Decisions about cultural and historical heritage conservation can be contentious. Improved insight into the economic benefits derived from preservation could be achieved through a better ...understanding of the underlying economics. In response to this challenge, a growing number of studies estimate the economic value of heritage sites. The purpose of this study is to identify common drivers of the economic value of cultural and historical heritage by conducting a meta-analysis of heritage valuation studies. We find that heritage sites in areas with higher population density hold higher value, and conservation that supports adaptive re-use of sites generates higher values then passive protection. Valuation studies of tangible heritage dominate our dataset, but our findings are robust across model specifications. We identify a need for more economic and interdisciplinary research on the value of non-built heritage to improve understanding of the composition and drivers of heritage value.
γ‐Valerolactone (GVL) has been identified as a potential intermediate for the production of fuels and chemicals based on renewable feedstocks. Numerous heterogeneous catalysts have been used for GVL ...production, alongside a range of reaction setups. This Minireview seeks to outline the development of heterogeneous catalysts for the targeted conversion of levulinic acid (LA) to GVL. Emphasis has been placed on discussing specific systems, including heterogeneous noble and base metal catalysts, transfer hydrogenation, and application of scCO2 as reaction medium, with the aim of critically highlighting both the achievements and remaining challenges associated with this field.
Processing wood and plants: Biomass‐derived γ‐valerolactone (GVL) can be used for manufacturing food, chemicals, and fuels. Numerous hydrogenation catalysts have been developed for the GVL synthesis, with heterogeneous systems arguably the most viable. We discuss current heterogeneous systems, with emphasis on catalyst innovation and development of integrated biomass processing.
Levulinic acid and alkyl-levulinates have been hydrogenated using a range of supported catalysts. The different reaction outcomes obtained in alternate solvents have been rationalized and the ...influence of varying catalyst supports examined. A range of solvent free conditions have been investigated with complete LA conversion obtained at temperatures as low as 25 degree C.
The displacement loop (D loop) is the product of homology search and DNA strand invasion, constituting a central intermediate in homologous recombination (HR). In eukaryotes, the Rad51 DNA strand ...exchange protein is assisted in D loop formation by the Rad54 motor protein. Curiously, Rad54 also disrupts D loops. How these opposing activities are coordinated toward productive recombination is unknown. Moreover, a seemingly disparate function of Rad54 is removal of Rad51 from heteroduplex DNA (hDNA) to allow HR-associated DNA synthesis. Here, we uncover features of D loop formation/dissociation dynamics, employing Rad51 filaments formed on ssDNAs that mimic the physiological length and structure of in vivo substrates. The Rad54 motor is activated by Rad51 bound to synapsed DNAs and guided by a ssDNA-binding domain. We present a unified model wherein Rad54 acts as an hDNA pump that drives D loop formation while simultaneously removing Rad51 from hDNA, consolidating both ATP-dependent activities of Rad54 into a single mechanistic step.
Display omitted
•The structure of hDNA branchpoints modulates Rad54-mediated D loop disruption•Rad51/Rad54 promote formation of multiple invasion joint molecules•The N-terminal, regulatory domain of Rad54 orients its motor activity•Rad54 stimulates D loop formation, acting as a heteroduplex DNA pump
Homologous recombination (HR) is critical for genome integrity. The displacement loop (D loop) constitutes a key HR intermediate. Rad51 forms D loops in concert with the Rad54 motor protein. Employing Rad51 nucleoprotein filaments that mimic the length and structure of in vivo substrates, Wright and Heyer analyze Rad54 function in D loop reaction and suggest a heteroduplex DNA (hDNA) pump model consolidating seemingly disparate activities: Rad54 drives D loop formation while removing Rad51 from hDNA.
Glutamatergic synapses are key cellular sites where cocaine experience creates memory traces that subsequently promote cocaine craving and seeking. In addition to making across-the-board synaptic ...adaptations, cocaine experience also generates a discrete population of new synapses that selectively encode cocaine memories. These new synapses are glutamatergic synapses that lack functionally stable AMPARs, often referred to as AMPAR-silent synapses or, simply, silent synapses. They are generated
in the NAc by cocaine experience. After drug withdrawal, some of these synapses mature by recruiting AMPARs, contributing to the consolidation of cocaine-associated memory. After cue-induced retrieval of cocaine memories, matured silent synapses alternate between two dynamic states (AMPAR-absent vs AMPAR-containing) that correspond with the behavioral manifestations of destabilization and reconsolidation of these memories. Here, we review the molecular mechanisms underlying silent synapse dynamics during behavior, discuss their contributions to circuit remodeling, and analyze their role in cocaine-memory-driven behaviors. We also propose several mechanisms through which silent synapses can form neuronal ensembles as well as cross-region circuit engrams for cocaine-specific behaviors. These perspectives lead to our hypothesis that cocaine-generated silent synapses stand as a distinct set of synaptic substrates encoding key aspects of cocaine memory that drive cocaine relapse.
The development of drug addiction is associated with functional adaptations within the reward circuitry, within which the nucleus accumbens (NAc) is anatomically positioned as an interface between ...motivational salience and behavioral output. The functional output of NAc is profoundly altered after exposure to drugs of abuse, and some of the functional changes continue to evolve during drug abstinence, contributing to numerous emotional and motivational alterations related drug taking, seeking, and relapse. As in most brain regions, the functional output of NAc is critically dependent on the dynamic interaction between excitation and inhibition. One of the most prominent sources of inhibition within the NAc arises from fast-spiking interneurons (FSIs). Each NAc FSI innervates hundreds of principal neurons, and orchestrates population activity through its powerful and sustained feedforward inhibition. While the role of NAc FSIs in the context of drug addiction remains poorly understood, emerging evidence suggests that FSIs and FSI-mediated local circuits are key targets for drugs of abuse to tilt the functional output of NAc toward a motivational state favoring drug seeking and relapse. In this review, we discuss recent findings and our conceptualization about NAc FSI-mediated regulation of motivated and cocaine-induced behaviors. We hope that the conceptual framework proposed in this review may provide a useful guidance for ongoing and future studies to determine how FSIs influence the function of NAc and related reward circuits, ultimately leading to addictive behaviors.
Never-in-mitosis A-related kinase 1 (Nek1) has established roles in apoptosis and cell cycle regulation. We show that human Nek1 regulates homologous recombination (HR) by phosphorylating Rad54 at ...Ser572 in late G2 phase. Nek1 deficiency as well as expression of unphosphorylatable Rad54 (Rad54-S572A) cause unresolved Rad51 foci and confer a defect in HR. Phospho-mimic Rad54 (Rad54-S572E), in contrast, promotes HR and rescues the HR defect associated with Nek1 loss. Although expression of phospho-mimic Rad54 is beneficial for HR, it causes Rad51 removal from chromatin and degradation of stalled replication forks in S phase. Thus, G2-specific phosphorylation of Rad54 by Nek1 promotes Rad51 chromatin removal during HR in G2 phase, and its absence in S phase is required for replication fork stability. In summary, Nek1 regulates Rad51 removal to orchestrate HR and replication fork stability.
Display omitted
•Nek1 functions during homologous recombination•Nek1 phosphorylates Rad54 at Ser572 in late G2 phase•Unphosphorylatable Rad54 mutants are defective in homologous recombination•Phospho-mimic Rad54 causes degradation of stalled replication forks
Spies et al. uncover the participation of the kinase Nek1 during homologous recombination. Nek1 phosphorylates Rad54 in G2 to promote Rad51 removal. Untimely phosphorylation of Rad54 and subsequent removal of Rad51 in S phase causes replication fork instability. The authors hereby demonstrate the physiological relevance of Rad54 regulation.
Viral (aseptic) meningitis: A review Wright, William F.; Pinto, Casey N.; Palisoc, Kathryn ...
Journal of the neurological sciences,
03/2019, Letnik:
398
Journal Article
Recenzirano
Viral meningitis is an inflammation of the meninges associated with acute onset of meningeal symptoms and fever, pleocytosis of the cerebrospinal fluid, and no growth on routine bacterial culture. It ...is sometimes associated with viral encephalitis and meningoencephalitis. Viruses reach the central nervous system (CNS) hematogenously or in a retrograde manner from nerve endings. The viral etiology varies according to age and country. Molecular diagnostics technology has helped improve the rate of pathogen detection reducing unnecessary antibiotic use and length of hospitalization. Most of the viral infections detailed in this article have no specific treatment other than supportive care. Many of the viruses discussed are preventable by vaccination and proper skin protection against transmitting vectors.
•Viral meningitis is a common disorder.•Common causes include non-polio human enteroviruses, mumps, lymphocytic choriomeningitis virus, and herpes viruses.•Kernig's, Brudzinski and jolt accentuation of headache are of limited clinical bedside diagnostic value.•Lumbar puncture with detection of viral pathogens by nucleic acid sequence-based amplification have emerged as the new diagnostic gold standard.•Pathophysiology, differential diagnosis, and management of viral meningitis is reviewed.
A practical, transition metal‐free method allows the enantioselective synthesis of α,α‐diarylmethylamines by asymmetric α‐arylation of benzylamines. Enantioselective lithiation of ...N′‐aryl‐N‐benzyl‐N‐isopropyl ureas using a chiral lithium amide base generates a benzyllithium that undergoes an unactivated stereospecific intramolecular nucleophilic aromatic substitution to generate an α,α‐diarylmethylamine in the form of its urea derivative, in up to >99 % ee. Treatment with acid induces an “azatropic shift” with retention of configuration, the product of which may be hydrolysed to the target amine.
The deprotonation of N′‐aryl urea derivatives with a chiral lithium amide base leads to an enantioselective C‐arylation of benzylamines. An unusual stereoretentive substitution reaction followed by N‐deprotection of the urea forms diarylmethylamine derivatives, including a synthetic intermediate en route to the drug levocetirizine.
The Asian monsoon system affects more than half of humanity worldwide, yet the dynamical processes that govern its complex spatiotemporal variability are not sufficiently understood to model and ...predict its behavior, due in part to inadequate long-term climate observations. Here we present the Monsoon Asia Drought Atlas (MADA), a seasonally resolved gridded spatial reconstruction of Asian monsoon drought and pluvials over the past millennium, derived from a network of tree-ring chronologies. MADA provides the spatiotemporal details of known historic monsoon failures and reveals the occurrence, severity, and fingerprint of previously unknown monsoon megadroughts and their close linkages to large-scale patterns of tropical Indo-Pacific sea surface temperatures. MADA thus provides a long-term context for recent monsoon variability that is critically needed for climate modeling, prediction, and attribution.
PDF
