The significance of alternative transcripts for Caenorhabditis elegans transcription factor genes, based on expression pattern analysis

Background: Sequence-specific DNA-binding proteins, with their paramount importance in the regulation of expression of the genetic material, are encoded by approximately 5% of the genes in an animal’s genome. But it is unclear to what extent alternative transcripts from these genes may further increase the complexity of the transcription factor complement. Results: Of the 938 potential C. elegans transcription factor genes, 197 were annotated in WormBase as encoding at least two distinct isoforms. Evaluation of prior evidence identified, with different levels of confidence, 50 genes with alternative transcript starts, 23 with alternative transcript ends, 35 with alternative splicing and 34 with alternative transcripts generated by a combination of mechanisms, leaving 55 that were discounted. Expression patterns were determined for transcripts for a sample of 29 transcription factor genes, concentrating on those with alternative transcript starts for which the evidence was strongest. Seamless fosmid recombineering was used to generate reporter gene fusions with minimal modification to assay expression of specific transcripts while maintaining the broad genomic DNA context and alternative transcript production. Alternative transcription factor gene transcripts were typically expressed with identical or substantially overlapping distributions rather than in distinct domains. Conclusions: Increasingly sensitive sequencing technologies will reveal rare transcripts but many of these are clearly non-productive. The majority of the transcription factor gene alternative transcripts that are productive may represent tolerable noise rather than encoding functionally distinct isoforms

Global Prediction of Tissue-Specific Gene Expression and Context-Dependent Gene Networks in Caenorhabditis elegans

Tissue-specific gene expression plays a fundamental role in metazoan biology and is an important aspect of many complex diseases. Nevertheless, an organism-wide map of tissue-specific expression remains elusive due to difficulty in obtaining these data experimentally. Here, we leveraged existing whole-animal Caenorhabditis elegans microarray data representing diverse conditions and developmental stages to generate accurate predictions of tissue-specific gene expression and experimentally validated these predictions. These patterns of tissue-specific expression are more accurate than existing high-throughput experimental studies for nearly all tissues; they also complement existing experiments by addressing tissue-specific expression present at particular developmental stages and in small tissues. We used these predictions to address several experimentally challenging questions, including the identification of tissue-specific transcriptional motifs and the discovery of potential miRNA regulation specific to particular tissues. We also investigate the role of tissue context in gene function through tissue-specific functional interaction networks. To our knowledge, this is the first study producing high-accuracy predictions of tissue-specific expression and interactions for a metazoan organism based on whole-animal data

Ethnobotany of the Samburu of Mt. Nyiru, South Turkana, Kenya

Traditional plant use is of extremely high importance in many societies, and prevalent in African communities. This knowledge is however dwindling rapidly due to changes towards a more Western lifestyle. The influence of modern tourism cannot be neglected in this context. This paper examines the plant use of the Samburu of the Mt. Nyiru area in Northern Kenya. The Samburu pastoralists of Kenya are still amongst the most traditional communities of the country and have retained most of their knowledge about the use of a large part of the plants in their environment for a wide variety of purposes. The results indicate that the local population has a very high knowledge of the plants in their surroundings, and attributes a purpose to a large percentage of the plants found. 448 plant species were collected, identified and their Samburu names and traditional uses recorded. 199 species were reported as of "no use". The high proportion of 249 plant species however had some traditional use: The highest number (180 species) was used as fodder, followed by 80 species that had medicinal use. Firewood (59 species), construction (42 species), tools (31 species), food (29 species) and ceremonial use (19 species) ranked far behind. Traditionally the Samburu attribute most illnesses to the effect of pollutants that block or inhibit digestion. This can include "polluted" food, contagion through sick people as well as witchcraft. In most cases the treatment of illness involves herbal purgatives to cleanse the patient. There are however frequent indications of plant use for common problems like wounds, parasites, body aches and burns. The change from a nomadic to a more sedentary lifestyle, often observed in other areas of the country, has affected the Samburu of remote Mt. Nyiru to a much lesser extent and did so far not lead to a major loss of traditional plant knowledge. However, overgrazing and over-exploitation of plant resources have already led to a decline of the plant material available

The CDK-Activating Kinase (CAK) Csk1 Is Required for Normal Levels of Homologous Recombination and Resistance to DNA Damage in Fission Yeast

BACKGROUND: Cyclin-dependent kinases (CDKs) perform essential roles in cell division and gene expression in all eukaryotes. The requirement for an upstream CDK-activating kinase (CAK) is also universally conserved, but the fission yeast Schizosaccharomyces pombe appears to be unique in having two CAKs with both overlapping and specialized functions that can be dissected genetically. The Mcs6 complex--orthologous to metazoan Cdk7/cyclin H/Mat1--activates the cell-cycle CDK, Cdk1, but its non-redundant essential function appears to be in regulation of gene expression, as part of transcription factor TFIIH. The other CAK is Csk1, an ortholog of budding yeast Cak1, which activates all three essential CDKs in S. pombe--Cdk1, Mcs6 and Cdk9, the catalytic subunit of positive transcription elongation factor b (P-TEFb)--but is not itself essential. METHODOLOGY/PRINCIPAL FINDINGS: Cells lacking csk1(+) are viable but hypersensitive to agents that damage DNA or block replication. Csk1 is required for normal levels of homologous recombination (HR), and interacts genetically with components of the HR pathway. Tests of damage sensitivity in csk1, mcs6 and cdk9 mutants indicate that Csk1 acts pleiotropically, through Cdk9 and at least one other target (but not through Mcs6) to preserve genomic integrity. CONCLUSIONS/SIGNIFICANCE: The two CAKs in fission yeast, which differ with respect to their substrate range and preferences for monomeric CDKs versus CDK/cyclin complexes as substrates, also support different functions of the CDK network in vivo. Csk1 plays a non-redundant role in safeguarding genomic integrity. We propose that specialized activation pathways dependent on different CAKs might insulate CDK functions important in DNA damage responses from those capable of triggering mitosis

Cerebral dural arteriovenous fistulae presenting with acute hemorrhage : a systematic review

Abstract: Background: Cerebral dural arteriovenous fistulae (dAVFs) are rare connections between arteries and veins or sinuses in the brain. dAVFs have a higher risk of intracranial hemorrhages due to increased venous pressure. Endovascular treatment is considered the first line treatment. However, it is unknown if surgery improves outcomes for patients presenting with an acute hemorrhage. Therefore, this systematic review assesses complete obliterations and recurrences of surgery and endovascular treatment in hemorrhagic dAVFs patients.Methods: A literature search in the PubMed and Web of Sciences database was conducted up till October 2021. Studies of surgical and endovascular treatments with hemorrhagic dAVFs were included. The Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group and the JBI critical appraisal checklist for case reports were used for risk of bias assessment.Results: Eleven articles were included. 681 dAVFs patients with 686 fistulae were reported. 245 (36 %) patients presented with an intracranial hemorrhage. Most fistulae were found in the transverse or sigmoid sinuses (n = 220; 32.1 %) and the majority were classified as Borden III. 571 endovascular treatments resulted in 390 (68.3 %) complete dAVF obliterations and there was a recurrence of 66 dAVFs (16.9 %). 183 surgeries resulted in the complete obliteration of 166 fistulae (91.8 %) with a recurrence of 2 dAVFs (1.2 %).Conclusions: Due to the lack of literature on hemorrhagic dAVFs exclusively, we cannot make a statement on the effectiveness of surgical interventions compared to endovascular treatments. Future studies should report out-comes based on location, previous treatments, and patient presentation

Dabigatran-associated spontaneous acute cervical epidural hematoma

publisher: Elsevier articletitle: Dabigatran-Associated Spontaneous Acute Cervical Epidural Hematoma journaltitle: World Neurosurgery articlelink: http://dx.doi.org/10.1016/j.wneu.2014.10.012 content_type: simple-article copyright: Copyright © 2015 Elsevier Inc. All rights reserved.status: publishe

Skeletal Muscle Fibre Characteristics of the Lumbar Multifidus Muscle in Patients Undergoing Microdiscectomy for Unilateral Lumbar Disc Herniation

Background. Lumbar disc herniation (LDH) is the most common diagnosed degenerative pathology in the lumbar spine. Because of its role in spinal stability there is an increased interest in the role of the Lumbar Multifidus muscle in low back pain research. Despite surgical treatment long-term, disability and pain remain a persistent problem. The aim of the study is to compare side-to-side Lumbar Multifidus muscle fibre characteristics in unilateral LDH patients, and compare both sides to a healthy control group. Methods. Thirty patients (n = 17 men and n = 13 women) scheduled for microdis-cectomy for unilateral disc herniation and ten healthy controls (n = 5 men and n = 5 women) were included in this study. Biopsies of the Lumbar Multifidus muscle were analysed by means of immunohistochemistry combined with immunofluorescence microscopy to determine type I and type II muscle fibre type distribution, cross-sec-tional area, myonuclear-and satellite cell content, inflammation and various indices of muscle fibre capillarisation. Results. The proportion of muscle fibres with centrally located myonuclei, various indicis of muscle fibre capillarisation and pro-and anti-inflammatory cell content were higher in the patients compared with the healthy controls. No differences were observed in type I and type II muscle fibre characteristics between the injured and uninjured side within the LDH patients. Conclusions. This study shows clear differences in Lumbar Multifidus muscle fibre characteristics between LDH patients, irrespective of injured or uninjured side, and healthy controls. Additional studies are warranted to establish the clinical signif-icance of these differences in muscle fibre morphology in LDH compared with healthy controls. Study registration. This trial was registered on ClinicalTrials.gov under the identifica-tion number NCT03753711

Skeletal Muscle Fibre Characteristics of the Lumbar Multifidus Muscle in Patients Undergoing Microdiscectomy for Unilateral Lumbar Disc Herniation

Background. Lumbar disc herniation (LDH) is the most common diagnosed degenerative pathology in the lumbar spine. Because of its role in spinal stability there is an increased interest in the role of the Lumbar Multifidus muscle in low back pain research. Despite surgical treatment long-term, disability and pain remain a persistent problem. The aim of the study is to compare side-to-side Lumbar Multifidus muscle fibre characteristics in unilateral LDH patients, and compare both sides to a healthy control group.Methods. Thirty patients (n = 17 men and n = 13 women) scheduled for microdiscectomy for unilateral disc herniation and ten healthy controls (n = 5 men and n = 5 women) were included in this study. Biopsies of the Lumbar Multifidus muscle were analysed by means of immunohistochemistry combined with immunofluorescence microscopy to determine type I and type II muscle fibre type distribution, cross-sectional area, myonuclear- and satellite cell content, inflammation and various indices of muscle fibre capillarisation.Results. The proportion of muscle fibres with centrally located myonuclei, various indicis of muscle fibre capillarisation and pro-and anti-inflammatory cell content were higher in the patients compared with the healthy controls. No differences were observed in type I and type II muscle fibre characteristics between the injured and uninjured side within the LDH patients.Conclusions. This study shows clear differences in Lumbar Multifidus muscle fibre characteristics between LDH patients, irrespective of injured or uninjured side, and healthy controls. Additional studies are warranted to establish the clinical significance of these differences in muscle fibre morphology in LDH compared with healthy controls