Endogenous transforming growth factor β1 suppresses inflammation and promotes survival in adult CNS

Transforming growth factor β1 (TGFβ1) is a pleiotropic cytokine with potent neurotrophic and immunosuppressive properties that is upregulated after injury, but also expressed in the normal nervous system. In the current study, we examined the regulation of TGFβ1 and the effects of TGFβ1 deletion on cellular response in the uninjured adult brain and in the injured and regenerating facial motor nucleus. To avoid lethal autoimmune inflammation within 3 weeks after birth in TGFβ1-deficient mice, this study was performed on a T- and B-cell-deficient RAG2-/- background. Compared with wild-type siblings, homozygous deletion of TGFβ1 resulted in an extensive inflammatory response in otherwise uninjured brain parenchyma. Astrocytes increased in GFAP and CD44 immunoreactivity; microglia showed proliferative activity, expression of phagocytosis-associated markers [αXβ2, B7.2, and MHC1 (major histocompatibility complex type 1)], and reduced branching. Ultrastructural analysis revealed focal blockade of axonal transport, perinodal damming of axonal organelles, focal demyelination, and myelin debris in granule-rich, phagocytic microglia. After facial axotomy, absence of TGFβ1 led to a fourfold increase in neuronal cell death (52 vs 13%), decreased central axonal sprouting, and significant delay in functional recovery. It also interfered with the microglial response, resulting in a diminished expression of early activation markers [ICAM1 (intercellular adhesion molecule 1), α6β1, and αMβ2] and reduced proliferation. In line with axonal and glial findings in the otherwise uninjured CNS, absence of endogenous TGFβ1 also caused an ∼10% reduction in the number of normal motoneurons, pointing to an ongoing and potent trophic role of this anti-inflammatory cytokine in the normal as well as in the injured brain. Copyright © 2007 Society for Neuroscience

Subcellular pathways through VGluT3-expressing mouse amacrine cells provide locally tuned object-motion-selective signals in the retina

VGluT3-expressing mouse retinal amacrine cells (VG3s) respond to small-object motion and connect to multiple types of bipolar cells (inputs) and retinal ganglion cells (RGCs, outputs). Because these input and output connections are intermixed on the same dendrites, making sense of VG3 circuitry requires comparing the distribution of synapses across their arbors to the subcellular flow of signals. Here, we combine subcellular calcium imaging and electron microscopic connectomic reconstruction to analyze how VG3s integrate and transmit visual information. VG3s receive inputs from all nearby bipolar cell types but exhibit a strong preference for the fast type 3a bipolar cells. By comparing input distributions to VG3 dendrite responses, we show that VG3 dendrites have a short functional length constant that likely depends on inhibitory shunting. This model predicts that RGCs that extend dendrites into the middle layers of the inner plexiform encounter VG3 dendrites whose responses vary according to the local bipolar cell response type

2004-2005 International Whaling Commission-Southern Ocean Whale and Ecosystem Research (IWC-SOWER) Cruise, Area III

We conducted the 27th annual IWC-SOWER (formerly IDCR) Cruise in Area III (000°-070°E) aboard the Japanese Research Vessels Shonan Maru and Shonan Maru No.2. The 65-day cruise departed Cape Town, South Africa on 4 January 2005 and returned to Fremantle, Australia on 9 March 2005. After transiting to the study area, we carried out a minke whale survey and several research experiments from 12 January to 25 February. A systematic minke whale survey was conducted in Area IIIW (000°-035°E) from 12 January until 8 February. The survey design was intentionally similar to that used during the IWC/IDCR second circumpolar series of cruises (CPII) to provide information towards addressing the effect of changing cruise track design on Antarctic minke whale abundance estimates. 000°-020°E was surveyed in two contiguous strata (Northern and Southern), from 64°30'S to the ice edge. Poor weather limited the coverage 020°E-035°E to the Southern Stratum only. A total of 1788.2 nmiles was surveyed (000°-035°E) including 935.5 nmiles in closing mode and 930.3 nmiles in independent observer mode, and a total of 466 minke whales were sighted. Minke whale visual dive time experiments were conducted during the minke whale survey. 35 trials were completed, recording surfacing cues for a total of 45.81 hours. From 10-22 February the ships conducted collaborative studies with the Japanese icebreaker, Shirase to investigate the relationship between minke whale abundance and the sea ice. During this study the SOWER vessels surveyed for minke whales in the near-ice area from 035°-050°E. 575.3 nmiles were covered and a total of 22 minke whales were detected. The Shirase surveyed in the pack ice zone 040°-050°E from 12-15 February. Two methods-testing experiments were carried out during the cruise: Adaptive Line Transect Sampling and ‘BT Mode.’ Adaptive Line Transect Sampling was tested during survey in Area IIIW. BT Mode trials were conducted 22-25 February in the area between 050° and 065°E. A direct electronic data acquisition program was evaluated during the cruise on both ships. Sightings for the entire cruise included: minke whales (237 groups/515 animals); blue whales (13 groups/46 individuals) of which 6 groups (28 individuals) were identified as true blue whales and 3 groups (3 individuals) were identified as pygmy blue whales; fin whales (14/132); humpback whales (251/646); sperm whales (35/49); killer whales (23/217); southern bottlenose whales (32/60); Gray’s beaked whales (1/7); Layard’s beaked whales (2/3); pilot whales (4/265); hourglass dolphins (4/17); striped dolphins (3/435) and common bottlenose dolphins (1/20). Opportunistic research during the cruise included blue whale research on 8 groups/29 animals resulting in 5 biopsies and images of 23 individuals for photo-identification studies. Biopsy samples and photo-ID images were also obtained opportunistically from other species. Biopsies were collected from 6 humpback whales and 1 southern right whale. Photo-ID images were collected from 45 humpback whales, 1 southern right whale and 8 groups of killer whales. Estimated Angle and Distance Training Exercise and Experiment were each completed on both vessels

IntAct—open source resource for molecular interaction data

IntAct is an open source database and software suite for modeling, storing and analyzing molecular interaction data. The data available in the database originates entirely from published literature and is manually annotated by expert biologists to a high level of detail, including experimental methods, conditions and interacting domains. The database features over 126 000 binary interactions extracted from over 2100 scientific publications and makes extensive use of controlled vocabularies. The web site provides tools allowing users to search, visualize and download data from the repository. IntAct supports and encourages local installations as well as direct data submission and curation collaborations. IntAct source code and data are freely available from

Pre- and early-postnatal nutrition modify gene and protein expressions of muscle energy metabolism markers and phospholipid fatty acid composition in a muscle type specific manner in sheep.

We previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key muscle determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD) and biceps femoris (BF)) and in the cardiac muscle (ventriculus sinister cordis (VSC)) of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM) or 50% (LOW) of their energy and protein requirements during the last trimester of gestation. From day-3 postpartum to 6-months of age (around puberty), twin offspring received a high-carbohydrate-high-fat (HCHF) or a moderate-conventional (CONV) diet, whereafter all males were slaughtered. Females were subsequently raised on a moderate diet and slaughtered at 2-years of age (young adults). The only long-term consequences of fetal undernutrition observed in adult offspring were lower expressions of the insulin responsive glucose transporter 4 (GLUT4) protein and peroxisome proliferator-activated receptor gamma, coactivator 1α (PGC1α) mRNA in BF, but increased PGC1α expression in VSC. Interestingly, the HCHF diet in early postnatal life was associated with somewhat paradoxically increased expressions in LD of a range of genes (but not proteins) related to glucose uptake, insulin signalling and fatty acid oxidation. Except for fatty acid oxidation genes, these changes persisted into adulthood. No persistent expression changes were observed in BF and VSC. The HCHF diet increased phospholipid ratios of n-6/n-3 polyunsaturated fatty acids in all muscles, even in adults fed identical diets for 1½ years. In conclusion, early postnatal, but not late gestation, nutrition had long-term consequences for a number of determinants of insulin action and metabolism in LD. Tissues other than muscle may account for reduced whole body insulin sensitivity in adult LOW sheep

CCN2/Connective Tissue Growth Factor Is Essential for Pericyte Adhesion and Endothelial Basement Membrane Formation during Angiogenesis

CCN2/Connective Tissue Growth Factor (CTGF) is a matricellular protein that regulates cell adhesion, migration, and survival. CCN2 is best known for its ability to promote fibrosis by mediating the ability of transforming growth factor β (TGFβ) to induce excess extracellular matrix production. In addition to its role in pathological processes, CCN2 is required for chondrogenesis. CCN2 is also highly expressed during development in endothelial cells, suggesting a role in angiogenesis. The potential role of CCN2 in angiogenesis is unclear, however, as both pro- and anti-angiogenic effects have been reported. Here, through analysis of Ccn2-deficient mice, we show that CCN2 is required for stable association and retention of pericytes by endothelial cells. PDGF signaling and the establishment of the endothelial basement membrane are required for pericytes recruitment and retention. CCN2 induced PDGF-B expression in endothelial cells, and potentiated PDGF-B-mediated Akt signaling in mural (vascular smooth muscle/pericyte) cells. In addition, CCN2 induced the production of endothelial basement membrane components in vitro, and was required for their expression in vivo. Overall, these results highlight CCN2 as an essential mediator of vascular remodeling by regulating endothelial-pericyte interactions. Although most studies of CCN2 function have focused on effects of CCN2 overexpression on the interstitial extracellular matrix, the results presented here show that CCN2 is required for the normal production of vascular basement membranes

El Conocimiento Didáctico del Contenido en ciencias: estado de la cuestión

This paper gives a descriptive overview of the literature related to Pedagogical Content Knowledge - PCK - in the sciences. It is expected that this review can contribute to a better understanding of PCK, pointing out what has been investigated about this concept. Specifically, we analyze: a) how PCK is defined, what are its main features and how it has been appropriated by teachers; b) the relationship between PCK, knowledge of the contents to be taught and students learning; c) how PCK was actually used in teachers' training and teachers' evaluation; and, d) the scientific areas in which PCK has been studied. It concludes that PCK is an essential tool for improving the quality of teacher training

Exendin-4 Ameliorates Motor Neuron Degeneration in Cellular and Animal Models of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by a progressive loss of lower motor neurons in the spinal cord. The incretin hormone, glucagon-like peptide-1 (GLP-1), facilitates insulin signaling, and the long acting GLP-1 receptor agonist exendin-4 (Ex-4) is currently used as an anti-diabetic drug. GLP-1 receptors are widely expressed in the brain and spinal cord, and our prior studies have shown that Ex-4 is neuroprotective in several neurodegenerative disease rodent models, including stroke, Parkinson's disease and Alzheimer's disease. Here we hypothesized that Ex-4 may provide neuroprotective activity in ALS, and hence characterized Ex-4 actions in both cell culture (NSC-19 neuroblastoma cells) and in vivo (SOD1 G93A mutant mice) models of ALS. Ex-4 proved to be neurotrophic in NSC-19 cells, elevating choline acetyltransferase (ChAT) activity, as well as neuroprotective, protecting cells from hydrogen peroxide-induced oxidative stress and staurosporine-induced apoptosis. Additionally, in both wild-type SOD1 and mutant SOD1 (G37R) stably transfected NSC-19 cell lines, Ex-4 protected against trophic factor withdrawal-induced toxicity. To assess in vivo translation, SOD1 mutant mice were administered vehicle or Ex-4 at 6-weeks of age onwards to end-stage disease via subcutaneous osmotic pump to provide steady-state infusion. ALS mice treated with Ex-4 showed improved glucose tolerance and normalization of behavior, as assessed by running wheel, compared to control ALS mice. Furthermore, Ex-4 treatment attenuated neuronal cell death in the lumbar spinal cord; immunohistochemical analysis demonstrated the rescue of neuronal markers, such as ChAT, associated with motor neurons. Together, our results suggest that GLP-1 receptor agonists warrant further evaluation to assess whether their neuroprotective potential is of therapeutic relevance in ALS