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Oct1 and BRCA1 staining in breast cancer tissues.

Supp. Figure S1 Differential metabolite levels in BRCA1 I26A compared to normal MEFs. Supp. Figure S2 Control immunofluorescence microscopy images using Oct1-deficient MEFs. Supp. Figure S3 Small increase in Oct1 proteins levels in MEFs with a C-terminal BRCA1 mutation. Supp. Figure S4 Equivalent infection rates in Oct1 and control CRISPR infection rates in BRCA1-I26A MEFs. Supp. Figure S5 Quality-control and validation of RNAseq. Supp. Figure S6 CRISPR-mediated Oct1 loss in either BRCA1-I26A MEFs or MCF-7 cells minimally affects HIF-1α and c-Myc levels. Supp. Figure S7 Equivalent infection rates in Oct1 and control CRISPR infection rates in MCF-7 cells. Supp. Figure S8 MG-132 treatment reveals ubiquitylated Oct1 bands in the presence of urea. Supp. Figure S9 O2 consumption rate (OCR) was assessed in MCF-7 cells transduced with either empty vector control (EV), or viruses expressing WT or K9/403R Oct1. Supp. Figure S10 Oct1 protein stability in WT and I26A MEFs. Supp. Figure S11 Immunoprecipitating in vitro ubiquitylation assay products with control rabbit IgG antibodies results in recovery of background ubiquitylation. Supp. Figure S12 The same as in Figure 6A except with individual datapoints (Supplemental Table S4) superimposed. Supp. Figure S13 Elevated Oct1 (Pou2f1) mRNA levels correlate with poor patient outcome in gastric but not breast cancer.

The tumor suppressor BRCA1 regulates the DNA damage response (DDR) and other processes that remain incompletely defined. Among these, BRCA1 heterodimerizes with BARD1 to ubiquitylate targets via its N-terminal E3 ligase activity. Here, it is demonstrated that BRCA1 promotes oxidative metabolism by degrading Oct1 (POU2F1), a transcription factor with proglycolytic and tumorigenic effects. BRCA1 E3 ubiquitin ligase mutation skews cells toward a glycolytic metabolic profile while elevating Oct1 protein. CRISPR-mediated Oct1 deletion reverts the glycolytic phenotype. RNA sequencing (RNAseq) confirms deregulation of metabolic genes downstream of Oct1. BRCA1 mediates Oct1 ubiquitylation and degradation, and mutation of two ubiquitylated Oct1 lysines insulates the protein against BRCA1-mediated destabilization. Oct1 deletion in MCF-7 breast cancer cells does not perturb growth in standard culture, but inhibits growth in soft agar and xenograft assays. In primary breast cancer clinical specimens, Oct1 protein levels correlate positively with tumor aggressiveness and inversely with BRCA1. These results identify BRCA1 as an Oct1 ubiquitin ligase that catalyzes Oct1 degradation to promote oxidative metabolism and restrict tumorigenicity. Mol Cancer Res; 16(3); 439–52. ©2018 AACR.

Legends for Supplementary Figures S1-S13, and Tables S1-S4

The quantum-to-classical correspondence is often quantified in dynamics by a quantity referred to as the out-of-time-order correlator (OTOC). In chaotic systems, the OTOC is expected to grow exponentially at early time, characteristic of a Lyapunov exponent, however, exponential growth can also occur for integrable systems. Here we investigate the OTOC for realistic diatomic molecular potentials in one degree of freedom, finding that the OTOC can grow exponentially near the dissociation energy of the moelcule. Further, this dynamics is tied to the classical dynamics of the atoms at the outer classical turning point of the potential. These results should serve to guide and interpret dynamical chaos in more complex molecules.

We analytically derive the transport tensor of thermal conductivity in an ultracold, but not yet quantum degenerate, gas of Bosonic lanthanide atoms using the Chapman-Enskog procedure. The tensor coefficients inherit an anisotropy from the anisotropic collision cross section for these dipolar species, manifest in their dependence on the dipole moment, dipole orientation, and $s$-wave scattering length. These functional dependencies open up a pathway for control of macroscopic gas phenomena via tuning of the microscopic atomic interactions. As an illustrative example, we analyze the time evolution of a temperature hot-spot which shows preferential heat diffusion orthogonal to the dipole orientation, a direct consequence of anisotropic thermal conduction., 9 pages, 5 figures

Freshwater ecosystems are increasingly impacted by anthropogenic elevated levels of suspended sediment that may negatively affect aquatic organisms, including salamanders. Although increasing fine sediment in streams has been suggested as a reason for population declines, to date no study has empirically assessed the effect of suspended sediment on gilled larval Eastern Hellbenders (Cryptobranchus alleganiensis (Sonnini de Manoncourt and Latreille, 1801)), a critical life-history stage and a species of conservation concern. We used custom respirometers to elucidate effects of suspended sediments on larval Eastern Hellbender oxygen uptake in trials conducted in situ in Georgia (USA) streams. Mean oxygen uptake increased and was significantly higher in trials when larval salamanders were exposed to suspended sediment (mean = 5.06 mg O2/L for 800 mg/L of sediment treatment vs. 2.25 mg O2/L for 0.00 mg/L of sediment control). This may indicate elevated physiological stress in response to short-term exposure to suspended sediments. Qualitatively, individuals in both groups exhibited rocking behavior in response to low oxygen (hypoxia), albeit at different frequencies (sediment exposure = 7.6 rocks/min and control = 2.1 rocks/min). Larval salamanders may be able to temporarily compensate for low oxygen through increased rocking behavior when high suspended sediment loads are present, with future respirometry research needed.