The organelle of differentiation in embryos: the cell state splitter

The cell state splitter is a membraneless organelle at the apical end of each epithelial cell in a developing embryo. It consists of a microfilament ring and an intermediate filament ring subtending a microtubule mat. The microtubules and microfilament ring are in mechanical opposition as in a tensegrity structure. The cell state splitter is bistable, perturbations causing it to contract or expand radially. The intermediate filament ring provides metastability against small perturbations. Once this snap-through organelle is triggered, it initiates signal transduction to the nucleus, which changes gene expression in one of two readied manners, causing its cell to undergo a step of determination and subsequent differentiation. The cell state splitter also triggers the cell state splitters of adjacent cells to respond, resulting in a differentiation wave. Embryogenesis may be represented then as a bifurcating differentiation tree, each edge representing one cell type. In combination with the differentiation waves they propagate, cell state splitters explain the spatiotemporal course of differentiation in the developing embryo. This review is excerpted from and elaborates on “Embryogenesis Explained” (World Scientific Publishing, Singapore, 2016).     

A prospective observational cohort study in primary care practices to identify factors associated with treatment failure in <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> skin and soft tissue infections

Background

The incidence of outpatient visits for skin and soft tissue infections (SSTIs) has substantially increased over the last decade. The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has made the management of S. aureus SSTIs complex and challenging. The objective of this study was to identify risk factors contributing to treatment failures associated with community-associated S. aureus skin and soft tissue infections SSTIs.

Methods

This was a prospective, observational study among 14 primary care clinics within the South Texas Ambulatory Research Network. The primary outcome was treatment failure within 90 days of the initial visit. Univariate associations between the explanatory variables and treatment failure were examined. A generalized linear mixed-effect model was developed to identify independent risk factors associated with treatment failure.

Results

Overall, 21% (22/106) patients with S. aureus SSTIs experienced treatment failure. The occurrence of treatment failure was similar among patients with methicillin-resistant S. aureus and those with methicillin-susceptible S. aureus SSTIs (19 vs. 24%; p = 0.70). Independent predictors of treatment failure among cases with S. aureus SSTIs was a duration of infection of ≥7 days prior to initial visit [aOR, 6.02 (95% CI 1.74–19.61)] and a lesion diameter size ≥5 cm [5.25 (1.58–17.20)].

Conclusions

Predictors for treatment failure included a duration of infection for ≥7 days prior to the initial visit and a wound diameter of ≥5 cm. A heightened awareness of these risk factors could help direct targeted interventions in high-risk populations.

     

Lizards possess the most complete tetrapod Hox gene repertoire despite pervasive structural changes in Hox clusters

Hox genes are a remarkable example of conservation in animal development and their nested expression along the head‐to‐tail axis orchestrates embryonic patterning. Early in vertebrate history, two duplications led to the emergence of four Hox clusters (A‐D) and redundancy within paralog groups has been partially accommodated with gene losses. Here we conduct an inventory of squamate Hox genes using the genomes of 10 lizard and 7 snake species. Although the HoxC1 gene has been hypothesized to be lost in the amniote ancestor, we reveal that it is retained in lizards. In contrast, all snakes lack functional HoxC1 and ‐D12 genes. Varying levels of degradation suggest differences in the process of gene loss between the two genes. The vertebrate HoxC1 gene is prone to gene loss and its functional domains are more variable than those of other Hox1 genes. We describe for the first time the HoxC1 expression patterns in tetrapods. HoxC1 is broadly expressed during development in the diencephalon, the neural tube, dorsal root ganglia, and limb buds in two lizard species. Our study emphasizes the value of revisiting Hox gene repertoires by densely sampling taxonomic groups and its feasibility owing to growing sequence resources in evaluating gene repertoires across taxa.     

Polarization of Myosin II Refines Tissue Material Properties to Buffer Mechanical Stress

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Prdm9 and Meiotic Cohesin Proteins Cooperatively Promote DNA Double-Strand Break Formation in Mammalian Spermatocytes

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Identification of flavonoids as regulators of YbeY activity in Liberibacter asiaticus

Liberibacter asiaticus is the prevalent causative pathogen of Huanglongbing or citrus greening disease, which has resulted in a devastating crisis in the citrus industry. A thorough understanding of this pathogen's physiology and mechanisms to control cell survival is critical in the identification of therapeutic targets. YbeY is a highly conserved bacterial RNase that has been implicated in multiple roles. In this study, we evaluated the biochemical characteristics of the L. asiaticus YbeY (CLIBASIA_01560) and assessed its potential as a target for antimicrobials. YbeY_Las was characterized as an endoribonuclease with activity on 3′ and 5′ termini of 16S and 23S rRNAs, and the capacity to suppress the E. coli ΔybeY phenotype. We predicted the YbeY_Las protein:ligand interface and subsequently identified a flavone compound, luteolin, as a selective inhibitor. Site-directed mutagenesis was subsequently used to identify key residues involved in the catalytic activity of YbeY_Las. Further evaluation of naturally occurring flavonoids in citrus trees indicated that both flavones and flavonols had potent inhibitory effects on YbeY_Las. Luteolin was subsequently examined for efficacy against L. asiaticus in Huanglongbing-infected citrus trees, where a significant reduction in L. asiaticus gene expression was observed.     

Blockade of TrkB but not p75NTR activates a subpopulation of quiescent neural precursor cells and enhances neurogenesis in the adult mouse hippocampus

Brain‐derived neurotrophic factor (BDNF) signaling plays a major role in the regulation of hippocampal neurogenesis in the adult brain. While the majority of studies suggest that this is due to its effect on the survival and differentiation of newborn neurons, it remains unclear whether this signaling directly regulates neural precursor cell (NPC) activity and which of its two receptors, TrkB or the p75 neurotrophin receptor (p75^NTR) mediates this effect. Here, we examined both the RNA and protein expression of these receptors and found that TrkB but not p75^NTR receptors are expressed by hippocampal NPCs in the adult mouse brain. Using a clonal neurosphere assay, we demonstrate that pharmacological blockade of TrkB receptors directly activates a distinct subpopulation of NPCs. Moreover, we show that administration of ANA‐12, a TrkB‐selective antagonist, in vivo either by systemic intraperitoneal injection or by direct infusion within the hippocampus leads to an increase in the production of new neurons. In contrast, we found that NPC‐specific knockout of p75^NTR had no effect on the proliferation of NPCs and did not alter neurogenesis in the adult hippocampus. Collectively, these results demonstrate a novel role of TrkB receptors in directly regulating the activity of a subset of hippocampal NPCs and suggest that the transient blockade of these receptors could be used to enhance adult hippocampal neurogenesis.