Establishing the evolutionary compatibility of potential sources of colonizers for overfished stocks: a population genomics approach

Identifying fish stock structure is fundamental to pinpoint stocks that might contribute colonizers to overfished stocks. However, a stock's potential to contribute to rebuilding hinges on demographic connectivity, a challenging parameter to measure. With genomics as a new tool, fisheries managers can detect signatures of natural selection and thus identify fishing areas likely to contribute evolutionarily compatible colonizers to an overfished area (i.e. colonizers that are not at a fitness disadvantage in the overfished area and able to reproduce at optimal rates). Identifying evolutionarily compatible stocks would help narrow the focus on establishing demographic connectivity where it matters. Here, we genotype 4723 SNPs in 616 orange roughy (Hoplostethus atlanticus) across five fishing areas off the Tasmanian coast in Australia. We ask whether these areas form a single genetic unit, and test for signatures of local adaptation. Results from amova , structure , discriminant analysis of principal components, bayesass and isolation by distance suggest that sampled locations are subjected to geneflow amounts that are above what is needed to establish ‘drift connectivity’. However, it remains unclear whether there is a single panmictic population or several highly connected populations. Most importantly, we did not find any evidence of local adaptation, suggesting that the examined orange roughy stocks are evolutionarily compatible. The data have helped test an assumption of the orange roughy management programme and to formulate hypotheses regarding stock demographic connectivity. Overall, our results demonstrate the potential of genomics to inform fisheries management, even when evidence for stock structure is sparse.     

Mast cells and dendritic cells form synapses that facilitate antigen transfer for T cell activation

Mast cells (MCs) produce soluble mediators such as histamine and prostaglandins that are known to influence dendritic cell (DC) function by stimulating maturation and antigen processing. Whether direct cell–cell interactions are important in modulating MC/DC function is unclear. In this paper, we show that direct contact between MCs and DCs occurs and plays an important role in modulating the immune response. Activation of MCs through FcεRI cross-linking triggers the formation of stable cell–cell interactions with immature DCs that are reminiscent of the immunological synapse. Direct cellular contact differentially regulates the secreted cytokine profile, indicating that MC modulation of DC populations is influenced by the nature of their interaction. Synapse formation requires integrin engagement and facilitates the transfer of internalized MC-specific antigen from MCs to DCs. The transferred material is ultimately processed and presented by DCs and can activate T cells. The physiological outcomes of the MC–DC synapse suggest a new role for intercellular crosstalk in defining the immune response.     

Case report: probable transmission of vaccine strain of yellow fever virus to an infant via breast milk

The 17D yellow fever vaccine is a live-virus vaccine that has been in use since the 1940s. The incidence of encephalitis after yellow fever vaccination among young infants is much higher than among children older than nine months of age. Until recently, avoidance of vaccination by breastfeeding women who have received yellow fever vaccine had been based on theoretical grounds only. We report the probable transmission of vaccine strain of yellow fever virus from a mother to her infant through breastfeeding.A previously healthy five-week-old male infant presented to hospital with a two-day history of fever and irritability. The day before his admission, he had been noted to have focal seizures on alternating sides. He had poor appetite and had vomited once, but did not develop diarrhea or rash. His fever was preceded by a two-week history of nonspecific rhinorrhea and cough.A left-sided focal seizure was witnessed in the emergency department. At that time, his temperature was 38°C, his respiratory rate was 60 breaths/min, his pulse was 164 beats/min and his oxygen saturation was 93% on room air. He was irritable, with a full anterior fontanelle, nasal congestion, supple neck, and normal tone and reflexes. The remainder of his examination was unremarkable.The patient had been born vaginally at term. His mother had tested positive on a vaginal swab test for group B streptococcus and had received appropriate intrapartum antibiotics. When the infant was 10 days of age, his mother had received pretravel advice and travel vaccinations. She had been given yellow fever vaccine along with inactivated typhoid vaccine and did not report substantial adverse effects. Three days later, the infant and his mother had departed to Venezuela for one week. They had stayed exclusively in the city of Caracas, and breastfeeding was continued. The baby had showed no insect bites nor had contact with sick people, nor had he been exposed to animals in Canada or abroad. There was no history of herpes infection in family members. He had not received any vaccinations before presentation. Before the onset of his symptoms, his sister (aged five years) and father had upper respiratory tract symptoms. The infant was brought to hospital 20 days after returning to Canada.Anticonvulsants were administered initially to control seizures, along with empiric ampicillin, cefotaxime and acyclovir at doses appropriate for treating meningitis. Abnormalities on results of a complete blood count included a platelet count of 740 (normal 150–400) × 10⁹/L and a total leukocyte count of 13.2 (normal 4.0–11.0) × 10⁹/L. Serum electrolytes and levels of calcium and magnesium were normal. A computed tomographic scan of the head was normal, and a lumbar puncture was performed. Cerebrospinal fluid parameters were abnormal, with a total leukocyte count of 128.9 × 10⁶ with 30% neutrophils, 32% lymphocytes and 36% monocytes. No red blood cells and no xanthochromia were seen. Glucose was 2.2 (serum 4.3) mmol/L and protein was elevated at 1.1 g/L. Bacterial cultures of blood, urine and cerebrospinal fluid were negative, as was polymerase chain reaction testing of cerebrospinal fluid for herpes simplex virus and enteroviruses. Nucleic acid sequence-based amplification on a nasopharyngeal specimen was also negative for enterovirus.An electroencephalogram was performed and showed multifocal, potentially epileptogenic discharges. A repeat study 10 days later showed lateral temporal spikes consistent with encephalitis. Magnetic resonance imaging of the head revealed meningeal enhancement in the frontoparietal regions that was consistent with meningoencephalitis. Antibiotics were discontinued after bacterial cultures were reported negative, and the infant was given a 21-day course of acyclovir. His fever resolved after two days, and he had no further seizures. He was discharged with no medication after completion of the course of acyclovir and a normal neurologic exam. A follow-up evaluation five months later confirmed normal development and absence of neurologic deficit. The timeline of events is shown in Figure 1.Open in a separate windowFigure 1:Timeline of events surrounding probable transmission of vaccine strain of yellow fever virus to an infant via breastfeeding.A serum sample taken on the patient’s admission to hospital was reported to be positive for yellow fever on an IgM capture enzyme-linked immunosorbent assay from the Centers for Disease Control and Prevention. A serum-dilution–plaque-reduction neutralization test for yellow fever was also positive at a titre of 1:5120, and the yellow fever hemagglutination inhibition titre was 1:160. Yellow fever IgG was negative. In addition, a sample of cerebrospinal fluid taken on admission was reported by the Centers for Disease Control and Prevention to be positive for yellow fever antigen by IgM capture enzyme-linked immunosorbent assay, but negative for yellow fever virus by polymerase chain reaction. There were no samples of breast milk available for testing.Convalescent serum testing four months after admission showed persistence of yellow fever virus IgM, with a drop in the plaque reduction neutralization test titre to 1:320, which was suggestive of recent exposure. Serologic testing for western and eastern equine encephalitis, St. Louis encephalitis, Powassan encephalitis and dengue were negative (National Microbiology Laboratory) along with Mayaro, Venezuelan equine encephalitis and West Nile viruses (Centers for Disease Control and Prevention).     

Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor which significantly decreases tumor volume in a mouse xenograft model

An extension of our previously reported series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. Addition of a second methyl group to the tether provided analogs that show increased potency in binding as well as cell-proliferation assays and, more importantly, are stable toward microsomes. We wish to disclose the discovery of a macrocycle which showed impressive biomarker activity 24-h post dosing and which demonstrated prolonged exposure in tumors. When studied in a lung cancer xenograft model, the compound demonstrated significant tumor size reduction.     

Birds flee en mass from New Year's Eve fireworks

Anthropogenic disturbances of wildlife, such as noise, human presence, hunting activity, and motor vehicles, are becoming an increasing concern in conservation biology. Fireworks are an important part of celebrations worldwide, and although humans often find fireworks spectacular, fireworks are probably perceived quite differently by wild animals. Behavioral responses to fireworks are difficult to study at night, and little is known about the negative effects fireworks may have on wildlife. Every year, thousands of tons of fireworks are lit by civilians on New Year's Eve in the Netherlands. Using an operational weather radar, we quantified the reaction of birds to fireworks in 3 consecutive years. Thousands of birds took flight shortly after midnight, with high aerial movements lasting at least 45 min and peak densities measured at 500 m altitude. The highest densities were observed over grasslands and wetlands, including nature conservation sites, where thousands of waterfowl rest and feed. The Netherlands is the most important winter staging area for several species of waterfowl in Europe. We estimate that hundreds of thousands of birds in the Netherlands take flight due to fireworks. The spatial and temporal extent of disturbance is substantial, and potential consequences are discussed. Weather radar provides a unique opportunity to study the reaction of birds to fireworks, which has otherwise remained elusive.     

Cell recovery comparison between plasma depletion/reduction- and red cell reduction-processing of umbilical cord blood

Background aimsLimited cell dose has hampered the use of cord blood transplantation (CBT) in adults. One method of minimizing nucleated cell loss in cord blood (CB) processing is to deplete or reduce plasma but not red blood cells - plasma depletion/reduction (PDR).MethodsThe nucleated cell loss of PDR was studied, and determined to be less than 0.1% in the discarded supernatant plasma fraction in validation experiments. After testing and archival sampling, the median nucleated cell recovery for PDR processing was 90%, and median CD34⁺ cell recovery 88%. In a CB bank inventory of 12 339 products with both pre- and post-processing total nucleated cells (TNC), PDR processing resulted in median post-processing TNC recoveries of 90.0% after testing and archival samples removal. Using the same 10 CB units divided into two halves, we compared directly the recovery of PDR against hydroxyethyl starch red cell reduction (RCR) for TNC, CD34⁺ cells and colony-forming units (CFU-GM, CFU-E, CFU-GEMM and total CFU) after parallel processing. We also compared the loss of very small embryonic-like stem cells (VSEL).ResultsWe demonstrated significantly higher recoveries using PDR for TNC (124%), CD34⁺ cells (121%), CFU-GM (225%), CFU-GEMM (201%), total CFU (186%) and VSEL (187%). The proportion of high TNC products was compared between 10 912 PDR and 38 819 RCR CB products and found to be 200% higher for products that had TNC ≥150 × 10⁷ (P = 0.0001) for the PDR inventory.ConclusionsOur data indicate that PDR processing of CB provides a significantly more efficient usage of this valuable and scarce resource.     

The multifaceted role of oestrogen in enhancing Chlamydia trachomatis infection in polarized human endometrial epithelial cells

The oestrogen receptor (ER) α-β+ HEC-1B and the ERα+β+ Ishikawa (IK) cell lines were investigated to dissect the effects of oestrogen exposure on several parameters of Chlamydia trachomatis infection. Antibody blockage of ERα or ERβ alone or simultaneously significantly decreased C. trachomatis infectivity (45-68%). Addition of the ERβ antagonist, tamoxifen, to IK or HEC-1B prior to or after chlamydial infection caused a 30-90% decrease in infectivity, the latter due to disrupted eukaryotic organelles. In vivo, endometrial glandular epithelial cells are stimulated by hormonally influenced stromal signals. Accordingly, chlamydial infectivity was significantly increased by 27% and 21% in IK and HEC-1B cells co-cultured with SHT-290 stromal cells exposed to oestrogen. Endometrial stromal cell/epithelial cell co-culture revealed indirect effects of oestrogen on phosphorylation of extracellular signal-regulated kinase and calcium-dependant phospholipase A2 and significantly increased production of interleukin (IL)-8 and IL-6 in both uninfected and chlamydiae-infected epithelial cells. These results indicate that oestrogen and its receptors play multiple roles in chlamydial infection: (i) membrane oestrogen receptors (mERs) aid in chlamydial entry into host cells, and (ii) mER signalling may contribute to inclusion development during infection. Additionally, enhancement of chlamydial infection is affected by hormonally influenced stromal signals in conjunction with direct oestrogen stimulation of the human epithelia.     

Communication and data-intensive science in the beginning of the 21st century

The advent of data-intensive science has sharpened our need for better communication within and between the fields of science and technology, to name a few. No one mind can encompass all that is necessary to be successful in controlling and analyzing the data deluge we are experiencing. Therefore, we must bring together diverse fields, communicate clearly, and build crossdisciplinary methods and tools to realize its potential. This article is a summary of the communication issues and challenges as discussed in the Data-Intensive Science (DIS) workshop in Seattle, September 19-20, 2010.