Effect of life history on microRNA expression during C. elegans development

Animals have evolved mechanisms to ensure the robustness of developmental outcomes to changing environments. MicroRNA expression may contribute to developmental robustness because microRNAs are key post-transcriptional regulators of developmental gene expression and can affect the expression of multiple target genes. Caenorhabditis elegans provides an excellent model to study developmental responses to environmental conditions. In favorable environments, C. elegans larvae develop rapidly and continuously through four larval stages. In contrast, in unfavorable conditions, larval development may be interrupted at either of two diapause stages: The L1 diapause occurs when embryos hatch in the absence of food, and the dauer diapause occurs after the second larval stage in response to environmental stimuli encountered during the first two larval stages. Dauer larvae are stress resistant and long lived, permitting survival in harsh conditions. When environmental conditions improve, dauer larvae re-enter development, and progress through two post-dauer larval stages to adulthood. Strikingly, all of these life history options (whether continuous or interrupted) involve an identical pattern and sequence of cell division and cell fates. To identify microRNAs with potential functions in buffering development in the context of C. elegans life history options, we used multiplex real-time PCR to assess the expression of 107 microRNAs throughout development in both continuous and interrupted life histories. We identified 17 microRNAs whose developmental profile of expression is affected by dauer life history and/or L1 diapause, compared to continuous development. Hence these microRNAs could function to regulate gene expression programs appropriate for different life history options in the developing worm

Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group.

Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches

Antimicrobial-producing Pseudoalteromonas from the marine environment of Panama shows a high phylogenetic diversity and clonal structure

Pseudoalteromonas is a genus of marine bacteria often found in association with other organisms. Although several studies have examined Pseudoalteromonas diversity and their antimicrobial activity, its diversity in tropical environments is largely unexplored. We investigated the diversity of Pseudoalteromonasin marine environments of Panama using a multilocus phylogenetic approach. Furthermore we tested their antimicrobial capacity and evaluated the effect of recombination and mutation in shaping their phylogenetic relationships. The reconstruction of clonal relationships among 78 strains including 15 reference Pseudoalteromonas species revealed 43 clonal lineages, divided in pigmented and non-pigmented strains. In total, 39 strains displayed moderate to high activity against Gram-positive and Gram-negative bacteria and fungi. Linkage disequilibrium analyses showed that the Pseudoalteromonas strains of Panama have a highly clonal structure and that, although present, recombination is not frequent enough to break the association among alleles. This clonal structure is in contrast to the high rates of recombination generally reported for aquatic and marine bacteria.We propose that this structure is likely due to the symbiotic association with marine invertebrates of most strains analyzed. Our results also show that there are several putative new species of Pseudoalteromonas in Panama to be described.Pseudoalteromonas is a genus of marine bacteria often found in association with other organisms. Although several studies have examined Pseudoalteromonas diversity and their antimicrobial activity, its diversity in tropical environments is largely unexplored. We investigated the diversity of Pseudoalteromonasin marine environments of Panama using a multilocus phylogenetic approach. Furthermore we tested their antimicrobial capacity and evaluated the effect of recombination and mutation in shaping their phylogenetic relationships. The reconstruction of clonal relationships among 78 strains including 15 reference Pseudoalteromonas species revealed 43 clonal lineages, divided in pigmented and non-pigmented strains. In total, 39 strains displayed moderate to high activity against Gram-positive and Gram-negative bacteria and fungi. Linkage disequilibrium analyses showed that the Pseudoalteromonas strains of Panama have a highly clonal structure and that, although present, recombination is not frequent enough to break the association among alleles. This clonal structure is in contrast to the high rates of recombination generally reported for aquatic and marine bacteria.We propose that this structure is likely due to the symbiotic association with marine invertebrates of most strains analyzed. Our results also show that there are several putative new species of Pseudoalteromonas in Panama to be described

Nanomechanical Detection of Itinerant Electron Spin Flip

Spin is an intrinsically quantum property, characterized by angular momentum. A change in the spin state is equivalent to a change in the angular momentum or mechanical torque. This spin-induced torque has been invoked as the intrinsic mechanism in experiments ranging from the measurements of angular momentum of photons g-factor of metals and magnetic resonance to the magnetization reversal in magnetic multi-layers A spin-polarized current introduced into a nonmagnetic nanowire produces a torque associated with the itinerant electron spin flip. Here, we report direct measurement of this mechanical torque and itinerant electron spin polarization in an integrated nanoscale torsion oscillator, which could yield new information on the itinerancy of the d-band electrons. The unprecedented torque sensitivity of 10^{-22} N m/ \sqrt{Hz} may enable applications for spintronics, precision measurements of CP-violating forces, untwisting of DNA and torque generating molecules.Comment: 14 pages, 4 figures. visit http://nano.bu.edu/ for related paper

Investigating rare haematological disorders - A celebration of 10 years of the Sherlock Holmes symposia

The Sherlock Holmes symposia have been educating haematologists on the need for prompt recognition, diagnosis and treatment of rare haematological diseases for 10 years. These symposia, which are supported by an unrestricted educational grant from Sanofi Genzyme, encourage haematologists to consider rare disorders in differential diagnoses. Improvement in rare disease awareness is important because diagnostics and the availability of effective therapies have improved considerably, meaning that rare haematological diseases can be accurately diagnosed and successfully managed, particularly if they are identified early. The Sherlock Holmes symposia programme includes real-life interactive clinical cases of rare haematological disorders that require awareness from the physician, to be diagnosed at an early stage. The audience are encouraged to examine each case as if they were detectives, look for clues from the clinical history and presentation, consider the potential causes, assess which tests would be required to make a definitive diagnosis and suggest optimal treatment options. To celebrate the 10-year anniversary of the Sherlock Holmes symposia, this article describes a number of clinical cases that include anaemia, thrombocytopaenia and splenomegaly among the presenting symptoms, to illustrate the importance of rigorous differential diagnosis in the identification of rare haematological disorders

Maternal neurofascin-specific autoantibodies bind to structures of the fetal nervous system during pregnancy, but have no long term effect on development in the rat

Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum. Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody. Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children

The continuum of spreading depolarizations in acute cortical lesion development: Examining Leão's legacy.

A modern understanding of how cerebral cortical lesions develop after acute brain injury is based on Aristides Leão's historic discoveries of spreading depression and asphyxial/anoxic depolarization. Treated as separate entities for decades, we now appreciate that these events define a continuum of spreading mass depolarizations, a concept that is central to understanding their pathologic effects. Within minutes of acute severe ischemia, the onset of persistent depolarization triggers the breakdown of ion homeostasis and development of cytotoxic edema. These persistent changes are diagnosed as diffusion restriction in magnetic resonance imaging and define the ischemic core. In delayed lesion growth, transient spreading depolarizations arise spontaneously in the ischemic penumbra and induce further persistent depolarization and excitotoxic damage, progressively expanding the ischemic core. The causal role of these waves in lesion development has been proven by real-time monitoring of electrophysiology, blood flow, and cytotoxic edema. The spreading depolarization continuum further applies to other models of acute cortical lesions, suggesting that it is a universal principle of cortical lesion development. These pathophysiologic concepts establish a working hypothesis for translation to human disease, where complex patterns of depolarizations are observed in acute brain injury and appear to mediate and signal ongoing secondary damage

Long-term organic carbon preservation enhanced by iron and manganese.

The balance between degradation and preservation of sedimentary organic carbon (OC) is important for global carbon and oxygen cycles1. The relative importance of different mechanisms and environmental conditions contributing to marine sedimentary OC preservation, however, remains unclear2-8. Simple organic molecules can be geopolymerized into recalcitrant forms by means of the Maillard reaction5, although reaction kinetics at marine sedimentary temperatures are thought to be slow9,10. More recent work in terrestrial systems suggests that the reaction can be catalysed by manganese minerals11-13, but the potential for the promotion of geopolymerized OC formation at marine sedimentary temperatures is uncertain. Here we present incubation experiments and find that iron and manganese ions and minerals abiotically catalyse the Maillard reaction by up to two orders of magnitude at temperatures relevant to continental margins where most preservation occurs4. Furthermore, the chemical signature of the reaction products closely resembles dissolved and total OC found in continental margin sediments globally. With the aid of a pore-water model14, we estimate that iron- and manganese-catalysed transformation of simple organic molecules into complex macromolecules might generate on the order of approximately 4.1 Tg C yr-1 for preservation in marine sediments. In the context of perhaps only about 63 Tg C yr-1 variation in sedimentary organic preservation over the past 300 million years6, we propose that variable iron and manganese inputs to the ocean could exert a substantial but hitherto unexplored impact on global OC preservation over geological time

Phase separation and suppression of critical dynamics at quantum transitions of itinerant magnets: MnSi and (Sr1−x_{1-x}Cax_{x})RuO3_{3}

Quantum phase transitions (QPTs) have been studied extensively in correlated electron systems. Characterization of magnetism at QPTs has, however, been limited by the volume-integrated feature of neutron and magnetization measurements and by pressure uncertainties in NMR studies using powderized specimens. Overcoming these limitations, we performed muon spin relaxation ($\mu$SR) measurements which have a unique sensitivity to volume fractions of magnetically ordered and paramagnetic regions, and studied QPTs from itinerant heli/ferro magnet to paramagnet in MnSi (single-crystal; varying pressure) and (Sr$_{1-x}$Ca$_{x}$)RuO$_{3}$ (ceramic specimens; varying $x$). Our results provide the first clear evidence that both cases are associated with spontaneous phase separation and suppression of dynamic critical behavior, revealed a slow but dynamic character of the ``partial order'' diffuse spin correlations in MnSi above the critical pressure, and, combined with other known results in heavy-fermion and cuprate systems, suggest a possibility that a majority of QPTs involve first-order transitions and/or phase separation.Comment: 11 pages, 4 figures, 21 authors, to appear in Nature Physic

Historical database cohort study addressing the clinical patterns prior to idiopathic pulmonary fibrosis (IPF) diagnosis in UK primary care

OBJECTIVE: To explore the clinical pathways, including signs and symptoms, and symptom progression patterns preceding idiopathic pulmonary fibrosis (IPF) diagnosis. DESIGN AND SETTING: A historical cohort study was conducted using primary care patient records from the Optimum Patient Care Research Database. PARTICIPANTS: Patients included were at least 30 years, had IPF diagnosis, identified via clinical-coding and free-text records and had a consultation with a chest specialist prior to IPF diagnosis. OUTCOME MEASURES: The signs and symptoms in the year prior to IPF diagnosis from clinical codes and free-text in primary care electronic records included: cough, dyspnoea, dry cough, weight loss, fatigue/malaise, loss of appetite, crackles and clubbed fingers. The time course of presentations of clinical features and investigations in the years prior to IPF diagnosis were mapped. RESULTS: Within 462 patients identified, the majority (77.9%) had a respiratory consultation within 365 days prior to the chest specialist visit preceding the IPF diagnosis recorded in their primary care records. The most common symptoms recorded in the 1 year prior to IPF diagnosis were dyspnoea (48.7%) and cough (40.9%); other signs and symptoms were rarely recorded (<5%). The majority of patients with cough (58.0%) and dyspnoea (55.0%) in the 1 year before IPF diagnosis had multiple recordings of the respective symptoms. Both cough and dyspnoea were recorded in 23.4% of patients in the year prior to diagnosis. Consultation rates for cough, dyspnoea and both, but not other signs or symptoms, began to increase 4 to 5 years prior diagnosis, with the sharpest increase in the last year. Cough and dyspnoea were often preceded by a reduction in measured weight over 5 years leading to IPF diagnosis. CONCLUSION: Prolonged cough and/or progressive dyspnoea, especially if accompanied with weight loss, should signal for a referral to specialist assessment at the earliest opportunity