ResearchPad - sciadv-r-articles https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Evolutionary trade-off in reproduction of Cambrian arthropods]]> https://www.researchpad.co/article/elastic_article_7741 Trade-offs play a crucial role in the evolution of life-history strategies of extant organisms by shaping traits such as growth pattern, reproductive investment, and lifespan. One important trade-off is between offspring number and energy (nutrition, parental care, etc.) allocated to individual offspring. Exceptional Cambrian fossils allowed us to trace the earliest evidence of trade-offs in arthropod reproduction. †Chuandianella ovata, from the early Cambrian Chengjiang biota of China, brooded numerous (≤100 per clutch), small (Ø, ~0.5 mm) eggs under carapace flaps. The closely related †Waptia fieldensis, from the middle Cambrian Burgess Shale of Canada, also brooded young, but carried fewer (≤ 26 per clutch), larger (Ø, ~2.0 mm) eggs. The notable differences in clutch/egg sizes between these two species suggest an evolutionary trade-off between quantity and quality of offspring. The shift toward fewer, larger eggs might be an adaptive response to marine ecosystem changes through the early-middle Cambrian. We hypothesize that reproductive trade-offs might have facilitated the evolutionary success of early arthropods.

]]>
<![CDATA[Mathematical prediction of clinical outcomes in advanced cancer patients treated with checkpoint inhibitor immunotherapy]]> https://www.researchpad.co/article/elastic_article_7740 We present a mechanistic mathematical model of immune checkpoint inhibitor therapy to address the oncological need for early, broadly applicable readouts (biomarkers) of patient response to immunotherapy. The model is built upon the complex biological and physical interactions between the immune system and cancer, and is informed using only standard-of-care CT. We have retrospectively applied the model to 245 patients from multiple clinical trials treated with anti–CTLA-4 or anti–PD-1/PD-L1 antibodies. We found that model parameters distinctly identified patients with common (n = 18) and rare (n = 10) malignancy types who benefited and did not benefit from these monotherapies with accuracy as high as 88% at first restaging (median 53 days). Further, the parameters successfully differentiated pseudo-progression from true progression, providing previously unidentified insights into the unique biophysical characteristics of pseudo-progression. Our mathematical model offers a clinically relevant tool for personalized oncology and for engineering immunotherapy regimens.

]]>
<![CDATA[A brief social-belonging intervention in college improves adult outcomes for black Americans]]> https://www.researchpad.co/article/elastic_article_7735 Could mitigating persistent worries about belonging in the transition to college improve adult life for black Americans? To examine this question, we conducted a long-term follow-up of a randomized social-belonging intervention delivered in the first year of college. This 1-hour exercise represented social and academic adversity early in college as common and temporary. As previously reported in Science, the exercise improved black students’ grades and well-being in college. The present study assessed the adult outcomes of these same participants. Examining adult life at an average age of 27, black adults who had received the treatment (versus control) exercise 7 to 11 years earlier reported significantly greater career satisfaction and success, psychological well-being, and community involvement and leadership. Gains were statistically mediated by greater college mentorship. The results suggest that addressing persistent social-psychological concerns via psychological intervention can shape the life course, partly by changing people’s social realities.

]]>
<![CDATA[Chemomechanical origin of directed locomotion driven by internal chemical signals]]> https://www.researchpad.co/article/elastic_article_7721 Asymmetry in the interaction between an individual and its environment is generally considered essential for the directional properties of active matter, but can directional locomotions and their transitions be generated only from intrinsic chemical dynamics and its modulation? Here, we examine this question by simulating the locomotion of a bioinspired active gel in a homogeneous environment. We find that autonomous directional locomotion emerges in the absence of asymmetric interaction with the environment and that a transition between modes of gel locomotion can be induced by adjusting the spatially uniform intensity of illumination or certain kinetic and mechanical system parameters. The internal wave dynamics and its structural modulation act as the impetus for signal-driven active locomotion in a manner similar to the way in which an animal’s locomotion is generated via driving by nerve pulses. Our results may have implications for the development of soft robots and biomimetic materials.

]]>
<![CDATA[Three-dimensional magnetism and the Dzyaloshinskii-Moriya interaction in <i>S</i> = 3/2 kagome staircase Co<sub>3</sub>V<sub>2</sub>O<sub>8</sub>]]> https://www.researchpad.co/article/elastic_article_7719 Time-of-flight neutron data reveal spin waves in the ferromagnetic ground state of the kagome staircase material Co3V2O8. While previous work has treated this material as quasi–two-dimensional, we find that an inherently three-dimensional description is needed to describe the spin wave spectrum throughout reciprocal space. Moreover, spin wave branches show gaps that point to an unexpectedly large Dzyaloshinskii-Moriya interaction on the nearest-neighbor bond, with D1J1/2. A better understanding of the Dzyaloshinskii-Moriya interaction in this material should shed light on the multiferroicity of the related Ni3V2O8. At a higher temperature where Co3V2O8 displays an antiferromagnetic spin density wave structure, there are no well-defined spin wave excitations, with most of the spectral weight observed in broad diffuse scattering centered at the (0, 0.5, 0) antiferromagnetic Bragg peak.

]]>
<![CDATA[Enhanced therapeutic index of an antimicrobial peptide in mice by increasing safety and activity against multidrug-resistant bacteria]]> https://www.researchpad.co/article/elastic_article_7718 The rising prevalence of antibiotic resistance underscores the urgent need for novel antimicrobial agents. Antimicrobial peptides (AMPs) are potentially effective therapeutics that disrupt bacterial membranes regardless of resistance to traditional antibiotics. We have developed engineered cationic AMPs (eCAPs) with broad activity against multidrug-resistant (MDR) bacteria, but stability remains an important concern. Therefore, we sought to enhance the clinical utility of eCAP WLBU2 in biological matrices relevant to respiratory infection. A designed substitution of d-Val for l-Val resulted in increased resistance to protease enzymatic degradation. We observed multiple gains of functions such as higher activity against bacteria in biofilm mode of growth, significantly lower toxicity to erythrocytes and white blood cells compared to WLBU2, with increased safety in mice. Direct airway delivery revealed a therapeutic index of >140 for the selected enantiomer compared to that of <35 for WLBU2. The data warrant clinical exploration by aerosolized delivery to mitigate MDR-related respiratory infection.

]]>
<![CDATA[Refined symmetry indicators for topological superconductors in all space groups]]> https://www.researchpad.co/article/elastic_article_7716 Topological superconductors are exotic phases of matter featuring robust surface states that could be leveraged for topological quantum computation. A useful guiding principle for the search of topological superconductors is to relate the topological invariants with the behavior of the pairing order parameter on the normal-state Fermi surfaces. The existing formulas, however, become inadequate for the prediction of the recently proposed classes of topological crystalline superconductors. In this work, we advance the theory of symmetry indicators for topological (crystalline) superconductors to cover all space groups. Our main result is the exhaustive computation of the indicator groups for superconductors under a variety of symmetry settings. We further illustrate the power of this approach by analyzing fourfold symmetric superconductors with or without inversion symmetry and show that the indicators can diagnose topological superconductors with surface states of different dimensionalities or dictate gaplessness in the bulk excitation spectrum.

]]>
<![CDATA[Vanadium spin qubits as telecom quantum emitters in silicon carbide]]> https://www.researchpad.co/article/elastic_article_7715 Solid-state quantum emitters with spin registers are promising platforms for quantum communication, yet few emit in the narrow telecom band necessary for low-loss fiber networks. Here, we create and isolate near-surface single vanadium dopants in silicon carbide (SiC) with stable and narrow emission in the O band, with brightness allowing cavity-free detection in a wafer-scale material. In vanadium ensembles, we characterize the complex d1 orbital physics in all five available sites in 4H-SiC and 6H-SiC. The optical transitions are sensitive to mass shifts from local silicon and carbon isotopes, enabling optically resolved nuclear spin registers. Optically detected magnetic resonance in the ground and excited orbital states reveals a variety of hyperfine interactions with the vanadium nuclear spin and clock transitions for quantum memories. Last, we demonstrate coherent quantum control of the spin state. These results provide a path for telecom emitters in the solid state for quantum applications.

]]>
<![CDATA[RasGRP1 is a causal factor in the development of <span style="font-variant: all-small-caps">l</span>-DOPA–induced dyskinesia in Parkinson’s disease]]> https://www.researchpad.co/article/elastic_article_7713 The therapeutic effects of l-3,4-dihydroxyphenylalanine (l-DOPA) in patients with Parkinson’s disease (PD) severely diminishes with the onset of abnormal involuntary movement, l-DOPA–induced dyskinesia (LID). However, the molecular mechanisms that promote LID remain unclear. Here, we demonstrated that RasGRP1 [(guanine nucleotide exchange factor (GEF)] controls the development of LID. l-DOPA treatment rapidly up-regulated RasGRP1 in the striatum of mouse and macaque model of PD. The lack of RasGRP1 in mice (RasGRP1−/−) dramatically diminished LID without interfering with the therapeutic effects of l-DOPA. Besides acting as a GEF for Ras homolog enriched in the brain (Rheb), the activator of the mammalian target of rapamycin kinase (mTOR), RasGRP1 promotes l-DOPA–induced extracellular signal-regulated kinase (ERK) and the mTOR signaling in the striatum. High-resolution tandem mass spectrometry analysis revealed multiple RasGRP1 downstream targets linked to LID vulnerability. Collectively, the study demonstrated that RasGRP1 is a critical striatal regulator of LID.

]]>
<![CDATA[Role of mechanical cues and hypoxia on the growth of tumor cells in strong and weak confinement: A dual in vitro–in silico approach]]> https://www.researchpad.co/article/N000b77f2-aed4-4674-904d-2b54ecc783f1

Dynamics of tumor cell growth is captured by an in silico model able to predicate effect of confinement observed in vitro.

]]>
<![CDATA[Bioenergetic-active materials enhance tissue regeneration by modulating cellular metabolic state]]> https://www.researchpad.co/article/Nf339299e-3ebd-42ea-b2c8-863f8ed912ab

We report a biodegradable synthetic material that opens a door to repair damaged tissue via boosting cellular energy metabolism.

]]>
<![CDATA[Nanoparticle interactions with immune cells dominate tumor retention and induce T cell–mediated tumor suppression in models of breast cancer]]> https://www.researchpad.co/article/N2259225b-addf-4964-8d14-1407d0ce1706

Systemic exposure to nanoparticles induces immune responses that lead to anticancer immune activation.

]]>
<![CDATA[Emergence of a Neolithic in highland New Guinea by 5000 to 4000 years ago]]> https://www.researchpad.co/article/N290f2c28-085e-4ee4-9ea5-22c54f73851a

Shift in human settlement patterns and technologies in New Guinea highlands is linked with changing food production strategies.

]]>
<![CDATA[Breath figure–derived porous semiconducting films for organic electronics]]> https://www.researchpad.co/article/N1215294b-77dc-45ec-8b56-9c4075319f1b

We show here that breath figure–derived semiconducting films are suitable and universal for porous organic electronics.

]]>
<![CDATA[The insulator functions of the Drosophila polydactyl C2H2 zinc finger protein CTCF: Necessity versus sufficiency]]> https://www.researchpad.co/article/Nf486e809-488a-4f61-8282-6f949bf72c0d

CTCF sufficiency depends on various combinations of architectural proteins.

]]>
<![CDATA[Isolation of an elusive phosphatetrahedrane]]> https://www.researchpad.co/article/Ne5e60fdc-f262-4bba-bad9-a5269ba3473a

Extreme strain eased with P-incorporation.

]]>
<![CDATA[Irradiated tumor cell–derived microparticles mediate tumor eradication via cell killing and immune reprogramming]]> https://www.researchpad.co/article/Nb59b3bae-dd68-420e-a28c-129a28dd0fa6

By mimicking the RIBE machinery, we provided an indirect radiotherapy approach based on RT-MP for eradication of MPE in mice.

]]>
<![CDATA[SKP1 drives the prophase I to metaphase I transition during male meiosis]]> https://www.researchpad.co/article/Nc0b792b4-e5e2-44cb-9b52-54dcf1ca8107

SKP1 coordinates chromosome synapsis and meiotic recombination with progression through the first meiotic cell division in mouse.

]]>
<![CDATA[DUSP6 SUMOylation protects cells from oxidative damage via direct regulation of Drp1 dephosphorylation]]> https://www.researchpad.co/article/N3056015d-60a1-4521-9064-22cbc64fdc24

Our work uncovers a novel SUMOylation-dependent regulation of DUSP6 stability and its activity, which regulates Drp1 function.

]]>
<![CDATA[Zero-energy bound states in the high-temperature superconductors at the two-dimensional limit]]> https://www.researchpad.co/article/Nebc4e9f6-2947-4436-b93e-4a4e0edc4d2c

Zero-energy bound states representing Majorana zero modes are detected in monolayer high-temperature superconducting films.

]]>