this high rate of cellular flux and the many entry and exit sites within a given LN, the number of lymphocytes present in a resting LN is extraordinary stable over time, raising the question of how this steady-state is maintained. Here we have examined the anatomic details of lymphocyte movement in HEVs, finding that HEVs create pockets within which lymphocytes reside for several minutes before entering the LN proper. The function of these pockets was revealed in experiments performed under conditions in which lymphocyte egress from the LN was compromised by any of several approaches. Under such conditions, the HEVs pockets behaved as "waiting areas" in which lymphocytes were held until space was made available to them for entry into the parenchyma.Thus, rather than being simple entry ports, HEVs act as gatekeepers able to stack, hold and grant lymphocytes access to LN parenchyma in proportion to the rate of lymphocyte egress from the LN, enabling the LN to maintain a constant steadystate cellularity while supporting the extensive cellular trafficking necessary for repertoire scanning. (Blood. 2011;118(23): 6115-6122) IntroductionDespite the constant entry and exit of lymphocytes in the noninflamed state, LNs manage to maintain their cellularity over time, indicating the existence of tightly regulated control mechanisms that balance access and egress of cells. 1 Naive lymphocytes enter LNs via HEVs and exit via lymphatic vessels. 2 The number of HEVs and lymphatic exit sites in an individual LN is quite high, with these sites showing substantial topographic separation throughout the LN. This raises the question of how a LN manages lymphocyte traffic at these many dispersed sites to maintain homeostasis, a critical issue because LNs provide key survival signals such as IL-7 and BAFF (B-cell activating factor) to T and B cells, respectively. 3,4 As a resting LN is believed to secrete defined amounts of such survival signals, increases in lymphocyte number beyond that properly supported by the survival factors available could lead to cell death and repertoire contraction. Likewise, too few cells would limit the number of specific cells available at any time for antigen-driven activation, diminishing the efficiency of immune responses. Interestingly, mice grafted with multiple thymi do not harbor massively enlarged LNs despite high numbers of circulating lymphocytes, suggesting that LNs autoregulate the number of cells they house and nourish. 5,6 Altogether, these observations suggest that LNs adapt lymphocyte entry and exit fluxes to constantly host a fixed number of lymphocytes under steady-state conditions. In this study, we investigate this possibility and demonstrate that, in addition of being passive entry doors for lymphocytes, HEVs are traffic control checkpoints able to create "waiting areas" in which lymphocytes accumulate and are hel...

The authors report on their macro- and microscopy study of bone lesions made by a sharp force instrument (a single blade knife), and a sharp-blunt instrument classified as a chopping weapon (a hatchet). The aim of this work was to attempt to identify the instrument by analyzing the general class characteristics of the cuts. Each weapon was used on human bones. The results indicate that macroscopic analysis is more problematic. The microscopic analysis assessed that characteristics examined were effective in distinguishing sharp from sharp-blunt injury to the bone. The microscope facilitates analysis unachievable with macroscopic methods, some three-dimensional characteristics not visible to the naked eye being clearly defined with its use. Emphasis has been placed on the value of SEM as an anthropologist's tool in bone lesion injuries.

Particulate forms of biphasic calcium phosphate (BCP) biomaterials below 500  μm are promising bone substitutes that provide with interconnected open porosity allowing free circulation of fluids and cells. Dispersion of the particles in the surrounding tissues at the time of implantation is a major drawback preventing from an easy use. We have asked whether blood clot could be a convenient natural hydrogel for handling BCP microparticles, and we hypothesized that blood clot might also confer osteoinductive properties to these particles. We show here that blood clotted around BCP microparticles constitutes a cohesive, moldable, and adaptable biomaterial that can be easily implanted in subcutaneous sites but also inserted and maintained in segmental bone defects, conversely to BCP microparticles alone. Moreover, implantation in bony and ectopic sites revealed that this composite biomaterial has osteogenic properties. It is able to repair a 6-mm critical femoral defect in rat and induced woven bone formation after subcutaneous implantation. Parameters such as particle size and loading into the clot are critical for its osteogenic properties. In conclusion, this blood/BCP microparticle composite is a moldable and osteoinductive biomaterial that could be used for bone defect filling in dental and orthopedic surgery.

International audienceCnidarian-dinoflagellate symbiosis disruption and subsequent bleaching are major concerns, especially regarding their ecological consequences on coral reefs and temperate coralligenous communities. Cnidarian bleaching is caused by a variety of environmental stressors, such as elevated seawater temperature associated with global climate change, and by pollutants, such as herbicides and metals. Several cellular events have been described to explain symbiosis dysfunction and bleaching. Excess or damaged Symbiodinium symbionts are removed through a variety of mechanisms, including exocytosis, apoptosis, necrosis and autophagy. However, few studies have compared in the same species the relative involvement of these mechanisms, according to the stress inducing the bleaching. In this study, we used two different treatments —temperature and menthol— to induce bleaching in the sea anemone Anemonia viridis. By monitoring the ultrastructural tissue modifications, in control specimens we observed a basal rate of in situ symbiont digestion —or symbiophagy— induced by starvation. Symbiophagy was strongly induced in menthol-treated specimens and was the main cellular process of bleaching, whereas apoptosis and necrosis predominated in hyperthermal-induced bleaching. These results suggested a host effect through autophagy in menthol-treated specimens. These observations also suggested that symbiont removal may result from reengagement of the phagosomal maturation process in the host. These overall data demonstrate that several Symbiodinium cell removal mechanisms coexist and that stressors can activate one or more of these pathways, depending on the stress type, intensity or duration

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Calcium phosphate (CaP)-based biomaterials are commonly used in bone reconstructive surgery to replace the damaged tissue, and can also serve as vectors for local drug delivery. Due to its inhibitory action on osteoclasts, the semi-metallic element gallium (Ga) is used for the systemic treatment of disorders associated with accelerated bone resorption. As it was demonstrated that Ga could be incorporated in the structure of CaP biomaterials, we investigated the biological properties of Ga-loaded CaP biomaterials. Culturing bone cells on Ga-CaP, we observed a decrease in osteoclast number and a downregulation of late osteoclastic markers expression, while Ga-CaP upregulated the expression of osteoblastic marker genes involved in the maturation of bone matrix. We next investigated in vivo bone reconstructive properties of different Ga-loaded biomaterials using a murine bone defect healing model. All implanted biomaterials showed a good osseointegration into the surrounding host tissue, accompanied by a successful bone ingrowth and bone marrow reconstruction, as evidenced by histological analysis. Moreover, quantitative micro-computed tomography analysis of implants revealed that Ga enhanced total defect filling. Lastly, we took advantage for the first time of a particular mode of non-linear microscopy (second harmonic generation) to quantify in vivo bone tissue reconstruction within a CaP bone substitute. By doing so, we showed that Ga exerted a positive impact on mature organized collagen synthesis. As a whole, our data support the hypothesis that Ga represents an attractive additive to CaP biomaterials for bone reconstructive surgery. Copyright © 2017 John Wiley & Sons, Ltd.