Characterization of Cre recombinase activity for in vivo targeting of adipocyte precursor cells.

The increased incidence of obesity and metabolic disease underscores the importance of elucidating the biology of adipose tissue development. The recent discovery of cell surface markers for prospective identification of adipose precursor cells (APCs) in vivo will greatly facilitate these studies, yet tools for specifically targeting these cells in vivo have not been identified. Here, we survey three transgenic mouse lines, Fabp4-Cre, PdgfRα-Cre, and Prx1-Cre, precisely assessing Cre-mediated recombination in adipose stromal populations and mature tissues. Our data provide key insights into the utility of these tools to modulate gene expression in adipose tissues. In particular, Fabp4-Cre is not effective to target APCs, nor is its activity restricted to these cells. PdgfRα-Cre directs recombination in the vast majority of APCs, but also targets other populations. In contrast, adipose expression of Prx1-Cre is chiefly limited to subcutaneous inguinal APCs, which will be valuable for dissection of APC functions among adipose depots

Macrophage-released ADAMTS1 promotes muscle stem cell activation.

Coordinated activation of muscle stem cells (known as satellite cells) is critical for postnatal muscle growth and regeneration. The muscle stem cell niche is central for regulating the activation state of satellite cells, but the specific extracellular signals that coordinate this regulation are poorly understood. Here we show that macrophages at sites of muscle injury induce activation of satellite cells via expression of Adamts1. Overexpression of Adamts1 in macrophages in vivo is sufficient to increase satellite cell activation and improve muscle regeneration in young mice. We demonstrate that NOTCH1 is a target of ADAMTS1 metalloproteinase activity, which reduces Notch signaling, leading to increased satellite cell activation. These results identify Adamts1 as a potent extracellular regulator of satellite cell activation and have significant implications for understanding the regulation of satellite cell activity and regeneration after muscle injury.Satellite cells are crucial for growth and regeneration of skeletal muscle. Here the authors show that in response to muscle injury, macrophages secrete Adamts1, which induces satellite cell activation by modulating Notch1 signaling

Ocean model-based covariates improve a marine fish stock assessment when observations are limited

The productivity of many fish populations is influenced by the environment, but developing environment-linked stock assessments remain challenging and current management of most commercial species assumes that stock productivity is time-invariant. In the Northeast United States, previous studies suggest that the recruitment of Southern New England-Mid Atlantic yellowtail flounder is closely related to the strength of the Cold Pool, a seasonally formed cold water mass on the continental shelf. Here, we developed three new indices that enhance the characterization of Cold Pool interannual variations using bottom temperature from a regional hindcast ocean model and a global ocean data assimilated hindcast. We associated these new indices to yellowtail flounder recruitment in a state–space, age-structured stock assessment framework using the Woods Hole Assessment Model. We demonstrate that incorporating Cold Pool effects on yellowtail flounder recruitment reduces the retrospective patterns and may improve the predictive skill of recruitment and, to a lesser extent, spawning stock biomass. We also show that the performance of the assessment models that incorporated ocean model-based indices is improved compared to the model using only the observation-based index. Instead of relying on limited subsurface observations, using validated ocean model products as environmental covariates in stock assessments may both improve predictions and facilitate operationalization.publishedVersio

On pp-filtrations of Weyl modules

This paper considers Weyl modules for a simple, simply connected algebraic group over an algebraically closed field $k$ of positive characteristic $p\not=2$. The main result proves, if $p\geq 2h-2$ (where $h$ is the Coxeter number) and if the Lusztig character formula holds for all (irreducible modules with) regular restricted highest weights, then any Weyl module $\Delta(\lambda)$ has a $\Delta^p$-filtration, namely, a filtration with sections of the form $\Delta^p(\mu_0+p\mu_1):=L(\mu_0)\otimes\Delta(\mu_1)^{[1]}$, where $\mu_0$ is restricted and $\mu_1$ is arbitrary dominant. In case the highest weight $\lambda$ of the Weyl module $\Delta(\lambda)$ is $p$-regular, the $p$-filtration is compatible with the $G_1$-radical series of the module. The problem of showing that Weyl modules have $\Delta^p$-filtrations was first proposed as a worthwhile ("w\"unschenswert") problem in Jantzen's 1980 Crelle paper.Comment: Latest version corrects minor mistakes in previous versions. A reference is made to Williamson's recent arXiv posting, providing some relevant discussion in a footnote. [Comments on earlier versions: Previous v. 1 with minor errors and statements corrected. Improved organization. Should replace v. 2 which is an older version (even older than v.1) and was mistakenly posted.

A mouse model displays host and bacterial strain differences in Aerococcus urinae urinary tract infection

In recent years, the clinical significance of Aerococcus urinae has been increasingly recognized. A. urinae has been implicated in cases of urinary tract infection (UTI; acute cystitis and pyelonephritis) in both male and female patients, ranging from children to older adults. Aerococcus urinae can also be invasive, causing urosepsis, endocarditis, and musculoskeletal infections. Mechanisms of pathogenesis in A. urinae infections are poorly understood, largely due to the lack of an animal model system. In response to this gap, we developed a model of A. urinae urinary tract infection in mice. We compared A. urinae UTI in female C3H/HeN and C57BL/6 mice and compared four clinical isolates of A. urinae isolated from patients with UTI, urgency urinary incontinence, and overactive bladder. Our data demonstrate that host genetic background modulates A. urinae UTI. Female C57BL/6 female mice rapidly cleared the infection. Female C3H/HeN mice, which have inherent vesicoureteral reflux that flushes urine from the bladder up into the kidneys, were susceptible to prolonged bacteriuria. This result is consistent with the fact that A. urinae infections most frequently occur in patients with underlying urinary tract abnormalities or disorders that make them susceptible to bacterial infection. Unlike uropathogens such as E. coli, which cause infection and inflammation both of the bladder and kidneys in C3H/HeN mice, A. urinae displayed tropism for the kidney, persisting in kidney tissue even after clearance of bacteria from the bladder. Aerococcus urinae strains from different genetic clades displayed varying propensities to cause persistent kidney infection. Aerococcus urinae infected kidneys displayed histological inflammation, neutrophil recruitment and increased pro-inflammatory cytokines. These results set the stage for future research that interrogates host-pathogen interactions between A. urinae and the urinary tract

STM Spectroscopy of ultra-flat graphene on hexagonal boron nitride

Graphene has demonstrated great promise for future electronics technology as well as fundamental physics applications because of its linear energy-momentum dispersion relations which cross at the Dirac point. However, accessing the physics of the low density region at the Dirac point has been difficult because of the presence of disorder which leaves the graphene with local microscopic electron and hole puddles, resulting in a finite density of carriers even at the charge neutrality point. Efforts have been made to reduce the disorder by suspending graphene, leading to fabrication challenges and delicate devices which make local spectroscopic measurements difficult. Recently, it has been shown that placing graphene on hexagonal boron nitride (hBN) yields improved device performance. In this letter, we use scanning tunneling microscopy to show that graphene conforms to hBN, as evidenced by the presence of Moire patterns in the topographic images. However, contrary to recent predictions, this conformation does not lead to a sizable band gap due to the misalignment of the lattices. Moreover, local spectroscopy measurements demonstrate that the electron-hole charge fluctuations are reduced by two orders of magnitude as compared to those on silicon oxide. This leads to charge fluctuations which are as small as in suspended graphene, opening up Dirac point physics to more diverse experiments than are possible on freestanding devices.Comment: Nature Materials advance online publication 13/02/201