The DARC side of metastasis: Shining a light on KAI1-mediated metastasis suppression in the vascular tunnel

Tumor cell metastasis to distant organs is an inefficient process that is limited in part by recently identified metastasis suppressors. Interactions between tumor cells and the surrounding stroma are thought to control much of cancer progression. In the August issue of Nature Medicine, Bandyopadhyay et al. (2006) demonstrate that specific cell surface interactions between the metastasis suppressor KAI1 on tumor cells and the decoy cytokine receptor DARC on adjacent vascular cells triggers senescence in the tumor cells and suppresses metastasis. These new observations demonstrate how metastasis suppressors can relay the restraint imposed by the stroma onto disseminating tumor cells

Reconfigurable Computing for Speech Recognition: Preliminary Findings

Continuous real-time speech recognition is a highly computationally-demanding task, but one which can take good advantage of a parallel processing system. To this end, we describe proposals for, and preliminary findings of, research in implementing in programmable logic the decoder part of a speech recognition system. Recognition via Viterbi decoding of Hidden Markov Models is outlined, along with details of current implementations, which aim to exploit properties of the algorithm that could make it well-suited for devices such as FPGAs. The question of how to deal with limited resources, by reconfiguration or otherwise, is also addressed

Recombinant Mitochondrial Transcription Factor A with N-terminal Mitochondrial Transduction Domain Increases Respiration and Mitochondrial Gene Expression in G11778A Leber's Hereditary Optic Neuropathy Cybrid Cells

Diseases involving mitochondrial defects usually manifest themselves in high-energy, post-mitotic tissues such as brain, retina, skeletal and cardiac muscle and frequently cause deficiencies in mitochondrial bioenergetics. We have developed a scalable procedure to produce recombinant human mitochondrial transcription factor A (TFAM) modified with an N-terminal protein transduction domain (PTD) and mitochondrial localization signal (MLS) that allow it to cross membranes and enter mitochondria through its "mitochondrial transduction domain" (MTD,=PTD+MLS). _In vitro_ studies in a classic mitochondrial disease cell model demonstrated that Alexa488-labeled MTD-TFAM rapidly entered the mitochondrial compartment. MTD-TFAM treatment of these cell lines reversibly increased oxygen consumption (respiration) rates 3-fold, levels of respiratory proteins and mitochondrial gene expression. _In vivo_ results demonstrated that respiration increased to lesser degrees in mitochondria from tissues of mice injected with MTD-TFAM. MTD-TFAM can alter mitochondrial bioenergetics and holds promise for treatment of mitochondrial diseases involving deficiencies of energy production

Cell Surface Remodeling by Plasmin: A New Function for an Old Enzyme

Plasmin, one of the most potent and reactive serine proteases, is involved in various physiological processes, including embryo development, thrombolysis, wound healing and cancer progression. The proteolytic activity of plasmin is tightly regulated through activation of its precursor, plasminogen, only at specific times and in defined locales as well as through inhibition of active plasmin by its abundant natural inhibitors. By exploiting the plasminogen activating system and overexpressing distinct components of the plasminogen activation cascade, such as pro-uPA, uPAR and plasminogen receptors, malignant cells can enhance the generation of plasmin which in turn, modifies the tumor microenvironment to sustain cancer progression. While plasmin-mediated degradation and modification of extracellular matrix proteins, release of growth factors and cytokines from the stroma as well as activation of several matrix metalloproteinase zymogens, all have been a focus of cancer research studies for decades, the ability of plasmin to cleave transmembrane molecules and thereby to generate functionally important cleaved products which induce outside-in signal transduction, has just begun to receive sufficient attention. Herein, we highlight this relatively understudied, but important function of the plasmin enzyme as it is generated de novo at the interface between cross-talking cancer and host cells

Neutrophil elastase facilitates tumor cell intravasation and early metastatic events

Functional roles of neutrophil elastase (NE) have not been examined in distinct steps of the metastatic cascade. NE, delivered to primary tumors as a purified enzyme or within intact neutrophils or neutrophil granule content, enhanced human tumor cell intravasation and subsequent dissemination via NE-mediated formation of dilated intratumoral vasculature. These effects depended on picomole range of NE activity, sensitive to its natural inhibitor, α1PI. I

The epidemiology of NCAA men’s lacrosse injuries, 2009/10-2014/15 academic years

BACKGROUND: Participation in lacrosse has grown at the collegiate levels. However, little research has examined the epidemiology of collegiate men's lacrosse injuries. This study describes the epidemiology of injuries in National Collegiate Athletic Association (NCAA) men's lacrosse during the 2009/10-2014/15 academic years. METHODS: Twenty-five men's lacrosse programs provided 63 team-seasons of data for the NCAA Injury Surveillance Program (NCAA-ISP) during the 2009/10-2014/15 academic years. Injuries occurred from participation in an NCAA-sanctioned practice or competition, and required attention from an AT or physician. Injuries were further classified as time loss (TL) injuries if the injury restricted participation for at least 24 h. Injuries were reported through electronic medical record application used by the team medical staff throughout the academic year. Injury rates per 1000 athlete-exposures (AE), injury rate ratios (RR), 95% confidence intervals (CI), and injury proportions were reported. RESULTS: Overall, 1055 men's lacrosse injuries were reported, leading to an injury rate of 5.29/1000AE; 95%CI: 4.98-5.61. The TL injury rate was 2.74/1000AE (95%CI: 2.51-2.96). The overall injury rate was higher in competition than practice (12.35 vs. 3.90/1000AE; RR = 3.16; 95%CI: 2.79-3.58). Most injuries were to the lower extremity (58.3%), particularly the ankle (14.1%) in competition and the upper leg (14.3%) in practice. Sprains and strains were the most common diagnoses in both competition (26.9 and 23.7%, respectively) and practice (20.2% and 27.4%, respectively). Most injuries in competitions and practices were due to player contact (32.8 and 17.5%, respectively) and non-contact (29.6 and 40.0%, respectively). CONCLUSIONS: Our estimated injury rates are lower than those from previous college men's lacrosse research. This may be due to increased injury awareness, advances in injury prevention exercise programs, or rule changes. Still, injury prevention can aim to continue reducing the incidence and severity of injury, particularly those sustained in competitions and to the lower extremity

Critical Review The Cell Surface Glycoprotein CDCP1 in Cancer-Insights, Opportunities, and Challenges

Summary In the last few years dysregulated expression of the cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) has been associated with several cancers and this cell surface molecule has been recognized both as a tumor marker and as a potential target to disrupt progression of cancer. Here we summarize what is known about CDCP1 including its structural features, expression in normal and cancerous tissues, and the in vitro experiments and studies in animal models that have provided the key insights into its potential role in tumor formation and metastasis in humans. We conclude by highlighting opportunities and challenges in targeting CDCP1 in cancer. 2009 IUBMB IUBMB Life, 61(7): [723][724][725][726][727][728][729][730] 200

Hierarchical complexity of the macro-scale neonatal brain

The human adult structural connectome has a rich nodal hierarchy, with highly diverse connectivity patterns aligned to the diverse range of functional specializations in the brain. The emergence of this hierarchical complexity in human development is unknown. Here, we substantiate the hierarchical tiers and hierarchical complexity of brain networks in the newborn period, assess correspondences with hierarchical complexity in adulthood, and investigate the effect of preterm birth, a leading cause of atypical brain development and later neurocognitive impairment, on hierarchical complexity. We report that neonatal and adult structural connectomes are both composed of distinct hierarchical tiers and that hierarchical complexity is greater in term born neonates than in preterms. This is due to diversity of connectivity patterns of regions within the intermediate tiers, which consist of regions that underlie sensorimotor processing and its integration with cognitive information. For neonates and adults, the highest tier (hub regions) is ordered, rather than complex, with more homogeneous connectivity patterns in structural hubs. This suggests that the brain develops first a more rigid structure in hub regions allowing for the development of greater and more diverse functional specialization in lower level regions, while connectivity underpinning this diversity is dysmature in infants born preterm