Root-secreted nucleosides: signaling chemoattractants of rhizosphere bacteria.

The rhizosphere is a complex ecosystem, consisting of a narrow soil zone influenced by plant roots and inhabited by soil-borne microorganisms. Plants actively shape the rhizosphere microbiome through root exudates. Some metabolites are signaling molecules specifically functioning as chemoattractants rather than nutrients. These elusive signaling molecules have been sought for several decades, and yet little progress has been made. Root-secreted nucleosides and deoxynucleosides were detected in exudates of various plants by targeted ultra-performance liquid chromatography-mass spectrometry/mass spectrometry. Rhizobacteria were isolated from the roots of Helianthemum sessiliflorum carrying the mycorrhizal desert truffle Terfezia boudieri. Chemotaxis was determined by a glass capillary assay or plate assays on semisolid agar and through a soil plate assay. Nucleosides were identified in root exudates of plants that inhabit diverse ecological niches. Nucleosides induced positive chemotaxis in plant beneficial bacteria Bacillus pumilus, Bacillus subtilis, Pseudomonas turukhanskensis spp., Serratia marcescens, and the pathogenic rhizobacterium Xanthomonas campestris and E coli. In a soil plate assay, nucleosides diffused to substantial distances and evoked chemotaxis under conditions as close as possible to natural environments. This study implies that root-secreted nucleosides are involved in the assembly of the rhizosphere bacterial community by inducing chemotaxis toward plant roots. In animals, nucleoside secretion known as "purinergic signaling" is involved in communication between cells, physiological processes, diseases, phagocytic cell migration, and bacterial activity. The coliform bacterium E. coli that inhabits the lower intestine of warm-blooded organisms also attracted to nucleosides, implying that nucleosides may serve as a common signal for bacterial species inhabiting distinct habitats. Taken together, all these may indicate that chemotaxis signaling by nucleosides is a conserved universal mechanism that encompasses living kingdoms and environments and should be given further attention in plant rhizosphere microbiome research.

Status of B-Lymphocyte Subsets and Their Homing Markers in Patients With Post-Kala-Azar Dermal Leishmaniasis.

In visceral leishmaniasis, the Type II helper T cell predominance results in B cell modulation and enhancement of anti-leishmanial IgG. However, information regarding its dermal sequel, post-kala-azar dermal leishmaniasis (PKDL), remains limited. Accordingly, this study aimed to elucidate the B cell-mediated antibody-dependent/independent immune profiles of PKDL patients. In the peripheral blood of PKDL patients, immunophenotyping of B cell subsets was performed by flow cytometry and by immunohistochemistry at lesional sites. The functionality of B cells was assessed in terms of skin IgG by immunofluorescence, while the circulating levels of B cell chemoattractants (CCL20, CXCL13, CCL17, CCL22, CCL19, CCL27, CXCL9, CXCL10 and CXCL11) were evaluated by a multiplex assay. In patients with PKDL as compared with healthy controls, there was a significant decrease in pan CD19+ B cells. However, within the CD19+ B cell population, there was a significantly raised proportion of switched memory B cells (CD19+IgD-CD27+) and plasma cells (CD19+IgD-CD38+CD27+). This was corroborated at lesional sites where a higher expression of CD20+ B cells and CD138+ plasma cells was evident; they were Ki67 negative and demonstrated a raised IgG. The circulating levels of B cell chemoattractants were raised and correlated positively with lesional CD20+ B cells. The increased levels of B cell homing markers possibly accounted for their enhanced presence at the lesional sites. There was a high proportion of plasma cells, which accounted for the increased presence of IgG that possibly facilitated parasite persistence and disease progression.

Female reproductive fluids 'rescue' sperm from phenotypic ageing in an external fertilizer.

Female reproductive fluids (FRFs) serve key reproductive functions in sexually reproducing animals, including modifying the way sperm swim and detect eggs, and influencing sperm lifespan. Despite the central role of FRF during fertilization, we know surprisingly little about sperm-FRF interactions under different environmental conditions. Theory suggests that in external fertilizers FRF may 'rescue' sperm from ageing effects as they search to fertilize eggs. Here, we test the interaction between these two fundamental properties of the fertilization environment, ejaculate age (i.e. time since ejaculation) and FRF, on a range of functional sperm phenotypes in a broadcast spawning mussel, Mytilus galloprovincialis. We found that the effects of ejaculate age on multivariate sperm motility traits and total sperm motility were altered by FRF, and that longer-lived sperm exhibit stronger, likely more advantageous, responses to FRF after periods of ageing. We also detected significant among-male variation in the relationship between sperm motility traits and ejaculate age; notably, these patterns were only revealed when sperm encountered FRF. Collectively these findings underscore the importance of considering female reproductive physiology when interpreting ageing-related declines in sperm motility, as doing so may expose importance sources of variation in sperm phenotypic plasticity among males and environments.

Neutrophils: Amoeboid Migration and Swarming Dynamics in Tissues.

Neutrophils are key cells of our innate immune response with essential roles for eliminating bacteria and fungi from tissues. They are also the prototype of an amoeboid migrating leukocyte. As one of the first blood-recruited immune cell types during inflammation and infection, these cells can invade almost any tissue compartment. Once in the tissue, neutrophils undergo rapid shape changes and migrate at speeds higher than most other immune cells. They move in a substrate-independent manner in interstitial spaces and do not follow predetermined tissue paths. Instead, neutrophil navigation is largely shaped by the chemokine and chemoattractant milieu around them. This highlights the decisive role of attractant-sensing G-protein coupled receptors (GPCRs) and downstream molecular pathways for controlling amoeboid neutrophil movement in tissues. A diverse repertoire of cell-surface expressed GPCRs makes neutrophils the perfect sentinel cell type to sense and detect danger-associated signals released from wounds, inflamed interstitium, dying cells, complement factors or directly from tissue-invading microbes. Moreover, neutrophils release attractants themselves, which allows communication and coordination between individual cells of a neutrophil population. GPCR-mediated positive feedback mechanisms were shown to underlie neutrophil swarming, a population response that amplifies the recruitment of amoeboid migrating neutrophils to sites of tissue injury and infection. Here we discuss recent findings and current concepts that counteract excessive neutrophil accumulation and swarm formation. In particular, we will focus on negative feedback control mechanisms that terminate neutrophil swarming to maintain the delicate balance between tissue surveillance, host protection and tissue destruction.

Ocean acidification alters sperm responses to egg-derived chemicals in a broadcast spawning mussel.

The continued emissions of anthropogenic carbon dioxide are causing progressive ocean acidification (OA). While deleterious effects of OA on biological systems are well documented in the growth of calcifying organisms, lesser studied impacts of OA include potential effects on gamete interactions that determine fertilization, which are likely to influence the many marine species that spawn gametes externally. Here, we explore the effects of OA on the signalling mechanisms that enable sperm to track egg-derived chemicals (sperm chemotaxis). We focus on the mussel Mytilus galloprovincialis, where sperm chemotaxis enables eggs to bias fertilization in favour of genetically compatible males. Using an experimental design based on the North Carolina II factorial breeding design, we test whether the experimental manipulation of seawater pH (comparing ambient conditions to predicted end-of-century scenarios) alters patterns of differential sperm chemotaxis. While we find no evidence that male-female gametic compatibility is impacted by OA, we do find that individual males exhibit consistent variation in how their sperm perform in lowered pH levels. This finding of individual variability in the capacity of ejaculates to respond to chemoattractants under acidified conditions suggests that climate change will exert considerable pressure on male genotypes that can withstand an increasingly hostile fertilization environment.

The Role of Streptococcal Cell-Envelope Proteases in Bacterial Evasion of the Innate Immune System.

Bacteria possess the ability to evolve varied and ingenious strategies to outwit the host immune system, instigating an evolutionary arms race. Proteases are amongst the many weapons employed by bacteria, which specifically cleave and neutralize key signalling molecules required for a coordinated immune response. In this article, we focus on a family of S8 subtilisin-like serine proteases expressed as cell-envelope proteases (CEPs) by group A and group B streptococci. Two of these proteases known as Streptococcus pyogenes CEP (SpyCEP) and C5a peptidase cleave the chemokine CXCL8 and the complement fragment C5a, respectively. Both CXCL8 and C5a are potent neutrophil-recruiting chemokines, and by neutralizing their activity, streptococci evade a key defence mechanism of innate immunity. We review the mechanisms by which CXCL8 and C5a recruit neutrophils and the characterization of SpyCEP and C5a peptidase, including both in vitro and in vivo studies. Recently described structural insights into the function of this CEP family are also discussed. We conclude by examining the progress of prototypic vaccines incorporating SpyCEP and C5a peptidase in their preparation. Since streptococci-producing SpyCEP and C5a peptidase are responsible for a considerable global disease burden, targeting these proteases by vaccination strategies or by small-molecule antagonists should provide protection from and promote the resolution of streptococcal infections.

Endogenous Stem Cell-Based In Situ Tissue Regeneration Using Electrostatically Interactive Hydrogel with a Newly Discovered Substance P Analog and VEGF-Mimicking Peptide.

The use of chemoattractants to promote endogenous stem cell-based in situ tissue regeneration has recently garnered much attention. This study is the first to assess the endogenous stem cell migration using a newly discovered substance P (SP) analog (SP1) by molecular dynamics simulations as an efficient chemoattractant. Further, a novel strategy based on electrostatic interaction using cationic chitosan (Ch) and anionic hyaluronic acid (HA) to prepare an SP1-loaded injectable C/H formulation without SP1 loss is developed. The formulation quickly forms an SP1-loaded C/H hydrogel in situ through in vivo injection. The newly discovered SP1 is found to possess human mesenchymal stromal cells (hMSCs) migration-inducing ability that is approximately two to three times higher than that of the existing SP. The designed VEGF-mimicking peptide (VP) chemically reacts with the hydrogel (C/H-VP) to sustain the release of VP, thus inducing vasculogenic differentiation of the hMSCs that migrate toward the C/H-VP hydrogel. Similarly, in animal experiments, SP1 attracts a large number of hMSCs toward the C/H-VP hydrogel, after which VP induces vasculogenic differentiation. Collectively, these findings indicate that SP1-loaded C/H-VP hydrogels are a promising strategy to facilitate endogenous stem cell-based in situ tissue regeneration.

Chemotactic behavior of Campylobacter fetus subspecies towards cervical mucus, bovine placenta and selected substances and ion.

The chemotaxis of C. fetus subsp. venerealis and C. fetus subsp. fetus was determined in the presence of bovine cervical mucus and bovine placental extract. Some reported substances and ion in those materials, such amino acids, ferrous iron, hormones, sugars and organic acids were also investigated. Bovine cervical mucus, bovine placenta extracts and some substances and ion of these materials namely L-fucose, L- aspartate, L-glutamate, L-serine, ferrous iron, fumarate, pyruvate and succinate were chemoattractants. The chemottraction was significantly larger in higher concentrations of the tested substances and ion and significant differences among tested strains were also observed. Meso-erythritol and hormones bovine placental lactogen, 17ß-estradiol, and progesterone did not elicit chemotactical response. In conclusion, this chemotactic behavior may guide the C. fetus navigation in the bovine host's genital tract and be an important cofactor of tissue tropism for this bacterium.

Unrestrained Gαi2 Signaling Disrupts Neutrophil Trafficking, Aging, and Clearance.

Neutrophil trafficking, homeostatic and pathogen elicited, depends upon chemoattractant receptors triggering heterotrimeric G-protein Gαißγ signaling, whose magnitude and kinetics are governed by RGS protein/Gαi interactions. RGS proteins typically limit Gαi signaling by reducing the duration that Gαi subunits remain GTP bound and able to activate downstream effectors. Yet how in totality RGS proteins shape neutrophil chemoattractant receptor activated responses remains unclear. Here, we show that C57Bl/6 mouse neutrophils containing a genomic knock-in of a mutation that disables all RGS protein-Gαi2 interactions (G184S) cannot properly balance chemoattractant receptor signaling, nor appropriately respond to inflammatory insults. Mutant neutrophils accumulate in mouse bone marrow, spleen, lung, and liver; despite neutropenia and an intrinsic inability to properly mobilize from the bone marrow. In vitro they rapidly adhere to ICAM-1 coated plates, but in vivo they poorly adhere to blood vessel endothelium. Those few neutrophils that cross blood vessels and enter tissues migrate haphazardly. Following Concanavalin-A administration fragmented G184S neutrophils accumulate in liver sinusoids leading to thrombo-inflammation and perivasculitis. Thus, neutrophil Gαi2/RGS protein interactions both limit and facilitate Gαi2 signaling thereby promoting normal neutrophil trafficking, aging, and clearance.

Chemoattractants driven and microglia based biomimetic nanoparticle treating TMZ-resistant glioblastoma multiforme.

Currently, clinical treatment for temozolomide (TMZ)-resistant glioblastoma multiforme (GBM) is still a difficult problem. The aim of this paper is to set up a new GBM-targeted drug delivery system to treat TMZ-resistant GBM. Zoledronate (ZOL) not only induces apoptosis of TMZ-resistant GBM cells by down-regulation of farnesyl pyrophosphate synthetase (FPPS) but also increases the proportion of M1-type GBM associated macrophages (GAM). Based on chemoattractants secreted by GBM cells, a ZOL loaded nanoparticle coated with microglia cell membrane (ZOL@CNPs) was prepared to deliver ZOL to central nervous system to treat TMZ-resistant GBM. ZOL@CNPs was actively recruited to TMZ-resistant GBM region by CX3CL1/CX3CR1 and CSF-1/CSF-1R signal axis, and the release of ZOL from ZOL@CNPs was triggered by glutathione in GBM cells. ZOL@CNPs inhibited the growth of TMZ-resistant GBM through inducing apoptosis and inhibiting the migration and invasion of TMZ-resistant GBM cells. Besides, the immunosuppressive and hypoxic microenvironment, playing an important role in the growth of TMZ-resistant GBM, was significantly improved by ZOL@CNPs through increasing the proportion of M1-type GAM and blocking the expression of HIF-1α. ZOL@CNPs has a great potential application in the treatment for TMZ-resistant GBM.

Sequential expression of neutrophil chemoattractants in cerebrospinal fluid after subarachnoid hemorrhage.

OBJECTIVE: Neutrophils induce inflammation through the exocytosis of cytotoxic granule proteins. Recently, neutrophils have been reported to be an independent parameter associated with unfavorable outcomes after subarachnoid hemorrhage (SAH). However, the mechanism by which neutrophils accumulate within the CSF after SAH remains undetermined. METHODS: Concentrations of C5a, epithelial neutrophil activating peptide 78 (ENA-78), interleukin-8 (IL-8), growth-regulated oncogene-α (GRO-α), neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase (MPO) were measured serially until day 14 in the CSF of 10 patients with SAH. CSF samples obtained from patients suffering from unruptured aneurysms were used as controls. RESULTS: The concentrations of C5a and ENA-78 were significantly increased on day 1, while those of IL-8 and GRO-α significantly increased during days 3-7 compared with those of the control samples. The levels of NGAL and MPO, components of neutrophil granules, significantly increased during days 1-5 and days 1-3, respectively, after SAH and gradually decreased thereafter. The correlations between ENA-78 and C5a on day 1, IL-8 and GRO-α on days 3-7, and NGAL and MPO on days 1-3 were significant. CONCLUSION: These neutrophil chemoattractants might be serially involved in the infiltration of neutrophils into the CSF after SAH. Migrated neutrophils play an important role in inflammatory reactions in the central nervous system after SAH.

Down-regulation of STAT3 enhanced chemokine expression and neutrophil recruitment in biliary atresia.

Biliary atresia (BA) is an immune-related disorder and signal transducer and activator of transcription 3 (STAT3) is a key signalling molecule in inflammation. The present study was designed to clarify the function of STAT3 in BA. STAT3 expression was examined in patients and a mouse BA model in which STAT3 levels were further altered with a specific inhibitor or activator. Neutrophil accumulation and the levels of the neutrophil chemoattractants (C-X-C motif) ligand 1 (CXCL1) and IL-8 were determined. The effects of STAT3 inhibition on IL-8 expression were examined in human biliary epithelial cell (BEC) cultures. Functional changes in liver STAT3+ neutrophils in the mouse model were analysed with 10× single cell RNA-seq methods. Results showed STAT3 and p-STAT3 expression was reduced in BA liver tissue compared with control samples. Administration of a STAT3 inhibitor increased jaundice and mortality and reduced body weight in BA mice. In contrast, the STAT3 activator ameliorated BA symptoms. Extensive neutrophil accumulation together with CXCL1 up-regulation, both of which were suppressed by an anti-CXCL1 antibody, were observed in the STAT3 inhibitor-treated group. Recombinant IL-8 administration increased disease severity in BA mice, and the STAT3 activator had the reverse effect. Inhibiting STAT3 increased apoptosis of human BECs together with up-regulated IL-8 expression. RNA-seq analysis revealed reduced the numbers of STAT3 expressing neutrophil in BA which was accompanied by marked enhanced interferon-related antiviral activities. In conclusion, STAT3 reduction, enhanced IL-8 and CXCL1 expression and promoted the accumulation of interferon-responsive neutrophils resulting in BEC damage in BA.

N-formyl-l-aspartate: A novel sperm chemoattractant identified in ovulatory phase oviductal fluid using a microfluidic chip.

BACKGROUND: Chemotaxis, as a mechanism for sperm guidance although known, has been difficult to demonstrate in vitro. Consequently, very few chemoattractants have been identified till date. OBJECTIVES: To investigate sperm motility behavior in response to ovulatory (OV) and preovulatory (preOV) oviductal fluid (OF) and identify potential chemotactic metabolites. MATERIALS AND METHODS: Intracellular calcium ([Ca2+ ]I ) influx in capacitating sperm was determined by spectrofluorimetry. The chemotactic response of rat caudal sperm to OF from the preOV- and OV- phases of normally cycling female rats was assessed in a microfluidic device developed by us. Hydrophilic metabolites extracted from the OF of both the phases were resolved and identified by LC-MS/MS, followed by data analysis using XCMS and MetaboAnalyst software, and chemotactic potential of the most promising compound was validated using the microfluidic device. RESULTS: Spectrofluorimetric analysis depicts a significant increase in sperm [Ca2+ ]I in response to OV-OF. With the microfluidic chemotaxis assay, sperm population shows a significantly increased directionality and velocity to an ascending gradient of 0.06 µg/µl OV-OF compared to preOV-OF. LC-MS/MS of the OFs demonstrates five and four metabolites to be exclusive to the OV-OF and preOV-OF, respectively, and 25 metabolites common to both, of which 14 metabolites, including N-formyl-l-aspartate (NFA), are increased in OV-OF; NFA was tested for its ability to influence sperm movement, and shows chemotaxis potential. DISCUSSION AND CONCLUSION(S): This is the first study that has systematically demonstrated sperm chemotaxis with OV phase rat OF, identified NFA present in this fluid as a novel chemoattractant to sperm, and proven the utility of the device to test putative chemoattractants. It remains to be seen whether NFA is present in the follicular fluid (FF) of infertile women, and whether it may likely be a reason for the failure of natural conception in idiopathic infertile women.

In Vitro Maturation of Cumulus-Oocyte Complexes and In Vitro Sperm Capacitation Significantly Increase the Expression and Enhance the Location of the CXCL12 and CXCR4 Anchoring Attractant Complex in Pigs.

Successful internal fertilization in mammals depends on several mechanisms, including those triggering the so-called "sperm attraction" towards the oocyte, which include some oocyte-derived sperm chemoattractants and interactive protein complexes, such as the cytokine C-X-C motif chemokine 12/C-X-C chemokine receptor type 4 (CXCL12-CXCR4) receptor complex. The presence and precise localization of these crucial proteins was determined hereby, for the first time, in porcine cumulus-oocyte complexes (COCs) and spermatozoa. CXCL12 was overexpressed in the cumulus cells of in vitro matured, compared to immature COCs (p < 0.05), with its receptor (CXCR4) being up-regulated in capacitated spermatozoa (p < 0.03) compared to uncapacitated spermatozoa. The CXCR4 appeared specifically localized in the sperm tail of non-capacitated spermatozoa and also in the sperm head of capacitated spermatozoa, suggesting that the CXCL12-CXCR4 signaling complex would play a pivotal role in attracting capacitated spermatozoa towards the oocyte, facilitating fertilization in pigs.

Curdlan, zymosan and a yeast-derived ß-glucan reshape tumor-associated macrophages into producers of inflammatory chemo-attractants.

Anti-cancer T-cell responses are often halted due to the immune-suppressive micro-environment, in part related to tumor-associated macrophages. In the current study, we assessed indigestible ß-glucans (oatßG, curdlan, grifolan, schizophyllan, lentinan, yeast whole glucan particles (yWGP), zymosan and two additional yeast-derived ß-glucans a and b) for their physicochemical properties as well as their effects on the plasticity of human monocyte-derived macrophages that were polarized with IL-4 to immune-suppressive macrophages. Beta-glucans were LPS/LTA free, and tested for solubility, molecular masses, protein and monosaccharide contents. Curdlan, yeast-b and zymosan re-polarized M(IL-4) macrophages towards an M1-like phenotype, in particular showing enhanced gene expression of CCR7, ICAM1 and CD80, and secretion of TNF-α and IL-6. Notably, differential gene expression, pathway analysis as well as protein expressions demonstrated that M(IL-4) macrophages treated with curdlan, yeast-b or zymosan demonstrated enhanced production of chemo-attractants, such as CCL3, CCL4, and CXCL8, which contribute to recruitment of monocytes and neutrophils. The secretion of chemo-attractants was confirmed when using patient-derived melanoma-infiltrating immune cells. Taken together, the bacterial-derived curdlan as well as the yeast-derived ß-glucans yeast-b and zymosan have the unique ability to preferentially skew macrophages towards a chemo-attractant-producing phenotype that may aid in anti-cancer immune responses.

Molecules, Mechanisms, and Disorders of Self-Domestication: Keys for Understanding Emotional and Social Communication from an Evolutionary Perspective.

The neural crest hypothesis states that the phenotypic features of the domestication syndrome are due to a reduced number or disruption of neural crest cells (NCCs) migration, as these cells differentiate at their final destinations and proliferate into different tissues whose activity is reduced by domestication. Comparing the phenotypic characteristics of modern and prehistoric man, it is clear that during their recent evolutionary past, humans also went through a process of self-domestication with a simultaneous prolongation of the period of socialization. This has led to the development of social abilities and skills, especially language, as well as neoteny. Disorders of neural crest cell development and migration lead to many different conditions such as Waardenburg syndrome, Hirschsprung disease, fetal alcohol syndrome, DiGeorge and Treacher-Collins syndrome, for which the mechanisms are already relatively well-known. However, for others, such as Williams-Beuren syndrome and schizophrenia that have the characteristics of hyperdomestication, and autism spectrum disorders, and 7dupASD syndrome that have the characteristics of hypodomestication, much less is known. Thus, deciphering the biological determinants of disordered self-domestication has great potential for elucidating the normal and disturbed ontogenesis of humans, as well as for the understanding of evolution of mammals in general.

Identification of Positive Chemotaxis in the Protozoan Pathogen Trypanosoma brucei.

To complete its infectious cycle, the protozoan parasite Trypanosoma brucei must navigate through diverse tissue environments in both its tsetse fly and mammalian hosts. This is hypothesized to be driven by yet unidentified chemotactic cues. Prior work has shown that parasites engaging in social motility in vitro alter their trajectory to avoid other groups of parasites, an example of negative chemotaxis. However, movement of T. brucei toward a stimulus, positive chemotaxis, has so far not been reported. Here, we show that upon encountering Escherichia coli, socially behaving T. brucei parasites exhibit positive chemotaxis, redirecting group movement toward the neighboring bacterial colony. This response occurs at a distance from the bacteria and involves active changes in parasite motility. By developing a quantitative chemotaxis assay, we show that the attractant is a soluble, diffusible signal dependent on actively growing E. coli Time-lapse and live video microscopy revealed that T. brucei chemotaxis involves changes in both group and single cell motility. Groups of parasites change direction of group movement and accelerate as they approach the source of attractant, and this correlates with increasingly constrained movement of individual cells within the group. Identification of positive chemotaxis in T. brucei opens new opportunities to study mechanisms of chemotaxis in these medically and economically important pathogens. This will lead to deeper insights into how these parasites interact with and navigate through their host environments.IMPORTANCE Almost all living things need to be able to move, whether it is toward desirable environments or away from danger. For vector-borne parasites, successful transmission and infection require that these organisms be able to sense where they are and use signals from their environment to direct where they go next, a process known as chemotaxis. Here, we show that Trypanosoma brucei, the deadly protozoan parasite that causes African sleeping sickness, can sense and move toward an attractive cue. To our knowledge, this is the first report of positive chemotaxis in these organisms. In addition to describing a new behavior in T. brucei, our findings enable future studies of how chemotaxis works in these pathogens, which will lead to deeper understanding of how they move through their hosts and may lead to new therapeutic or transmission-blocking strategies.

Effect of different stimuli on twitching behavior of endophytic bacteria isolated from Loranthus sp. Jacq.

Bacteria need to adopt to different behavioral tuning depending on the dynamic eco-physiological conditions they are exposed to. One of these adaptive strategies is the use of motility. Here we report the twitching motility response of four endophytic isolates of Bacillus sp. when exposed to different eco-physiological stimuli like different nutrient sources, and mechanical and chemical antagonists on solid surfaces. These endophytic bacteria were isolated from different parts of a hemiparasite Loranthus sp. Jacq. (Loranthaceae) growing on economically important mango trees. The results show that the twitching motility of these bacteria was more when exposed to organic acids, metals salts (among nutrients) and mechanical shearing (stress) than the other factors. Their motility is not affected by surface lubrication or EPS production, but instead is influenced by shear-sensitive structures and affinity to metal ions. Further molecular studies are needed to elucidate the basis of this twitching behaviour on solid surfaces.

Endogenous cell recruitment strategy for articular cartilage regeneration.

In the absence of timely and proper treatments, injuries to articular cartilage (AC) can lead to cartilage degeneration and ultimately result in osteoarthritis. Regenerative medicine and tissue engineering techniques are emerging as promising approaches for AC regeneration and repair. Although the use of cell-seeded scaffolds prior to implantation can regenerate and repair cartilage lesions to some extent, these approaches are still restricted by limited cell sources, excessive costs, risks of disease transmission and complex manufacturing practices. Recently developed acellular scaffold approaches that rely on the recruitment of endogenous cells to the injured sites avoid these drawbacks and offer great promise for in situ AC regeneration. Multiple endogenous stem/progenitor cells (ESPCs) are found in joint-resident niches and have the capability to migrate to sites of injury to participate in AC regeneration. However, the natural recruitment of ESPCs is insufficient, and the local microenvironment is hostile after injury. Hence, an endogenous cell recruitment strategy based on the combination of chemoattractants and acellular scaffolds to effectively and specifically recruit ESPCs and improve local microenvironment may provide new insights into in situ AC regeneration. This review provides a brief overview of: (1) the status of endogenous cell recruitment strategy; (2) the subpopulations, potential migration routes (PMRs) of joint-resident ESPCs and their immunomodulatory and reparative effects; (3) chemoattractants and their potential adverse effects; (4) scaffold-based drug delivery systems (SDDSs) that are utilized for in situ AC regeneration; and (5) the challenges and future perspectives of endogenous cell recruitment strategy for AC regeneration. STATEMENT OF SIGNIFICANCE: Although the endogenous cell recruitment strategy for articular cartilage (AC) regeneration has been investigated for several decades, much work remains to be performed in this field. Future studies should have the following aims: (1) reporting the up-to-date progress in the endogenous cell recruitment strategies; (2) determining the subpopulations of ESPCs, the cellular and molecular mechanisms underlying the migration of these cells and their anti-inflammatory, immunomodulatory and reparative effects; (3) elucidating the chemoattractants that enhance ESPC recruitment and their potential adverse effects; and (4) developing advanced SDDSs for chemoattractant dispatch. Herein, we present a systematic overview of the aforementioned issues to provide a better understanding of endogenous cell recruitment strategies for AC regeneration and repair.

Molecular cues involved in the regulation of B cell dynamics: Assistants of antigen hunting.

The ability of a cell to migrate, adhere, and change its morphology is determinant in developing its functions; these capacities reach their maximum relevance in immune cells. For an efficient immune response, immune cells must localize in the right place at the right time; that implies crossing tissue barriers and migrating in the interstitial space of the tissues at high velocities. The dependency on trafficking abilities is even higher for B cells, one of the arms of the adaptive immune system, considering that they must encounter specific antigens for their clonal receptor in the enormous tissue volume of the secondary lymphoid organs (spleen, lymph nodes, Peyer patches). The regulated interplay between cell motility and cell adhesion allows B cells to reach distinct lymphoid tissues and, within them, to explore the stromal cell networks where antigen might be exposed. In this meeting-invited review, I summarize the current knowledge on the molecular cues and mechanisms that shapes B cell dynamics at the initial phase of the humoral immune response, including homeostatic chemoattractants and innate/inflammatory stimuli. I also revised the B cell behavior alterations caused by BCR recognition of antigen and the molecular mechanisms involved.