An in vitro-identified high-affinity nucleosome-positioning signal is capable of transiently positioning a nucleosome in vivo

<p>Abstract</p> <p>Background</p> <p>The physiological function of eukaryotic DNA occurs in the context of nucleosomal arrays that can expose or obscure defined segments of the genome. Certain DNA sequences are capable of strongly positioning a nucleosome <it>in vitro</it>, suggesting the possibility that favorable intrinsic signals might reproducibly structure chromatin segments. As high-throughput sequencing analyses of nucleosome coverage <it>in vitro </it>and <it>in vivo </it>have become possible, a vigorous debate has arisen over the degree to which intrinsic DNA:nucleosome affinities orchestrate the <it>in vivo </it>positions of nucleosomes, thereby controlling physical accessibility of specific sequences in DNA.</p> <p>Results</p> <p>We describe here the <it>in vivo </it>consequences of placing a synthetic high-affinity nucleosome-positioning signal, the 601 sequence, into a DNA plasmid vector in mice. Strikingly, the 601 sequence was sufficient to position nucleosomes during an early phase after introduction of the DNA into the mice (when the plasmid vector transgene was active). This positioning capability was transient, with a loss of strong positioning at a later time point when the transgenes had become silent.</p> <p>Conclusions</p> <p>These results demonstrate an ability of DNA sequences selected solely for nucleosome affinity to organize chromatin <it>in vivo</it>, and the ability of other mechanisms to overcome these interactions in a dynamic nuclear environment.</p

Large-Scale Turnover of Functional Transcription Factor Binding Sites in Drosophila

The gain and loss of functional transcription factor binding sites has been proposed as a major source of evolutionary change in cis-regulatory DNA and gene expression. We have developed an evolutionary model to study binding-site turnover that uses multiple sequence alignments to assess the evolutionary constraint on individual binding sites, and to map gain and loss events along a phylogenetic tree. We apply this model to study the evolutionary dynamics of binding sites of the Drosophila melanogaster transcription factor Zeste, using genome-wide in vivo (ChIP–chip) binding data to identify functional Zeste binding sites, and the genome sequences of D. melanogaster, D. simulans, D. erecta, and D. yakuba to study their evolution. We estimate that more than 5% of functional Zeste binding sites in D. melanogaster were gained along the D. melanogaster lineage or lost along one of the other lineages. We find that Zeste-bound regions have a reduced rate of binding-site loss and an increased rate of binding-site gain relative to flanking sequences. Finally, we show that binding-site gains and losses are asymmetrically distributed with respect to D. melanogaster, consistent with lineage-specific acquisition and loss of Zeste-responsive regulatory elements

Etiology, Risk Factors and Outcome of Spontaneous Intracerebral Hemorrhage in Young Adults Admitted to Tertiary Care Hospital in Mogadishu, Somalia

Mohamed Sheikh Hassan,1,2 Ahmet Bakir,1 Nor Osman Sidow,1 Umut Erkok,3 Said Abdirahman Ahmed,4 Maryan Dahir Abshir,5 Ayhan Ayhan Köksal6 1Department of Neurology, Mogadishu Somalia Turkish Training and Research Hospital, Mogadishu, Somalia; 2Faculty of Medicine and Surgery, Mogadishu University, Mogadishu, Somalia; 3Department of Gynecology and Obstetrics, Mogadishu Somalia Turkish Training and Research Hospital, Mogadishu, Somalia; 4Department of Cardiology, Mogadishu Somalia Turkish Training and Research Hospital, Mogadishu, Somalia; 5Department of Medical Laboratory, Mogadishu Somalia Turkish Training and Research Hospital, Mogadishu, Somalia; 6University of Health Sciences, Istanbul Ba&scedil;ak&scedil;ehir Cam and Sakura City Hospital, Istanbul, TurkiyeCorrespondence: Mohamed Sheikh Hassan, Mogadishu Somalia Turkish Training and Research Hospital, Mogadishu, Somalia, Email [email protected]: Spontaneous Intracerebral hemorrhage (ICH) in young patients is less common and not well studied compared to ICH in older patients. The etiology, risk factors and outcome of ICH in young patients may have regional and ethnic differences. The study aims to investigate the clinical characteristics, risk factors, etiology and outcome of spontaneous intracerebral hemorrhage in young adults in Somalia.Methods: The study enrolled 168 young patients with ICH (16– 50 years) admitted to the neurology department of a tertiary hospital from 2019 to 2022. The information about the demographic details, documented ICH risk factors, etiology and patients’ clinical status were retrieved. The etiology of ICH was determined based on clinical, laboratory and radiological findings. Intra-hospital survival status and associated factors were assessed.Results: The mean age of the patients was 35± 8.6 years. 99 (59%) of patients were male while 69 (41%) were females. Hypertension 48 (29%) was the most common risk factor, followed by substance abuse. Hypertensive hemorrhage was the most common etiology of ICH 60 (35.7%), followed by cerebral venous thrombosis (CVT) 5(15%), substance abuse 23 (13.7%) and arteriovenous malformation (AVM) in 10 (6%). AVM, CVT, cavernoma, eclampsia, substance abuse and cryptogenic etiology were more common in the 2nd and 3rd decades whereas hypertension was more common in the 4th and 5th decade. Intrahospital mortality was 28% in this study. Factors predicting intrahospital mortality were hematoma volume of greater than 30mL, thrombolytic etiology, brainstem ICH location, substance abuse related etiology, presence of associated mass effect, low GCS score on admission, high systolic blood pressure on admission, and the presence of chronic renal failure.Conclusion: In this study, hypertension, substance abuse, CVT and vascular malformation are the leading causes of ICH in young adults. Intracerebral hemorrhage in the young has different spectrum of etiologies and factors associated with short-term mortality compared to older patients.Keywords: intracerebral hemorrhages, young patients, etiology, outcom

Undiagnosed Epileptic Case Since Childhood of Sturge-Weber Syndrome: First Case Report from Somalia

Said Abdi Mohamed,1 Nor Osman Sidow,1,2 Bakar Ali Adam,1 Mohamed Sheikh Hassan,1,3 Abdiwahid Ahmed Ibrahim,1 Mohamed Farah Osman,1 Abdulkadir Ahmed,1 Abdullahi Ali Roble4 1Department of Neurology, Mogadishu-Somalia Turkey Recep Tayyip Erdo&gbreve;an Training and Research Hospital, Mogadishu, Somalia; 2Faculty of Medicine and Surgery, Jazeera University, Mogadishu, Somalia; 3Faculty of Medicine and Surgery, Mogadishu University, Mogadishu, Somalia; 4Department of Ophthalmology, Mogadishu-Somalia Turkey Recep Tayyip Erdo&gbreve;an Training and Research Hospital, Mogadishu, SomaliaCorrespondence: Nor Osman Sidow, Tel +252618300616, Email [email protected]: Sturge-Weber syndrome is a rare, sporadic, progressive neurocutaneous condition that presents with congenital hamartomatous malformations, epilepsy, and a variety of facial symptoms. We discussed a rare case of an eighteen-year-old female child who came to our neurology department with status epilepticus, mental impairment, and a port-wine in the lateral left side of her face. We diagnosed Sturge-Weber syndrome after a thorough neurological and radiological evaluation. The purpose of presenting this case is to illustrate both the characteristic presentation and the complications associated with managing Sturge-Weber syndrome.Keywords: sturge-weber, seizure, port-win

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

SHRiMP: Accurate Mapping of Short Color-space Reads

The development of Next Generation Sequencing technologies, capable of sequencing hundreds of millions of short reads (25–70 bp each) in a single run, is opening the door to population genomic studies of non-model species. In this paper we present SHRiMP - the SHort Read Mapping Package: a set of algorithms and methods to map short reads to a genome, even in the presence of a large amount of polymorphism. Our method is based upon a fast read mapping technique, separate thorough alignment methods for regular letter-space as well as AB SOLiD (color-space) reads, and a statistical model for false positive hits. We use SHRiMP to map reads from a newly sequenced Ciona savignyi individual to the reference genome. We demonstrate that SHRiMP can accurately map reads to this highly polymorphic genome, while confirming high heterozygosity of C. savignyi in this second individual. SHRiMP is freely available at http://compbio.cs.toronto.edu/shrimp