The rockefeller university

Radiation therapy to the brain is a powerful tool in the management of many cancers, but it is associated with significant and irreversible long-term side effects, including cognitive decline and impairment of motor coordination. Depletion of oligodendrocyte progenitors and demyelination are major pathological features that are particularly pronounced in younger individuals and severely limit therapeutic options. Here we tested whether human ESC-derived oligodendrocytes can functionally remyelinate the irradiated brain using a rat model. We demonstrate the efficient derivation and prospective isolation of human oligodendrocyte progenitors, which, upon transplantation, migrate throughout the major white matter tracts resulting in both structural and functional repair. Behavioral testing showed complete recovery of cognitive function while additional recovery from motor deficits required concomitant transplantation into the cerebellum. The ability to repair radiation-induced damage to the brain could dramatically improve the outlook for cancer survivors and enable more effective use of radiation therapies, especially in children.

Oil palm (Elaeis guinensis Jacquin) is the most important source of vegetable oil and fat. Several linkage maps had been constructed using dominant and co-dominant markers to facilitate mapping of QTL. However, dominant markers are not easily transferable among different laboratories. We constructed a consensus linkage map for oil palm using co-dominant markers (i.e. microsatellite and SNPs) and two F-1 breeding populations generated by crossing Dura and Pisifera individuals. Four hundreds and forty-four microsatellites and 36 SNPs were mapped onto 16 linkage groups. The map length was 1565.6 cM, with an average marker space of 3.72 cM. Agenome-wide scan of QTL identified a major QTL for stem height on the linkage group 5, which explained 51% of the phenotypic variation. Genes in the QTL were predicted using the palm genome sequence and bioinformatic tools. The linkage map supplies a base for mapping QTL for accelerating the genetic improvement, and will be also useful in the improvement of the assembly of the genome sequences. Markers linked to the QTL may be used in selecting dwarf trees. Genes within the QTL will be characterized to understand the mechanisms underlying dwarfing.

Statistical coupling analysis (SCA) is a method for analyzing multiple sequence alignments that was used to identify groups of coevolving residues termed "sectors". The method applies spectral analysis to a matrix obtained by combining correlation information with sequence conservation. It has been asserted that the protein sectors identified by SCA are functionally significant, with different sectors controlling different biochemical properties of the protein. Here we reconsider the available experimental data and note that it involves almost exclusively proteins with a single sector. We show that in this case sequence conservation is the dominating factor in SCA, and can alone be used to make statistically equivalent functional predictions. Therefore, we suggest shifting the experimental focus to proteins for which SCA identifies several sectors. Correlations in protein alignments, which have been shown to be informative in a number of independent studies, would then be less dominated by sequence conservation.

We present a comprehensive review of the physics results obtained by the CDF and DO collaborations up to summer 2014, with emphasis on those achieved in the Run II of the Tevatron collider which delivered a total integrated luminosity of similar to 10 fb(-1) at root s = 1.96 TeV. The results are presented in six main physics topics: QCD, Heavy Flavor, Electroweak, Top quark, Higgs boson and searches for New Particles and Interactions. The characteristics of the accelerator, detectors, and the techniques used to achieve these results are also briefly summarized.

Subsets of long-lived, tumor-initiating stem cells often escape cancer therapies. However, sources and mechanisms that generate tumor heterogeneity and drug-resistant cell population are still unfolding. Here, we devise a functional reporter system to lineage trace and/or genetic ablate signaling in TGF-beta-activated squannous cell carcinoma stem cells (SCC-SCs). Dissecting TGF-beta's impact on malignant progression, we demonstrate that TGF-beta concentrating near tumor-vasculature generates heterogeneity in TGF-beta signaling at tumor-stroma interface and bestows slower-cycling properties to neighboring SCC-SCs. While non-responding progenies proliferate faster and accelerate tumor growth, TGF-beta-responding progenies invade, aberrantly differentiate, and affect gene expression. Intriguingly, TGF-beta-responding SCC-SCs show increased protection against anti-cancer drugs, but slowercycling alone does not confer survival. Rather, TGF-beta transcriptionally activates p21, which stabilizes NRF2, thereby markedly enhancing glutathione metabolism and diminishing effectiveness of anticancer therapeutics. Together, these findings establish a surprising non-genetic paradigm for TGF-beta signaling in fueling heterogeneity in SCC-SCs, tumor characteristics, and drug resistance.

Usage of the term 'theory of mind' (ToM) has exploded across fields ranging from developmental psychology to social neuroscience and psychiatry research. However, its meaning is often vague and inconsistent, its biological bases are a subject of debate, and the methods used to study it are highly heterogeneous. Most crucially, its original definition does not permit easy downward translation to more basic processes such as those studied by behavioral neuroscience, leaving the interpretation of neuroimaging results opaque. We argue for a reformulation of ToM through a systematic two-stage approach, beginning with a deconstruction of the construct into a comprehensive set of basic component processes, followed by a complementary reconstruction from which a scientifically tractable concept of ToM can be recovered.

How do the lifestyles (free-living unparasitized, free-living parasitized, and parasitic) of animal species affect major ecological power-law relationships? We investigated this question in metazoan communities in lakes of Otago, New Zealand. In 13,752 samples comprising 1,037,058 organisms, we found that species of different lifestyles differed in taxonomic distribution and body mass and were well described by three power laws: a spatial Taylor's law (the spatial variance in population density was a power-law function of the spatial mean population density); density-mass allometry (the spatial mean population density was a power-law function of mean body mass); and variance-mass allometry (the spatial variance in population density was a power-law function of mean body mass). To our knowledge, this constitutes the first empirical confirmation of variance-mass allometry for any animal community. We found that the parameter values of all three relationships differed for species with different lifestyles in the same communities. Taylor's law and density-mass allometry accurately predicted the form and parameter values of variance-mass allometry. We conclude that species of different lifestyles in these metazoan communities obeyed the same major ecological power-law relationships but did so with parameters specific to each lifestyle, probably reflecting differences among lifestyles in population dynamics and spatial distribution.

All the human primary immunodeficiencies (PIDs) recognized as such in the 1950s were Mendelian traits and, whether autosomal or X-linked, displayed recessive inheritance. The first autosomal dominant (AD) PID, hereditary angioedema, was recognized in 1963. However, since the first identification of autosomal recessive (AR), X-linked recessive (XR) and AD PID-causing genes in 1985 (ADA; severe combined immunodeficiency), 1986 (CYBB, chronic granulomatous disease) and 1989 (SERPING1; hereditary angioedema), respectively, the number of genetically defined AD PIDs has increased more rapidly than that of any other type of PID. AD PIDs now account for 61 of the 260 known conditions (23%). All known AR PIDs are caused by alleles with some loss-of-function (LOF). A single XR PID is caused by gain-of-function (GOF) mutations (WASP-related neutropenia, 2001). In contrast, only 44 of 61 AD defects are caused by LOF alleles, which exert dominance by haploinsufficiency or negative dominance. Since 2003, up to 17 AD disorders of the third kind, due to GOF alleles, have been described. Remarkably, six of the 17 genes concerned also harbor monoallelic (STAT3), biallelic (C3, CFB, CARD11, PIK3R1) or both monoallelic and biallelic (STAT1) LOF alleles in patients with other clinical phenotypes. Most heterozygous GOF alleles result in auto-inflammation, auto-immunity, or both, with a wide range of immunological and clinical forms. Some also underlie infections and, fewer, allergies, by impairing or enhancing immunity to non-self. Malignancies are also rare. The enormous diversity of immunological and clinical phenotypes is thought provoking and mirrors the diversity and pleiotropy of the underlying genotypes. These experiments of nature provide a unique insight into the quantitative regulation of human immunity.

Although CD8(+) T cells are shown to mediate the protective immunity against the liver stages of malaria parasites in mice, whether the direct presentation of malaria antigen by major histocompatibility complex (MHC) class I molecules expressed on the liver of infected host is required for anti-plasmodial activity of CD8(+) T cells is still unknown. Presently, there is only one CD8(+) epitope, SYVPSAEQI, derived from the circumsporozoite protein of Plasmodium yoelii (PyCS), that mediates anti-malarial protection and is presented in the context of a K-d molecule. Therefore, to investigate the mode of anti-plasmodial activity of CD8+ T cells, we have previously generated C57BL/6 transgenic (Tg) mice, in which a K-d molecule is expressed only on hepatocyte (Alb-K-d) or dendritic cell (DC; CD11c-K-d), by using albumin promoter or CD11c promoter, respectively. We have also generated MHC-I-K-d Tg mice, which express the K-d molecule under the MHC class I (MHC-I) promoter, as a positive control. From splenocytes collected from CD11c-K-d Tg mice immunized with a synthetic peptide, SYVPSAEQI, which corresponds to the CD8(+) T-cell epitope of PyCS, emulsified in incomplete Freund's adjuvant, a PyCS-specific CD8(+) T-cell line was generated. This PyCS-specific CD8(+) T-cell line was then adoptively transferred into a cohort of either MHC-K-d Tg or Alb-K-d Tg mice listed above, as well as wild-type C57BL/6 mice. Then both transferred and non-transferred mice were challenged with live malaria parasites. We found that the adoptive transfer of a PyCS-specific CD8(+) T-cell line resulted in a significant inhibition of the parasite burden in the liver of Alb-K-d Tg, as well as MHC-I-K-d Tg mice, but not of C57BL/6 mice. These results indicate that the K-d molecule expressed by hepatocytes is sufficient in mediating the anti-plasmodial activity of PyCS-specific CD8(+) T cells in vivo.