Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Rhodococcus fascians cytokinins and their modus operandi to reshape the plant

Decades ago, the importance of cytokinins (CKs) during Rhodococcus fascians pathology had been acknowledged, and an isopentenyltransferase gene had been characterized in the fas operon of the linear virulence plasmid, but hitherto, no specific CK(s) could be associated with virulence. We show that the CK receptors AHK3 and AHK4 of Arabidopsis thaliana are essential for symptom development, and that the CK perception machinery is induced upon infection, underlining its central role in the symptomatology. Three classical CKs [isopentenyladenine, trans-zeatin, and cis-zeatin (cZ)] and their 2-methylthio (2MeS)-derivatives were identified by CK profiling of both the pathogenic R. fascians strain D188 and its nonpathogenic derivative D188–5. However, the much higher CK levels in strain D188 suggest that the linear plasmid is responsible for the virulence-associated production. All R. fascians CKs were recognized by AHK3 and AHK4, and, although they individually provoked typical CK responses in several bioassays, the mixture of bacterial CKs exhibited clear synergistic effects. The cis- and 2MeS-derivatives were poor substrates of the apoplastic CK oxidase/dehydrogenase enzymes and the latter were not cytotoxic at high concentrations. Consequently, the accumulating 2MeScZ (and cZ) in infected Arabidopsis tissue contribute to the continuous stimulation of tissue proliferation. Based on these results, we postulate that the R. fascians pathology is based on the local and persistent secretion of an array of CKs.
Protein tyrosine phosphatases PTP-1B and TC-PTP play nonredundant roles in macrophage development and IFN-γ signaling

The control of tyrosine phosphorylation depends on the fine balance between kinase and phosphatase activities. Protein tyrosine phosphatase 1B (PTP-1B) and T cell protein tyrosine phosphatase (TC-PTP) are 2 closely related phosphatases known to control cytokine signaling. We studied the functional redundancy of PTP-1B and TC-PTP by deleting 1 or both copies of these genes by interbreeding TC-PTP and PTP-1B parental lines. Our results indicate that the double mutant (tcptp−/−ptp1b−/−) is lethal at day E9.5–10.5 of embryonic development with constitutive phosphorylation of Stat1. Mice heterozygous for TC-PTP on a PTP-1B–deficient background (tcptp+/−ptp1b−/−) developed signs of inflammation. Macrophages from these animals were highly sensitive to IFN-γ, as demonstrated by increased Stat1 phosphorylation and nitric oxide production. In addition, splenic T cells demonstrated increased IFN-γ secretion capacity. Mice with deletions of single copies of TC-PTP and PTP-1B (tcptp+/−ptp1b+/−) exhibited normal development, confirming that these genes are not interchangeable. Together, these data indicate a nonredundant role for PTP-1B and TC-PTP in the regulation of IFN signaling.
Global distribution of conformational states derived from redundant models in the PDB points to non-uniqueness of the protein structure

It is commonly accepted that proteins have evolutionarily conserved 3-dimensional structures, uniquely defined by their amino acid sequence. Here, we question the direct association of structure to sequence by comparing multiple models of identical proteins. Rapidly growing structural databases contain models of proteins determined independently multiple times. We have collected these models in the database of the redundant sets of protein structures and then derived their conformational states by clustering the models with low root-mean-square deviations (RMSDs). The distribution of conformational states represented in these sets is wider than commonly believed, in fact exceeding the possible range of structure determination errors, by at least an order of magnitude. We argue that differences among the models represent the natural distribution of conformational states. Our results suggest that we should change the common notion of a protein structure by augmenting a single 3-dimensional model by the width of the ensemble distribution. This width must become an indispensible attribute of the protein description. We show that every protein contains regions of high rigidity (solid-like) and regions of high mobility (liquid-like) in different and characteristic contribution. We also show that the extent of local flexibility is correlated with the functional class of the protein. This study suggests that the protein-folding problem has no unique solution and should be limited to defining the folding class of the solid-like fragments even though they may constitute only a small part of the protein. These results limit the capability of modeling protein structures with multiple conformational states.
High catalytic activity of Au/CeOx/TiO2(110) controlled by the nature of the mixed-metal oxide at the nanometer level

Mixed-metal oxides play a very important role in many areas of chemistry, physics, materials science, and geochemistry. Recently, there has been a strong interest in understanding phenomena associated with the deposition of oxide nanoparticles on the surface of a second (host) oxide. Here, scanning tunneling microscopy, photoemission, and density-functional calculations are used to study the behavior of ceria nanoparticles deposited on a TiO2(110) surface. The titania substrate imposes nontypical coordination modes on the ceria nanoparticles. In the CeOx/TiO2(110) systems, the Ce cations adopt an structural geometry and an oxidation state (+3) that are quite different from those seen in bulk ceria or for ceria nanoparticles deposited on metal substrates. The increase in the stability of the Ce3+ oxidation state leads to an enhancement in the chemical and catalytic activity of the ceria nanoparticles. The codeposition of ceria and gold nanoparticles on a TiO2(110) substrate generates catalysts with an extremely high activity for the production of hydrogen through the water–gas shift reaction (H2O + CO → H2 + CO2) or for the oxidation of carbon monoxide (2CO + O2 → 2CO2). The enhanced stability of the Ce3+ state is an example of structural promotion in catalysis described here on the atomic level. The exploration of mixed-metal oxides at the nanometer level may open avenues for optimizing catalysts through stabilization of unconventional surface structures with special chemical activity.
Immunization by vaccine-coated microneedle arrays protects against lethal influenza virus challenge

Influenza prophylaxis would benefit from a simple method to administer influenza vaccine into skin without the need for hypodermic needles. In this study, solid metal microneedle arrays (MNs) were investigated as a system for cutaneous vaccine delivery using influenza virus antigen. The MNs with 5 monument-shaped microneedles per array were produced and coated with inactivated influenza virus A/PR/8/34 (IIV). As much as 10 μg of viral proteins could be coated onto an array of 5 microneedles, and the coated IIV was delivered into skin at high efficiency within minutes. The coated MNs were used to immunize mice in comparison with conventional intramuscular injection at the same dose. Analysis of immune responses showed that a single immunization with IIV-coated MNs induced strong antibody responses against influenza virus, with significant levels of hemagglutination inhibition activities (>1:40), which were comparable to those induced by conventional intramuscular immunization. Moreover, mice immunized by a single dose of IIV coated on MNs were effectively protected against lethal challenge by a high dose of mouse-adapted influenza virus A/PR/8/34. These results show that MNs are highly effective as a simple method of vaccine delivery to elicit protective immune responses against virus infection.
Looking Beyond Fibrillar Features to Scale Gecko‐Like Adhesion

Hand-sized gecko-inspired adhesives with reversible force capacities as high as 2950 N (29.5 N cm(-2) ) are designed without the use of fibrillar features through a simple scaling theory. The scaling theory describes both natural and synthetic gecko-inspired adhesives, over 14 orders of magnitude in adhesive force capacity, from nanoscopic to macroscopic length scales.
A national study of job satisfaction factors among faculty in physician assistant education

The purpose of this study was to examine the job satisfaction factors for physician assistant (PA) faculty. Job satisfaction factors were divided into two categories: intrinsic factors about the respondents (work itself and opportunities for advancement) and extrinsic factors about the institutional faculty support (salary, supervisory support, and coworker relations). The theoretical approach used in this study to examine job satisfaction among PA faculty was Herzberg’s (1966) two-factor theory of motivation. Additionally to enhance Herzberg’s theory regarding intrinsic and extrinsic factors, Smith, Kendall, and Hulin’s (1969) facet-specific job satisfaction theory (i.e., Job Description Index (JDI)) was utilized. A Web-based survey instrument was distributed by email communication to all PA faculty members who were affiliated with the Physician Assistant Education Association. This study evaluated physician assistant faculty’s attitudes and perceptions regarding job satisfaction. After expert panel review of the Web-based survey instrument, the total population of PA program faculty members (N = 1142) was asked to complete the survey. Five hundred eighteen faculty members responded, a 45% response rate. Frequencies, percentages, and appropriate summary statistics were computed for the personal and professional characteristics. Cronbach’s alpha was computed to measure the internal consistency of the five JDI factors and the overall job satisfaction scale. The mean and standard deviation for each factor was documented. Spearman’s correlation was computed for the JDI factors’ relationship to overall satisfaction. Multiple regression analysis was used to determine the predictors of overall satisfaction. Overall, PA faculty members were more satisfied than dissatisfied with their jobs. First, Web-based surveys are a relatively new methodology, and this study utilized this
Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity

Abstract Methylation of histone H3 lysine 36 (H3K36me) by yeast Set2 is critical for the maintenance of chromatin structure and transcriptional fidelity. However, we do not know the full range of Set2/H3K36me functions or the scope of mechanisms that regulate Set2-dependent H3K36 methylation. Here, we show that the APC/CCDC20 complex regulates Set2 protein abundance during the cell cycle. Significantly, absence of Set2-mediated H3K36me causes a loss of cell cycle control and pronounced defects in the transcriptional fidelity of cell cycle regulatory genes, a class of genes that are generally long, hence highly dependent on Set2/H3K36me for their transcriptional fidelity. Because APC/C also controls human SETD2, and SETD2 likewise regulates cell cycle progression, our data imply an evolutionarily conserved cell cycle function for Set2/SETD2 that may explain why recurrent mutations of SETD2 contribute to human disease.
Ligand-induced global transitions in the catalytic domain of protein kinase A

Conformational transitions play a central role in the phosphorylation mechanisms of protein kinase. To understand the nature of these transitions, we investigated the dynamics of nucleotide binding to the catalytic domain of PKA, a prototype for the protein kinase enzyme family. The open-to-closed transition in PKA was constructed as a function of ATP association by using available X-ray data and Brownian dynamics. Analyzing the multiple kinetic trajectories at the residue level, we find that the spatial rearrangement of the residues around the nucleotide-binding pocket, along with suppressed local fluctuations, controls the compaction of the entire molecule. In addition, to accommodate the stresses induced by ATP binding at the early transition stage, partial unfoldings (cracking) and reformations of several native contacts occur at the interfaces between the secondary structure motifs enveloping the binding pocket. This suggests that the enzyme experiences local structural deformations while reaching its functional, ATP-bound state. Our dynamical view of the ligand-induced transitions in PKA suggests that the kinetic hierarchy of local and global dynamics, the variable fluctuation of residues and the necessity of partial local unfolding may be fundamental components in other large scale allosteric transitions.
Icephobic/Anti‐Icing Properties of Micro/Nanostructured Surfaces

using materials such as fl uorocarbons, organic materials, and inorganic materials, [ 6 ] which demonstrate signifi cant hydrophobic properties. Whereas the robust superhydrophobicity of these materials exists at around room temperature, the overwhelming majority of them will fail when put into a subzero degree environment. [ 7 ] It is well known that hydrophobicity and icephobicity properties are extremely important to favor cold environment devices, [ 8 ] such as aerofoils, power towers, ships, radars, and even pipes of airconditioners or refrigerators. Once ice forms on this equipment, they may fail to work normally or may even be damaged. Anti-icing surfaces have been studied since the 1950s. [ 9 ] However, it is still a great challenge to design and fabricate more effi cient ice repellent surfaces, which has aroused the interest of many researchers. [ 7 , 10–25 ]
How does temperature impact the conformation of single DNA molecules below melting temperature?

Abstract The double stranded DNA molecule undergoes drastic structural changes during biological processes such as transcription during which it opens locally under the action of RNA polymerases. Local spontaneous denaturation could contribute to this mechanism by promoting it. Supporting this idea, different biophysical studies have found an unexpected increase in the flexibility of DNA molecules with various sequences as a function of the temperature, which would be consistent with the formation of a growing number of locally denatured sequences. Here, we take advantage of our capacity to detect subtle changes occurring on DNA by using high throughput tethered particle motion to question the existence of bubbles in double stranded DNA under physiological salt conditions through their conformational impact on DNA molecules ranging from several hundreds to thousands of base pairs. Our results strikingly differ from previously published ones, as we do not detect any unexpected change in DNA flexibility below melting temperature. Instead, we measure a bending modulus that remains stable with temperature as expected for intact double stranded DNA.
Secondary anchor polymorphism in the HA-1 minor histocompatibility antigen critically affects MHC stability and TCR recognition

T cell recognition of minor histocompatibility antigens (mHags) underlies allogeneic immune responses that mediate graft-versus-host disease and the graft-versus-leukemia effect following stem cell transplantation. Many mHags derive from single amino acid polymorphisms in MHC-restricted epitopes, but our understanding of the molecular mechanisms governing mHag immunogenicity and recognition is incomplete. Here we examined antigenic presentation and T-cell recognition of HA-1, a prototypic autosomal mHag derived from single nucleotide dimorphism (HA-1H versus HA-1R) in the HMHA1 gene. The HA-1H peptide is restricted by HLA-A2 and is immunogenic in HA-1R/R into HA-1H transplants, while HA-1R has been suggested to be a “null allele” in terms of T cell reactivity. We found that proteasomal cleavage and TAP transport of the 2 peptides is similar and that both variants can bind to MHC. However, the His>Arg change substantially decreases the stability and affinity of HLA-A2 association, consistent with the reduced immunogenicity of the HA-1R variant. To understand these findings, we determined the structure of an HLA-A2-HA-1H complex to 1. 3Å resolution. Whereas His-3 is accommodated comfortably in the D pocket, incorporation of the lengthy Arg-3 is predicted to require local conformational changes. Moreover, a soluble TCR generated from HA-1H-specific T-cells bound HA-1H peptide with moderate affinity but failed to bind HA-1R, indicating complete discrimination of HA-1 variants at the level of TCR/MHC interaction. Our results define the molecular mechanisms governing immunogenicity of HA-1, and highlight how single amino acid polymorphisms in mHags can critically affect both MHC association and TCR recognition.
17β‐Oestradiol enhances the acute hypotensive effect of captopril in female ovariectomized spontaneously hypertensive rats

The objective of this study was to investigate whether the acute haemodynamic effects of angiotensin‐converting enzyme inhibition with captopril could be enhanced by oestrogen administration, and then to evaluate the mechanisms involved in this enhancement. All experiments were performed in 18‐week‐old female spontaneously hypertensive rats arranged in three experimental groups: intact; ovariectomized (OVX); and ovariectomized plus treatment with 17β‐oestradiol (OVX + E2). These groups were used to evaluate the effects of captopril administration alone, or following bradykinin B2 receptor blockade or nitric oxide synthase inhibition, on a number of haemodynamic parameters (mean arterial pressure, cardiac index, vascular resistance and heart rate). The drop in mean arterial pressure and vascular resistance index in response to captopril was more pronounced in intact and ovariectomized rats treated with 17β‐oestradiol than in ovariectomized animals. Blockade of bradykinin B2 receptors or inhibition of nitric oxide synthesis attenuated the synergy between 17β‐oestradiol and captopril. It is concluded that ovariectomy blunted the blood pressure and vascular resistance index drop observed in intact rats in response to captopril. Treatment with 17β‐oestradiol prevented the blunted response to captopril in ovariectomized rats. Kinins and nitric oxide may be involved in the mechanisms of 17β‐oestradiol potentiation of the haemodynamic effects of captopril.
Biomechanics of the Temporomandibular Joint

Temporomandibular joint (TMJ) connects the mandible or the lower jaw to the skull and regulates the movement of the jaw (see Figure 1). The TMJ is one of the most complex, delicate and highly used joints in a human body (Alomar et al., 2007). The most important functions of the TMJ are mastication and speech. Temporomandibular disorder (TMD) is a generic term used for any problem concerning the jaw joint. Injury to the jaw, the TMJ, or muscles of the head and neck can cause TMD. Other possible causes include grinding or clenching the teeth; dislocation of the disc; presence of osteoarthritis or rheumatoid arthritis in the TMJ; stress, which can cause a person to tighten facial and jaw muscles or clench the teeth; aging (Bakke et al., 2001; Detamore et al., 2007; Ingawale and Goswami, 2009; Tanaka et al., 2000). The most common TMJ disorders are pain dysfunction syndrome, internal derangement, arthritis, and traumas (Breul et al., 1999; Chen et al., 1998). TMDs are seen most commonly in people between the ages of 20 and 40 years, and occur more often in women than in men (Detamore and Athanasiou, 2003; Detamore et al., 2007; Tanaka et al., 2008a). Some surveys have reported that 20-25% of the population exhibit one or more symptoms of TMD (Detamore et al., 2007; Ingawale and Goswami, 2009). With a large part of population suffering from TMDs, it is a problem that should be looked at more fully. Relations between muscle tensions, jaw motions, bite and joint force, and craniofacial morphology are not fully understood. A large fraction of TMD causes are currently unexplained. There is a great need of better understanding of the etiology of TMDs to develop methods to prevent, diagnose, and cure joint disorders (Beek et al., 2003; Ingawale and Goswami, 2009). This chapter provides a state-of-the-art review of TMJ anatomy, disorders, and biomechanics; and briefly discusses our approach toward threedimensional (3D) anatomical and finite element (FE) modeling to understand the interaction between structure and function of the TMJ.
Control of cell membrane tension by myosin-I

All cell functions that involve membrane deformation or a change in cell shape (e.g., endocytosis, exocytosis, cell motility, and cytokinesis) are regulated by membrane tension. While molecular contacts between the plasma membrane and the underlying actin cytoskeleton are known to make significant contributions to membrane tension, little is known about the molecules that mediate these interactions. We used an optical trap to directly probe the molecular determinants of membrane tension in isolated organelles and in living cells. Here, we show that class I myosins, a family of membrane-binding, actin-based motor proteins, mediate membrane/cytoskeleton adhesion and thus, make major contributions to membrane tension. These studies show that class I myosins directly control the mechanical properties of the cell membrane; they also position these motor proteins as master regulators of cellular events involving membrane deformation.
Mn2+ Dopant‐Controlled Synthesis of NaYF4:Yb/Er Upconversion Nanoparticles for in vivo Imaging and Drug Delivery

Pure dark red emission (650-670 nm) of NaYF(4):Yb/Er upconversion nanoparticles (UCNPs) is achieved by manganese ions (Mn(2+)) doping. In addition, the Mn(2+)-doping can also control the crystalline phase and size of the resulting UCNPs simultaneously. Drug delivery studies suggest the promise of these UCNPs as drug carriers for intracellular drug delivery and eventually as a multifunctional nanoplatform for simultaneous diagnosis and therapy.
Mental Health in New York City After the September 11 Terrorist Attacks: Results From Two Population Surveys

On the morning of September 11, 2001, four commercial airliners were hijacked from U.S. airports. Two of the planes crashed into the twin towers of the World Trade Center (WTC) in lower Manhattan, New York City. The WTC towers collapsed in the hours after they were hit. Although most people working inside the twin towers evacuated the buildings soon after the planes hit, the collapse of the towers resulted in the death of more than 3,000 people. Among the dead were office workers in the buildings at the time of their collapse and rescue personnel who had been climbing the towers in an attempt to bring survivors down to ground level. The terrorist attacks of September 11 were the largest single terrorist attack ever on U.S. soil.
Heterotypic gap junction channels as voltage-sensitive valves for intercellular signaling

Gap junction (GJ) channels assembled from connexin (Cx) proteins provide a structural basis for direct electrical and metabolic cell–cell communication. By combining fluorescence imaging and dual whole-cell voltage clamp methods, we demonstrate that in response to transjunctional voltage (Vj) Cx43/Cx45 heterotypic GJs exhibit both Vj-gating and dye transfer asymmetries. The later is affected by ionophoresis of charged fluorescent dyes and voltage-dependent gating. We demonstrate that small differences in resting (holding) potentials of communicating cells can fully block (at relative negativity on Cx45 side) or enhance (at relative positivity on Cx45 side) dye transfer. Similarly, series of high frequency Vj pulses resembling bursts of action potentials (APs) can fully block or increase the transjunctional flux (Jj) of dye depending on whether pulses are generated in the cell expressing Cx43 or Cx45, respectively. Asymmetry of Jj-Vj dependence is enhanced or reduced when ionophoresis and Vj-gating act synergistically or antagonistically, whereas single channel permeability (Pγ) remains unaffected. This modulation of intercellular signaling by Vj can play a crucial role in many aspects of intercellular communication in the adult, in embryonic development, and in tissue regeneration.