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Few fields of academic research are surrounded by so many misunderstandings and misconceptions as the study of Western esotericism. For twenty years now, the Centre for History of Hermetic Philosophy and Related Currents (University of Amsterdam) has been at the forefront of international scholarship in this domain. This anniversary volume seeks to make the modern study of Western esotericism known beyond specialist circles, while addressing a range of misconceptions, biases, and prejudices that still tend to surround it. Thirty major scholars in the field respond to questions about a wide range of unfamiliar ideas, traditions, practices, problems, and personalities that are central to this area of research. By challenging many taken-for-granted assumptions about religion, science, philosophy, and the arts, this volume demonstrates why the academic study of esotericism leads us to reconsider much that we thought we knew about the story of Western culture.

Post-stroke cognitive impairment (PSCI) includes all forms of cognitive decline that develop after stroke, even if not severe enough to fit the criteria of dementia. Our aims were to investigate the predictive value of a brief bedside examination (Montreal Cognitive Assessment, MoCA) in the acute phase of stroke on the diagnosis of mid-term PSCI, taking into account other clinical, cognitive, functional, and neuroimaging predictors. Consecutive patients admitted to a stroke unit were evaluated with MoCA between 5 and 9 days after stroke. At baseline, clinical, functional, and neuroimaging data were collected. Patients were reassessed between 6 and 9 months after stroke by means of an extensive neuropsychological and functional evaluation. Out of 137 enrolled stroke patients, 80 (58.4 %) were followed up (mean age 68.2 ± 14.6 years, males 66 %, mean NIHSS score 3.6 ± 4.8). PSCI was diagnosed in 47 patients (59 %; 35 mild cognitive impairment, 12 dementia). Controlling for age, education, functional and cognitive pre-morbid status, stroke severity, and pre-existing lacunar infarcts, MoCA baseline score [OR (95 % CI) = 1.4(1.1–1.8)] for each point] and leukoaraiosis severity [OR (95 % CI) = 0.4(0.2–0.9)] for each point of the van Swieten scale] were independently associated with PSCI. Using a ROC analysis, a cut-off of 21 predicted the diagnosis of PSCI with 91.4 % sensitivity, 75.8 % specificity, 80 % positive predictive value, and 89.3 % negative predictive value. In a sample of mild stroke patients, MoCA seems to be a good predictor of mid-term PSCI, making it a possible candidate for a brief cognitive screening in the acute stroke setting.

Structural fluctuations of nucleosomes modulate the access to internal DNA in eukaryotic cells; clearly characterisation of this fundamental process is crucial to understanding gene regulation. Here we apply PhAST (Photochemical Analysis of Structural Transitions) to monitor at a base pair level, structural alterations induced all along the DNA upon histone binding or release. By offering the first reliable, detailed comparison of nucleosome assembly and disassembly in vitro , we reveal similarities and differences between the two processes. We identify multiple, sequential intermediate states characterised by specific PhAST signals whose localisation and amplitude reflect asymmetries of DNA/histone interactions with respect to the nucleosome pseudo dyad. These asymmetries involve not only the DNA extremities but also regions close to the pseudo dyad. Localisations of asymmetries develop in a consistent manner during both assembly and disassembly processes; they primarily reflect the DNA sequence effect on the efficiency of DNA-histone binding. More unexpectedly, the amplitude component of PhAST signals not only evolves as a function of intermediate states but does so differently between assembly and disassembly pathways. Our observation of differences between assembly and disassembly opens up new avenues to define the role of the DNA sequence in processes underlying the regulation of gene expression. Overall, we provide new insights into how the intrinsic properties of DNA are integrated into a holistic mechanism that controls chromatin structure.

In this neuropathological study, we investigated neuroinflammation surrounding recent and old cerebral microbleeds (CMBs) and cerebral microinfarcts (CMIs) in 18 cases of cerebral amyloid angiopathy (CAA). We used several serial stainings and immunolabellings to identify microvascular lesions, define their recent or old stage, and characterize neuroinflammatory response (scavenging activity and astrogliosis). We found that both CMBs and CMIs induce a neuroinflammatory response, which was more pronounced in old lesion than recent. Astrogliosis and scavenging activity were differentially prominent according to the ischemic/hemorrhagic nature of the lesion. Our findings provide insights into the pathophysiology of microvascular injuries in CAA.

HIV-1 Gag polyprotein orchestrates the assembly of viral particles. Its C-terminus consists of the nucleocapsid (NC) domain that interacts with nucleic acids, and p1 and p6, two unstructured regions, p6 containing the motifs to bind ALIX, the cellular ESCRT factor TSG101 and the viral protein Vpr. The processing of Gag by the viral protease subsequently liberates NCp15 (NC-p1-p6), NCp9 (NC-p1) and NCp7, NCp7 displaying the optimal chaperone activity of nucleic acids. This review focuses on the nucleic acid binding properties of the NC domain in the different maturation states during the HIV-1 viral cycle.

Background Cognitive impairment and depressive symptoms are highly prevalent after Intracerebral Hemorrhage (ICH). We leveraged Latent Profile Analysis (LPA) to identify profiles for cognitive decline and depression onset after ICH. We also investigated differences in clinical, genetic and neuroimaging characteristics across patients’ profiles. Methods We analyzed data from the ICH study conducted at Massachusetts General Hospital between January 1998 and December 2019. We collected information from electronical health records, follow-up interviews, CT and MRI imaging, and APOE genotype. We conducted LPA and multinomial logistic regression analyses to: 1) identify distinct profiles for cognitive decline and depression onset after ICH; 2) identify clinical, neuroimaging and genetic factors predicting individuals’ likelihood to express a specific profile. Results We followed 784 ICH survivors for a median of 45.8 months. We identified four distinct profiles in cognitive and depressive symptoms after ICH: low depression and dementia risk, early-onset depression and dementia, late-onset depression and dementia, high depression with low dementia risk. Cerebral small vessel disease severity and APOE genotype were specifically associated with the late-onset profile (both p <  0.05). Acute hematoma characteristics (size, intraventricular extension) and functional disability were specifically associated with the early-onset profile (all p <  0.05). Conclusion We identified four distinct profiles for cognitive and depressive symptoms after ICH, each displaying specific associations with individual patients’ clinical, genetic and neuroimaging data. These associations reflect separate biological mechanisms influencing dementia and depression risk after ICH. Our findings support employing LPA in future ICH studies, and is likely applicable to stroke survivors at large.

Networks and clusters of intramolecular interactions, as well as their \"communication\" across the three-dimensional architecture have a prominent role in determining protein stability and function. Special attention has been dedicated to their role in thermal adaptation. In the present contribution, seven previously experimentally characterized mutants of a cold-adapted α-amylase, featuring mesophilic-like behavior, have been investigated by multiple molecular dynamics simulations, essential dynamics and analyses of correlated motions and electrostatic interactions. Our data elucidate the molecular mechanisms underlying the ability of single and multiple mutations to globally modulate dynamic properties of the cold-adapted α-amylase, including both local and complex unpredictable distal effects. Our investigation also shows, in agreement with the experimental data, that the conversion of the cold-adapted enzyme in a warm-adapted variant cannot be completely achieved by the introduction of few mutations, also providing the rationale behind these effects. Moreover, pivotal residues, which are likely to mediate the effects induced by the mutations, have been identified from our analyses, as well as a group of suitable candidates for protein engineering. In fact, a subset of residues here identified (as an isoleucine, or networks of mesophilic-like salt bridges in the proximity of the catalytic site) should be considered, in experimental studies, to get a more efficient modification of the features of the cold-adapted enzyme.

The nucleocapsid domain (NCd), located at the C-terminus of the HIV-1 Gag protein, is involved in numerous stages of the replication cycle, such as the packaging of the viral genome and reverse transcription. It exists under different forms through the viral life cycle, depending on the processing of Gag by the HIV-1 protease. NCd is constituted of two adjacent zinc knuckles (ZK1 and ZK2), separated by a flexible linker and flanked by disordered regions. Here, conformational equilibria between a major and two minor states were highlighted exclusively in ZK2, by using CPMG and CEST NMR experiments. These minor states appear to be temperature dependent, and their populations are highest at physiological temperature. These minor states are present both in NCp7, the mature form of NCd, and in NCp9 and NCp15, the precursor forms of NCd, with increased populations. The role of these minor states in the targeting of NCd by drugs and its binding properties is discussed.

Cerebral microbleeds (CMBs) are defined as hypointense foci visible on T2*-weighted and susceptible-weighted MRI sequences. CMBs are increasingly recognised with the widespread use of MRI in healthy individuals as well as in the context of cerebrovascular disease or dementia. They can also be encountered in major critical medical conditions such as in patients requiring extracorporeal mechanical oxygenation. The advent of MRI-guided postmortem neuropathological examinations confirmed that, in the context of cerebrovascular disease, the vast majority of CMBs correspond to recent or old microhaemorrhages. Detection of CMBs is highly influenced by MRI parameters, in particular field strength, postprocessing methods used to enhance T2* contrast and three dimensional sequences. Despite recent progress, harmonising imaging parameters across research studies remains necessary to improve cross-study comparisons. CMBs are helpful markers to identify the nature and the severity of the underlying chronic small vessel disease. In daily clinical practice, presence and numbers of CMBs often trigger uncertainty for clinicians especially when antithrombotic treatments and acute reperfusion therapies are discussed. In the present review, we discuss those clinical dilemmas and address the value of CMBs as diagnostic and prognostic markers for future vascular events.

This volume is published on the occasion of the 20th anniversary of the Centre for History of Hermetic Philosophy and Related Currents at the University of Amsterdam Few fields of academic research are surrounded by so many misunderstandings and misconceptions as the study of Western esotericism. For twenty years now, the Centre for History of Hermetic Philosophy and Related Currents (University of Amsterdam) has been at the forefront of international scholarship in this domain. This anniversary volume seeks to make the modern study of Western esotericism known beyond specialist circles, while addressing a range of misconceptions, biases, and prejudices that still tend to surround it. Thirty major scholars in the field respond to questions about a wide range of unfamiliar ideas, traditions, practices, problems, and personalities that are central to this area of research. By challenging many taken-for-granted assumptions about religion, science, philosophy, and the arts, this volume demonstrates why the academic study of esotericism leads us to reconsider much that we thought we knew about the story of Western culture.