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  • 1
    Language: English
    In: Science (New York, N.Y.), 12 April 2013, Vol.340(6129), pp.163-5
    Description: [Index to Australopithecus sediba special section][1] The site of Malapa, South Africa, has yielded perhaps the richest assemblage of early hominin fossils on the continent of Africa. The fossil remains of Au. sediba were discovered in August of 2008, and the species was named in 2010 ([ 1 ][2])
    Keywords: Fossils ; Bone and Bones -- Anatomy & Histology ; Hominidae -- Anatomy & Histology
    ISSN: 00368075
    E-ISSN: 1095-9203
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  • 2
    In: Nature, 2011, Vol.476(7359), p.163
    Description: This year, 2011, marks the forty-year anniversary of the statistical analysis of retinoblastoma that provided the first evidence that tumorigenesis can be initiated by as few as two mutations. This work provided the foundation for the two-hit hypothesis that explained the role of recessive tumour suppressor genes (TSGs) in dominantly inherited cancer susceptibility syndromes. However, four decades later, it is now known that even partial inactivation of tumour suppressors can critically contribute to tumorigenesis. Here we analyse this evidence and propose a continuum model of TSG function to explain the full range of TSG mutations found in cancer.
    Keywords: Sciences (General) ; Physics;
    ISSN: 0028-0836
    E-ISSN: 14764687
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  • 3
    Language: English
    In: Biochemical and Biophysical Research Communications, 17 June 2011, Vol.409(4), pp.610-615
    Description: ► TUDCA inhibits the expression of ER stress markers in intestinal epithelial cells. ► TUDCA prohibits the activation of the unfolded protein response in these cells. ► UDCA but not taurine mediates the inhibitory effects of TUDCA. ► The hydrophobic parts of TUDCA prohibit the aggregation of denatured proteins. Inflammatory bowel diseases (IBD) are chronically relapsing and immune-mediated disorders of the gastrointestinal tract. Endoplasmic reticulum (ER) stress mechanisms in the epithelium have been demonstrated to be implemented into the pathogenesis of intestinal inflammation. Chemical chaperones have been demonstrated to exhibit beneficial effects in various diseases associated with ER stress mechanisms by prohibiting the unfolded protein response (UPR). In a structure–function analysis, we tested the potential of the conjugated bile salt sodium tauroursodeoxycholate (TUDCA), naturally present in the small bowel, to resolve ER stress in intestinal epithelial cells. TUDCA efficiently inhibited the expression of UPR dependent genes like GRP78 triggered by the ER stressor tunicamycin in the small intestinal epithelial cell line Mode-K. TUDCA inhibited upstream signaling events in all three branches of the UPR cascade and diminished binding of UPR activated transcription factors to the promoter. A structure–function analysis revealed that UDCA but not its conjugation partner taurine, known as a chemical chaperone, is responsible for the inhibition of GRP78 induction and that UDCA is 10 times more effective than its taurine conjugate. This inhibitory effect was confirmed in a cell free assay, where TUDCA and UDCA but not taurine effectively inhibited the aggregation of thermally denatured BSA. We conclude that TUDCA and UDCA are potent anti-aggregants for the resolution of ER stress in intestinal epithelial cells and should be considered as a potential drug target to resolve ER stress mechanisms underlying the pathology of IBD.
    Keywords: Inflammatory Bowel Disease ; Endoplasmic Reticulum Stress ; Unfolded Protein Response ; Chemical Chaperone ; Tauroursodeoxycholic Acid ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0006-291X
    E-ISSN: 1090-2104
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  • 4
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 2011, Vol.108(13), pp.5419-5424
    Description: Neuronal circuitry is often considered a clean slate that can be dynamically and arbitrarily molded by experience. However, when we investigated synaptic connectivity in groups of pyramidal neurons in the neocortex, we found that both connectivity and synaptic weights were surprisingly predictable. Synaptic weights follow very closely the number of connections in a group of neurons, saturating after only 20% of possible connections are formed between neurons in a group. When we examined the network topology of connectivity between neurons, we found that the neurons cluster into small world networks that are not scale-free, with less than 2 degrees of separation. We found a simple clustering rule where connectivity is directly proportional to the number of common neighbors, which accounts for these small world networks and accurately predicts the connection probability between any two neurons. This pyramidal neuron network clusters into multiple groups of a few dozen neurons each. The neurons composing each group are surprisingly distributed, typically more than 100 μm apart, allowing for multiple groups to be interlaced in the same space. In summary, we discovered a synaptic organizing principle that groups neurons in a manner that is common across animals and hence, independent of individual experiences. We speculate that these elementary neuronal groups are prescribed Lego-like building blocks of perception and that acquired memory relies more on combining these elementary assemblies into higher-order constructs. ; p. 5419-5424.
    Keywords: Neocortex ; Animals ; Probability ; Neurons ; Memory
    ISSN: 0027-8424
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  • 5
    Language: Spanish
    In: Conservation Biology, October 2012, Vol.26(5), pp.769-777
    Description: Alces alcesp p p Ovibos moschatus
    Keywords: Conservation Policy ; Moose ; Muskoxen ; Orphans ; Overwinter Survival ; Photogrammetry ; Alce ; Buey Almizclero ; Fotogrametría ; Huérfanos ; Políticas De Conservación ; Supervivencia A La Hibernación
    ISSN: 0888-8892
    E-ISSN: 1523-1739
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  • 6
    In: Conservation Biology, August 2013, Vol.27(4), pp.679-689
    Description: . , , , , , . Globalización del Mercado de Cachemira y la Declinación de Mamíferos Mayores en Asia Central Pseudois nayaur: Saiga tartarica, Pantholops hodgsoni, Camelus bactrianus, Panthera uncial, Equus hemionus, E. kiang, E. przewalski Bos mutus.
    Keywords: Fashion ; Herders ; India ; Mongolia ; Saiga ; Trade ; Comercio ; India ; Moda ; Mongolia ; Pastores ; Saiga
    ISSN: 0888-8892
    E-ISSN: 1523-1739
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  • 7
    Language: English
    In: Science (New York, N.Y.), 09 September 2011, Vol.333(6048), pp.1411-7
    Description: Hand bones from a single individual with a clear taxonomic affiliation are scarce in the hominin fossil record, which has hampered understanding the evolution of manipulative abilities in hominins. Here we describe and analyze a nearly complete wrist and hand of an adult female [Malapa Hominin 2 (MH2)] Australopithecus sediba from Malapa, South Africa (1.977 million years ago). The hand presents a suite of Australopithecus-like features, such as a strong flexor apparatus associated with arboreal locomotion, and Homo-like features, such as a long thumb and short fingers associated with precision gripping and possibly stone tool production. Comparisons to other fossil hominins suggest that there were at least two distinct hand morphotypes around the Plio-Pleistocene transition. The MH2 fossils suggest that Au. sediba may represent a basal condition associated with early stone tool use and production.
    Keywords: Biological Evolution ; Fossils ; Hand -- Anatomy & Histology ; Hand Bones -- Anatomy & Histology ; Hominidae -- Anatomy & Histology
    ISSN: 00368075
    E-ISSN: 1095-9203
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  • 8
    Language: English
    In: Biochemical and Biophysical Research Communications, 13 July 2012, Vol.423(4), pp.785-788
    Description: ► Report of an unbiased quantification of the birefringence of muscle of fish larvae. ► Quantification method readily identifies level of overall muscle damage. ► Compare zebrafish muscle mutants for level of phenotype severity. ► Proposed tool to survey treatments that aim to ameliorate muscular dystrophy. Muscular dystrophies are a group of genetic disorders that progressively weaken and degenerate muscle. Many zebrafish models for human muscular dystrophies have been generated and analysed, including dystrophin-deficient zebrafish mutants that model Duchenne Muscular Dystrophy. Under polarised light the zebrafish muscle can be detected as a bright area in an otherwise dark background. This light effect, called birefringence, results from the diffraction of polarised light through the pseudo-crystalline array of the muscle sarcomeres. Muscle damage, as seen in zebrafish models for muscular dystrophies, can readily be detected by a reduction in the birefringence. Therefore, birefringence is a very sensitive indicator of overall muscle integrity within larval zebrafish. Unbiased documentation of the birefringence followed by densitometric measurement enables the quantification of the birefringence of zebrafish larvae. Thereby, the overall level of muscle integrity can be detected, allowing the identification and categorisation of zebrafish muscle mutants. In addition, we propose that the establish protocol can be used to analyse treatments aimed at ameliorating dystrophic zebrafish models.
    Keywords: Muscle ; Zebrafish ; Muscular Dystrophy ; Birefringence ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0006-291X
    E-ISSN: 1090-2104
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  • 9
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 28 January 2014, Vol.111(4), pp.1533-8
    Description: Acute kidney injury (AKI) is associated with high morbidity and mortality. Recent genetic fate mapping studies demonstrated that recovery from AKI occurs from intrinsic tubular cells. It is unresolved whether these intrinsic cells (so-called "scattered tubular cells") represent fixed progenitor cells or whether recovery involves any surviving tubular cell. Here, we show that the doxycycline-inducible parietal epithelial cell (PEC)-specific PEC-reverse-tetracycline transactivator (rtTA) transgenic mouse also efficiently labels the scattered tubular cell population. Proximal tubular cells labeled by the PEC-rtTA mouse coexpressed markers for scattered tubular cells (kidney injury molecule 1, annexin A3, src-suppressed C-kinase substrate, and CD44) and showed a higher proliferative index. The PEC-rtTA mouse labeled more tubular cells upon different tubular injuries but was independent of cellular proliferation as determined in physiological growth of the kidney. To resolve whether scattered tubular cells are fixed progenitors, cells were irreversibly labeled before ischemia reperfusion injury (genetic cell fate mapping). During recovery, the frequency of labeled tubular cells remained constant, arguing against a fixed progenitor population. In contrast, when genetic labeling was induced during ischemic injury and subsequent recovery, the number of labeled cells increased significantly, indicating that scattered tubular cells arise from any surviving tubular cell. In summary, scattered tubular cells do not represent a fixed progenitor population but rather a phenotype that can be adopted by almost any proximal tubular cell upon injury. Understanding and modulating these phenotypic changes using the PEC-rtTA mouse may lead to more specific therapies in AKI.
    Keywords: Cell Fate Tracking ; Lineage Tracing ; Regeneration ; Stem Cells ; Regeneration ; Acute Kidney Injury -- Physiopathology ; Kidney Tubules -- Physiology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 10
    Language: English
    In: Bioorganic & Medicinal Chemistry Letters, 01 October 2015, Vol.25(19), pp.4131-4135
    Description: The specific binding of the NMDA receptor (NR) channel ligand [ H]MK-801 to rat brain membranes is sensitive to positively charged buffer ingredients as to tris(hydroxymethyl)aminomethane (Tris), to Na , or to protons. Here we demonstrate that 16 non-competitive NR antagonists, including 5 long-chain diamines, classical NR channel blockers and several less known compounds, differ widely in their sensitivities to cationic buffer constituents. Although chemically distinguished either as extended di-cationic or as compact mono-cationic, their sensitivities to cationic buffer ingredients did not suggest this grouping. While the di-cationic compounds are known for their sensitivity to spermine ( ), also some of the mono-cationic blockers exhibited this feature. They might share as common target a recently described negatively charged extracellular GluN1/GluN2B interface.
    Keywords: Nmda Receptor ; Polyamines ; Sodium ; Potassium ; [3h]Mk-801 ; Magnesium ; Medicine ; Chemistry ; Anatomy & Physiology
    ISSN: 0960-894X
    E-ISSN: 1464-3405
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