Vsx2 in the zebrafish retina: restricted lineages through derepression

<p>Abstract</p> <p>Background</p> <p>The neurons in the vertebrate retina arise from multipotent retinal progenitor cells (RPCs). It is not clear, however, which progenitors are multipotent or why they are multipotent.</p> <p>Results</p> <p>In this study we show that the homeodomain transcription factor Vsx2 is initially expressed throughout the retinal epithelium, but later it is downregulated in all but a minor population of bipolar cells and all Müller glia. The Vsx2-negative daughters of Vsx2-positive RPCs divide and give rise to all other cell types in the retina. Vsx2 is a repressor whose targets include transcription factors such as Vsx1, which is expressed in the progenitors of distinct non-Vsx2 bipolars, and the basic helix-loop-helix transcription factor Ath5, which restricts the fate of progenitors to retinal ganglion cells, horizontal cells, amacrine cells and photoreceptors fates. Foxn4, expressed in the progenitors of amacrine and horizontal cells, is also negatively regulated by Vsx2.</p> <p>Conclusion</p> <p>Our data thus suggest Vsx2-positive RPCs are fully multipotent retinal progenitors and that when Vsx2 is downregulated, Vsx2-negative progenitors escape Vsx2 repression and so are able to express factors that restrict lineage potential.</p

Seasonal sub-basin-scale runoff predictions: A regional hydrometeorological Ensemble Kalman Filter framework using global datasets

Study region The São Francisco River Basin (SFRB) in Brazil Study focus In semi-arid regions, interannual variability of seasonal rainfall and climate change is expected to stress water availability and increase the recurrence and intensity of extreme events such as droughts or floods. Local decision makers therefore need reliable long-term hydro-meteorological forecasts to support the seasonal management of water resources, reservoir operations and agriculture. In this context, an Ensemble Kalman Filter framework is applied to predict sub-basin-scale runoff employing global freely available datasets of reanalysis precipitation (ERA5-Land) as well as bias-corrected and spatially disaggregated seasonal forecasts (SEAS5-BCSD). Runoff is estimated using least squares predictions, exploiting the covariance structures between runoff and precipitation. The performance of the assimilation framework was assessed using different ensemble skill scores. New hydrological insights for the region Our results show that the quality of runoff predictions are closely linked to the performance of the rainfall seasonal predictions and allows skillful predictions up to two months ahead in most sub-basins. The anthropogenic conditions such as in the Western Bahia state, however, must be taken under consideration, since non-stationary runoff time-series have poorer skill as such unnatural variations can not be captured by long-term covariances. In sub-basins which are dominated by little anthropogenic influence, the presented framework provides a promising and easily transferable approach for skillful operational seasonal runoff predictions on sub-basin scale

The relationship between blood–brain barrier dysfunction and neurocognitive impairments in first-episode psychosis: findings from a retrospective chart analysis

Background Even before the onset of psychotic symptoms, individuals with schizophrenia display cognitive impairments. Simultaneously, increasing amounts of individuals exhibit dysfunction of the blood–brain barrier (BBB). However, the impact of BBB dysfunction on neurocognitive impairment in people with first-episode psychosis has not yet been investigated. Aims To advance understanding of said relationship, we considered one of the largest first-episode psychosis cohorts with cerebrospinal fluid parameters available, and investigated whether BBB dysfunction is related to working memory, working speed and attention. Method We conducted a retrospective chart review of 121 in-patients diagnosed with a first episode of a schizophrenia spectrum disorder. Patients underwent neurocognitive testing and a lumbar puncture within routine clinical care. To define BBB dysfunction, albumin cerebrospinal fluid/serum quotients, immunoglobulin G ratios and oligoclonal band types were evaluated, and gender-specific differences investigated. Neurocognitive functioning was assessed by the Wechsler Adult Intelligence Scale, Test of Attentional Performance and Repeatable Battery for the Assessment of Neuropsychological Status. We performed simple and multiple linear regression analyses to interpret associations of interest. Results Of those tested, 16% showed an alteration in albumin quotients and 12% had an oligoclonal band type indicating BBB dysfunction. Notably, male patients were more likely to have an increased albumin quotient and a higher immunoglobulin G ratio than female patients. We found no significant association between BBB dysfunction and neurocognitive assessments. Conclusions The hypothesised relationship between BBB and neurocognitive impairments was not detectable in our retrospective cohort. Further cerebrospinal fluid-based studies with a longitudinal assessment of cognitive functioning and disease trajectory are urgently needed

The Λp\bf{\Lambda p} interaction studied via femtoscopy in p + Nb reactions at sNN=3.18 GeV\mathbf{\sqrt{s_{NN}}=3.18} ~\mathrm{\bf{GeV}}

We report on the first measurement of $p\Lambda$ and $pp$ correlations via the femtoscopy method in p+Nb reactions at $\mathrm{\sqrt{s_{NN}}=3.18} ~\mathrm{GeV}$, studied with the High Acceptance Di-Electron Spectrometer (HADES). By comparing the experimental correlation function to model calculations, a source size for $pp$ pairs of $r_{0,pp}=2.02 \pm 0.01(\mathrm{stat})^{+0.11}_{-0.12} (\mathrm{sys}) ~\mathrm{fm}$ and a slightly smaller value for $p\Lambda$ of $r_{0,\Lambda p}=1.62 \pm 0.02(\mathrm{stat})^{+0.19}_{-0.08}(\mathrm{sys}) ~\mathrm{fm}$ is extracted. Using the geometrical extent of the particle emitting region, determined experimentally with $pp$ correlations as reference together with a source function from a transport model, it is possible to study different sets of scattering parameters. The $p\Lambda$ correlation is proven sensitive to predicted scattering length values from chiral effective field theory. We demonstrate that the femtoscopy technique can be used as valid alternative to the analysis of scattering data to study the hyperon-nucleon interaction.Comment: 12 pages, 11 figure

Sources of Community Health Worker Motivation: A Qualitative Study in Morogoro Region, Tanzania.

There is a renewed interest in community health workers (CHWs) in Tanzania, but also a concern that low motivation of CHWs may decrease the benefits of investments in CHW programs. This study aimed to explore sources of CHW motivation to inform programs in Tanzania and similar contexts. We conducted semi-structured interviews with 20 CHWs in Morogoro Region, Tanzania. Interviews were digitally recorded, transcribed, and coded prior to translation and thematic analysis. The authors then conducted a literature review on CHW motivation and a framework that aligned with our findings was modified to guide the presentation of results. Sources of CHW motivation were identified at the individual, family, community, and organizational levels. At the individual level, CHWs are predisposed to volunteer work and apply knowledge gained to their own problems and those of their families and communities. Families and communities supplement other sources of motivation by providing moral, financial, and material support, including service fees, supplies, money for transportation, and help with farm work and CHW tasks. Resistance to CHW work exhibited by families and community members is limited. The organizational level (the government and its development partners) provides motivation in the form of stipends, potential employment, materials, training, and supervision, but inadequate remuneration and supplies discourage CHWs. Supervision can also be dis-incentivizing if perceived as a sign of poor performance. Tanzanian CHWs who work despite not receiving a salary have an intrinsic desire to volunteer, and their motivation often derives from support received from their families when other sources of motivation are insufficient. Policy-makers and program managers should consider the burden that a lack of remuneration imposes on the families of CHWs. In addition, CHWs' intrinsic desire to volunteer does not preclude a desire for external rewards. Rather, adequate and formal financial incentives and in-kind alternatives would allow already-motivated CHWs to increase their commitment to their work

Species Richness, rRNA Gene Abundance, and Seasonal Dynamics of Airborne Plant-Pathogenic Oomycetes

Oomycetes, also named Peronosporomycetes, are one of the most important and widespread groups of plant pathogens, leading to significant losses in the global agricultural productivity. They have been studied extensively in ground water, soil, and host plants, but their atmospheric transport vector is not well characterized. In this study, the occurrence of airborne Oomycetes was investigated by Sanger sequencing and quantitative PCR of coarse and fine aerosol particle samples (57 filter pairs) collected over a 1-year period (2006–2007) and full seasonal cycle in Mainz, Germany. In coarse particulate matter, we found 55 different hypothetical species (OTUs), of which 54 were plant pathogens and 29 belonged to the genus Peronospora (downy mildews). In fine particulate matter (&lt;3 μm), only one species of Hyaloperonospora was found in one sample. Principal coordinate analysis of the species composition revealed three community clusters with a dependence on ambient temperature. The abundance of Oomycetes rRNA genes was low in winter and enhanced during spring, summer, and fall, with a dominance of Phytophthora, reaching a maximum concentration of ∼1.6 × 106 rRNA genes per cubic meter of sampled air in summer. The presence and high concentration of rRNA genes in air suggests that atmospheric transport, which can lead to secondary infection, may be more important than currently estimated. This illustrates the need for more current and detailed datasets, as potential seasonal shifts due to changing meteorological conditions may influence the composition of airborne Oomycetes. An insight into the dynamics of airborne plant pathogens and their major drivers should be useful for improved forecasting and management of related plant diseases

Ectopic Expression of Neurogenin 2 Alone is Sufficient to Induce Differentiation of Embryonic Stem Cells into Mature Neurons

Recent studies show that combinations of defined key developmental transcription factors (TFs) can reprogram somatic cells to pluripotency or induce cell conversion of one somatic cell type to another. However, it is not clear if single genes can define a cell̀s identity and if the cell fate defining potential of TFs is also operative in pluripotent stem cells in vitro. Here, we show that ectopic expression of the neural TF Neurogenin2 (Ngn2) is sufficient to induce rapid and efficient differentiation of embryonic stem cells (ESCs) into mature glutamatergic neurons. Ngn2-induced neuronal differentiation did not require any additional external or internal factors and occurred even under pluripotency-promoting conditions. Differentiated cells displayed neuron-specific morphology, protein expression, and functional features, most importantly the generation of action potentials and contacts with hippocampal neurons. Gene expression analyses revealed that Ngn2-induced in vitro differentiation partially resembled neurogenesis in vivo, as it included specific activation of Ngn2 target genes and interaction partners. These findings demonstrate that a single gene is sufficient to determine cell fate decisions of uncommitted stem cells thus giving insights into the role of key developmental genes during lineage commitment. Furthermore, we present a promising tool to improve directed differentiation strategies for applications in both stem cell research and regenerative medicine