Ancient agricultural and pastoral landscapes on the south side of lake Issyk-Kul: preliminary surveys of the Juuku Valley and Lower Kizil Suu Valley, archaeobotanical results of three stratigraphic profiles, and GIS modeling of Iron Age in Lower Kizil Suu

The main goal of this paper is to present results of preliminary archaeological research on the south side of Lake Issyk-Kul in Kyrgyzstan. We test the hypothesis that agropastoral land use changed over four millennia from the Bronze Age through the ethnographic Kirghiz period due to economic, socio-political, and religious changes in the prehistoric and historic societies of this region. Our research objectives are to: (1) describe and analyze survey results from Lower Kizil Suu Valley; (2) discuss the results of radiometric and archaeobotanical samples taken from three stratigraphic profiles from three settlements from the Juuku Valley, including these chronological periods: the Wusun period (200 to 400 CE), the Qarakhanid period (1100 to 1200 CE), and the ethnographic Kirghiz period (1700 to 1900 CE); and (3) conduct preliminary GIS spatial analyses on the Iron Age mortuary remains (Saka and Wusun period). This research emerges out of the first archaeological surveys conducted in 2019 - 2021 and includes the Lower Kizil Suu alluvial fan; it is an initial step toward developing a model for agropastoral land use for upland valleys of the Inner Tian Shan Mountains.1. Introduction 2. Materials and Methods 2.1. Study Area 2.2. Description of Survey Methods 2.3. Stratigraphic Profiles at Juuku Valley settlements 2.4. Radiometric Dating 2.5. Archaeobotanical Methods 2.6. GIS Methods for Spatial Analysis 3. Results 3.1. Survey results 3.2. Stratigraphic Profiles 3.2.1. Profile at Site-EJS1 (Wusun Period Settlement) 3.2.2. Profile at Site-EJS2 (Qarakhanid Period Settlement) 3.3. Results of Radiometric Dating 3.4. Results of Archaeobotanical Analyses 3.4.1. Site-EJS1 (Eastern Juuku – Settlement-1) 3.4.2. Site-EJS2 (Eastern Juuku – Settlement-2) 3.4.3. Site-LJS3 (Lower Juuku – Settlement-2) 3.5. Results of the GIS Spatial Analyses 4. Discussion 5. Conclusion

Photometric Observations Constraining the Size, Shape, and Albedo of 2003 El61, a Rapidly Rotating, Pluto-Sized Object in the Kuiper Belt

We present measurements at optical wavelengths of the spectral reflectance, rotational light curve, and solar phase curve of 2003 EL61. With apparent visual magnitude 17.5 at 51 AU from the sun, this newly discovered member of the classical Kuiper Belt is now the third brightest KBO after Pluto and 2005 FY9. Our observations reveal an unambiguous, double-peaked rotational light curve with period 3.9154 +/- 0.0002 hours and peak to peak amplitude 0.28 +/- 0.04 mag. This is the fastest rotation period reliably determined for any body in the solar system larger than 100 km. Assuming the body has relaxed over time to the shape taken by a homogenous fluid body, our observations tightly constrain the shape and density. Given the mass we recently determined for 2003 EL61 from the orbit of a small satellite, we also constrain the size and albedo. We find a total length of 1960 to 2500 km, a mean density of 2600 to 3340 kg m-3, and a visual albedo greater than 0.6. We also measure a neutral reflectance at visible wavelengths and a linear phase curve with slope varying from 0.09 mag deg-1 in the B band to 0.13 mag deg-1 in the I band. The absolute V-band magnitude is 0.444+/-0.021.Comment: 27 pages, six figure

Regulation of pituitary MT1 melatonin receptor expression by gonadotrophin-releasing hormone (GnRH) and early growth response factor-1 (Egr-1) : in vivo and in vitro studies

Copyright: © 2014 Bae et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC; grant BB/F020309/1; http://www.bbsrc.ac.uk/home/home.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Egr-1 Induces a Profibrotic Injury/Repair Gene Program Associated with Systemic Sclerosis

Transforming growth factor-ß (TGF-ß) signaling is implicated in the pathogenesis of fibrosis in scleroderma or systemic sclerosis (SSc), but the precise mechanisms are poorly understood. The immediate-early gene Egr-1 is an inducible transcription factor with key roles in mediating fibrotic TGF-ß responses. To elucidate Egr-1 function in SSc-associated fibrosis, we examined change in gene expression induced by Egr-1 in human fibroblasts at the genome-wide level. Using microarray expression analysis, we derived a fibroblast “Egr-1-responsive gene signature” comprising over 600 genes involved in cell proliferation, TGF-ß signaling, wound healing, extracellular matrix synthesis and vascular development. The experimentally derived “Egr-1-responsive gene signature” was then evaluated in an expression microarray dataset comprising skin biopsies from 27 patients with localized and systemic forms of scleroderma and six healthy controls. We found that the “Egr-1 responsive gene signature” was substantially enriched in the “diffuse-proliferation” subset comprising exclusively of patients with diffuse cutaneous SSc (dcSSc) of skin biopsies. A number of Egr-1-regulated genes was also associated with the “inflammatory” intrinsic subset. Only a minority of Egr-1-regulated genes was concordantly regulated by TGF-ß. These results indicate that Egr-1 induces a distinct profibrotic/wound healing gene expression program in fibroblasts that is associated with skin biopsies from SSc patients with diffuse cutaneous disease. These observations suggest that targeting Egr-1 expression or activity might be a novel therapeutic strategy to control fibrosis in specific SSc subsets

Expression of Human Frataxin Is Regulated by Transcription Factors SRF and TFAP2

Friedreich ataxia is an autosomal recessive neurodegenerative disease caused by reduced expression levels of the frataxin gene (FXN) due to expansion of triplet nucleotide GAA repeats in the first intron of FXN. Augmentation of frataxin expression levels in affected Friedreich ataxia patient tissues might substantially slow disease progression.We utilized bioinformatic tools in conjunction with chromatin immunoprecipitation and electrophoretic mobility shift assays to identify transcription factors that influence transcription of the FXN gene. We found that the transcription factors SRF and TFAP2 bind directly to FXN promoter sequences. SRF and TFAP2 binding sequences in the FXN promoter enhanced transcription from luciferase constructs, while mutagenesis of the predicted SRF or TFAP2 binding sites significantly decreased FXN promoter activity. Further analysis demonstrated that robust SRF- and TFAP2-mediated transcriptional activity was dependent on a regulatory element, located immediately downstream of the first FXN exon. Finally, over-expression of either SRF or TFAP2 significantly increased frataxin mRNA and protein levels in HEK293 cells, and frataxin mRNA levels were also elevated in SH-SY5Y cells and in Friedreich ataxia patient lymphoblasts transfected with SRF or TFAP2.We identified two transcription factors, SRF and TFAP2, as well as an intronic element encompassing EGR3-like sequence, that work together to regulate expression of the FXN gene. By providing new mechanistic insights into the molecular factors influencing frataxin expression, our results should aid in the discovery of new therapeutic targets for the treatment of Friedreich ataxia

Twenty-first century brain banking. Processing brains for research: the Columbia University methods

Carefully categorized postmortem human brains are crucial for research. The lack of generally accepted methods for processing human postmortem brains for research persists. Thus, brain banking is essential; however, it cannot be achieved at the cost of the teaching mission of the academic institution by routing brains away from residency programs, particularly when the autopsy rate is steadily decreasing. A consensus must be reached whereby a brain can be utilizable for diagnosis, research, and teaching. The best diagnostic categorization possible must be secured and the yield of samples for basic investigation maximized. This report focuses on integrated, novel methods currently applied at the New York Brain Bank, Columbia University, New York, which are designed to reach accurate neuropathological diagnosis, optimize the yield of samples, and process fresh-frozen samples suitable for a wide range of modern investigations. The brains donated for research are processed as soon as possible after death. The prosector must have a good command of the neuroanatomy, neuropathology, and the protocol. One half of each brain is immersed in formalin for performing the thorough neuropathologic evaluation, which is combined with the teaching task. The contralateral half is extensively dissected at the fresh state. The anatomical origin of each sample is recorded using the map of Brodmann for the cortical samples. The samples are frozen at −160°C, barcode labeled, and ready for immediate disbursement once categorized diagnostically. A rigorous organization of freezer space, coupled to an electronic tracking system with its attached software, fosters efficient access for retrieval within minutes of any specific frozen samples in storage. This report describes how this achievement is feasible with emphasis on the actual processing of brains donated for research

A Genome-Scale Metabolic Reconstruction of Mycoplasma genitalium, iPS189

With a genome size of ∼580 kb and approximately 480 protein coding regions, Mycoplasma genitalium is one of the smallest known self-replicating organisms and, additionally, has extremely fastidious nutrient requirements. The reduced genomic content of M. genitalium has led researchers to suggest that the molecular assembly contained in this organism may be a close approximation to the minimal set of genes required for bacterial growth. Here, we introduce a systematic approach for the construction and curation of a genome-scale in silico metabolic model for M. genitalium. Key challenges included estimation of biomass composition, handling of enzymes with broad specificities, and the lack of a defined medium. Computational tools were subsequently employed to identify and resolve connectivity gaps in the model as well as growth prediction inconsistencies with gene essentiality experimental data. The curated model, M. genitalium iPS189 (262 reactions, 274 metabolites), is 87% accurate in recapitulating in vivo gene essentiality results for M. genitalium. Approaches and tools described herein provide a roadmap for the automated construction of in silico metabolic models of other organisms

Albumin and multiple sclerosis

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Leakage of the blood–brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth