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Shape-controlled single-crystal growth of InP at low temperatures down to 220 °C (2019)

Hettick, Mark ; Li, Hao ; Lien, Der-Hsien ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2019; 117(2): 902-906. Published 2019 Dec 31. doi: 10.1073/pnas.1915786117.

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Publikationsdatum: 2019-12-31

Beschreibung: III–V compound semiconductors are widely used for electronic and optoelectronic applications. However, interfacing III–Vs with other materials has been fundamentally limited by the high growth temperatures and lattice-match requirements of traditional deposition processes. Recently, we developed the templated liquid-phase (TLP) crystal growth method for enabling direct growth of shape-controlled single-crystal III-Vs on amorphous substrates. Although in theory, the lowest temperature for TLP growth is that of the melting point of the group III metal (e.g., 156.6 °C for indium), previous experiments required a minimum growth temperature of 500 °C, thus being incompatible with many application-specific substrates. Here, we demonstrate low-temperature TLP (LT-TLP) growth of single-crystalline InP patterns at substrate temperatures down to 220 °C by first activating the precursor, thus enabling the direct growth of InP even on low thermal budget substrates such as plastics and indium-tin-oxide (ITO)–coated glass. Importantly, the material exhibits high electron mobilities and good optoelectronic properties as demonstrated by the fabrication of high-performance transistors and light-emitting devices. Furthermore, this work may enable integration of III–Vs with silicon complementary metal-oxide-semiconductor (CMOS) processing for monolithic 3D integrated circuits and/or back-end electronics.

Print ISSN: 0027-8424

Digitale ISSN: 1091-6490

Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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Combinatorial interactions of the LEC1 transcription factor specify diverse developmental programs during soybean seed development (2019)

Jo, Leonardo ; Pelletier, Julie M. ; Hsu, Ssu-Wei ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2019; 117(2): 1223-1232. Published 2019 Dec 31. doi: 10.1073/pnas.1918441117.

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Publikationsdatum: 2019-12-31

Beschreibung: The LEAFY COTYLEDON1 (LEC1) transcription factor is a central regulator of seed development, because it controls diverse biological programs during seed development, such as embryo morphogenesis, photosynthesis, and seed maturation. To understand how LEC1 regulates different gene sets during development, we explored the possibility that LEC1 acts in combination with other transcription factors. We identified and compared genes that are directly transcriptionally regulated by ABA-RESPONSIVE ELEMENT BINDING PROTEIN3 (AREB3), BASIC LEUCINE ZIPPER67 (bZIP67), and ABA INSENSITIVE3 (ABI3) with those regulated by LEC1. We showed that LEC1 operates with specific sets of transcription factors to regulate different gene sets and, therefore, distinct developmental processes. Thus, LEC1 controls diverse processes through its combinatorial interactions with other transcription factors. DNA binding sites for the transcription factors are closely clustered in genomic regions upstream of target genes, defining cis-regulatory modules that are enriched for DNA sequence motifs that resemble sequences known to be bound by these transcription factors. Moreover, cis-regulatory modules for genes regulated by distinct transcription factor combinations are enriched for different sets of DNA motifs. Expression assays with embryo cells indicate that the enriched DNA motifs are functional cis elements that regulate transcription. Together, the results suggest that combinatorial interactions between LEC1 and other transcription factors are mediated by cis-regulatory modules containing clustered cis elements and by physical interactions that are documented to occur between the transcription factors.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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Microglial IRF5-IRF4 regulatory axis regulates neuroinflammation after cerebral ischemia and impacts stroke outcomes (2019)

Al Mamun, Abdullah ; Chauhan, Anjali ; Qi, Shaohua ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2019; 117(3): 1742-1752. Published 2019 Dec 31. doi: 10.1073/pnas.1914742117.

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Publikationsdatum: 2019-12-31

Beschreibung: Microglial activation plays a central role in poststroke inflammation and causes secondary neuronal damage; however, it also contributes in debris clearance and chronic recovery. Microglial pro- and antiinflammatory responses (or so-called M1-M2 phenotypes) coexist and antagonize each other throughout the disease progress. As a result of this balance, poststroke immune responses alter stroke outcomes. Our previous study found microglial expression of interferon regulatory factor 5 (IRF5) and IRF4 was related to pro- and antiinflammatory responses, respectively. In the present study, we genetically modified the IRF5 and IRF4 signaling to explore their roles in stroke. Both in vitro and in vivo assays were utilized; IRF5 or IRF4 small interfering RNA (siRNA), lentivirus, and conditional knockout (CKO) techniques were employed to modulate IRF5 or IRF4 expression in microglia. We used a transient middle cerebral artery occlusion model to induce stroke and examined both acute and chronic stroke outcomes. Poststroke inflammation was evaluated with flow cytometry, RT-PCR, MultiPlex, and immunofluorescence staining. An oscillating pattern of the IRF5-IRF4 regulatory axis function was revealed. Down-regulation of IRF5 signaling by siRNA or CKO resulted in increased IRF4 expression, enhanced M2 activation, quenched proinflammatory responses, and improved stroke outcomes, whereas down-regulation of IRF4 led to increased IRF5 expression, enhanced M1 activation, exacerbated proinflammatory responses, and worse functional recovery. Up-regulation of IRF4 or IRF5 by lentivirus induced similar results. We conclude that the IRF5-IRF4 regulatory axis is a key determinant in microglial activation. The IRF5-IRF4 regulatory axis is a potential therapeutic target for neuroinflammation and ischemic stroke.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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Reward does not facilitate visual perceptual learning until sleep occurs (2019)

Tamaki, Masako ; Berard, Aaron V. ; Barnes-Diana, Tyler ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2019; 117(2): 959-968. Published 2019 Dec 31. doi: 10.1073/pnas.1913079117.

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Publikationsdatum: 2019-12-31

Beschreibung: A growing body of evidence indicates that visual perceptual learning (VPL) is enhanced by reward provided during training. Another line of studies has shown that sleep following training also plays a role in facilitating VPL, an effect known as the offline performance gain of VPL. However, whether the effects of reward and sleep interact on VPL remains unclear. Here, we show that reward interacts with sleep to facilitate offline performance gains of VPL. First, we demonstrated a significantly larger offline performance gain over a 12-h interval including sleep in a reward group than that in a no-reward group. However, the offline performance gains over the 12-h interval without sleep were not significantly different with or without reward during training, indicating a crucial interaction between reward and sleep in VPL. Next, we tested whether neural activations during posttraining sleep were modulated after reward was provided during training. Reward provided during training enhanced rapid eye movement (REM) sleep time, increased oscillatory activities for reward processing in the prefrontal region during REM sleep, and inhibited neural activation in the untrained region in early visual areas in non-rapid eye movement (NREM) and REM sleep. The offline performance gains were significantly correlated with oscillatory activities of visual processing during NREM sleep and reward processing during REM sleep in the reward group but not in the no-reward group. These results suggest that reward provided during training becomes effective during sleep, with excited reward processing sending inhibitory signals to suppress noise in visual processing, resulting in larger offline performance gains over sleep.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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BTZ black hole with Korteweg–de Vries-type boundary conditions: Thermodynamics revisited (2019)

Erices, Cristián ; Riquelme, Miguel ; Rodríguez, Pablo

American Physical Society

In: Physical Review D. 2019; 100(12): 126026. Published 2019 Dec 31. doi: 10.1103/physrevd.100.126026.

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Publikationsdatum: 2019-12-31

Print ISSN: 2470-0010

Digitale ISSN: 2470-0029

Thema: Physik

Publiziert von American Physical Society

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Proteome-wide observation of the phenomenon of life on the edge of solubility (2019)

Vecchi, Giulia ; Sormanni, Pietro ; Mannini, Benedetta ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2019; 117(2): 1015-1020. Published 2019 Dec 31. doi: 10.1073/pnas.1910444117.

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Publikationsdatum: 2019-12-31

Beschreibung: To function effectively proteins must avoid aberrant aggregation, and hence they are expected to be expressed at concentrations safely below their solubility limits. By analyzing proteome-wide mass spectrometry data of Caenorhabditis elegans, however, we show that the levels of about three-quarters of the nearly 4,000 proteins analyzed in adult animals are close to their intrinsic solubility limits, indeed exceeding them by about 10% on average. We next asked how aging and functional self-assembly influence these solubility limits. We found that despite the fact that the total quantity of proteins within the cellular environment remains approximately constant during aging, protein aggregation sharply increases between days 6 and 12 of adulthood, after the worms have reproduced, as individual proteins lose their stoichiometric balances and the cellular machinery that maintains solubility undergoes functional decline. These findings reveal that these proteins are highly prone to undergoing concentration-dependent phase separation, which on aging is rationalized in a decrease of their effective solubilities, in particular for proteins associated with translation, growth, reproduction, and the chaperone system.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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Crystal structure of human LDB1 in complex with SSBP2 (2019)

Wang, Hongyang ; Kim, Juhyun ; Wang, Zhizhi ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2019; 117(2): 1042-1048. Published 2019 Dec 31. doi: 10.1073/pnas.1914181117.

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Publikationsdatum: 2019-12-31

Beschreibung: The Lim domain binding proteins (LDB1 and LDB2 in human and Chip in Drosophila) play critical roles in cell fate decisions through partnership with multiple Lim-homeobox and Lim-only proteins in diverse developmental systems including cardiogenesis, neurogenesis, and hematopoiesis. In mammalian erythroid cells, LDB1 dimerization supports long-range connections between enhancers and genes involved in erythropoiesis, including the β-globin genes. Single-stranded DNA binding proteins (SSBPs) interact specifically with the LDB/Chip conserved domain (LCCD) of LDB proteins and stabilize LDBs by preventing their proteasomal degradation, thus promoting their functions in gene regulation. The structural basis for LDB1 self-interaction and interface with SSBPs is unclear. Here we report a crystal structure of the human LDB1/SSBP2 complex at 2.8-Å resolution. The LDB1 dimerization domain (DD) contains an N-terminal nuclear transport factor 2 (NTF2)-like subdomain and a small helix 4–helix 5 subdomain, which together form the LDB1 dimerization interface. The 2 LCCDs in the symmetric LDB1 dimer flank the core DDs, with each LCCD forming extensive interactions with an SSBP2 dimer. The conserved linker between LDB1 DD and LCCD covers a potential ligand-binding pocket of the LDB1 NTF2-like subdomain and may serve as a regulatory site for LDB1 structure and function. Our structural and biochemical data provide a much-anticipated structural basis for understanding how LDB1 and the LDB1/SSBP interactions form the structural core of diverse complexes mediating cell choice decisions and long-range enhancer–promoter interactions.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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A general-purpose protein design framework based on mining sequence–structure relationships in known protein structures (2019)

Zhou, Jianfu ; Panaitiu, Alexandra E. ; Grigoryan, Gevorg

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2019; 117(2): 1059-1068. Published 2019 Dec 31. doi: 10.1073/pnas.1908723117.

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Publikationsdatum: 2019-12-31

Beschreibung: Current state-of-the-art approaches to computational protein design (CPD) aim to capture the determinants of structure from physical principles. While this has led to many successful designs, it does have strong limitations associated with inaccuracies in physical modeling, such that a reliable general solution to CPD has yet to be found. Here, we propose a design framework—one based on identifying and applying patterns of sequence–structure compatibility found in known proteins, rather than approximating them from models of interatomic interactions. We carry out extensive computational analyses and an experimental validation for our method. Our results strongly argue that the Protein Data Bank is now sufficiently large to enable proteins to be designed by using only examples of structural motifs from unrelated proteins. Because our method is likely to have orthogonal strengths relative to existing techniques, it could represent an important step toward removing remaining barriers to robust CPD.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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Switching sides—Reengineered primary charge separation in the bacterial photosynthetic reaction center (2019)

Laible, Philip D. ; Hanson, Deborah K. ; Buhrmaster, James C. ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2019; 117(2): 865-871. Published 2019 Dec 31. doi: 10.1073/pnas.1916119117.

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Publikationsdatum: 2019-12-31

Beschreibung: We report 90% yield of electron transfer (ET) from the singlet excited state P* of the primary electron-donor P (a bacteriochlorophyll dimer) to the B-side bacteriopheophytin (HB) in the bacterial photosynthetic reaction center (RC). Starting from a platform Rhodobacter sphaeroides RC bearing several amino acid changes, an Arg in place of the native Leu at L185—positioned over one face of HB and only ∼4 Å from the 4 central nitrogens of the HB macrocycle—is the key additional mutation providing 90% yield of P+HB−. This all but matches the near-unity yield of A-side P+HA− charge separation in the native RC. The 90% yield of ET to HB derives from (minimally) 3 P* populations with distinct means of P* decay. In an ∼40% population, P* decays in ∼4 ps via a 2-step process involving a short-lived P+BB− intermediate, analogous to initial charge separation on the A side of wild-type RCs. In an ∼50% population, P* → P+HB− conversion takes place in ∼20 ps by a superexchange mechanism mediated by BB. An ∼10% population of P* decays in ∼150 ps largely by internal conversion. These results address the long-standing dichotomy of A- versus B-side initial charge separation in native RCs and have implications for the mechanism(s) and timescale of initial ET that are required to achieve a near-quantitative yield of unidirectional charge separation.

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Digitale ISSN: 1091-6490

Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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