Dppa3 / Pgc7 / stella is a maternal factor and is not required for germ cell specification in mice

BACKGROUND: In mice, germ cells are specified through signalling between layers of cells comprising the primitive embryo. The function of Dppa3 (also known as Pgc7 or stella), a gene expressed in primordial germ cells at the time of their emergence in gastrulating embryos, is unknown, but a recent study has claimed that it plays a central role in germ cell specification. RESULTS: To test Dppa3's role in germ cell development, we disrupted the gene in mouse embryonic stem cells and generated mutant animals. We were able to obtain viable and fertile Dppa3-deficient animals of both sexes. Examination of embryonic and adult germ cells and gonads in Dppa3-deficient animals did not reveal any defects. However, most embryos derived from Dppa3-deficient oocytes failed to develop normally beyond the four-cell stage. CONCLUSION: We found that Dppa3 is an important maternal factor in the cleavage stages of mouse embryogenesis. However, it is not required for germ cell specification

Singlet oxygen initiates a plastid signal controlling photosynthetic gene expression.

Retrograde signals from the plastid regulate photosynthesis-associated nuclear genes and are essential to successful chloroplast biogenesis. One model is that a positive haem-related signal promotes photosynthetic gene expression in a pathway that is abolished by the herbicide norflurazon. Far-red light (FR) pretreatment and transfer to white light also results in plastid damage and loss of photosynthetic gene expression. Here, we investigated whether norflurazon and FR pretreatment affect the same retrograde signal. We used transcriptome analysis and real-time reverse transcription-polymerase chain reaction (RT-PCR) to analyse the effects of these treatments on nuclear gene expression in various Arabidopsis (Arabidopsis thaliana) retrograde signalling mutants. Results showed that the two treatments inhibited largely different nuclear gene sets, suggesting that they affected different retrograde signals. Moreover, FR pretreatment resulted in singlet oxygen (1 O2 ) production and a rapid inhibition of photosynthetic gene expression. This inhibition was partially blocked in the executer1executer2 mutant, which is impaired in 1 O2 signalling. Our data support a new model in which a 1 O2 retrograde signal, generated by chlorophyll precursors, inhibits expression of key photosynthetic and chlorophyll synthesis genes to prevent photo-oxidative damage during de-etiolation. Such a signal would provide a counterbalance to the positive haem-related signal to fine tune regulation of chloroplast biogenesis.This work was funded by BBSRC grants 51/P17214 and BB/ J018139/1 to M.J.T. and BB/J018694/1 to A.G.S

Margaret Page Hood Correspondence

Entries include letters typed by Hood and a letter from an editor on Coward-McCann, Inc., stationery, publisher advertisements clipped from newspapers, and a biographical sketch

Adaptive forecasting of phytoplankton communities

The global proliferation of harmful algal blooms poses an increasing threat to water resources, recreation and ecosystems. Predicting the occurrence of these blooms is therefore needed to assist water managers in making management decisions to mitigate their impact. Evaluation of the potential for forecasting of algal blooms using the phytoplankton community model PROTECH was undertaken in pseudo-real-time. This was achieved within a data assimilation scheme using the Ensemble Kalman Filter to allow uncertainties and model nonlinearities to be propagated to forecast outputs. Tests were made on two mesotrophic lakes in the English Lake District, which differ in depth and nutrient regime. Some forecasting success was shown for chlorophyll a, but not all forecasts were able to perform better than a persistence forecast. There was a general reduction in forecast skill with increasing forecasting period but forecasts for up to four or five days showed noticeably greater promise than those for longer periods. Associated forecasts of phytoplankton community structure were broadly consistent with observations but their translation to cyanobacteria forecasts was challenging owing to the interchangeability of simulated functional species

Wt1 functions in the development of germ cells in addition to somatic cell lineages of the testis

AbstractThe Wilms' tumor suppressor gene, Wt1, encodes a transcription factor critical for development of the urogenital system. To identify lineages within the developing urogenital system that have a cell-autonomous requirement for Wt1, chimeric mice were generated from Wt1-null ES cells. Males with large contributions of Wt1−/− cells showed hypoplastic and dysgenic testes, with seminiferous tubules lacking spermatogonia. Wt1-null cells contributed poorly to both somatic and germ cell lineages within the developing gonad, suggesting an unexpected role for Wt1 in germ cell development in addition to a role in the development of the somatic lineages of the gonad. Wt1 expression was detected in embryonic germ cells beginning at embryonic day 11.5 after migrating primordial germ cells (PGCs) have entered the gonad. Germ cells isolated from Wt1-null embryos showed impaired growth in culture, further demonstrating a role for Wt1 in germ cell proliferation or survival. Therefore, Wt1 plays important, and in some cases previously unrecognized, roles in multiple lineages during urogenital development

Toward a Consistent Description of the PNC Experiments in A=18-21 Nuclei

The experimental PNC results in $^{18}$F, $^{19}$F, $^{21}$Ne and the current theoretical analysis show a discrepancy . If one interprets the small limit of the experimentally extracted PNC matrix element for $^{21}$Ne as a destructive interference between the isoscalar and the isovector contribution, then it is difficult to understand why the isovector contribution in $^{18}$F is so small while the isoscalar + isovector contribution in $^{19}$F is relatively large. In order to understand the origin of this discrepancy a comparison of the calculated PNC matrix elements was performed. It is shown that the $^{18}$F and $^{21}$Ne matrix elements contain important contributions from 3$\hbar \omega$ and 4$\hbar \omega$ configuration and that the (0+1)$\hbar \omega$ calculations give distorted results.Comment: REVTEX, 16 pages, 1 postscriptum figure uuencoded and appende

Comparative population structure of <i>Plasmodium malariae</i> and <i>Plasmodium falciparum</i> under different transmission settings in Malawi

&lt;b&gt;Background:&lt;/b&gt; Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P. falciparum, making its study increasingly important. This study compares the population parameters of the two species in two districts of Malawi with different malaria transmission patterns - one seasonal, one perennial - to explore the effects of transmission on population structures. &lt;BR/&gt; &lt;b&gt;Methods:&lt;/b&gt; Six species-specific microsatellite markers were used to analyse 257 P. malariae samples and 257 P. falciparum samples matched for age, gender and village of residence. Allele sizes were scored to within 2 bp for each locus and haplotypes were constructed from dominant alleles in multiple infections. Analysis of multiplicity of infection (MOI), population differentiation, clustering of haplotypes and linkage disequilibrium was performed for both species. Regression analyses were used to determine association of MOI measurements with clinical malaria parameters. &lt;BR/&gt; &lt;b&gt;Results:&lt;/b&gt; Multiple-genotype infections within each species were common in both districts, accounting for 86.0% of P. falciparum and 73.2% of P. malariae infections and did not differ significantly with transmission setting. Mean MOI of P. falciparum was increased under perennial transmission compared with seasonal (3.14 vs 2.59, p = 0.008) and was greater in children compared with adults. In contrast, P. malariae mean MOI was similar between transmission settings (2.12 vs 2.11) and there was no difference between children and adults. Population differentiation showed no significant differences between villages or districts for either species. There was no evidence of geographical clustering of haplotypes. Linkage disequilibrium amongst loci was found only for P. falciparum samples from the seasonal transmission setting. &lt;BR/&gt; &lt;b&gt;Conclusions:&lt;/b&gt; The extent of similarity between P. falciparum and P. malariae population structure described by the high level of multiple infection, the lack of significant population differentiation or haplotype clustering and lack of linkage disequilibrium is surprising given the differences in the biological features of these species that suggest a reduced potential for out-crossing and transmission in P. malariae. The absence of a rise in P. malariae MOI with increased transmission or a reduction in MOI with age could be explained by differences in the duration of infection or degree of immunity compared to P. falciparum

A pleurocidin analogue with greater conformational flexibility, enhanced antimicrobial potency and in vivo therapeutic efficacy.

Antimicrobial peptides (AMPs) are a potential alternative to classical antibiotics that are yet to achieve a therapeutic breakthrough for treatment of systemic infections. The antibacterial potency of pleurocidin, an AMP from Winter Flounder, is linked to its ability to cross bacterial plasma membranes and seek intracellular targets while also causing membrane damage. Here we describe modification strategies that generate pleurocidin analogues with substantially improved, broad spectrum, antibacterial properties, which are effective in murine models of bacterial lung infection. Increasing peptide-lipid intermolecular hydrogen bonding capabilities enhances conformational flexibility, associated with membrane translocation, but also membrane damage and potency, most notably against Gram-positive bacteria. This negates their ability to metabolically adapt to the AMP threat. An analogue comprising D-amino acids was well tolerated at an intravenous dose of 15 mg/kg and similarly effective as vancomycin in reducing EMRSA-15 lung CFU. This highlights the therapeutic potential of systemically delivered, bactericidal AMPs

Phylogenetic inference under recombination using Bayesian stochastic topology selection

Motivation: Conventional phylogenetic analysis for characterizing the relatedness between taxa typically assumes that a single relationship exists between species at every site along the genome. This assumption fails to take into account recombination which is a fundamental process for generating diversity and can lead to spurious results. Recombination induces a localized phylogenetic structure which may vary along the genome. Here, we generalize a hidden Markov model (HMM) to infer changes in phylogeny along multiple sequence alignments while accounting for rate heterogeneity; the hidden states refer to the unobserved phylogenic topology underlying the relatedness at a genomic location. The dimensionality of the number of hidden states (topologies) and their structure are random (not known a priori) and are sampled using Markov chain Monte Carlo algorithms. The HMM structure allows us to analytically integrate out over all possible changepoints in topologies as well as all the unknown branch lengths