Antimonide-based membranes synthesis integration and strain engineering
Marziyeh Zamiri, Farhana Anwar, Brianna A. Klein, Amin Rasoulof, Noel M. Dawson, Ted Schuler-Sandy, Christoph F. Deneke, Sukarno O. Ferreira, Francesca Cavallo, and Sanjay Krishna
In this work we present a versatile method to fabricate antimonide-based heterostructures in membrane form, and we demonstrate the potential of these materials to enable hybrid integration and elastic strain engineering. The relevance of our work is threefold. First, integration of Sb-based compound membranes with Si substrates will potentially solve a number of technological challenges in the fabrication of IR optoelectronic devices based on type II superlattices. Second, transfer of Sb compounds to insulating materials will enable a thorough investigation of electrical transport in the heterostructure via Hall and Van der Pauw measurements. Third, membrane technology applied to Sb-based structures will enable one to engineer strain distributions, which are not obtainable within the limitations of epitaxial growth processes. (See pp. E1–E8.)
Persistence and biodegradation of oil at the ocean floor following Deepwater Horizon
Sarah C. Bagby, Christopher M. Reddy, Christoph Aeppli, G. Burch Fisher, and David L. Valentine
The Deepwater Horizon event led to an unprecedented discharge of ∼4.1 million barrels of oil to the Gulf of Mexico. The deposition of ∼4–31% of this oil to the seafloor has been quantified previously on a bulk basis. In this work, we assess the extent of degradation over 4 y postspill for each of 125 petroleum hydrocarbons that contaminated the seafloor. As expected, chemically simpler compounds broke down more quickly than complex compounds, but degradation rates also depended on environmental context: Breakdown often was faster before seafloor deposition than after and for oil trapped in small droplets than for oil in large particles. These results provide a basis to predict the long-term fate of seafloor oil. (See pp. E9–E18.)
Chiral twist drives raft formation and organization in membranes composed of rod-like particles
Louis Kang and Tom C. Lubensky
Chiral objects are different from their mirror images and have properties that are physically forbidden for achiral objects. We show theoretically how one of these properties, the preference for chiral rods to adopt twisted configurations, generates an array of rafts in membranes formed by rod-like particles. Our theory can predict the composition, size, and interactions of these rafts based on measurable attributes of the rods, and its agreement with experimental data from a virus-based system supports its validity. Moreover, it proposes a mechanism for the stabilization of rafts in cell membranes, which are composed of chiral molecules. These lipid rafts are hypothesized to have important biological functions, and their manipulation may rely on a command of molecular chirality. (See pp. E19–E27.)
Mechanism of membrane fusion induced by vesicular stomatitis virus G protein
Irene S. Kim, Simon Jenni, Megan L. Stanifer, Eatai Roth, Sean P. J. Whelan, Antoine M. van Oijen, and Stephen C. Harrison
Enveloped viruses—those with a lipid-bilayer membrane such as influenza, dengue, and human immunodeficiency viruses—enter cells by fusion of the viral membrane with a membrane of the cell. A viral surface glycoprotein, known as its “fusion protein,” facilitates this step. Previous work studying the kinetics of single virus particles fusing with a target membrane has outlined a mechanism by which conformational changes in the fusion protein accelerate merger of the two bilayers. In this paper, we extend that mechanism to a structurally distinct class of viral fusion proteins, providing strong evidence for its general applicability to all viral membrane fusion processes. (See pp. E28–E36.)
Dynamic NHERF interaction with TRPC4/5 proteins is required for channel gating by diacylglycerol
Ursula Storch, Anna-Lena Forst, Franziska Pardatscher, Serap Erdogmus, Maximilian Philipp, Manuel Gregoritza, Michael Mederos y Schnitzler, and Thomas Gudermann
Transient receptor potential cation (TRPC) 4 and 5 channels are nonselective cation channels activated via G protein-coupled receptors. In contrast to all other TRPC channels, they are regarded as insensitive to the phospholipase C (PLC) product diacylglycerol (DAG). Deeper insight into the G protein-dependent activation mechanism of TRPC4/5 channels is lacking. In this study we unravel the Gq/11 protein-mediated signaling pathway leading to TRPC4/5 activation. Depletion of phosphatidylinositol 4,5-bisphosphate causes a conformational change of the TRPC5 C terminus leading to dissociation of Na+/H+ exchanger regulatory factor (NHERF) proteins thereby inducing a DAG-sensitive channel state. Our findings reveal a previously unidentified activation mechanism of TRPC4/5 channels with NHERF proteins as dynamic regulators of channel activity. Moreover, we demonstrate that TRPC channels are DAG sensitive. (See pp. E37–E46.)
Linking parasite populations in hosts to parasite populations in space through Taylor's law and the negative binomial distribution
Joel E. Cohen, Robert Poulin, and Clément Lagrue
The spatial distribution of individuals of any species is a basic concern of ecology. The spatial distribution of parasites matters to control and conservation of parasites that affect human and nonhuman populations. This paper develops a quantitative theory to predict the spatial distribution of parasites based on the distribution of parasites in hosts and the spatial distribution of hosts. The theory is tested using observations of metazoan hosts and parasites in the littoral zone of four lakes in Otago, New Zealand. We infer that the spatial distribution of parasites depends crucially on high local correlations of hosts' parasite loads. If so, local hotspots of correlated parasite loads should be considered in parasite control and conservation. (See pp. E47–E56.)
Modifications to a LATE MERISTEM IDENTITY1 gene are responsible for the major leaf shapes of Upland cotton (Gossypium hirsutum L.)
Ryan J. Andres, Viktoriya Coneva, Margaret H. Frank, John R. Tuttle, Luis Fernando Samayoa, Sang-Won Han, Baljinder Kaur, Linglong Zhu, Hui Fang, Daryl T. Bowman, Marcela Rojas-Pierce, Candace H. Haigler, Don C. Jones, James B. Holland, Daniel H. Chitwood, and Vasu Kuraparthy
Leaves are the primary source of photoassimilate in crop plants. A precise understanding of the genetic architecture underlying leaf morphology is critical to engineering climate-resilient crop varieties. An ideal cotton cultivar would produce a lower canopy of broad, normal leaves before transitioning to an upper canopy of highly lobed, okra leaves. Here we show that the major leaf shapes of cotton are controlled by the okra locus, which encodes an HD-Zip transcription factor Gossypium hirsutum LATE MERISTEM IDENTITY1-D1b (GhLMI1-D1b). Using gene silencing, we temporarily induced normal leaf formation in okra, thus validating the candidate gene and creating the leaf shape ideotype in cotton. This study, identifying a single locus responsible for cotton leaf shape, expands the genetic toolbox for breeders to produce superior cotton varieties. (See pp. E57–E66.)
Gfi1-Foxo1 axis controls the fidelity of effector gene expression and developmental maturation of thymocytes
Lewis Zhichang Shi, Jordy Saravia, Hu Zeng, Nishan S. Kalupahana, Clifford S. Guy, Geoffrey Neale, and Hongbo Chi
A fundamental question in immunology is the mechanism of thymocyte development, but how differentiating CD4+CD8+ double-positive thymocytes progress into CD4+ or CD8+ single-positive cells remains poorly defined. We have now determined that the transcription repressor Growth factor independent 1 (Gfi1) plays a central role in controlling double-positive cell fate and thymocyte maturation. Deletion of Gfi1 in double-positive thymocytes induces premature induction of single-positive–specific effector genes and transcription factors Foxo1 and Klf2 and accelerated transition into single-positive cells. These defects are largely rectified upon partial loss of Foxo1 functions, indicating the critical contribution of aberrant Foxo1 induction to disrupted thymocyte maturation. Our study establishes a molecular mechanism that actively maintains double-positive cell identity and shapes the proper generation of mature T cells. (See pp. E67–E74.)
Disrupting the blood–brain barrier by focused ultrasound induces sterile inflammation
Zsofia I. Kovacs, Saejeong Kim, Neekita Jikaria, Farhan Qureshi, Blerta Milo, Bobbi K. Lewis, Michele Bresler, Scott R. Burks, and Joseph A. Frank
Pulsed focused ultrasound (pFUS) with systemic microbubble (MB) infusion is a noninvasive technique that opens the blood–brain barrier (BBB) and is currently advocated for increasing drug or gene delivery in neurological diseases. The opening of the BBB by pFUS+MB resulted in immediate damage-associated molecular patterns that led to a sterile inflammation response within the parenchyma that lasted 24 h. Currently, pFUS+MB exposure is under consideration as an adjuvant in the treatment in malignancy or neurodegenerative disease. These results demonstrate that pFUS+MB induces a sterile inflammatory response compatible with ischemia or mild traumatic brain injury. Further investigation will be required before translation to clinical trials. (See pp. E75–E84.)
Early pancreatic cancer lesions suppress pain through CXCL12-mediated chemoattraction of Schwann cells
Ihsan Ekin Demir, Kristina Kujundzic, Paulo L. Pfitzinger, Ömer Cemil Saricaoglu, Steffen Teller, Timo Kehl, Carmen Mota Reyes, Linda S. Ertl, Zhenhua Miao, Thomas J. Schall, Elke Tieftrunk, Bernhard Haller, Kalliope Nina Diakopoulos, Magdalena U. Kurkowski, Marina Lesina, Achim Krüger, Hana Algül, Helmut Friess, and Güralp O. Ceyhan
Pancreatic ductal adenocarcinoma cancer (PDAC) cells have an exceptional propensity to invade nerves via pronounced crosstalk between nerves and cancer cells, but the mechanisms of this early neural invasion are yet unknown. By using genetically engineered mouse models, we show that in the precursor stage PDAC induces the generation of ready-to-use nerves for dissemination by secreting the chemokine CXCL12 that attracts glia (Schwann) cells of nerves. This migration of glia cells to cancerous cells at this very early stage intriguingly attenuates cancer-associated pain via downregulation of pain-associated targets in Schwann cells and via suppression of central glia. Hence, malignant transformed cells seem to disguise cancer-associated symptoms (such as pain) actively and thereby delay the early diagnosis of cancer. (See pp. E85–E94.)
The brain parenchyma has a type I interferon response that can limit virus spread
Eugene Drokhlyansky, Didem Göz Aytürk, Timothy K. Soh, Ryan Chrenek, Elaine O’Loughlin, Charlotte Madore, Oleg Butovsky, and Constance L. Cepko
The brain parenchyma is considered to be “immune privileged” based upon differences between the innate and adaptive immune responses of the brain and those of the periphery. This work provides a clear demonstration of an innate immune response to direct infection by a virus, a response that is capable of limiting the spread of the virus along neuronal circuitry. The question of the brain parenchyma’s response to a viral infection has implications for the use of viruses as tools by neuroscientists, for vaccine development, and for potential clinical applications. Additionally, the approach used here provides a framework for further examination of the immunologic state of the brain as well as the mechanisms by which encephalitic viruses circumvent this response. (See pp. E95–E104.)