Functional and Structural Investigation of Songbird Brain Projection Neurons with Shuttle and Find

Extended abstract of a paper presented at Microscopy and Microanalysis 2011 in Nashville, Tennessee, USA, August 7-August 11, 201

Spinal Cord T-Cell Infiltration in the Rat Spared Nerve Injury Model: A Time Course Study.

The immune system is involved in the development of neuropathic pain. In particular, the infiltration of T-lymphocytes into the spinal cord following peripheral nerve injury has been described as a contributor to sensory hypersensitivity. We used the spared nerve injury (SNI) model of neuropathic pain in Sprague Dawley adult male rats to assess proliferation, and/or protein/gene expression levels for microglia (Iba1), T-lymphocytes (CD2) and cytotoxic T-lymphocytes (CD8). In the dorsal horn ipsilateral to SNI, Iba1 and BrdU stainings revealed microglial reactivity and proliferation, respectively, with different durations. Iba1 expression peaked at D4 and D7 at the mRNA and protein level, respectively, and was long-lasting. Proliferation occurred almost exclusively in Iba1 positive cells and peaked at D2. Gene expression observation by RT-qPCR array suggested that T-lymphocytes attracting chemokines were upregulated after SNI in rat spinal cord but only a few CD2/CD8 positive cells were found. A pronounced infiltration of CD2/CD8 positive T-cells was seen in the spinal cord injury (SCI) model used as a positive control for lymphocyte infiltration. Under these experimental conditions, we show early and long-lasting microglia reactivity in the spinal cord after SNI, but no lymphocyte infiltration was found

'Drowning in here in his bloody sea' : exploring TV cop drama's representations of the impact of stress in modern policing

The Criminal Justice System is a part of society that is both familiar and hidden. It is familiar in that a large part of daily news and television drama is devoted to it (Carrabine, 2008; Jewkes, 2011). It is hidden in the sense that the majority of the population have little, if any, direct contact with the Criminal Justice System, meaning that the media may be a major force in shaping their views on crime and policing (Carrabine, 2008). As Reiner (2000) notes, the debate about the relationship between the media, policing, and crime has been a key feature of wider societal concerns about crime since the establishment of the modern police force. He outlines the recurring themes in post-war debates in this field. For Conservatives there has been an ongoing concern that the media is criminongenic, as it serves to undermine traditional institutions, including the police. From the viewpoint of radical criminology, the impact of the media is two-fold: it exaggerates legitimate concerns about crime and emphasises the bureaucratic and other restrictions under which the police operate (Reiner, 2000). This is seen as undermining due process and legitimatising what can be termed a ‘maverick’ approach to policing. An early example of this can be seen in Clint Eastwood’s Dirty Harry movies (Siegel, 1971) where Harry Callaghan acts as a one-man law enforcement system outside of the formal legal process, a process portrayed as corrupt, inefficient, and concerned with offenders’ rights rather than protecting victims. From a policing perspective, Reiner (2000) argues that film and TV drama creates a simplistic narrative of crime solving that is almost completely divorced from the reality of modern police work, a finding consistent with more recent work by Cummins et al., (2014)

Fibroblasts—a key host cell type in tumor initiation, progression, and metastasis

Tumor initiation, growth, invasion, and metastasis occur as a consequence of a complex interplay between the host environment and cancer cells. Fibroblasts are now recognized as a key host cell type involved in host–cancer signaling. This review discusses some recent studies that highlight the roles of fibroblasts in tumor initiation, early progression, invasion, and metastasis. Some clinical studies describing the prognostic significance of fibroblast-derived markers and signatures are also discussed

Differential Matrix Rigidity Response in Breast Cancer Cell Lines Correlates with the Tissue Tropism

Metastasis to a variety of distant organs, such as lung, brain, bone, and liver, is a leading cause of mortality in the breast cancer patients. The tissue tropism of breast cancer metastasis has been recognized and studied extensively, but the cellular processes underlying this phenomenon, remain elusive. Modern technologies have enabled the discovery of a number of the genetic factors determining tissue tropism of malignant cells. However, the effect of these genetic differences on the cell motility and invasiveness is poorly understood. Here, we report that cellular responses to the mechanical rigidity of the extracellular matrix correlate with the rigidity of the target tissue. We tested a series of single cell populations isolated from MDA-MB-231 breast cancer cell line in a variety of assays where the extracellular matrix rigidity was varied to mimic the environment that these cells might encounter in vivo. There was increased proliferation and migration through the matrices of rigidities corresponding to the native rigidities of the organs where metastasis was observed. We were able to abolish the differential matrix rigidity response by knocking down Fyn kinase, which was previously identified as a critical component of the FN rigidity response pathway in healthy cells. This result suggests possible molecular mechanisms of the rigidity response in the malignant cells, indicating potential candidates for therapeutic interventions

Class II MHC Self-Antigen Presentation in Human B and T Lymphocytes

Human CD4[superscript +] T cells process and present functional class II MHC-peptide complexes, but the endogenous peptide repertoire of these non-classical antigen presenting cells remains unknown. We eluted and sequenced HLA-DR-bound self-peptides presented by CD4[superscript +] T cells in order to compare the T cell-derived peptide repertoire to sequences derived from genetically identical B cells. We identified several novel epitopes derived from the T cell-specific proteome, including fragments of CD4 and IL-2. While these data confirm that T cells can present peptides derived from the T-cell specific proteome, the vast majority of peptides sequenced after elution from MHC were derived from the common proteome. From this pool, we identified several identical peptide epitopes in the T and B cell repertoire derived from common endogenous proteins as well as novel endogenous epitopes with promiscuous binding. These findings indicate that the endogenous HLA-DR-bound peptide repertoire, regardless of APC type and across MHC isotype, is largely derived from the same pool of self-protein.National Institutes of Health (U.S.) (grant P01AI039671)National Institutes of Health (U.S.) (P01AI045757

Neuropathic Pain Phenotype Does Not Involve the NLRP3 Inflammasome and Its End Product Interleukin-1β in the Mice Spared Nerve Injury Model.

The NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is one of the main sources of interleukin-1β (IL-1β) and is involved in several inflammatory-related pathologies. To date, its relationship with pain has not been studied in depth. The aim of our study was to elucidate the role of NLRP3 inflammasome and IL-1β production on neuropathic pain. Results showed that basal pain sensitivity is unaltered in NLRP3-/- mice as well as responses to formalin test. Spared nerve injury (SNI) surgery induced the development of mechanical allodynia and thermal hyperalgesia in a similar way in both genotypes and did not modify mRNA levels of the NLRP3 inflammasome components in the spinal cord. Intrathecal lipopolysaccharide (LPS) injection increases apoptosis-associated speck like protein (ASC), caspase-1 and IL-1β expression in both wildtype and NLRP3-/- mice. Those data suggest that NLRP3 is not involved in neuropathic pain and also that other sources of IL-1β are implicated in neuroinflammatory responses induced by LPS

The evolution of the upright posture and gait—a review and a new synthesis

During the last century, approximately 30 hypotheses have been constructed to explain the evolution of the human upright posture and locomotion. The most important and recent ones are discussed here. Meanwhile, it has been established that all main hypotheses published until the last decade of the past century are outdated, at least with respect to some of their main ideas: Firstly, they were focused on only one cause for the evolution of bipedality, whereas the evolutionary process was much more complex. Secondly, they were all placed into a savannah scenario. During the 1990s, the fossil record allowed the reconstruction of emerging bipedalism more precisely in a forested habitat (e.g., as reported by Clarke and Tobias (Science 269:521–524, 1995) and WoldeGabriel et al. (Nature 412:175–178, 2001)). Moreover, the fossil remains revealed increasing evidence that this part of human evolution took place in a more humid environment than previously assumed. The Amphibian Generalist Theory, presented first in the year 2000, suggests that bipedalism began in a wooded habitat. The forests were not far from a shore, where our early ancestor, along with its arboreal habits, walked and waded in shallow water finding rich food with little investment. In contrast to all other theories, wading behaviour not only triggers an upright posture, but also forces the individual to maintain this position and to walk bipedally. So far, this is the only scenario suitable to overcome the considerable anatomical and functional threshold from quadrupedalism to bipedalism. This is consistent with paleoanthropological findings and with functional anatomy as well as with energetic calculations, and not least, with evolutionary psychology. The new synthesis presented here is able to harmonise many of the hitherto competing theories