ZmARF1 positively regulates low phosphorus stress tolerance via modulating lateral root development in maize.

Phosphorus (P) deficiency is one of the most critical factors for plant growth and productivity, including its inhibition of lateral root initiation. Auxin response factors (ARFs) play crucial roles in root development via auxin signaling mediated by genetic pathways. In this study, we found that the transcription factor ZmARF1 was associated with low inorganic phosphate (Pi) stress-related traits in maize. This superior root morphology and greater phosphate stress tolerance could be ascribed to the overexpression of ZmARF1. The knock out mutant zmarf1 had shorter primary roots, fewer root tip number, and lower root volume and surface area. Transcriptomic data indicate that ZmLBD1, a direct downstream target gene, is involved in lateral root development, which enhances phosphate starvation tolerance. A transcriptional activation assay revealed that ZmARF1 specifically binds to the GC-box motif in the promoter of ZmLBD1 and activates its expression. Moreover, ZmARF1 positively regulates the expression of ZmPHR1, ZmPHT1;2, and ZmPHO2, which are key transporters of Pi in maize. We propose that ZmARF1 promotes the transcription of ZmLBD1 to modulate lateral root development and Pi-starvation induced (PSI) genes to regulate phosphate mobilization and homeostasis under phosphorus starvation. In addition, ZmERF2 specifically binds to the ABRE motif of the promoter of ZmARF1 and represses its expression. Collectively, the findings of this study revealed that ZmARF1 is a pivotal factor that modulates root development and confers low-Pi stress tolerance through the transcriptional regulation of the biological function of ZmLBD1 and the expression of key Pi transport proteins.

A case of minimally invasive small-incision off-pump ligation of a coronary artery fistula monitored by transesophageal echocardiography.

This case demonstrated intraoperative real-time transesophageal echocardiographic monitoring in minimally invasive small-incision Off-pump ligation of a coronary artery fistula,demonstrating the importance of esophageal echocardiography in surgical monitoring.

Multimodal imaging diagnosis of left ventricular outflow tract obstruction due to abnormal papillary muscle insertion.

This article reports a case of LV outflow obstruction caused by abnormalities of the anterior leaflet connection of the mitral papillary muscle, aiming to highlight the importance of combined multimodal imaging in the differential diagnosis of the etiology of LV outflow obstruction.

A case of cardiac tamponade occurred 1 day after transcatheter atrial septal defect closure.

Transesophageal echocardiography (TEE) shows pericardial effusion and a gap between the left atrium and the aortic sinus by atrial septal defect occluder.

Effects of square spatial periodic forcing on oscillatory hexagon patterns in coupled reaction-diffusion systems.

One of the central issues in pattern formation is understanding the response of pattern-forming systems to an external stimulus. While significant progress has been made in systems with only one instability, much less is known about the response of complex patterns arising from the interaction of two or more instabilities. In this paper, we consider the effects of square spatial periodic forcing on oscillatory hexagon patterns in a two-layer coupled reaction diffusion system which undergoes both Turing and Hopf instabilities. Two different types of additive forcings, namely direct and indirect forcing, have been applied. It is shown that the coupled system exhibits different responses towards the spatial forcing under different forcing types. In the indirect case, the oscillatory hexagon pattern transitions into other oscillatory Turing patterns or resonant Turing patterns, depending on the forcing wavenumber and strength. In the direct forcing case, only non-resonant Turing patterns can be obtained. Our results may provide new insight into the modification and control of spatio-temporal patterns in multilayered systems, especially in biological and ecological systems.

Lsh/HELLS is required for B lymphocyte development and immunoglobulin class switch recombination.

Mutation of HELLS (Helicase, Lymphoid-Specific)/Lsh in human DNA causes a severe immunodeficiency syndrome, but the nature of the defect remains unknown. We assessed here the role of Lsh in hematopoiesis using conditional Lsh knockout mice with expression of Mx1 or Vav Cre-recombinase. Bone marrow transplantation studies revealed that Lsh depletion in hematopoietic stem cells severely reduced B cell numbers and impaired B cell development in a hematopoietic cell-autonomous manner. Lsh-deficient mice without bone marrow transplantation exhibited lower Ig levels in vivo compared to controls despite normal peripheral B cell numbers. Purified B lymphocytes proliferated normally but produced less immunoglobulins in response to in vitro stimulation, indicating a reduced capacity to undergo class switch recombination (CSR). Analysis of germline transcripts, examination of double-stranded breaks using biotin-labeling DNA break assay, and End-seq analysis indicated that the initiation of the recombination process was unscathed. In contrast, digestion-circularization PCR analysis and high-throughput sequencing analyses of CSR junctions and a chromosomal break repair assay indicated an impaired ability of the canonical end-joining pathway in Lsh-deficient B cells. Our data suggest a hematopoietic cell-intrinsic role of Lsh in B cell development and in CSR providing a potential target for immunodeficiency therapy.

Unruptured sinus of valsalva aneurysm diagnosed by multimodal imaging.

We describe a rare case of unruptured right SOVA in a 52-year-old man who was successfully treated with right SOVA repair and right coronary artery reconstruction. Our case demonstrates the usefulness of transthoracic echocardiography, contrastive echocardiography, and transesophageal echocardiography in diagnosing SOVA.

Selective cadmium regulation mediated by a cooperative binding mechanism in CadR.

Detoxification of the highly toxic cadmium element is essential for the survival of living organisms. Pseudomonas putida CadR, a MerR family transcriptional regulator, has been reported to exhibit an ultraspecific response to the cadmium ion. Our crystallographic and spectroscopic studies reveal that the extra cadmium selectivity of CadR is mediated by the unexpected cooperation of thiolate-rich site I and histidine-rich site II. Cadmium binding in site I mediates the reorientation of protein domains and facilitates the assembly of site II. Subsequently, site II bridge-links 2 DNA binding domains through ligands His140/His145 in the C-terminal histidine-rich tail. With dynamic transit between 2 conformational states, this bridge could stabilize the regulator into an optimal conformation that is critical for enhancing the transcriptional activity of the cadmium detoxification system. Our results provide dynamic insight into how nature utilizes the unique cooperative binding mechanism in multisite proteins to recognize cadmium ions specifically.

Imaging appearance of atypical aortic dissection in a 7-year-old boy with Loeys-Dietz syndrome.

This article described a rare case of atypical aortic dissection in a 7-year-old boy with Loeys-Dietz syndrome, and emergency procedure was performed successfully. The imaging appearance of echocardiography and CT in atypical dissection was described.

Maize Transcription Factor ZmARF4 Confers Phosphorus Tolerance by Promoting Root Morphological Development.

Plant growth and development are closely related to phosphate (Pi) and auxin. However, data regarding auxin response factors (ARFs) and their response to phosphate in maize are limited. Here, we isolated ZmARF4 in maize and dissected its biological function response to Pi stress. Overexpression of ZmARF4 in Arabidopsis confers tolerance of Pi deficiency with better root morphology than wild-type. Overexpressed ZmARF4 can partially restore the absence of lateral roots in mutant arf7 arf19. The ZmARF4 overexpression promoted Pi remobilization and up-regulated AtRNS1, under Pi limitation while it down-regulated the expression of the anthocyanin biosynthesis genes AtDFR and AtANS. A continuous detection revealed higher activity of promoter in the Pi-tolerant maize P178 line than in the sensitive 9782 line under low-Pi conditions. Meanwhile, GUS activity was specifically detected in new leaves and the stele of roots in transgenic offspring. ZmARF4 was localized to the nucleus and cytoplasm of the mesophyll protoplast and interacted with ZmILL4 and ZmChc5, which mediate lateral root initiation and defense response, respectively. ZmARF4 overexpression also conferred salinity and osmotic stress tolerance in Arabidopsis. Overall, our findings suggest that ZmARF4, a pleiotropic gene, modulates multiple stress signaling pathways, and thus, could be a candidate gene for engineering plants with multiple stress adaptation.

Experimental Demonstration of a Dusty Plasma Ratchet Rectification and Its Reversal.

The naturally persistent flow of hundreds of dust particles is experimentally achieved in a dusty plasma system with the asymmetric sawteeth of gears on the electrode. It is also demonstrated that the direction of the dust particle flow can be controlled by changing the plasma conditions of the gas pressure or the plasma power. Numerical simulations of dust particles with the ion drag inside the asymmetric sawteeth verify the experimental observations of the flow rectification of dust particles. Both experiments and simulations suggest that the asymmetric potential and the collective effect are the two keys in this dusty plasma ratchet. With the nonequilibrium ion drag, the dust flow along the asymmetric orientation of this electric potential of the ratchet can be reversed by changing the balance height of dust particles using different plasma conditions.

Structural basis of Zn(II) induced metal detoxification and antibiotic resistance by histidine kinase CzcS in Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) is a major opportunistic human pathogen, causing serious nosocomial infections among immunocompromised patients by multi-determinant virulence and high antibiotic resistance. The CzcR-CzcS signal transduction system in P. aeruginosa is primarily involved in metal detoxification and antibiotic resistance through co-regulating cross-resistance between Zn(II) and carbapenem antibiotics. Although the intracellular regulatory pathway is well-established, the mechanism by which extracellular sensor domain of histidine kinase (HK) CzcS responds to Zn(II) stimulus to trigger downstream signal transduction remains unclear. Here we determined the crystal structure of the CzcS sensor domain (CzcS SD) in complex with Zn(II) at 1.7 Å resolution. This is the first three-dimensional structural view of Zn(II)-sensor domain of the two-component system (TCS). The CzcS SD is of α/ß-fold in nature, and it senses the Zn(II) stimulus at micromole level in a tetrahedral geometry through its symmetry-related residues (His55 and Asp60) on the dimer interface. Though the CzcS SD resembles the PhoQ-DcuS-CitA (PDC) superfamily member, it interacts with the effector in a novel domain with the N-terminal α-helices rather than the conserved ß-sheets pocket. The dimerization of the N-terminal H1 and H1' α-helices is of primary importance for the activity of HK CzcS. This study provides preliminary insight into the molecular mechanism of Zn(II) sensing and signaling transduction by the HK CzcS, which will be beneficial to understand how the pathogen P. aeruginosa resists to high levels of heavy metals and antimicrobial agents.

Enhancing Cytotoxicity of a Monofunctional Platinum Complex via a Dual-DNA-Damage Approach.

Mitochondrial DNA (mtDNA) is an attractive cellular target for anticancer agents in addition to nuclear DNA (nDNA). The cationic platinum(II) complex cis-[Pt(NP)(NH3)2Cl]NO3 (PtNP, NP = N-(2-ethylpyridine)-1,8-naphthalimide) bearing the DNA-intercalating moiety NP was designed. The structure of PtNP was fully characterized by single-crystal X-ray crystallography, NMR, and HRMS. PtNP is superior to cisplatin in both in vitro and in vivo anticancer activities with low systemic toxicity. The interaction of PtNP with CT-DNA demonstrated that PtNP could effectively bind to DNA through both covalent and noncovalent double binding modes. In addition to causing significant damage to nDNA and remarkable inhibition to DNA damage repair, PtNP also distributed in mitochondria, inducing mtDNA damage and affecting the downstream transcriptional level of mitochondrion-encoded genes. In addition, PtNP disturbed the physiological processes of mitochondria by reducing the mitochondrial membrane potential and promoting the generation of reactive oxygen species. Mechanistic studies demonstrate that PtNP induced apoptosis via mitochondrial pathways by upregulating Bax and Puma and downregulating Bcl-2 proteins, leading to the release of cytochrome c and activation of caspase-3 and caspase-9. As a dual-DNA-damage agent, PtNP is able to improve the anticancer activity by damaging both nuclear and mitochondrial DNA, thus providing a new anticancer mechanism of action for the naphthalimide monofunctional platinum(II) complexes.

Rectification of chiral active particles driven by transversal temperature difference.

Rectification of chiral active particles driven by transversal temperature difference is investigated in a two-dimensional periodic channel. Chiral active particles can be rectified by transversal temperature difference. Transport behaviors are qualitatively different for different wall boundary conditions. For the sliding boundary condition, the direction of transport completely depends on the chirality of particles. The average velocity is a peaked function of angular velocity or temperature difference. The average velocity increases linearly with the self-propulsion speed, while it decreases monotonically with the increase in the packing fraction. For randomized boundary condition, the transport behaviors become complex. When self-propulsion speed is small, in contrast with the sliding boundary condition, particles move in the opposite direction. However, for large self-propulsion speed, current reversals can occur by continuously changing the system parameters (angular velocity, temperature difference, packing fraction, and width of the channel).

Restraining Cancer Cells by Dual Metabolic Inhibition with a Mitochondrion-Targeted Platinum(II) Complex.

Cancer cells usually adapt metabolic phenotypes to chemotherapeutics. A defensive strategy against this flexibility is to modulate signaling pathways relevant to cancer bioenergetics. A triphenylphosphonium-modified terpyridine platinum(II) complex (TTP) was designed to inhibit thioredoxin reductase (TrxR) and multiple metabolisms of cancer cells. TTP exhibited enhanced cytotoxicity against cisplatin-insensitive human ovarian cancer cells in a caspase-3-independent manner and showed preferential inhibition to mitochondrial TrxR. The morphology and function of mitochondria were severely damaged, and the levels of mitochondrial and cellular reactive oxygen species were decreased. As a result, TTP exerted strong inhibition to both mitochondrial and glycolytic bioenergetics, thus inducing cancer cells to enter a hypometabolic state.

Modulating Conformation of Aß-Peptide: An Effective Way to Prevent Protein-Misfolding Disease.

Alzheimer's disease (AD) is a typical protein-misfolding disease. Aggregation of amyloid ß-peptide (Aß) plays a key role in the etiology of AD. The misfolding of Aß results in the formation of ß-sheet-rich aggregates and damages the function of neurons. A modified polyoxometalate (POM), [CoL(H2O)]2[CoL]2[HAsVMoV6MoVI6O40] [CAM, L = 2-(1 H-pyrazol-3-yl)pyridine], was designed to disaggregate the Aß aggregates, where L acts as an Aß-targeting group and POM as a conformational modulator. X-ray crystallography shows that CAM is composed of a ε-Keggin unit and four coordination units. CAM can disaggregate the ß-sheet-rich fibrils and metal-induced or self-aggregated Aß aggregates, and it further inhibits the production of ROS; as a result, it can protect the neurons from synaptic toxicity induced by Zn2+- or Cu2+-Aß aggregates or Aß self-aggregation. The mechanism of disaggregation involves a transformation of Aß conformation from ß-sheet to other conformers. The nature of the process is an interference of the ß-sheet conformation by CAM via hydrogen bonding. CAM specifically interacts with Aß aggregates but does not disturb the cerebral metal homeostasis and enzymatic systems. Molecular simulation suggests that the appropriate size of CAM and the cavity of ß-sheets facilitate the interaction between CAM and Aß aggregates; additionally, the H-bonding-favored amino acid residues in the cavity provide a precondition for the interaction. Moreover, CAM is lipophilic and capable of penetrating the blood-brain barrier, and it is metabolizable without causing an untoward effect to mice at high dosages. In view of the significant inhibitory effect on the Aß aggregation and related neurotoxicity, CAM represents a new type of leading compounds with a distinctive mechanism of action for the treatment of Alzheimer' disease. The conception of this study may be applied to other protein-misfolding diseases caused by conformational changes.

Giant negative mobility of inertial particles caused by the periodic potential in steady laminar flows.

Transport of an inertial particle advected by a two-dimensional steady laminar flow is numerically investigated in the presence of a constant force and a periodic potential. Within particular parameter regimes, this system exhibits absolute negative mobility, which means that the particle can travel in a direction opposite to the constant force. It is found that the profile of the periodic potential plays an important role in the nonlinear response regime. Absolute negative mobility can be drastically enhanced by applying appropriate periodic potential, the parameter regime for this phenomenon becomes larger and the amplitude of negative mobility grows exceedingly large (giant negative mobility). In addition, giant positive mobility is also observed in the presence of appropriate periodic potential.