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Effective treatment of maternal antenatal depression may ameliorate adverse neurodevelopmental outcomes in offspring. We performed two follow-up rounds of children at age 2 and age 5 whose mothers had received either specialized cognitive-behavioural therapy or routine care for depression while pregnant. Of the original cohort of 54 women, renewed consent was given by 28 women for 2-year follow-up and by 24 women for 5-year follow-up. Child assessments at the 2-year follow-up included the Parenting Stress Index (PSI), Bayley Scales of Infant Development (BSID-III) and the Child Behaviour Checklist (CBCL). The 5-year follow-up included the Wechsler Preschool and Primary Scales of Intelligence (WPPSI-III) and again the CBCL. Treatment during pregnancy showed significant benefits for children’s development at age 2, but not at age 5. At 2 years, intervention effects were found with lower scores on the PSI Total score, Parent Domain and Child domain (d=1.44, 1.47, 0.96 respectively). A non-significant trend favoured the intervention group on most subscales of the CBCL and the BSID-III (most notably motor development: d =0.52). In contrast, at 5-year follow-up, no intervention effects were found. Also, irrespective of treatment allocation, higher depression or anxiety during pregnancy was associated with higher CBCL and lower WPPSI-III scores at 5 years. This is one of the first controlled studies to evaluate the long-term effect of antenatal depression treatment on infant neurodevelopmental outcomes, showing some benefit. Nevertheless, caution should be taken interpreting the results because of a small sample size, and larger studies are warranted.
We use ceramic and obsidian data from the ancient Maya port site of Vista Alegre to discuss long-distance exchange during the Terminal Classic (c. AD 850–1100) period. This is a time often associated with increased international trade relations and the growth of Chichen Itza as a dominant regional power in the northern Maya lowlands. Critical to the increased volume of international trade were the merchants who transported goods along the coast of Yucatan in large trading canoes. By combining a macroscopic assessment of the ceramics with visual, XRF, and INAA analyses of the obsidian artifacts, we gain insight into the various socioeconomic forces at work moving goods around the Peninsula. Given the paucity of Terminal Classic settlement in the interior Yalahau region, Vista Alegre appears to be an isolated site during this period, approximately 40 km from the nearest coastal neighbor. This allows us to focus on coastal exchange as the sole means by which goods arrived at the site. Our preliminary data contribute to the growing literature on the role market economies played in the Maya area, and the increased opportunities this afforded coastal peoples as circum-peninsular trade became more common through time.
On 27 April 2015, Washington health authorities identified Escherichia coli O157:H7 infections associated with dairy education school field trips held in a barn 20–24 April. Investigation objectives were to determine the magnitude of the outbreak, identify the source of infection, prevent secondary illness transmission and develop recommendations to prevent future outbreaks. Case-finding, hypothesis generating interviews, environmental site visits and a case–control study were conducted. Parents and children were interviewed regarding event activities. Odds ratios (OR) and 95% confidence intervals (CI) were computed. Environmental testing was conducted in the barn; isolates were compared to patient isolates using pulsed-field gel electrophoresis (PFGE). Sixty people were ill, 11 (18%) were hospitalised and six (10%) developed haemolytic uremic syndrome. Ill people ranged in age from <1 year to 47 years (median: 7), and 20 (33%) were female. Twenty-seven case-patients and 88 controls were enrolled in the case–control study. Among first-grade students, handwashing (i.e. soap and water, or hand sanitiser) before lunch was protective (adjusted OR 0.13; 95% CI 0.02–0.88, P = 0.04). Barn samples yielded E. coli O157:H7 with PFGE patterns indistinguishable from patient isolates. This investigation provided epidemiological, laboratory and environmental evidence for a large outbreak of E. coli O157:H7 infections from exposure to a contaminated barn. The investigation highlights the often overlooked risk of infection through exposure to animal environments as well as the importance of handwashing for disease prevention. Increased education and encouragement of infection prevention measures, such as handwashing, can prevent illness.
Advances in DNA sequencing, based on fluorescent microscopy, have transformed many areas of biological research. However, only relatively short molecules can be sequenced by these technologies. Dramatic improvements in genomic research will require accurate sequencing of long (>10,000 base-pairs), intact DNA molecules. Our approach directly visualizes the sequence of DNA molecules using electron microscopy. This report represents the first identification of DNA base pairs within intact DNA molecules by electron microscopy. By enzymatically incorporating modified bases, which contain atoms of increased atomic number, direct visualization and identification of individually labeled bases within a synthetic 3,272 base-pair DNA molecule and a 7,249 base-pair viral genome have been accomplished. This proof of principle is made possible by the use of a dUTP nucleotide, substituted with a single mercury atom attached to the nitrogenous base. One of these contrast-enhanced, heavy-atom-labeled bases is paired with each adenosine base in the template molecule and then built into a double-stranded DNA molecule by a template-directed DNA polymerase enzyme. This modification is small enough to allow very long molecules with labels at each A-U position. Image contrast is further enhanced by using annular dark-field scanning transmission electron microscopy (ADF-STEM). Further refinements to identify additional base types and more precisely determine the location of identified bases would allow full sequencing of long, intact DNA molecules, significantly improving the pace of complex genomic discoveries.
A thermally-activated micelle consisting of a crystallizable poly(caprolactone), PCL, core and a poly(ethylene glycol), PEG, corona was developed to contain magnetic nanoparticles and anti-cancer agent doxorubicin as well as display a targeting RGD peptide. This system has the potential to target cancer cells, deliver combination hyperthermia and chemotherapy, and offer magnetic resonance imaging contrast. The micelles self-assemble in aqueous solutions and form a crystalline core with a melting transition ranging from 40 to 50 °C, depending on the length of the PCL blocks, with dynamic light scattering showing micelle sizes typically ranging from 20 to 100 nm, depending on block lengths and added drug or nanoparticles. The micelles become unstable as they are heated above their melting point, creating a thermally-activated drug release mechanism. By adding magnetite (Fe3O4) nanoparticles into the PCL core, the micelles can be heated using an externally applied AC magnetic field to induce hyperthermia in combination with the thermally-activated drug release. The polymers and magnetic nanoparticles (MNPs) were synthesized and characterized in our laboratories. The melting transitions of the PCL micelle cores were investigated using microcalorimetry. The heating of nanoparticles and magnetomicelles was conducted using a custom-built hyperthermia coil capable of generating fields of several hundred Oersteds at frequencies ranging from 50 to 450 kHz. Heating of MNPs was maximized at high field intensities. RGD peptides were attached to the PEG corona using maleimide chemistry, and the ability of the RGD-derivatized micelles to target integrin-expressing cells was investigated using fluorescent dye PKH26 to identify the localization of micelles in cultured human kidney (293) cells in vitro. The crystallizable (and meltable) cores in these micelles were designed to overcome drug leakage common in liposome systems and release the drug on demand after a period of time for localization to integrin receptors.
The seventh annual Teaching and Learning Conference (TLC) was held in Philadelphia, Pennsylvania, from February 5 to 7, 2010, with 224 attendees onsite. The theme for the meeting was “Advancing Excellence in Teaching Political Science.” Using the working-group model, the TLC track format encourages in-depth discussion and debate on research dealing with the scholarship of teaching and learning.
The restriction of phage λ.C by K(P1) cells is reduced when the cells are subjected to an EDTA cold-wash treatment which has been shown to remove surface-localized enzymes. We conclude that a surface-localized enzyme plays an essential role in host-controlled restriction.
Strains with altered properties of host-induced modification (HIM) have been isolated. Someof these variants were stable on first isolation but the majority of them are unstable. They segregate during many generations two different stable HIM phenotypes and a third type which continues to segregate. Usually this instability disappears during repeated serial single colonyisolation, but in one case it still persisted after nine such single colony isolation steps. Evidence suggesting that they are unstable partial diploids is discussed.
In zygotes from matings between Hfr, F′ or F+ donors of E. coli K and F− recipients of E. coli B the restriction of λ. K and λ.C is 100 times less than in unmated B cells. This decrease in the capacity of zygotes to restrict phage λ is transient and is not related to the transfer of genes controlling host-induced modification during the cross.
Escherichia coli strain W was found to be lysogenic for a temperate phage Wφ. This phage, which plates on E. coli C, forms λ-like plaques 2–3 mm. diameter with turbid centres. It is serologically unrelated to λ but is closely related to P2 which it resembles in the electron microscope. Its buoyant density in CsCl has been measured and it is different from λ but similar to P2. E. coli C made lysogenic for Wφ restricts the growth of λ, and elsewhere (Kerszman, Glover & Aronovitch, 1967) it has been shown that the DNA of phage λ is degraded shortly after infection of bacteria lysogenic for Wφ. A mutant of Wφ has been isolated which has lost the property of restricting the growth of λ.
Growth of K(P1) bacteria under conditions which lead to a reduction in the level of nucleases also leads to a reduction of their ability to restrict the growth of λ.C. Experiments designed to estimate the time after adsorption at which restriction takes place indicate that phage DNA is probably restricted by a nuclease while passing through the periplasm.
The major type I insert sequence for the 28S rRNA genes of Drosophila melanogaster has been mapped within the chromosomes using a probe synthesized from a cloned sequence containing the entire 5·4 kb segment. The genomic distribution was shown to be complex in that the insert sequence occurred next to many different types of sequences, in addition to occurring as an insert in the 28S rRNA genes of the X chromosome. In situ hybridization of mitotic chromosomes showed most of the insert units not contained in the ribosomal genes to be located near the ribosomal gene cluster on the X chromosome. Additional sites were detected in polytene chromosomes in region 102C, 8–12 and in the hetero-chromatin of the autosomes.
Sixty-two mutants of E. coli K-12 resistant to 40 μg./ml. valine were isolated from a sensitive strain. Transduction experiments using phage P1 showed that one group of these mutants, val-r-C, is closely linked to leu, another group, val-r-B is closely linked to thr, and a third mutant, val-r-D57, lies between leu and thr. Conjugation experiments showed that the remainder of the mutants could be divided into three groups, val-r-A, val-r-E and val-r-F on the basis of their different times of transfer from Vhf donors to val-s F− recipients. All the mutants are sensitive to 10,000 μg./ml. valine; val-r-B and val-r-D mutants are resistant up to 80 μg./ml. valine; val-r-C mutants are resistant up to 1000 μg./ml. valine, and val-r-A, val-r-E and val-r-F mutants up to 5000 μg./ml. The functional significance of the genetic locations of these groups is discussed.
Evidence from a functional analysis of host-specificity mutants in merodiploids is presented which supports the suggestion that three genes, hss, hsr and hsm, are necessary for the expression of host-controlled restriction and modification. The host-specificity phenotype expressed by the merodiploids provides evidence that at least two genes, hss and hsr, are concerned in the expression of host-specific restriction of DNA and one of these genes, hss, is responsible for the strain specificity of the restriction enzyme. A class of modification-deficient mutants isolated from restriction-deficient, modification-proficient mutants, was also tested for complementation in merodiploids and the phenotype of these merodiploids provides evidence that at least two genes, hss and hsm, are concerned in the expression of host-specific modification of DNA and one of these genes, hss, is responsible for the strain specificity of the modification enzyme. How these three genes function at the molecular level is discussed in terms of models based on the interaction of subunits to form oligomeric enzymes.
Escherichia coli strain W adsorbs phage λ very efficiently but the phage does not form plaques on this strain because the DNA of λ is broken down in a majority of the infected cells shortly after adsorption. In a 10−3 to 10−4 fraction of the infected cells λ grows and small bursts of phage are produced. This phage does not carry the W-specific host modification and is unable to complete a second round of infection in W (Kerszman, Glover & Aronovitch, 1967). λω mutants have been isolated which are able to escape this restriction process and which plate on W with an efficiency of 1·0 and when grown in W these mutants carry a W-specific host modification.
The sites of mutations affecting host-controlled modification (HCM) have been mapped in E. coli K and E. coli B by conjugation and transduction experiments between mutants. These mutations all map close to the serB locus on the opposite side to the marker thr. Non-parental HCM has been observed among colonies obtained from Pl transduction experiments between HCM mutants. Control experiments have shown that these non-parental recombinants can not be accounted for by reversion of either parent and must result from recombination between mutants. Several genetic models are suggested which could account for these recombinants and an attempt is made to distinguish between various models by testing for complementation between mutants in a zygotic induction complementation test.