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Journal Proc Natl Acad Sci U S A

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Nonequilibrium models of optimal enhancer function.

Rok Grah, Benjamin Zoller, Gašper Tkačik,

In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene-expression levels that is compatible with in vivo and in vitro biophysical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Polyphosphate is an extracellular signal that can facilitate bacterial survival in eukaryotic cells.

Ramesh Rijal, Louis A Cadena, Morgan R Smith, Joseph F Carr, Richard H Gomer,

Polyphosphate is a linear chain of phosphate residues and is present in organisms ranging from bacteria to humans. Pathogens such as <i>Mycobacterium tuberculosis</i> accumulate polyphosphate, and reduced expression of the polyphosphate kinase that synthesizes polyphosphate decreases their survival. How polyphosphate potentiates pathogenicity is poorly understood. <i>Escherichia coli</i> K-12 do not ... Read more >>

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[2020, :]

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Targeting progesterone signaling prevents metastatic ovarian cancer.

Olga Kim, Eun Young Park, Sun Young Kwon, Sojin Shin, Robert E Emerson, Yong-Hyun Shin, Francesco J DeMayo, John P Lydon, Donna M Coffey, Shannon M Hawkins, Lawrence A Quilliam, Dong-Joo Cheon, Facundo M Fernández, Kenneth P Nephew, Adam R Karpf, Martin Widschwendter, Anil K Sood, Robert C Bast, Andrew K Godwin, Kathy D Miller, Chi-Heum Cho, Jaeyeon Kim,

Effective cancer prevention requires the discovery and intervention of a factor critical to cancer development. Here we show that ovarian progesterone is a crucial endogenous factor inducing the development of primary tumors progressing to metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC), the most common and ... Read more >>

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[2020, :]

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Awareness-driven behavior changes can shift the shape of epidemics away from peaks and toward plateaus, shoulders, and oscillations.

Joshua S Weitz, Sang Woo Park, Ceyhun Eksin, Jonathan Dushoff,

The COVID-19 pandemic has caused more than 1,000,000 reported deaths globally, of which more than 200,000 have been reported in the United States as of October 1, 2020. Public health interventions have had significant impacts in reducing transmission and in averting even more deaths. Nonetheless, in many jurisdictions, the decline ... Read more >>

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[2020, :]

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Genome analyses reveal the hybrid origin of the staple crop white Guinea yam (Dioscorea rotundata).

Yu Sugihara, Kwabena Darkwa, Hiroki Yaegashi, Satoshi Natsume, Motoki Shimizu, Akira Abe, Akiko Hirabuchi, Kazue Ito, Kaori Oikawa, Muluneh Tamiru-Oli, Atsushi Ohta, Ryo Matsumoto, Paterne Agre, David De Koeyer, Babil Pachakkil, Shinsuke Yamanaka, Satoru Muranaka, Hiroko Takagi, Ben White, Robert Asiedu, Hideki Innan, Asrat Asfaw, Patrick Adebola, Ryohei Terauchi,

White Guinea yam (<i>Dioscorea rotundata</i>) is an important staple tuber crop in West Africa. However, its origin remains unclear. In this study, we resequenced 336 accessions of white Guinea yam and compared them with the sequences of wild <i>Dioscorea</i> species using an improved reference genome sequence of <i>D. rotundata</i> In ... Read more >>

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[2020, :]

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Targeting presynaptic H3 heteroreceptor in nucleus accumbens to improve anxiety and obsessive-compulsive-like behaviors.

Xiao-Yang Zhang, Shi-Yu Peng, Li-Ping Shen, Qian-Xing Zhuang, Bin Li, Shu-Tao Xie, Qian-Xiao Li, Ming-Run Shi, Tian-Yu Ma, Qipeng Zhang, Jian-Jun Wang, Jing-Ning Zhu,

Anxiety commonly co-occurs with obsessive-compulsive disorder (OCD). Both of them are closely related to stress. However, the shared neurobiological substrates and therapeutic targets remain unclear. Here we report an amelioration of both anxiety and OCD via the histamine presynaptic H3 heteroreceptor on glutamatergic afferent terminals from the prelimbic prefrontal cortex ... Read more >>

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[2020, :]

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A thermogenic fat-epithelium cell axis regulates intestinal disease tolerance.

Kevin Man, Christopher Bowman, Kristina N Braverman, Veronica Escalante, Yuan Tian, Jordan E Bisanz, Kirthana Ganeshan, Biao Wang, Andrew Patterson, James R Bayrer, Peter J Turnbaugh, Ajay Chawla,

Disease tolerance, the capacity of tissues to withstand damage caused by a stimulus without a decline in host fitness, varies across tissues, environmental conditions, and physiologic states. While disease tolerance is a known strategy of host defense, its role in noninfectious diseases has been understudied. Here, we provide evidence that ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Profile of Se-Jin Lee.

Sandeep Ravindran,

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Structure of the Plasmodium-interspersed repeat proteins of the malaria parasite.

Thomas E Harrison, Adam J Reid, Deirdre Cunningham, Jean Langhorne, Matthew K Higgins,

The deadly symptoms of malaria occur as <i>Plasmodium</i> parasites replicate within blood cells. Members of several variant surface protein families are expressed on infected blood cell surfaces. Of these, the largest and most ubiquitous are the <i>Plasmodium</i>-interspersed repeat (PIR) proteins, with more than 1,000 variants in some genomes. Their functions ... Read more >>

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[2020, :]

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Visual motion assists in social cognition.

Arvid Guterstam, Michael S A Graziano,

Recent evidence suggests a link between visual motion processing and social cognition. When person A watches person B, the brain of A apparently generates a fictitious, subthreshold motion signal streaming from B to the object of B's attention. These previous studies, being correlative, were unable to establish any functional role ... Read more >>

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[2020, :]

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Seasonal plasticity in the adult somatosensory cortex.

Saikat Ray, Miao Li, Stefan Paul Koch, Susanne Mueller, Philipp Boehm-Sturm, Hong Wang, Michael Brecht, Robert Konrad Naumann,

Seasonal cycles govern life on earth, from setting the time for the mating season to influencing migrations and governing physiological conditions like hibernation. The effect of such changing conditions on behavior is well-appreciated, but their impact on the brain remains virtually unknown. We investigate long-term seasonal changes in the mammalian ... Read more >>

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[2020, :]

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The potential harms of the Tor anonymity network cluster disproportionately in free countries.

Eric Jardine, Andrew M Lindner, Gareth Owenson,

The Tor anonymity network allows users to protect their privacy and circumvent censorship restrictions but also shields those distributing child abuse content, selling or buying illicit drugs, or sharing malware online. Using data collected from Tor entry nodes, we provide an estimation of the proportion of Tor network users that ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Inverse correlation between fatty acid transport protein 4 and vision in Leber congenital amaurosis associated with RPE65 mutation.

Songhua Li, William C Gordon, Nicolas G Bazan, Minghao Jin,

Fatty acid transport protein 4 (FATP4), a transmembrane protein in the endoplasmic reticulum (ER), is a recently identified negative regulator of the ER-associated retinal pigment epithelium (RPE)65 isomerase necessary for recycling 11-<i>cis</i>-retinal, the light-sensitive chromophore of both rod and cone opsin visual pigments. The role of FATP4 in the disease ... Read more >>

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[2020, :]

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Fuel and oxygen harvesting from Martian regolithic brine.

Pralay Gayen, Shrihari Sankarasubramanian, Vijay K Ramani,

NASA's current mandate is to land humans on Mars by 2033. Here, we demonstrate an approach to produce ultrapure H<sub>2</sub> and O<sub>2</sub> from liquid-phase Martian regolithic brine at ∼-36 °C. Utilizing a Pb<sub>2</sub>Ru<sub>2</sub>O<sub>7-δ</sub> pyrochlore O<sub>2</sub>-evolution electrocatalyst and a Pt/C H<sub>2</sub>-evolution electrocatalyst, we demonstrate a brine electrolyzer with >25× the O<sub>2</sub> ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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A highly immunogenic and effective measles virus-based Th1-biased COVID-19 vaccine.

Cindy Hörner, Christoph Schürmann, Arne Auste, Aileen Ebenig, Samada Muraleedharan, Kenneth H Dinnon, Tatjana Scholz, Maike Herrmann, Barbara S Schnierle, Ralph S Baric, Michael D Mühlebach,

The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread worldwide, with millions of cases and more than 1 million deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates ... Read more >>

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[2020, :]

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Radiation with reticulation marks the origin of a major malaria vector.

Scott T Small, Frédéric Labbé, Neil F Lobo, Lizette L Koekemoer, Chadwick H Sikaala, Daniel E Neafsey, Matthew W Hahn, Michael C Fontaine, Nora J Besansky,

Advances in genomics have led to an appreciation that introgression is common, but its evolutionary consequences are poorly understood. In recent species radiations the sharing of genetic variation across porous species boundaries can facilitate adaptation to new environments and generate novel phenotypes, which may contribute to further diversification. Most <i>Anopheles</i> ... Read more >>

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[2020, :]

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The Fast Track intervention's impact on behaviors of despair in adolescence and young adulthood.

Jennifer W Godwin, ,

How to mitigate the dramatic increase in the number of self-inflicted deaths from suicide, alcohol-related liver disease, and drug overdose among young adults has become a critical public health question. A promising area of study looks at interventions designed to address risk factors for the behaviors that precede these -often ... Read more >>

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[2020, :]

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Time-dependent discrimination advantages for harmonic sounds suggest efficient coding for memory.

Malinda J McPherson, Josh H McDermott,

Perceptual systems have finite memory resources and must store incoming signals in compressed formats. To explore whether representations of a sound's pitch might derive from this need for compression, we compared discrimination of harmonic and inharmonic sounds across delays. In contrast to inharmonic spectra, harmonic spectra can be summarized, and ... Read more >>

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[2020, :]

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Micellar TIA1 with folded RNA binding domains as a model for reversible stress granule formation.

Keith J Fritzsching, Yizhuo Yang, Emily M Pogue, Joseph B Rayman, Eric R Kandel, Ann E McDermott,

TIA1, a protein critical for eukaryotic stress response and stress granule formation, is structurally characterized in full-length form. TIA1 contains three RNA recognition motifs (RRMs) and a C-terminal low-complexity domain, sometimes referred to as a "prion-related domain" or associated with amyloid formation. Under mild conditions, full-length (fl) mouse TIA1 spontaneously ... Read more >>

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[2020, :]

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Fruiting body form, not nutritional mode, is the major driver of diversification in mushroom-forming fungi.

Marisol Sánchez-García, Martin Ryberg, Faheema Kalsoom Khan, Torda Varga, László G Nagy, David S Hibbett,

With ∼36,000 described species, Agaricomycetes are among the most successful groups of Fungi. Agaricomycetes display great diversity in fruiting body forms and nutritional modes. Most have pileate-stipitate fruiting bodies (with a cap and stalk), but the group also contains crust-like resupinate fungi, polypores, coral fungi, and gasteroid forms (e.g., puffballs ... Read more >>

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[2020, :]

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FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho.

Yoshihisa Suzuki, Ekaterina Kuzina, Seong J An, Francisco Tome, Jyotidarsini Mohanty, Wenxue Li, Sangwon Lee, Yansheng Liu, Irit Lax, Joseph Schlessinger,

The three members of the endocrine-fibroblast growth factor (FGF) family, FGF19, 21, and 23 are circulating hormones that regulate critical metabolic processes. FGF23 stimulates the assembly of a signaling complex composed of α-Klotho (KLA) and FGF receptor (FGFR) resulting in kinase activation, regulation of phosphate homeostasis, and vitamin D levels. ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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A wireless, skin-interfaced biosensor for cerebral hemodynamic monitoring in pediatric care.

Alina Y Rwei, Wei Lu, Changsheng Wu, Kelia Human, Emily Suen, Daniel Franklin, Monica Fabiani, Gabriele Gratton, Zhaoqian Xie, Yujun Deng, Sung Soo Kwak, Lizhu Li, Carol Gu, Alanna Liu, Casey M Rand, Tracey M Stewart, Yonggang Huang, Debra E Weese-Mayer, John A Rogers,

The standard of clinical care in many pediatric and neonatal neurocritical care units involves continuous monitoring of cerebral hemodynamics using hard-wired devices that physically adhere to the skin and connect to base stations that commonly mount on an adjacent wall or stand. Risks of iatrogenic skin injuries associated with adhesives ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Fluctuating optimum and temporally variable selection on breeding date in birds and mammals.

Pierre de Villemereuil, Anne Charmantier, Debora Arlt, Pierre Bize, Patricia Brekke, Lyanne Brouwer, Andrew Cockburn, Steeve D Côté, F Stephen Dobson, Simon R Evans, Marco Festa-Bianchet, Marlène Gamelon, Sandra Hamel, Johann Hegelbach, Kurt Jerstad, Bart Kempenaers, Loeske E B Kruuk, Jouko Kumpula, Thomas Kvalnes, Andrew G McAdam, S Eryn McFarlane, Michael B Morrissey, Tomas Pärt, Josephine M Pemberton, Anna Qvarnström, Ole Wiggo Røstad, Julia Schroeder, Juan Carlos Senar, Ben C Sheldon, Martijn van de Pol, Marcel E Visser, Nathaniel T Wheelwright, Jarle Tufto, Luis-Miguel Chevin,

Temporal variation in natural selection is predicted to strongly impact the evolution and demography of natural populations, with consequences for the rate of adaptation, evolution of plasticity, and extinction risk. Most of the theory underlying these predictions assumes a moving optimum phenotype, with predictions expressed in terms of the temporal ... Read more >>

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An angular motion of a conserved four-helix bundle facilitates alternating access transport in the TtNapA and EcNhaA transporters.

Gal Masrati, Ramakanta Mondal, Abraham Rimon, Amit Kessel, Etana Padan, Erik Lindahl, Nir Ben-Tal,

There is ongoing debate regarding the mechanism through which cation/proton antiporters (CPAs), like <i>Thermus thermophilus</i> NapA (TtNapA) and Escherichia coli NapA (EcNhaA), alternate between their outward- and inward-facing conformations in the membrane. CPAs comprise two domains, and it is unclear whether the transition is driven by their rocking-bundle or elevator ... Read more >>

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[2020, :]

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Oxygen limitation may affect the temperature and size dependence of metabolism in aquatic ectotherms.

Juan G Rubalcaba, Wilco C E P Verberk, A Jan Hendriks, Bart Saris, H Arthur Woods,

Both oxygen and temperature are fundamental factors determining metabolic performance, fitness, ecological niches, and responses of many aquatic organisms to climate change. Despite the importance of physical and physiological constraints on oxygen supply affecting aerobic metabolism of aquatic ectotherms, ecological theories such as the metabolic theory of ecology have focused ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
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