When rats rescue robots

Robots are increasingly being used to monitor and even participate in social interactions with animals in their own environments. Robotic animals enable social behaviors to be observed in natural environments, or specifically elicited under the control of an experimenter. It is an open question to what extent animals will form positive social connections with such robots. To test this, we familiarized rats to two rat-sized robots, one exhibiting “social” behaviors, including helping, while the other was also mobile but not helpful. When given an opportunity to release the robots from restrainers, as they do for conspecifics, we found that rats did release the robots, and moreover, were significantly more likely to release the helpful than the unhelpful robot. These findings indicate that robots can elicit helpful behavior from rats, and that rats will even discriminate between robots on the basis of their behaviors

The Seoul National University AGN Monitoring Project. IV. Hα Reverberation Mapping of Six AGNs and the Hα Size–Luminosity Relation

The broad-line region (BLR) size–luminosity relation has paramount importance for estimating the mass of black holes in active galactic nuclei (AGNs). Traditionally, the size of the Hβ BLR is often estimated from the optical continuum luminosity at 5100 Å, while the size of the Hα BLR and its correlation with the luminosity is much less constrained. As a part of the Seoul National University AGN Monitoring Project, which provides 6 yr photometric and spectroscopic monitoring data, we present our measurements of the Hα lags of high-luminosity AGNs. Combined with the measurements for 42 AGNs from the literature, we derive the size–luminosity relations of the Hα BLR against the broad Hα and 5100 Å continuum luminosities. We find the slope of the relations to be 0.61 ± 0.04 and 0.59 ± 0.04, respectively, which are consistent with the Hβ size–luminosity relation. Moreover, we find a linear relation between the 5100 Å continuum luminosity and the broad Hα luminosity across 7 orders of magnitude. Using these results, we propose a new virial mass estimator based on the Hα broad emission line, finding that the previous mass estimates based on scaling relations in the literature are overestimated by up to 0.7 dex at masses lower than 107M⊙

Prevalence and detection of low-allele-fraction variants in clinical cancer samples

Accurate detection of genomic alterations using high-throughput sequencing is an essential component of precision cancer medicine. We characterize the variant allele fractions (VAFs) of somatic single nucleotide variants and indels across 5095 clinical samples profiled using a custom panel, CancerSCAN. Our results demonstrate that a significant fraction of clinically actionable variants have low VAFs, often due to low tumor purity and treatment-induced mutations. The percentages of mutations under 5% VAF across hotspots in EGFR, KRAS, PIK3CA, and BRAF are 16%, 11%, 12%, and 10%, respectively, with 24% for EGFR T790M and 17% for PIK3CA E545. For clinical relevance, we describe two patients for whom targeted therapy achieved remission despite low VAF mutations. We also characterize the read depths necessary to achieve sensitivity and specificity comparable to current laboratory assays. These results show that capturing low VAF mutations at hotspots by sufficient sequencing coverage and carefully tuned algorithms is imperative for a clinical assay

TCB2, a new anti-human interleukin-2 antibody, facilitates heterodimeric IL-2 receptor signaling and improves anti-tumor immunity

IL-2 is a pleiotropic cytokine that plays an essential role in the survival, expansion, and function of CD8 T cells, regulatory T cells (Tregs), and natural killer (NK) cells. Previous studies showed that binding IL-2 with an anti-IL-2 monoclonal antibody (mAb) with a particular specificity could block its interaction with IL-2R alpha, which is mainly expressed on Tregs. This selectivity can enhance the anti-tumor effects of IL-2 by activating CD8 T and NK cells, while disfavoring Treg stimulation. Based on this, we newly developed a series of anti-human IL-2 (hIL-2) mAbs (TCB1-3) that selectively stimulate CD8 T and NK cells without overtly activating Tregs. Among them, the hIL-2/TCB2 complex (hIL-2/TCB2c) exerted the best efficacy by inducing a prodigious expansion of host memory phenotype (MP) CD8 T (60-fold) and NK cells (18-fold) with less efficient Treg proliferation (5-fold). As a result, there was an average eightfold increase in the ratio of MP CD8 to Tregs. Accordingly, hIL-2/TCB2c strongly inhibited the growth of B16F10, MC38, and CT26 tumors. More remarkably, hIL-2/TCB2c showed synergy with checkpoint inhibitors such as anti-CTLA-4 or PD1 antibodies, and resulted in almost complete regression of implanted tumors and resistance to secondary tumor challenge. For direct clinical use, we generated a humanized form of TCB2 that had equal immunostimulatory and anti-tumor efficacy as a murine one. Collectively, these results show that TCB2 can provide a potent immunotherapeutic modality either alone or together with checkpoint inhibitors in cancer patients11Nsciescopu

Fine-scaled climate variation in equatorial Africa revealed by modern and fossil primate teeth

Variability in resource availability is hypothesized to be a significant driver of primate adaptation and evolution, but most paleoclimate proxies cannot recover environmental seasonality on the scale of an individual lifespan. Oxygen isotope compositions (δ18O values) sampled at high spatial resolution in the dentitions of modern African primates (n = 2,352 near weekly measurements from 26 teeth) track concurrent seasonal precipitation, regional climatic patterns, discrete meteorological events, and niche partitioning. We leverage these data to contextualize the first δ18O values of two 17 Ma Afropithecus turkanensis individuals from Kalodirr, Kenya, from which we infer variably bimodal wet seasons, supported by rainfall reconstructions in a global Earth system model. Afropithecus’ δ18O fluctuations are intermediate in magnitude between those measured at high resolution in baboons (Papio spp.) living across a gradient of aridity and modern forest-dwelling chimpanzees (Pan troglodytes verus). This large-bodied Miocene ape consumed seasonally variable food and water sources enriched in 18O compared to contemporaneous terrestrial fauna (n = 66 fossil specimens). Reliance on fallback foods during documented dry seasons potentially contributed to novel dental features long considered adaptations to hard-object feeding. Developmentally informed microsampling recovers greater ecological complexity than conventional isotope sampling; the two Miocene apes (n = 248 near weekly measurements) evince as great a range of seasonal δ18O variation as more time-averaged bulk measurements from 101 eastern African Plio-Pleistocene hominins and 42 papionins spanning 4 million y. These results reveal unprecedented environmental histories in primate teeth and suggest a framework for evaluating climate change and primate paleoecology throughout the Cenozoic

A list of significant TWAS genes associated with UF (P < 1.90 × 10⁻⁶).

A list of significant TWAS genes associated with UF (P −6).</p

Colocalization test results of COLOC-prioritized and significant TWAS genes.

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Gene sets enriched with positively associated TWAS genes provided by the Metascape.

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Gene sets enriched with negatively associated TWAS genes provided by the Metascape.

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A Manhattan plot of the TWAS results for UF.

Each dot corresponds to the gene of which predicted expression is associated with UF. The X-axis denotes the chromosome numbers of the genes and the Y-axis denotes −log10(TWAS P-values). The yellow line indicates a Bonferroni significant threshold (P −6). Nine significant TWAS genes are represented as red dots with gene labels.</p