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

The clinical features of polymerase proof-reading associated polyposis (PPAP) and recommendations for patient management

Pathogenic germline exonuclease domain (ED) variants of POLE and POLD1 cause the Mendelian dominant condition polymerase proof-reading associated polyposis (PPAP). We aimed to describe the clinical features of all PPAP patients with probably pathogenic variants. We identified patients with a variants mapping to the EDs of POLE or POLD1 from cancer genetics clinics, a colorectal cancer (CRC) clinical trial, and systematic review of the literature. We used multiple evidence sources to separate ED variants into those with strong evidence of pathogenicity and those of uncertain importance. We performed quantitative analysis of the risk of CRC, colorectal adenomas, endometrial cancer or any cancer in the former group. 132 individuals carried a probably pathogenic ED variant (105 POLE, 27 POLD1). The earliest malignancy was colorectal cancer at 14. The most common tumour types were colorectal, followed by endometrial in POLD1 heterozygotes and duodenal in POLE heterozygotes. POLD1-mutant cases were at a significantly higher risk of endometrial cancer than POLE heterozygotes. Five individuals with a POLE pathogenic variant, but none with a POLD1 pathogenic variant, developed ovarian cancer. Nine patients with POLE pathogenic variants and one with a POLD1 pathogenic variant developed brain tumours. Our data provide important evidence for PPAP management. Colonoscopic surveillance is recommended from age 14 and upper-gastrointestinal surveillance from age 25. The management of other tumour risks remains uncertain, but surveillance should be considered. In the absence of strong genotype–phenotype associations, these recommendations should apply to all PPAP patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10689-021-00256-y

Camouflage Effects of Various Colour-Marking Morphs against Different Microhabitat Backgrounds in a Polymorphic Pygmy Grasshopper Tetrix japonica

Colour-marking polymorphism is widely distributed among cryptic species. To account for the adaptive significance of such polymorphisms, several hypotheses have been proposed to date. Although these hypotheses argue over the degree of camouflage effects of marking morphs (and the interactions between morphs and their microhabitat backgrounds), as far as we know, most empirical evidence has been provided under unnatural conditions (i.e., using artificial prey).Tetrix japonica, a pygmy grasshopper, is highly polymorphic in colour-markings and occurs in both sand and grass microhabitats. Even within a microhabitat, T. japonica is highly polymorphic. Using humans as dummy predators and printed photographs in which various morphs of grasshoppers were placed against different backgrounds, we addressed three questions to test the neutral, background heterogeneity, and differential crypsis hypotheses in four marking-type morphs: 1) do the morphs differ in the degree of crypsis in each microhabitat, 2) are different morphs most cryptic in specific backgrounds of the microhabitats, and 3) does the morph frequency reflect the degree of crypsis?The degree of camouflage differed among the four morphs; therefore, the neutral hypothesis was rejected. Furthermore, the order of camouflage advantage among morphs differed depending on the two types of backgrounds (sand and grass), although the grass background consistently provided greater camouflage effects. Thus, based on our results, we could not reject the background heterogeneity hypothesis. Under field conditions, the more cryptic morphs comprised a minority of the population. Overall, our results demonstrate that the different morphs were not equivalent in the degree of crypsis, but the degree of camouflage of the morphs was not consistent with the morph frequency. These findings suggest that trade-offs exist between the camouflage benefit of body colouration and other fitness components, providing a better understanding of the adaptive significance of colour-markings and presumably supporting the differential crypsis hypothesis

The density-matrix renormalization group

The density-matrix renormalization group (DMRG) is a numerical algorithm for the efficient truncation of the Hilbert space of low-dimensional strongly correlated quantum systems based on a rather general decimation prescription. This algorithm has achieved unprecedented precision in the description of one-dimensional quantum systems. It has therefore quickly acquired the status of method of choice for numerical studies of one-dimensional quantum systems. Its applications to the calculation of static, dynamic and thermodynamic quantities in such systems are reviewed. The potential of DMRG applications in the fields of two-dimensional quantum systems, quantum chemistry, three-dimensional small grains, nuclear physics, equilibrium and non-equilibrium statistical physics, and time-dependent phenomena is discussed. This review also considers the theoretical foundations of the method, examining its relationship to matrix-product states and the quantum information content of the density matrices generated by DMRG.Comment: accepted by Rev. Mod. Phys. in July 2004; scheduled to appear in the January 2005 issu

Endogenous TGF-beta 1 suppresses inflammation and promotes survival in adult CNJS

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

Breast cancer cell lines carry cell line-specific genomic alterations that are distinct from aberrations in breast cancer tissues: Comparison of the CGH profiles between cancer cell lines and primary cancer tissues

<p>Abstract</p> <p>Background</p> <p>Cell lines are commonly used in various kinds of biomedical research in the world. However, it remains uncertain whether genomic alterations existing in primary tumor tissues are represented in cell lines and whether cell lines carry cell line-specific genomic alterations. This study was performed to answer these questions.</p> <p>Methods</p> <p>Array-based comparative genomic hybridization (CGH) was employed with 4030 bacterial artificial chromosomes (BACs) that cover the genome at 1.0 megabase resolution to analyze DNA copy number aberrations (DCNAs) in 35 primary breast tumors and 24 breast cancer cell lines. DCNAs were compared between these two groups. A tissue microdissection technique was applied to primary tumor tissues to reduce the contamination of samples by normal tissue components.</p> <p>Results</p> <p>The average number of BAC clones with DCNAs was 1832 (45.3% of spotted clones) and 971 (24.9%) for cell lines and primary tumor tissues, respectively. Gains of 1q and 8q and losses of 8p, 11q, 16q and 17p were detected in >50% of primary cancer tissues. These aberrations were also frequently detected in cell lines. In addition to these alterations, the cell lines showed recurrent genomic alterations including gains of 5p14-15, 20q11 and 20q13 and losses of 4p13-p16, 18q12, 18q21, Xq21.1 and Xq26-q28 that were barely detected in tumor tissue specimens. These are considered to be cell line-specific DCNAs. The frequency of the HER2 amplification was high in both cell lines and tumor tissues, but it was statistically different between cell lines and primary tumors (P = 0.012); 41.3 ± 29.9% for the cell lines and 15.9 ± 18.6% for the tissue specimens.</p> <p>Conclusions</p> <p>Established cell lines carry cell lines-specific DCNAs together with recurrent aberrations detected in primary tumor tissues. It must therefore be emphasized that cell lines do not always represent the genotypes of parental tumor tissues.</p

Decoration Increases the Conspicuousness of Raptor Nests

Avian nests are frequently concealed or camouflaged, but a number of species builds noticeable nests or use conspicuous materials for nest decoration. In most cases, nest decoration has a role in mate choice or provides thermoregulatory or antiparasitic benefits. In territorial species however, decorations may serve additional or complementary functions, such as extended phenotypic signaling of nest-site occupancy and social status to potential intruders. The latter may benefit both signaler and receiver by minimizing the risk of aggressive interactions, especially in organisms with dangerous weaponry. Support for this hypothesis was recently found in a population of black kites (Milvus migrans), a territorial raptor that decorates its nest with white artificial materials. However, the crucial assumption that nest decorations increased nest-site visibility to conspecifics was not assessed, a key aspect given that black kite nests may be well concealed within the canopy. Here, we used an unmanned aircraft system to take pictures of black kite nests, with and without an experimentally placed decoration, from different altitudes and distances simulating the perspective of a flying and approaching, prospecting intruder. The pictures were shown to human volunteers through a standardized routine to determine whether detection rates varied according the nest decoration status and distance. Decorated nests consistently showed a higher detection frequency and a lower detection-latency, compared to undecorated versions of the same nests. Our results confirm that nest decoration in this species may act as a signaling medium that enhances nest visibility for aerial receivers, even at large distances. This finding complements previous work on this communication system, which showed that nest decoration was a threat informing trespassing conspecifics on the social dominance, territory quality and fighting capabilities of the signaler

Seasonal Changes in Colour: A Comparison of Structural, Melanin- and Carotenoid-Based Plumage Colours

Plumage coloration is important for bird communication, most notably in sexual signalling. Colour is often considered a good quality indicator, and the expression of exaggerated colours may depend on individual condition during moult. After moult, plumage coloration has been deemed fixed due to the fact that feathers are dead structures. Still, many plumage colours change after moult, although whether this affects signalling has not been sufficiently assessed.) displaying various coloration types (melanin-, carotenoid-based and structural). Birds were caught regularly during three years to measure plumage reflectance. We used models of avian colour vision to derive two variables, one describing chromatic and the other achromatic variation over the year that can be compared in magnitude among different colour types. All studied plumage patches but one (yellow breast of the blue tit) showed significant chromatic changes over the year, although these were smaller than for a typical dynamic trait (bill colour). Overall, structural colours showed a reduction in relative reflectance at shorter wavelengths, carotenoid-based colours the opposite pattern, while no general pattern was found for melanin-based colours. Achromatic changes were also common, but there were no consistent patterns of change for the different types of colours.Changes of plumage coloration independent of moult are probably widespread; they should be perceivable by birds and have the potential to affect colour signalling