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Neuronal loss is the central issue in Alzheimer's disease (AD), yet no treatment developed so far can halt AD-associated neurodegeneration. Here, we developed a monoclonal antibody (mAb2A7) against 217 site-phosphorylated human tau (p-tau217) and observed that p-tau217 levels positively correlated with brain atrophy and cognitive impairment in AD patients. Intranasal administration efficiently delivered mAb2A7 into male PS19 tauopathic mouse brain with target engagement and reduced tau pathology/aggregation with little effect on total soluble tau. Further, mAb2A7 treatment blocked apoptosis-associated neuronal loss and brain atrophy, reversed cognitive deficits, and improved motor function in male tauopathic mice. Proteomic analysis revealed that mAb2A7 treatment reversed alterations mainly in proteins associated with synaptic functions observed in murine tauopathy and AD brain. An antibody (13G4) targeting total tau also attenuated tau-associated pathology and neurodegeneration but impaired the motor function of male tauopathic mice. These results implicate p-tau217 as a potential therapeutic target for AD-associated neurodegeneration. • P-tau217 correlates with brain atrophy and cognitive impairment in AD patients • Antibody against p-tau217 attenuates pathology and neuronal loss in tauopathic mice • P-tau217 antibody restores brain function and proteostasis in tauopathic mice • An antibody targeting total tau leads to motor deficits in tauopathic mice Zhang et al. demonstrate that passive immunotherapy targeting p-tau217 is an effective strategy for intervening in tau-associated pathology and neurodegeneration in a mouse model of tauopathy, with potentially little side effect. [ABSTRACT FROM AUTHOR]

The mass- and field-shift parameters of the two 2s 2S1/2 → 2p 2P1/2,3/2 transitions in the Li-like Ca ions are calculated by using multi-configuration Dirac–Hartree–Fock (MCDHF) and the relativistic configuration interaction (RCI) methods with the inclusion of the transverse photon (Breit) interaction, vacuum polarization and self-energy corrections. In addition, the mass shift and field shift of these two transitions are calculated, where the field shift is calculated by using the evaluated value δ〈 r2〉 obtained by [Atomic Data and Nuclear Data Tables 99 69 (2013)]. It is found that the mass shift of Li-like Ca ions is greater than the field shift. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disorder seen in age-dependent dementia. There is currently no effective treatment for AD, which may be attributed in part to lack of a clear underlying mechanism. Studies within the last few decades provide growing evidence for a central role of amyloid β (Aβ) and tau, as well as glial contributions to various molecular and cellular pathways in AD pathogenesis. Herein, we review recent progress with respect to Aβ- and tau-associated mechanisms, and discuss glial dysfunction in AD with emphasis on neuronal and glial receptors that mediate Aβ-induced toxicity. We also discuss other critical factors that may affect AD pathogenesis, including genetics, aging, variables related to environment, lifestyle habits, and describe the potential role of apolipoprotein E (APOE), viral and bacterial infection, sleep, and microbiota. Although we have gained much towards understanding various aspects underlying this devastating neurodegenerative disorder, greater commitment towards research in molecular mechanism, diagnostics and treatment will be needed in future AD research. [ABSTRACT FROM AUTHOR]

Abstract The gamma-type inhibitor of snake venom phospholipase A 2 (PLIγ) is expressed extensively in livers of both venomous and non-venomous snakes. It is not clear why PLIγs from different snake species possess diverse activities. To obtain high activity PLIγs and interpret the sequence-function relationships, we used DNA shuffling to hybridize the PLIγs of Sinonatrix annularis (saPLIγ) and Elaphe carinata (ecPLIγ). Chimera PLIγs (cPLIγ) of ∼550 bp were obtained by a series of gene manipulations including DNase I digestion, primer-free PCR, and PCR amplification with PLIγs primer pair. After successful insertion of cPLIγs into pCANTAB5e phage vector, the transformed TG1 strain of Esherichia coli was achieved. The cPLIγ phage library was produced and panned in a five-pace snake venom-coated immune tube. Three high affinity cPLIγ isoforms survived two rounds of panning. Prokaryote expression by the pET28c vector was employed for production of the three cPLIγs and the two parental PLIγs. These all showed anti-hemorrhage activity with cPLIγ 2 demonstrating superior inhibition to the parent PLIγs. Sequence alignment showed that the three kinds of cPLIγ were produced by gene splicing of S. annularis and E. carinata at different sites. Primary sequence changes brought regional changes in secondary and tertiary structure, which may explain the differences in PLIγ activity. Highlights • PLIγ can neutralize snake venom PLA2s, and is regarded as a promising antivenom candidate. • DNA shuffling and phage surface display is an effective way for PLIγ directed evolution. • The chimera PLIγ 2 showed even superior anti-hemorrhage activity than the parent PLIγs. • The α-helix of 150–155aa was believed to be correlative to the activity of PLIγ. [ABSTRACT FROM AUTHOR]

SaPLIγ is a natural phospholipase A 2 (PLA 2 ) inhibitor, isolated from Sinonatrix annularis, that has been demonstrated to protect against envenomation by other venomous snakes. As snake venom PLA 2 s and mammalian secretory PLA 2 s are similar, saPLIγ is thought to have potential to alleviate inflammatory reactions in which PLA 2 s act as a key enzyme for arachidonic acid release. The aim of this study was to investigate the anti-inflammatory effects and mechanisms of action of saPLIγ in an animal model of carrageenan-induced acute inflammation. The results indicated that saPLIγ inhibited PLA 2 subtypes extensively, especially IIA-PLA 2 , in a dose-dependent manner. Paw swelling in mice was reduced markedly by intraperitoneal saPLIγ 2 .5 mg/kg, and the effect was significantly better than observed with dexamethasone at the same dose. Lower neutrophil infiltration and tissue edema was observed in the paws of saPLIγ-treated mice. Additionally, carrageenan-induced cyclooxygenase- 2 (COX- 2 ) and pro-inflammatory cytokines (TNFα and IL-1β) were also significantly down-regulated by saPLIγ in a dose-dependent manner. These results suggested that saPLIγ had effective anti-inflammatory effects in vivo, and these were produced by blocking mammalian IB, IIA, V and X sPLA2 subtypes. [ABSTRACT FROM AUTHOR]

The excitation energies of the Be-like ions (4 ≤ Z ≤ 74) doubly excited state 1 s 2 2 p 2 and doubly core-excited state 2 s 2 p 3 are calculated using the multi-configuration Dirac–Hartree–Fock method. The contributions of relativistic effects, Breit interaction, and QED effects to the excitation energies are analyzed and discussed in detail. A reasonable electron correlation model has been constructed using the active set method. The electron correlation and the finite size of the atomic nucleus correction have also been appropriately considered. The calculated results agree with the available theoretical and experimental data. It is found that the contribution of relativistic effects, Breit interaction, and QED effects to the excitation energy becomes significant with increasing Z. The contribution of the relativistic effects reaches about 8.5% at Z=74. The 3 P 0 level of the doubly excited state 1 s 2 2 p 2 is sensitive to the Breit interaction and the QED effects, but these two contributions cancel each other out. For the doubly core-excited state 2 s 2 p 3 , the Breit interaction and the QED effects are almost equally important, and their maximum contribution is about 0.5%. These results are expected to help future experimental and theoretical work. [ABSTRACT FROM AUTHOR]

[Display omitted] • A venom affinity column was constructed and adapted for active inhibitors mining. • Venom inhibitors and toxin receptors were identified in the serum and liver of the snake species S. annularis. • Fifteen toxins from D. acutus venom were pooled using venom binding proteins-affinity column Various snake species and snake predators have natural neutralization against snake toxins, which their antidotal abilities are commonly attributed to the intrinsic inhibitors produced by the liver, e.g., phospholipase A 2 inhibitor (PLI) and metalloproteinase inhibitor (SVMPI). Sinonatrix annularis was found to possess broad-spectrum neutralization to different snake venoms in our lab. Although the anti-venom compound PLIγ has been previously characterized in our laboratory, the mechanism of resistance of S. annularis to snake venoms remains obscure. In this research, a venom affinity chromatography was constructed by immobilizing D. acutus venom to NHS-agarose beads and applied for antitoxins mining from S. annularis. The binding capacity of the venom column was validated using a self-prepared rabbit antivenom against D. acutus. Serum and liver homogenate of S. annularis were then applied to the column, the bound components were profiled using SDS-PAGE and mass spectrometry. PLIs, snake venom metalloproteins inhibitor (SVMPI), small serum protein (SSP), heat shock proteins, etc were identified. To identify their toxin targets in D. acutus venom, a reverse separation was conducted by coupling the fractionated S. annularis serum proteins to NHS-agarose beads. Fifteen toxins of five families were captured and identified as follows: PLA 2 s, metalloproteinases, cysteine-rich secretory proteins, snake venom serine proteinases, and C-type lectins. These discoveries increased our understanding of the capacity and mechanism of the natural neutralization of S. annularis to snake venom. These natural inhibitors are medically significant due to their powerful and broad antidotal activities, which may provide alternative and promising drug candidates for snakebite treatment. [ABSTRACT FROM AUTHOR]

The wavelengths and transition rates of W40+-W42+ ions within the range of 40–140 Å, have been calculated using the Flexible Atomic Code of the Dirac-Fock-Slater method with a central potential. We investigated the charge state distribution of W38+-W45+ ions at different temperatures by constructing an appropriate rate equation and demonstrate the importance of the dielectronic recombination process. Additionally, we simulated the emission spectra of W40+-W42+ ions in a Tokamak plasma environment using collisional-radiative modeling. Our findings demonstrate strong agreement with experimental results and other related theoretical investigations. Finally, we propose certain pairs of transition lines as diagnostic tools for plasma temperature and density, leveraging the correlation between line intensity ratio and electron temperature and density. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by cognitive impairment with few therapeutic options. Despite many failures in developing AD treatment during the past 20 years, significant advances have been achieved in passive immunotherapy of AD very recently. Here, we review characteristics, clinical trial data, and mechanisms of action for monoclonal antibodies (mAbs) targeting key players in AD pathogenesis, including amyloid-β (Aβ), tau and neuroinflammation modulators. We emphasized the efficacy of lecanemab and donanemab on cognition and amyloid clearance in AD patients in phase III clinical trials and discussed factors that may contribute to the efficacy and side effects of anti-Aβ mAbs. In addition, we provided important information on mAbs targeting tau or inflammatory regulators in clinical trials, and indicated that mAbs against the mid-region of tau or pathogenic tau have therapeutic potential for AD. In conclusion, passive immunotherapy targeting key players in AD pathogenesis offers a promising strategy for effective AD treatment. ● Passive immunotherapy is a major strategy under clinical development for AD treatment. ● Monoclonal antibodies against Aβ including lecanemab and donanemab showed significant efficacy in phase III clinical trials. ● ARIA and brain atrophy cannot be ignored in Aβ-targeted immunotherapy. ● Passive immunotherapy targeting tau and neuroinflammation is at an early stage of development. [ABSTRACT FROM AUTHOR]

The properties and spectrum of the highly charged tungsten ions draw more and more attention, due to its potential application in the next generation fusion reactor. The transition wavelength and rate of the magnetic-dipole transition between the levels of the ground configuration of W53+ ion in the range of 10 − 20 nm were calculated by Dirac–Fock–Slater (DFS) method with a local central potential and Multi-Configuration Dirac-Hartree-Fock (MCDHF) method, respectively. The results are consistent with the previous EBIT experimental data and other theoretical data. A collisional-radiative model was constructed, and the spectrum of magnetic-dipole transition of W53+ ion observed on EBIT (Y. Ralchenko et al., Phys. Rev. A. 83 , 032517, 2011) was reproduced theoretically. Another two new transitions near the wavelength of 16.683 nm and 18.018 nm are also assigned to the M1 transition of W53+ ion. • The EBIT spectrum of W53+ ion was reproduced and analyzed by CRM with accurate atomic data. • The new M1 transition between the ground configuration of W53+ ions were assigned to the experimental spectrum. • The MCDHF transition wavelength was used instead of DFS results to get better agreement with the experiments. [ABSTRACT FROM AUTHOR]

Phospholipase A2s (PLA2) is a major component of snake venom with diverse pathologic toxicities and, therefore, a potential target for antivenom therapy. Varespladib was initially designed as an inhibitor of mammal PLA2s, and was recently repurposed to a broad-spectrum inhibitor of PLA2 in snake venom. To evaluate the protective abilities of varespladib to hemorrhage, myonecrosis, and systemic toxicities that are inflicted by different crude snake venoms, subcutaneous ecchymosis, muscle damage, and biochemical variation in serum enzymes derived from the envenomed mice were determined, respectively. Varespladib treatment showed a significant inhibitory effect to snake venom PLA2, which was estimated by IC50 in vitro and ED50 in vivo. In animal models, the severely hemorrhagic toxicity of D. acutus and A. halys venom was almost fully inhibited after administration of varespladib. Moreover, signs of edema in gastrocnemius muscle were remarkably attenuated by administration of varespladib, with a reduced loss of myonecrosis and desmin. Serum levels of creatine kinase, lactate dehydrogenase isoenzyme 1, aspartate transaminase, and alanine transaminase were down-regulated after treatment with varespladib, which indicated the protection to viscera injury. In conclusion, varespladib may be a potential first-line drug candidate in snakebite envenomation first aid or clinical therapy. [ABSTRACT FROM AUTHOR]

The dielectronic recombination of Li-like Xe (2s) ions was studied using the flexible atomic code based on the relativistic configuration interaction method. The resonance energies, radiative and autoionization rates, and resonance strengths were calculated systematically for the doubly excited states (2 p n l )( n = 18−32) and (2 p n′ l )( n′ = 9−27) of Be-like Xe ions. For the higher Rydberg resonance states with n ≥ 33 and n′ ≥ 28, the resonance energies and strengths were obtained by extrapolation based on quantum defect theory. The theoretical rate coefficients, covering the center-of-mass energy range 0-505 eV, are in a better agreement with the experimental results measured at the heavy-ion storage ring ESR than the Multi-Configuration Dirac-Fock calculations, especially at the resonance energy range close to the series limits. Graphical abstract: [ABSTRACT FROM AUTHOR]

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation. Reference 1 Wang Y., Zhang J., Zhang D., Xiao H., Xiong S., Huang C. Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation. The authors would like to correct an error in the original publication [[1]]. [Extracted from the article]

The energy levels of 1s2, 1s2s, and 2s2p configurations for He-like ions (4 ≤ Z ≤ 54) are calculated using the multi-configuration Dirac–Hartree–Fock​ methods. The transition energies, transition rates, and oscillator strengths of 2s2p → 1s2 and 2s2p → 1s2s are also calculated. A parallel calculation based on the Dirac–Fock–Slater method with a local central potential is performed using the Flexible Atomic Code to cross-check the accuracy of the data. The Breit interaction and quantum electrodynamics effects, including self-energy and vacuum polarization, are included as perturbations in these calculations. The average relative standard deviation of the energy levels from the available NIST data is about 0.2% for both methods. The transition energies and rates are in reasonable agreement with other available theoretical and experimental data, and the consistency between the transition energies calculated by the two methods reaches 99.9%. These results are expected to help future investigations on double K-shell vacancy decays of He-like ions. [ABSTRACT FROM AUTHOR]

• The electron correlation model was constructed for double K hole states of highly charged Xe q + ions. • The multi-configuration Dirac-Hartree-Fock method was used with electron correlation, Breit and QED effects corrections. • The spectator electron effects on the transition energy shift was determined to be 240 eV per 2p spectator electron. • The synthetic spectrum of the bare Xe ions interacting with carbon target were provided. The double electron E1 transition energies, probabilities, and oscillator strengths between the 2 s 2 p n and 1 s 2 2 p n − 1 (1 ≤ n ≤ 6) configurations of Xe q + (47 ≤ q ≤ 52) ions with different spectator electrons have been calculated based on the multi-configuration Dirac-Hartree-Fock method. A reasonable electron correlation model is constructed with the aid of the active space method. The finite mass of nuclear, Breit interaction and QED effects have also been included. The calculated results are in good agreement with the available data. The theoretical spectra of different spectator electrons of the double K hole state have been predicted. The spectator electron effects on the transition spectra have been analyzed in detail. The present results will be helpful for analyzing the high energy X-ray spectrum observed from the interaction between high energy highly charged ions and the surface. [ABSTRACT FROM AUTHOR]

Background: Late blight disease (LBD) caused by the pathogen Phytophthora infestans (PI), is the most devastating disease limiting potato (Solanum tuberosum) production globally. Currently, this disease pathogen is re-emerging and appearing in new areas at a very high intensity. A better understanding of the natural defense mechanisms against PI in different potato cultivars especially at the protein level is still lacking. Therefore, to elucidate potato proteome response to PI, we investigated changes in the proteome and leaf morphology of three potato cultivars, namely; Favorita (FA), Mira (MA), and E-malingshu N0.14 (E14) infected with PI by using the iTRAQ-based quantitative proteomics analysis. Results: A total of 3306 proteins were found in the three potato genotypes, and 2044 proteins were quantified. Cluster analysis revealed MA and E14 clustered together separately from FA. The protein profile and related functions revealed that the cultivars shared a typical hypersensitive response to PI, including induction of elicitors, oxidative burst, and suppression of photosynthesis in the potato leaves. Meanwhile, MA and E14 deployed additional specific response mechanism different from FA, involving high induction of protease inhibitors, serine/threonine kinases, terpenoid, hormone signaling, and transport, which contributed to MA tolerance of LBD. Furthermore, inductions of pathogenesis-related proteins, LRR receptor-like kinases, mitogen-activated protein kinase, WRKY transcription factors, jasmonic acid, and phenolic compounds mediate E14 resistance against LBD. These proteins were confirmed at the transcription level by a quantitative polymerase chain reaction and at the translation level by western-blot. Conclusions: We found several proteins that were differentially abundant among the cultivars, that includes common and cultivar specific proteins which highlighted similarities and significant differences between FA, MA, and E14 in terms of their defense response to PI. Here the specific accumulation of mitogen-activated protein kinase, Serine/threonine kinases, WRKY transcription played a positive role in E14 immunity against PI. The candidate proteins identified reported in this study will form the basis of future studies and may improve our understanding of the molecular mechanisms of late blight disease resistance in potato. [ABSTRACT FROM AUTHOR]

K‐shell dielectronic, trielectronic, and quadruelectronic recombination and polarization of X‐ray emission have been studied for the highly charged Si9+ ions in the initial ground state 2P1/2 and the metastable state 2P3/2 using the Flexible Atomic Code. It is found that the resonant recombination cross section from the long‐lived metastable state is comparable in magnitude with that of the ground state, so it is important for plasma diagnostics. For Si9+(2P1/2), trielectronic recombination contributions of nearly 25% to the total resonant recombination strength are predicted, which is less than previous calculations. We compare the degree of linear polarization for the eleven dominant resonant recombination satellite lines from the initial parent Si9+(2P1/2) and Si9+(2P3/2) ions. For the same X‐ray lines, large variations of polarization are found between 2P1/2 and 2P3/2, which can be employed to diagnose formation mechanisms of intermediate resonance states and corresponding X‐ray lines. [ABSTRACT FROM AUTHOR]

• A systematic study of spatiotemporal evolution of extreme ultraviolet spectra in laser-produced silver (Ag) plasmas is performed with aid of a spatio-temporally resolved emission spectroscopy and multiconfiguration Hartree-Fock calculations. • Complex spectral structures were accurately revealed based on the assumption of a normalized Boltzmann distribution among the excited states and a steady-state collision-radiative model, which are dominated from the contributions of 4p and 4d excitations of Ag7+–Ag13+ ions. • Theoretical plasma-state parameters near the target surface at the initial stage of the laser-produced Ag plasma were determined via the steady-state collision-radiation model. Experimental and theoretical analyses are reported for the spatiotemporal evolution of extreme ultraviolet spectra in laser-produced silver (Ag) plasmas. The time-resolved spectra were acquired 1.5 mm from the target surface. The 4p and 4d excitations of Ag7+–Ag13+ ions were calculated with the aid of multiconfiguration Hartree-Fock calculations. The spectral line distributions of transitions in the dominant 4p and 4d excitation configurations and their variations with the degree of ionization were analyzed. Complex spectral structures were accurately revealed based on the assumption of a normalized Boltzmann distribution among the excited states and a steady-state collision-radiative model. Experimental peak origins were identified by comparing experimental and simulated spectra. These results will provide data for energy-level structures of highly-charged ions of middle- and high-Z elements and their radiative characteristics in plasmas. [ABSTRACT FROM AUTHOR]

Snake venom is a complex cocktail of toxins which induces a series of clinical and pathophysiological manifestations in victims, including severe local tissue damage and systemic alterations. Deinagkistrodon acutus (D. acutus) ranks among the “big four” life-threatening venomous species in China, whose venom possesses strong myotoxicity and hematotoxicity that often lead to permanent disability or muscle atrophy. Varespladib, an inhibitor of mammalian phospholipase A2 (PLA2), has been recently reproposed as an effective antidote against snakebite envenomation. The present study aimed at evaluating the protective role of varespladib on muscle regeneration in envenomed mice. Mice were grouped and subjected to inoculation with D. acutus venom or a mixture of venom and varespladib or control vehicle in the gastrocnemius muscle. Local injuries including hemorrhage, myonecrosis, ulceration, and systemic damages including general dysfunction, visceral failure, and inflammatory responses were observed at 1, 3, 7, 14, and 21 days. The results indicated that most of the muscle myonecrosis and hemorrhage were alleviated by varespladib. Besides, the pretreated mice recovered rapidly with lesser atrophy and muscle fibrosis. In conclusion, the findings of the present study suggested that varespladib is an effective antidote that could neutralize D. acutus venom and allow for earlier and improved rehabilitation outcome. [ABSTRACT FROM AUTHOR]

Stipa purpurea is among constructive endemic species in the alpine steppe on the Qinghai-Xizang Plateau. To reveal the fungal community structure and diversity in the rhizosphere and roots of this important grass and to analyze the potential influence of different habitats on the structure of fungal communities, we explored the root endophyte and the directly associated rhizosphere communities of S. purpurea by using internal transcribed spacer rRNA cloning and sequencing methods. We found that the roots of S. purpurea are associated with a diverse consortium of Basidiomycota (59.8%) and Ascomycota (38.5%). Most fungi obtained from rhizosphere soil in S. purpurea have been identified as Ascomycetes, while the high proportion detected in roots were basidiomycetous endophytes. The species richness, diversity, and evenness of fungal assemblages were higher in roots than in the rhizosphere soil. Fungi inhabiting the rhizosphere and roots of S. purpurea are significantly different, and the rhizosphere and endophyte communities are largely independent with little overlap in the dominant phyla or operational taxonomic units. Taken together, these results suggested that a wide variety of fungal communities are associated with the roots and rhizosphere soil of S. purpurea and that the fungal assemblages are strongly influenced by different habitats. [ABSTRACT FROM AUTHOR]

Coumarin derivatives are highly valuable compounds in drug discovery. Herein, we have developed two new coupling reactions that involve coumarins and either aldehydes or di- tert-butyl peroxide (DTBP) in the presence of inexpensive copper or iron catalysts. Both of these reactions proceed through a C(sp2)-H functionalization process to regioselectivity generate keto- or methyl-substituted coumarin derivatives in moderate to good yields These coupling reactions will enrich current coumarin chemistry. [ABSTRACT FROM AUTHOR]

An efficient synthetic route toward the highly congested [5-6-7] tricyclic core of calyciphylline A-type alkaloids has been developed. This approach features a highly efficient intramolecular Diels-Alder cycloaddition to establish the aza-five-membered C ring as well as the C1 all-carbon quaternary center, and a subsequent cyclopropanation together with a ring-expansion reaction of the resulted adduct to construct the seven-membered D ring. [ABSTRACT FROM AUTHOR]

Mechanistic target of rapamycin (MTOR) plays a critical role in the regulation of cell growth and in the response to energy state changes. Drugs inhibiting MTOR are increasingly used in antineoplastic therapies. Myocardial MTOR activity changes during hypertrophy and heart failure (HF). However, whether MTOR exerts a positive or a negative effect on myocardial function remains to be fully elucidated. Here, we show that ablation of Mtor in the adult mouse myocardium results in a fatal, dilated cardiomyopathy that is characterized by apoptosis, autophagy, altered mitochondrial structure, and accumulation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). 4E-BP1 is an MTOR-containing multiprotein complex-1 (MTORC1) substrate that inhibits translation initiation. When subjected to pressure overload, Mtor-ablated mice demonstrated an impaired hypertrophic response and accelerated HF progression. When the gene encoding 4E-BP1 was ablated together with Mtor, marked improvements were observed in apoptosis, heart function, and survival. Our results demonstrate a role for the MTORC1 signaling network in the myocardial response to stress. In particular, they highlight the role of 4E-BP1 in regulating cardiomyocyte viability and in HF. Because the effects of reduced MTOR activity were mediated through increased 4E-BP1 inhibitory activity, blunting this mechanism may represent a novel therapeutic strategy for improving cardiac function in clinical HF. [ABSTRACT FROM AUTHOR]

In order to get a better understanding of protein association during Solanum tuberosum (cv. Sarpo Mira)–Phytophthora infestans incompatible interaction, we investigated the proteome dynamics of cv. Sarpo Mira, after foliar application of zoospore suspension from P. infestans isolate, at three key time-points: zero hours post inoculation (hpi) (Control), 48 hpi (EI), and 120 hpi (LI); divided into early and late disease stages by the tandem mass tagging (TMT) method. A total of 1229 differentially-expressed proteins (DEPs) were identified in cv. Sarpo Mira in a pairwise comparison of the two disease stages, including commonly shared DEPs, specific DEPs in early and late disease stages, respectively. Over 80% of the changes in protein abundance were up-regulated in the early stages of infection, whereas more DEPs (61%) were down-regulated in the later disease stage. Expression patterns, functional category, and enrichment tests highlighted significant coordination and enrichment of cell wall-associated defense response proteins during the early stage of infection. The late stage was characterized by a cellular protein modification process, membrane protein complex formation, and cell death induction. These results, together with phenotypic observations, provide further insight into the molecular mechanism of P. infestans resistance in potatos. [ABSTRACT FROM AUTHOR]

An abstract of the article "Regioselective Coupling Reactions of Coumarins with Aldehydes or Di-tert-Butyl Peroxide (DTBP) Through a C(sp2)-H Functionalization Process" by Wannian Zhao and colleagues is presented.

A highly efficient intramolecular Diels-Alder cycloaddition for the establishment of the aza-five-membered ring and the C-1 quaternary center is the key step for the construction of the title tricyclic core, followed by cyclopropanation together with a ring-expansion for the construction of the seven-membered ring. [ABSTRACT FROM AUTHOR]