RNA polymerase functions like a molecular motor that can convert chemical energy into the work of strand separation and translocation along the DNA during transcription. The structures of phage T7 RNA polymerase in an elongation phase substrate complex that includes the incoming nucleoside triphosphate and a pretranslocation product complex that includes the product pyrophosphate (PPi) are described here. These structures and the previously determined posttranslocation elongation complex demonstrate that two enzyme conformations exist during a cycle of single nucleotide addition. One orientation of a five-helix subdomain is stabilized by the phosphates of either the incoming NTP or by the product PPi. A second orientation of this subdomain is stable in their absence and is associated with translocation of the heteroduplex product as well as strand separation of the downstream DNA. We propose that the dissociation of the product PPi after nucleotide addition produces the protein conformational change resulting in translocation and strand separation.

To make messenger RNA transcripts, bacteriophage T7 RNA polymerase (T7 RNAP) undergoes a transition from an initiation phase, which only makes short RNA fragments, to a stable elongation phase. We have determined at 2.1 angstrom resolution the crystal structure of a T7 RNAP elongation complex with 30 base pairs of duplex DNA containing a "transcription bubble" interacting with a 17-nucleotide RNA transcript. The transition from an initiation to an elongation complex is accompanied by a major refolding of the amino-terminal 300 residues. This results in loss of the promoter binding site, facilitating promoter clearance, and creates a tunnel that surrounds the RNA transcript after it peels off a seven-base pair heteroduplex. Formation of the exit tunnel explains the enhanced processivity of the elongation complex. Downstream duplex DNA binds to the fingers domain, and its orientation relative to upstream DNA in the initiation complex implies an unwinding that could facilitate formation of the open promoter complex.

ambient mechanical energy, [8][9][10][11][12][13][14] because they exhibit the desirable characteristics of simple structure, low cost, lightweight, high effi ciency, and high power density, as well as the prospect of broad applications. Widely distributed water kinetic energy is an abundant source for large-scale applications, and the energy provided by water is much less dependent on seasonality, daylight, weather, and/or temperature. [ 15,16 ] However, since liquid water can inherently make the two electrodes in a TENG shortcircuit, [ 17 ] a TENG with an open structure cannot work under harsh conditions in the presence of water. Although some TENGs used for harvesting wave energy have been fabricated and sealed in enclosed casings based on rolling structures, [18][19][20][21] they all utilized single-electrode and attachedelectrode modes. For single-electrode mode designs, [19][20][21] their performance is fundamentally limited by the electrostatic shield effect, so such a kind of structure is mainly for sensor purpose and its output is low as an energy harvester. [ 22 ] For attached-electrode mode designs, [ 18 ] it requires that the two triboelectric materials must be fully contacted; even an air gap with tens of microns will largely degrade their performance. [ 23 ] However, the ocean wave energy is a random energy source, resulting in a not optimized performance of such devices for practical application. More importantly, all the previous design's natural frequency is beyond 10 Hz, which is much larger than the vibration frequency of water wave. Therefore, there still lacks a feasible triboelectric nanogenerator design that can effectively harvest the water wave energy.To solve the above problem, this paper demonstrates a rolling-structured, freestanding triboelectric-layer-based nanogenerator (RF-TENG) for harvesting energy from low-frequency wave movements. A TENG was initially fabricated by using a rolling Nylon ball to contact with a Kapton fi lm in an enclosed spherical shell. Relying on the surface contact electrifi cation effect between conventional polymers, this RF-TENG is extremely lightweight, low cost, and capable of fl oating on the surface for wave energy harvesting. The freestanding design has a relatively linear charge transfer curve that assures good charge transfer effi ciency, even under low-amplitude vibration. [ 24 ] In addition, the rolling design greatly reduces the Water waves are increasingly regarded as a promising source for large-scale energy applications. Triboelectric nanogenerators (TENGs) have been recognized as one of the most promising approaches for harvesting wave energy. This work examines a freestanding, fully enclosed TENG that encloses a rolling ball inside a rocking spherical shell. Through the optimization of materials and structural parameters, a spherical TENG of 6 cm in diameter actuated by water waves can provide a peak current of 1 µA over a wide load range from a short-circuit condition to 10 GΩ, with an instantaneous output power of up to 10 mW. A multielect...

Summary Human mitochondrial DNA polymerase (Pol γ) is the sole replicase in mitochondria. Pol γ is vulnerable to non-selective anti-retroviral drugs and is increasingly associated with mutations from mitochondriopathic patients. We determined a crystal structure of human Pol γ holoenzyme and, separately, a variant of its processivity factor Pol γB. This is the first atomic structure of any human DNA replicase. The structures reveal that the catalytic subunit Pol γA interacts asymmetrically with the homodimeric Pol γB. A spacer domain of Pol γA, absent in other DNA Pol I family members, is critical for processive DNA synthesis. Pol γ represents a new class of DNA replicase that is structurally and mechanistically different from its eukaryotic and prokaryotic counterparts. The Pol γ structure rationalizes the phenotypes of certain disease-related mutant enzymes that hitherto were inexplicable, and provides a foundation for understanding the molecular basis of toxicity of anti-retroviral drugs targeting HIV reverse transcriptase.

No abstract

Researchers report a scalable approach for highly deformable and stretchable energy harvesters and self-powered sensors.

Background: There are no clear expert consensus or guidelines on how to treat 2019 coronavirus disease . The objective of this study is to investigate the short-term effect of risk-adapted treatment strategy on patients with COVID-19. Methods: We collected the medical records of 55 COVID-19 patients for analysis. We divided these patients into mild, moderate and severe groups, and risk-adapted treatment approaches were given according to the illness severity. Results: Twelve patients were in mild group and 22 were in moderate group (non-severe group, n = 34), and 21 patients were in severe group. At the end of the first two weeks after admission, clinical manifestations had completely despeared in 31(91.2%)patients in non-severe group, and 18(85.7%) patients in severe group (p = 0.85). Both groups had a satisfied chest CT imaging recovery, which includes 22(64.7%) patients in non-severe group and 12(57.1%) patients in severe group recovered at least 50% of the whole leisions in the first week, and 28(82.4%) and 16(76.2%) recovered at least 75% in the second week, respectively. There were no significant differences in SARS-CoV-2 nucleic acid negativity (p = 0.92). There were also no significant differences in the levels of SARS-CoV-2-IgM and IgG antibody production between the two groups (p = 0.13, 0.62). There were 45 cases were discharged from the hospital, and no patients died at the time of this clinical analysis. Conclusions: Risk-adapted treatment strategy was associated with significant clinical manifestations alleviation and clinical imaging recovery. In severe COVID-19 patients, early and short-term use of lowdose methylprednisolone was beneficial and did not delay SARS-CoV-2 nucleic acid clearance and influence IgG antibody production.

To promote the development of supercapacitors and their applications in modern electronics, it is crucial to explore novel supercapacitor electrode materials. As a representative member of the rising 2D MXenes,...