Circulation and Chemotaxis of Fetal Hematopoietic Stem Cells

The major site of hematopoiesis transitions from the fetal liver to the spleen and bone marrow late in fetal development. To date, experiments have not been performed to evaluate functionally the migration and seeding of hematopoietic stem cells (HSCs) during this period in ontogeny. It has been proposed that developmentally timed waves of HSCs enter the bloodstream only during distinct windows to seed the newly forming hematopoietic organs. Using competitive reconstitution assays to measure HSC activity, we determined the localization of HSCs in the mid-to-late gestation fetus. We found that multilineage reconstituting HSCs are present at low numbers in the blood at all timepoints measured. Seeding of fetal bone marrow and spleen occurred over several days, possibly while stem cell niches formed. In addition, using dual-chamber migration assays, we determined that like bone marrow HSCs, fetal liver HSCs migrate in response to stromal cell-derived factor-1α (SDF-1α); however, unlike bone marrow HSCs, the migratory response of fetal liver HSCs to SDF-1α is greatly increased in the presence of Steel factor (SLF), suggesting an important role for SLF in HSC homing to and seeding of the fetal hematopoietic tissues. Together, these data demonstrate that seeding of fetal organs by fetal liver HSCs does not require large fluxes of HSCs entering the fetal bloodstream, and that HSCs constitutively circulate at low levels during the gestational period from 12 to 17 days postconception. Newly forming hematopoietic tissues are seeded gradually by HSCs, suggesting initial seeding is occurring as hematopoietic niches in the spleen and bone marrow form and become capable of supporting HSC self-renewal. We demonstrate that fetal and adult HSCs exhibit specific differences in chemotactic behavior. While both migrate in response to SDF-1α, fetal HSCs also respond significantly to the cytokine SLF. In addition, the combination of SDF-1α and SLF results in substantially enhanced migration of fetal HSCs, leading to migration of nearly all fetal HSCs in this assay. This finding indicates the importance of the combined effects of SLF and SDF-1α in the migration of fetal HSCs, and is, to our knowledge, the first demonstration of a synergistic effect of two chemoattractive agents on HSCs

Predicting and Changing Intentions to Avoid Driving into Urban Flash Flooding

Driving into floodwater is a leading cause of fatal and non-fatal drowning during times of flood. The present research aimed to understand drivers’ beliefs and intentions in relation to driving into floodwater caused by flash floods in an urban area (Newcastle City, Australia), using the theory of planned behavior as a framework. The study (N = 217) used a survey-based design to identify the psychological processes (attitude, subjective norm, perceived behavioral control, planning, moral norm) underpinning drivers’ intention to avoid driving into floodwater in Newcastle; and to concurrently investigate the potential effects of a brief planning intervention on drivers’ willingness to drive into floodwater in Newcastle. The structural equation model explained 49% of the variance in intention to avoid driving into floodwater in Newcastle, with subjective norm, perceived behavioral control, and planning each significant independent predictors of drivers’ intention to avoid driving into urban floodwater in Newcastle. Paired samples t-tests revealed participants’ willingness to stay at their location and not drive if a flood alert was received, and willingness to drive into floodwater when there is perceived pressure from other drivers, significantly changed after a brief planning intervention. These findings can inform intervention targets and development of prevention strategies targeting personal mitigation measures, particularly in the context of driver behaviour during flash flooding in an urban area

Metabolites from the Marine-Derived Fungus Chromocleista sp. Isolated from a Deep-Water Sediment Sample Collected in the Gulf of Mexico

As part of our ongoing chemical investigation of biologically active metabolites from marine fungi, three new compounds, p-hydroxyphenopyrrozin (1) and diketopiperazines (3, 4), have been isolated from the marine-derived fungus Chromocleista sp. In addition, the fungus gave the known compound phenopyrrozin (2), four known diketopiperazines (6-9), N-acetyltryptamine (10), and agathic acid (11). Another new diketopiperazine (5) was separated and identified as a decomposition product of 3 and 4. The structures of the new metabolites were determined on the basis of mass spectroscopy, NMR experiments, and derivatization methods. The absolute configuration of 1 was determined by X-ray crystallography studies

The Discovery of Infrared Rings in the Planetary Nebula NGC 1514 During the WISE All-Sky Survey

We report the discovery of a pair of infrared, axisymmetric rings in the planetary nebula NGC 1514 during the course of the WISE all-sky mid-infrared survey. Similar structures are seen at visible wavelengths in objects such as the "Engraved Hourglass Nebula" (MyCn 18) and the "Southern Crab Nebula" (Hen 2-104). However, in NGC 1514 we see only a single pair of rings and they are easily observed only in the mid-infrared. These rings are roughly 0.2 pc in diameter, are separated by 0.05 pc, and are dominated by dust emission with a characteristic temperature of 160 K. We compare the morphology and color of the rings to the other nebular structures seen at visible, far-infrared, and radio wavelengths, and close with a discussion of a physical model and formation scenario for NGC 1514.Comment: 16 pages, 10 figures, final version published in 2010 December Astronomical Journa

Hematopoietic Stem Cells Are Uniquely Selective in Their Migratory Response to Chemokines

Although hematopoietic stem cell (HSC) migration into and out of sites of active hematopoiesis is poorly understood, it is a critical process that underlies modern clinical stem cell transplantation and may be important for normal hematopoietic homeostasis. Given the established roles of chemotactic cytokine (chemokine)-directed migration of other leukocyte subsets, the migration of murine HSC to a large panel of CC and CXC chemokines was investigated. HSC migrated only in response to stromal derived factor-1α, the ligand for the CXC chemokine receptor 4 (CXCR4). CXCR4 expression by HSC was confirmed by reverse transcription polymerase chain reaction analysis. Surprisingly, HSC also expressed mRNA for CCR3 and CCR9, although they failed to migrate to the ligands for these receptors. The sharply restricted chemotactic responsiveness of HSC is unique among leukocytes and may be necessary for the specific homing of circulating HSC to bone marrow, as well as for the maintenance of HSC in hematopoietic microenvironments

The MEDGICarb-Study: Design of a multi-center randomized controlled trial to determine the differential health-promoting effects of low- and high-glycemic index Mediterranean-style eating patterns

Adults with central adiposity and other features of the metabolic syndrome have a markedly elevated risk of developing type 2 diabetes (T2D) and cardiovascular disease (CVD). A Mediterranean-style healthy eating pattern (MED-HEP) and consumption of foods with a lower glycemic index (GI) are potential dietary approaches to curb the T2D and CVD epidemic. However, experimental evidence of the effectiveness of MED-HEP and of the contribution of GI towards improving indices of glucose homeostasis, especially among non-diabetic people, are lacking. Therefore, we developed the MedGI-Carb trial, a multi-center (Italy, Sweden, and United States) intervention in adults with at least two components of the metabolic syndrome (elevated waist circumference + one other component) that aims to improve markers of glucose homeostasis through dietary modification. All participants were randomized to consume an isocaloric high- or low-GI MED-HEP for 12 weeks. We hypothesized that indexes of insulinemia (primary outcome: postprandial insulin and glucose after standardized breakfast and lunch; secondary outcomes: fasting plasma glucose and insulin, HbA1c, 24-h continuous glucose monitoring) would be improved more with the low-GI versus the high-GI MED-HEP. Additionally, we hypothesized that consumption of a MED-HEP would improve other markers of cardiometabolic health and well-being (fasting blood pressure, fasting lipid profile, sleep quality, satiety, global metabolic alterations in the plasma metabolome, changes in the gut microbiota, subjective health and well-being), with no difference between groups. Collectively, the design of MEDGI-Carb allows several different research questions to be explored. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03410719

Whole Genome Sequencing for Public Health Surveillance of Shiga Toxin-Producing Escherichia coli Other than Serogroup O157

Shiga toxin-producing Escherichia coli (STEC) are considered to be a significant threat to public health due to the severity of gastrointestinal symptoms associated with human infection. In England STEC O157 is the most commonly detected STEC serogroup, however, the implementation of PCR at local hospital laboartories has resulted in an increase in the detection of STEC other than serogroup O157 (non-O157 STEC). The aim of this study was to evaluate the use of whole genome sequencing (WGS) for routine public health surveillance of non-O157 STEC by comparing this approach to phenotypic serotyping and PCR for subtyping the stx-encoding genes. Of the 102 isolates where phenotypic and genotypic serotyping could be compared, 98 gave fully concordant results. The most common non-O157 STEC serogroups detected were O146 (22) and O26 (18). All but one of the 38 isolates that could not be phenotypically serotyped (designated O unidentifiable or O rough) were serotyped using the WGS data. Of the 73 isolates where a flagella type was available by traditional phenotypic typing, all results matched the H-type derived from the WGS data. Of the 140 sequenced non-O157 isolates, 52 (37.1%) harboured stx1 only, 42 (30.0%) had stx2 only, 46 (32.9%) carried stx1 and stx2. Of these, stx subtyping PCR results were available for 131 isolates and 121 of these had concordant results with the stx subtype derived from the WGS data. Non-specific primer binding during PCR amplification, due to the similarity of the stx2 subtype gene sequences was the most likely cause. The results of this study showed WGS provided a reliable and robust one-step process for characterisation of STEC. Deriving the full serotype from WGS data in real time has enabled us to report a higher level of strain discrimination while stx subtyping provides data on the pathogenic potential of each isolate, enabling us to predict clinical outcome of each case and to monitor the emergence of hyper-virulent strains

Age Differences in LGBT Attitudes Toward Marriage Equality

The purpose of this study was to compare attitudes of older versus younger lesbian, gay, bisexual, and transgender (LGBT) individuals regarding marriage equality. Data were collected via self-report questionnaires from 350 LGBT adults in a mid-size city in the southern United States. Older and younger LGBT cohorts did not differ significantly in voter registration, political party affiliation, awareness of LGBT political issues, or voting on social issues. Older LGBT adults were less likely to find same-sex marriage important. Yet, age cohorts did not differ significantly on legalizing same-sex marriage. Social work implications are discussed regarding this policy area

Cerebellar tDCS: A Novel Approach to Augment Language Treatment Post-stroke

People with post-stroke aphasia may have some degree of chronic deficit for which current rehabilitative treatments are variably effective. Accumulating evidence suggests that transcranial direct current stimulation (tDCS) may be useful for enhancing the effects of behavioral aphasia treatment. However, it remains unclear which brain regions should be stimulated to optimize effects on language recovery. Here, we report on the therapeutic potential of right cerebellar tDCS in augmenting language recovery in SMY, who sustained bilateral MCA infarct resulting in aphasia and anarthria. We investigated the effects of 15 sessions of anodal cerebellar tDCS coupled with spelling therapy using a randomized, double-blind, sham controlled within-subject crossover trial. We also investigated changes in functional connectivity using resting state functional magnetic resonance imaging before and 2 months post-treatment. Both anodal and sham treatments resulted in improved spelling to dictation for trained and untrained words immediately after and 2 months post-treatment. However, there was greater improvement with tDCS than with sham, especially for untrained words. Further, generalization to written picture naming was only noted during tDCS but not with sham. The resting state functional connectivity data indicate that improvement in spelling was accompanied by an increase in cerebro-cerebellar network connectivity. These results highlight the therapeutic potential of right cerebellar tDCS to augment spelling therapy in an individual with large bilateral chronic strokes