Adaptive evolution in new or changing environments can be difficult to predict because the functional connections between genotype, phenotype, and fitness are complex. Here, we make these explicit connections by combining field and laboratory experiments in wild mice. We first directly estimate natural selection on pigmentation traits and an underlying pigment locus, Agouti, by using experimental enclosures of mice on different soil colors. Next, we show how a mutation in Agouti associated with survival causes...

File containing plant functional traits data and plant composition data used for analyzing the responses of plant functional traits to soil inoculation treatments.

Additional file 2: Supplementary Table S2. Immune Gene Expression Scores. Gene expression scores for all samples used in analyses.

The somatosensory nervous system is critical for the organism’s ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1)IB4+SNS-Cre/TdTomato+, 2)IB4-SNS-Cre/TdTomato+, and 3)Parv-Cre/TdTomato+ cells, encompassing the...

Akt is a critical protein kinase that governs cancer cell growth and metabolism. Akt appears to be autoinhibited by an intramolecular interaction between its N-terminal pleckstrin homology (PH) domain and kinase domain, which is relieved by C-tail phosphorylation, but the precise molecular mechanisms remain elusive. Here we use a combination of protein semisynthesis, NMR, and enzymological analysis to characterize structural features of the PH domain in its autoinhibited and activated states. We find that Akt...

Additional file 4: Supplementary Table S8. List of the downregulated differentially expressed genes from RNA sequencing results in Tsc2-/- MEFs and Tsc2+/+ MEFs. All genes were identified with FDR-adjusted p-value<0.05 and absolute value of log2(FC)>1.

Additional file 3: Supplementary Table S7. List of the predict target genes of miR-130b-3p from prediction softwares TargetScan, RNA22, PicTar, miRDB and miRWalk.

Aim: To formulate an injectable thermosensitive micelle–hydrogel hybrid system loaded with celastrol (celastrol-loaded micelle hydrogel: CMG) to prevent posterior capsule opacification (PCO). Materials & methods: Celastrol-loaded micelles were embedded in a thermosensitive hydrogel matrix to enable controlled on-demand celastrol delivery into the residual capsule. The efficacy and mechanisms of the system for eliminating PCO were evaluated in rabbits. Results: Celastrol-loaded micelles inhibited the migration and proliferation of lens epithelial cells induced by TGF-β1. Celastrol prevents...

Aim: To formulate an injectable thermosensitive micelle–hydrogel hybrid system loaded with celastrol (celastrol-loaded micelle hydrogel: CMG) to prevent posterior capsule opacification (PCO). Materials & methods: Celastrol-loaded micelles were embedded in a thermosensitive hydrogel matrix to enable controlled on-demand celastrol delivery into the residual capsule. The efficacy and mechanisms of the system for eliminating PCO were evaluated in rabbits. Results: Celastrol-loaded micelles inhibited the migration and proliferation of lens epithelial cells induced by TGF-β1. Celastrol prevents...

Additional file 3: Supplementary Table S3. Spearman's correlation of individual signature score with immune marker immunohistochemistry (IHC).

In mammals, numerous autosomal genes are subject to mitotically stable monoallelic expression (MAE), including genes that play critical roles in a variety of human diseases. Due to challenges posed by the clonal nature of MAE, very little is known about its regulation; in particular, no molecular features have been specifically linked to MAE. Here we report an approach that distinguishes MAE genes in human cells with great accuracy: a chromatin signature consisting of chromatin marks...

Additional file 4: Supplementary Table S8. List of the downregulated differentially expressed genes from RNA sequencing results in Tsc2-/- MEFs and Tsc2+/+ MEFs. All genes were identified with FDR-adjusted p-value<0.05 and absolute value of log2(FC)>1.

Additional file 5: Supplementary Table 9. List of the downregulated differentially expressed genes from DEGs in angiofibroma(AF) of TSC patients vs. normal skin. All genes were identified with FDR-adjusted p-value < 0.05 and absolute value of log2(FC) > 1.

File containing plant functional traits data and plant composition data used for analyzing the responses of plant functional traits to soil inoculation treatments.

A major goal in translational cancer research is to identify biological signatures driving cancer progression and metastasis. A common technique applied in genomics research is to cluster patients using gene expression data from a candidate prognostic gene set, and if the resulting clusters show statistically significant outcome stratification, to associate the gene set with prognosis, suggesting its biological and clinical importance. Recent work has questioned the validity of this approach by showing in several breast...

Irisin, a skeletal-muscle secreted myokine, facilitates muscle-bone crosstalk and skeletal remodeling in part by its action on osteoblasts and osteocytes. In this study, we investigated whether irisin directly regulates osteoclasts. In vitro, irisin (2–10 ng/mL) increased osteoclast differentiation in C57BL/6J mouse bone marrow progenitors; however, this increase was blocked by a neutralizing antibody to integrin αVβ5. Irisin also increased bone resorption on several substrates in situ. RNAseq revealed differential gene expression induced by irisin including...

Additional file 5: Supplementary Table 9. List of the downregulated differentially expressed genes from DEGs in angiofibroma(AF) of TSC patients vs. normal skin. All genes were identified with FDR-adjusted p-value < 0.05 and absolute value of log2(FC) > 1.

Additional file 2: Supplementary Table S2. Immune Gene Expression Scores. Gene expression scores for all samples used in analyses.

The transcription factor TEAD, together with its coactivator YAP/TAZ, is a key transcriptional modulator of the Hippo pathway. Activation of TEAD transcription by YAP has been implicated in a number of malignancies, and this complex represents a promising target for drug discovery. Here, we employed covalent fragment screening approach followed by structure-based design to develop an irreversible TEAD inhibitor MYF-03-69. Using a range of in vitro and cell-based assays we demonstrated that through a covalent...

Dataset used to produce figures for the paper and supporting information submitted to Geophysical Research Letters with the title "Plasma Wave and Particle Dynamics During Interchange Events in the Jovian Magnetosphere Using Juno Observations"

The chromosome breakage-fusion-bridge (BFB) cycle is a mutational process that produces gene amplification and genome instability. Signatures of BFB cycles can be observed in cancer genomes alongside chromothripsis, another catastrophic mutational phenomenon. Here, we explain this association by elucidating a mutational cascade, downstream of the single cell division error of chromosome bridge formation, that rapidly generates extreme genomic complexity. We show that actomyosin forces are required for initial bridge breakage and mutagenesis, following which chromothripsis...

PTEN is a phosphatidylinositol-3,4,5-triphosphate (PIP3) phospholipid phosphatase that is commonly mutated or silenced in cancer. PTEN's catalytic activity, cellular membrane localization, and stability are orchestrated by a cluster of C-terminal phosphorylation events on Ser380, Thr382, Thr383, and Ser385, but the molecular details of this multifaceted regulation have remained uncertain. Here we use a combination of protein semisynthesis, biochemical analysis, NMR, X-ray crystallography, and computational simulations on human PTEN and its sea squirt homolog VSP to...

Additional file 3: Supplementary Table S3. Spearman's correlation of individual signature score with immune marker immunohistochemistry (IHC).

Additional file 3: Supplementary Table S7. List of the predict target genes of miR-130b-3p from prediction softwares TargetScan, RNA22, PicTar, miRDB and miRWalk.

Dataset used to produce figures for the paper and supporting information submitted to Geophysical Research Letters with the title "Plasma Wave and Particle Dynamics During Interchange Events in the Jovian Magnetosphere Using Juno Observations"