Search

Background: Respiratory motion is known to deteriorate positron emission tomography (PET) images and may lead to potential diagnostic errors when a standardized uptake value (SUV) cut-off threshold is used to discriminate between benign and malignant lesions. Purpose: To evaluate and compare ungated and respiratory-gated 18F-fluorodeoxyglucose PET/computed tomography (CT) methods for the characterization of pulmonary nodules. Material and Methods: The list-mode acquisition during respiratory-gated PET was combined with a short breath-hold CT scan to form the CT-based images. We studied 48 lesions in 43 patients. PET images were analyzed in terms of the maximum SUV (SUV(max)) and the lesion location. Results: Using receiver-operating characteristic (ROC) curves, the optimal SUV cut-off thresholds for the ungated and CT-based methods were calculated to be 2.0 and 2.2, respectively. The corresponding sensitivity values were 83% and 92%, respectively, with a specificity of 67% for both methods. The two methods gave equivalent performance levels for the upper and middle lobes (sensitivity 93%, specificity 62%). They differed for the lower lobes, where the CT-based method outperformed the ungated method (sensitivity values of 90% and 70%, respectively, and a specificity of 73% with both methods) - especially for lesions smaller than 15 mm. Conclusion: The CT-based method increased sensitivity and did not diminish specificity, compared with the ungated method. It was more efficient than the ungated method for imaging the lower lobes and smallest lesions, which are most affected by respiratory motion. [ABSTRACT FROM AUTHOR]

Precursor-mRNA (pre-mRNA) splicing requires the assembly, remodelling and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome 1 . Recent studies have shed light on spliceosome assembly and remodelling for catalysis 2-6 , but the mechanism of disassembly remains unclear. Here we report cryo-electron microscopy structures of nematode and human terminal intron lariat spliceosomes along with biochemical and genetic data. Our results uncover how four disassembly factors and the conserved RNA helicase DHX15 initiate spliceosome disassembly. The disassembly factors probe large inner and outer spliceosome surfaces to detect the release of ligated mRNA. Two of these factors, TFIP11 and C19L1, and three general spliceosome subunits, SYF1, SYF2 and SDE2, then dock and activate DHX15 on the catalytic U6 snRNA to initiate disassembly. U6 therefore controls both the start 5 and end of pre-mRNA splicing. Taken together, our results explain the molecular basis of the initiation of canonical spliceosome disassembly and provide a framework to understand general spliceosomal RNA helicase control and the discard of aberrant spliceosomes., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Pre-mRNA splicing by the spliceosome requires the biogenesis and recycling of its small nuclear ribonucleoprotein (snRNP) complexes, which are consumed in each round of splicing. The human U5 snRNP is the ~1 MDa 'heart' of the spliceosome and is recycled through an unknown mechanism involving major architectural rearrangements and the dedicated chaperones CD2BP2 and TSSC4. Late steps in U5 snRNP biogenesis similarly involve these chaperones. Here we report cryo-electron microscopy structures of four human U5 snRNP-CD2BP2-TSSC4 complexes, revealing how a series of molecular events primes the U5 snRNP to generate the ~2 MDa U4/U6.U5 tri-snRNP, the largest building block of the spliceosome., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The dissemination of clinical trial results is an important scientific and ethical endeavour. This survey of completed interventional studies in a French academic center describes their reporting status., Methods: We explored all interventional studies sponsored by Rennes University Hospital identified on the French Open Science Monitor which tracks trials registered on EUCTR or clinicaltrials.gov, and provides an automatic assessment of the reporting of results. For each study, we ascertained the actual reporting of results using systematic searches on the hospital internal database, bibliographic databases (Google Scholar, PubMed), and by contacting all principal investigators (PIs). We describe several features (including total budget and numbers of trial participants) of the studies that did not report any results., Results: The French Open Science Monitor identified 93 interventional studies, among which 10 (11%) reported results. In contrast, our survey identified 36 studies (39%) reporting primary analysis results and an additional 18 (19%) reporting results for secondary analyses (without results for their primary analysis). The overall budget for studies that did not report any results was estimated to be €5,051,253 for a total of 6,735 trial participants. The most frequent reasons for the absence of results reported by PIs were lack of time for 18 (42%), and logistic difficulties (e.g. delay in obtaining results or another blocking factor) for 12 (28%). An association was found between non-publication and negative results (adjusted Odds Ratio = 4.70, 95% Confidence Interval [1.67;14.11])., Conclusions: Even allowing for the fact that automatic searches underestimate the number of studies with published results, the level of reporting was disappointingly low. This amounts to a waste of trial participants' implication and money. Corrective actions are needed., Trial Registration: https://osf.io/q5hcs., (© 2024. The Author(s).)

Newly made mRNAs are processed and packaged into mature ribonucleoprotein complexes (mRNPs) and are recognized by the essential transcription-export complex (TREX) for nuclear export 1,2 . However, the mechanisms of mRNP recognition and three-dimensional mRNP organization are poorly understood 3 . Here we report cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNPs bound to the 2-MDa TREX complex. We show that mRNPs are recognized through multivalent interactions between the TREX subunit ALYREF and mRNP-bound exon junction complexes. Exon junction complexes can multimerize through ALYREF, which suggests a mechanism for mRNP organization. Endogenous mRNPs form compact globules that are coated by multiple TREX complexes. These results reveal how TREX may simultaneously recognize, compact and protect mRNAs to promote their packaging for nuclear export. The organization of mRNP globules provides a framework to understand how mRNP architecture facilitates mRNA biogenesis and export., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Arundo donax lectin (ADL) is a 170 amino acid protein that can be purified from the rhizomes of the giant reed or giant cane by exploiting its selective binding to chitin followed by elution with N-acetylglucosamine. The lectin is listed in the UniProt server, the largest protein sequence database, as an uncharacterized protein with chitin-binding domains (A0A0A9P802). This paper reports the purification, structure and ligand-binding properties of ADL. The lectin is a homodimer in which the two protomers are linked by two disulfide bridges. Each polypeptide chain presents four carbohydrate-binding modules that belong to carbohydrate-binding module family 18. A high degree of sequence similarity is observed among the modules present in each protomer. We have determined the X-ray structure of the apo-protein to a resolution of 1.70 Å. The carbohydrate-binding modules, that span a sequence of approximately 40 amino acids, present four internal disulfide bridges, a very short antiparallel central beta sheet and three short alpha helices, two on one side of the beta sheet and one on the other. The structures of the complexes of the lectin with N-acetylglucosamine, N-acetyllactosamine, N-acetylneuraminic acid and N-N'diacetylchitobiose reveal that ADL has two primary and two secondary carbohydrate-binding sites per dimer. They are located at the interface between the two protomers, and each binding site involves residues of both chains. The lectin presents structural similarity to the wheat germ agglutinin family, in particular, to isoform 3., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The export of mRNA from nucleus to cytoplasm requires the conserved and essential transcription and export (TREX) complex (THO-UAP56/DDX39B-ALYREF). TREX selectively binds mRNA maturation marks and licenses mRNA for nuclear export by loading the export factor NXF1-NXT1. How TREX integrates these marks and achieves high selectivity for mature mRNA is poorly understood. Here, we report the cryo-electron microscopy structure of the human THO-UAP56/DDX39B complex at 3.3 Å resolution. The seven-subunit THO-UAP56/DDX39B complex multimerizes into a 28-subunit tetrameric assembly, suggesting that selective recognition of mature mRNA is facilitated by the simultaneous sensing of multiple, spatially distant mRNA regions and maturation marks. Two UAP56/DDX39B RNA helicases are juxtaposed at each end of the tetramer, which would allow one bivalent ALYREF protein to bridge adjacent helicases and regulate the TREX-mRNA interaction. Our structural and biochemical results suggest a conserved model for TREX complex function that depends on multivalent interactions between proteins and mRNA., Competing Interests: TP, UH, LF, BP, US, JB, CP No competing interests declared, (© 2020, Pühringer et al.)

Good clinical practice (GCP) is an international ethical and scientific quality standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials. Before the start of a clinical trial, investigators commit to perform the research in accordance with GCPs, regulatory dispositions and protocol. The sponsors are responsible for investigators' selection and for controlling their skills. Whereas industrial sponsors systematically require a certificate of GCP training, academic sponsors seem to be less demanding. We have carried out two surveys between April and June 2018. A first questionnaire was sent to the 40 French academic directions of clinical research and innovation in order to determine their requirements about the GCP training of the investigators participating in their trials. The second questionnaire was transmitted to physicians of the "Bretagne recherche clinique hospitalière network": Rennes, Saint-Malo, Saint-Brieuc, Vannes, Lorient and Pontivy hospitals, in order to determine the GCP certification rate, and their needs in terms of clinical research training. Twenty-eight (70%) directions of clinical research answered the first survey, among which 18 (64%) required systematically the investigators' GCP certification in case of category 1 interventional studies. This rate decreased for category 2 (50%) and non-interventional category 3 (18%) studies. A total of 345 physicians answered the second survey, among which 263 (76%) had already been clinical trial investigators. However, only 29% of all physicians and 54% of those who had been principal investigator were certified for GCP training. These results support the need for large campaigns of GCP training in public hospitals., (Copyright © 2020 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

A 59-year-old man presented with proximal myopathy, myalgia, and weight loss, with the initial markedly elevated serum creatine kinase at 11,000 U/L. Due to his refusal for muscle biopsy, he was initially treated as inflammatory myositis and responded well with the corticosteroids. However, he subsequently had a relapse of the symptoms with more extensive systemic involvement, i.e., hypercalcemia, lymphadenopathy and subcutaneous nodules. Finally, a biopsy of the thigh and subcutaneous nodule revealed non-caseating granulomatous inflammation, consistent with sarcoidosis. He responded well to the corticosteroids, and finally, azathioprine was added as a steroid-sparing agent. Including our series, there are 103 cases of symptomatic muscle involvement in sarcoidosis patients published in the English literature to date. Further pool analysis of the cases will be reported in this review.

The Cannabinoid Receptor Interacting Protein 1 (Cnrip1) was discovered as an interactor with the intracellular region of Cannabinoid Receptor 1 (CB1R, also known as Cnr1 or CB1). Functional assays in mouse show cannabinoid sensitivity changes and Cnrip1 has recently been suggested to control eye development in Xenopus laevis. Two Cnrip1 genes are described in zebrafish, cnrip1a and cnrip1b. In situ mRNA hybridisation revealed accumulation of mRNA encoding each gene primarily in brain and spinal cord, but also elsewhere. For example, cnrip1b is expressed in forming skeletal muscle. CRISPR/Cas9 genome editing generated predicted null mutations in cnrip1a and cnrip1b. Each mutation triggered nonsense-mediated decay of the respective mRNA transcript. No morphological or behavioural phenotype was observed in either mutant. Moreover, fish lacking both Cnrip1a and Cnrip1b both maternally and zygotically are viable and fertile and no phenotype has so far been detected despite strong evolutionary conservation over at least 400 Myr.

Background & Aims: Several prognostic classifications (PCs) have been developed for use in palliative care in patients with hepatocellular carcinoma (HCC). We have recently suggested that CLIP combined with WHO PS has the greatest discriminative power. We evaluated the prognostic value of quality of life (QoL) data and whether the latter could improve classification of palliative HCC patients., Methods: This was a reanalysis from the CHOC trial with an evaluation of the discriminative power for overall survival (OS) of the established CLIP/GRETCH/BCLC/BoBar prognostic systems alone and then in association with each of the following groups of parameters: selected clinical factors, QoL as continuous variables, dichotomized QoL, selected clinical factors and continuous QoL, selected clinical factors and dichotomized QoL. Baseline QoL was assessed using the EORTC QLQ-C30. Discriminative power was evaluated with the Harrell's C-index and net reclassification improvement., Results: Quality of life was available in 79% of the patients (n=271). Univariate analysis revealed that better role functioning (HR=0.991 [0.987-0.995]) and better physical functioning (0.991 [0.984-0.997]) scores were associated with longer survival. In contrast, poorer score for fatigue (1.011 [1.006-1.015]) and diarrhoea (1.008 [1.002-1.013]) were associated with shorter survival. After adjustment for clinical and sociodemographic variables, only better role functioning score (0.993 [0.988-0.998]) was associated with longer survival. Adding oedema, hepatomegaly, fatigue and diarrhoea QoL scales to CLIP resulted in the best performance., Conclusions: Our results confirm that QoL scales are independent prognostic factors of OS in palliative HCC patients. Incorporation of QoL data improved all the studied PCs., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: In 18F-fluorodeoxyglucose PET/CT, respiratory motion induces bias in image interpretations (i.e. organ misregistration or lesion omission/underestimation)., Objective: The present study applied our custom gating method (referred to as 'CT-based gated PET' and that has already been validated by our research group) to PET imaging of the liver and compared its per lesion sensitivity with that of standard clinical (i.e. ungated) PET., Methods: A total of 13 patients scheduled for liver surgery were referred to our department for PET/CT imaging. Each patient underwent both ungated and CT-based gated PET imaging protocols. Two independent, blinded observers interpreted the two sets of PET images and reached a consensus when necessary. Image interpretations were combined with histological analysis and/or intraoperative ultrasound examination to compute each method's per lesion sensitivity and true positive fraction. Analyses were also performed by considering lesions according to their size (longest axis over 10 mm or over 15 mm)., Results: Forty-eight lesions were confirmed by pathology reports. When considering all the uptakes, the ungated and the CT-based gated PET methods had sensitivities of 54.2 and 64.6% (P=0.025) and true positive fractions of 83.9 and 86.1%, respectively. When considering uptakes greater than 10 mm in size, ungated and CT-based gated PET had sensitivities of 74.3 and 88.6% (P=0.025), respectively. For lesions greater than 15 mm in size, the corresponding sensitivities were 85.2 and 100% (P=0.046)., Conclusion: CT-based gated PET yielded a higher lesion-based sensitivity than routine, ungated PET did. Hence, this method improves the detection of intrahepatic colorectal metastases--especially for lesions that are close in size to the detection limit of the PET gantry.

Background: ¹⁸F-fluorodeoxyglucose positron emission tomography has proven relevance in oncological diagnosis, staging and follow-up. The standardized uptake value (SUV) is one of the most widely used semi-quantitative criteria in PET imaging. However, factors such as noise and image resolution affect the measurement of the SUV. We reported earlier that a device-dedicated projector [attenuation-weighted ordered-subsets expectation maximization detector response (AW-OSEM DR), based on point-source measurements] introduces less noise than a geometrical model (AW-OSEM)., Objective: The aim of this study was to investigate the AW-OSEM DR method's impact on SUV measurements under clinical conditions., Methods: We first performed a bias analysis to assess the accuracy of the quantitation for the two reconstruction methods as a function of target size and the number of iterations, with 14 acquisitions of the NEMA IEC/2001 phantom. We then used each method to calculate the maximum and average SUVs, respectively for 32 lesions., Results: For all spheres and all iterations, the bias was significantly lower with AW-OSEM DR than with AW-OSEM (P=0.012). Moreover, a paired Student's t-test showed significant intermethod differences for maximum SUV and average SUV (both P<0.001) in cancer patients. Conversely, the two methods did not differ significantly in terms of the mean SUV and signal-to-noise ratio calculated in the liver for each patient (P=0.5 and 0.08, respectively)., Conclusion: Phantom and patient studies were performed to quantify the effects of AW-OSEM DR on PET images. The phantom study highlighted the fact that our method produces more accurate images in terms of the SUV, which is an essential quality for ensuring correct diagnosis, follow-up and treatment planning.

Respiratory motion correction in positron emission tomography (PET) seeks to incorporate motion information into an image reconstruction algorithm by using the full counting statistics of an acquisition to generate a single, motion-free volume. Here, we present a motion-incorporated ordered subsets expectation maximization (MOSEM) reconstruction based on a device-dedicated tomographic projector in which each matrix element is calculated directly from the voxels' Cartesian coordinates alone. The motion is corrected by updating this projector as a function of the respiratory level. The performance of the reconstruction method was investigated with three datasets: two simulations of a transaxially or axially moving lesion on a patient acquisition and a third acquisition of a moving sphere. After the 16th sub-iteration, the normalized mean square error (NMSE, with a motionless acquisition as reference) was 0.20 for the non-corrected (ungated) image and 0.01 for the MOSEM image with transaxial motion simulation. Likewise, NMSE was 0.30 for the ungated image and 0.03 for MOSEM image with axial motion simulation. For the phantom, ungated reconstruction yielded an error of 0.78, whereas MOSEM yielded 0.43. The error reduction resulted from enhancement and reduced spreading of the moving uptake. Our results show that MOSEM reconstruction yields motion-corrected images which are similar to motionless reference images.

In whole-body positron emission tomography (PET) imaging, the detection of small uptake foci (i.e., around two or three times the tomograph's spatial resolution) is a critical issue. Indeed, spatial resolution is altered by postreconstruction smoothing operations used to reduce the noise introduced by (among other things) an inaccurate system matrix. The authors previously proposed a device-dedicated projector, easily applicable on a clinical gantry, based on point-source measurements, which introduces less noise than a geometrical model. In the present study, they took advantage of the lower noise levels by reducing the postfilter and then quantified the approach's impact on image quality. This study was performed on an IEC Body Phantom Set filled with 18F (sphere-to-background activity ratio: 4:1). The same 3 min acquisition was reconstructed with either (i) a clinical system based on a geometrical tomographic operator (OSEM&#95;CL) or (ii) an OSEM algorithm using the suggested system matrix (OSEM&#95;DR). In order to compare the resulting images, they set the 3D Gaussian postfilter (3DGPF) for OSEM&#95;DR so as to obtain similar background signal-to-noise ratio (SNR) to that of OSEM&#95;CL with a Gaussian postfilter full width at half maximum of 5 mm (as recommended for whole-body imaging on a Biograph6). They then assessed the contrast-to-noise ratio (CNR) and quantitation [contrast recovery (CR)] for the phantom's four smallest spheres (with internal diameters of 10, 13, 17, and 22 mm). Evaluation of 3DGPFs ranging from 2.2 to 2.6 mm showed that a value of 2.4 mm in OSEM&#95;DR gave the closest background SNR to that of OSEM&#95;CL with a 3DGPF of 5 mm. For all studied targets, the CNR was higher with OSEM&#95;DR than with OSEM&#95;CL. For the 10 and 13 mm spheres, OSEM&#95;DR increased the size of the CNR peaks by 37% and 20%, relative to OSEM&#95;CL. The OSEM&#95;DR technique yielded higher CR values than OSEM&#95;CL did. For the 10, 13, 17, and 22 mm spheres, the CR values at eight iterations were 0.5, 0.6, 1.1, and 1.0 for OSEM&#95;DR and 0.3, 0.4, 0.9, and 0.8 for OSEM&#95;CL. They evaluated a practical method for determining a device-dedicated system matrix based on point-source acquisitions. This tomographic operator is more realistic than geometrical system matrix and introduces less noise into PET images during statistical reconstruction; it thus reduces the extent of postfiltering operations required. Thus, spatial resolution is better maintained with OSEM&#95;DR than with clinical reconstruction. They showed that this method improves the contrast-to-noise ratio and quantification of uptake foci (especially those that are at the system's limit of detection) and, in a clinical context, could allow better detection and earlier diagnosis.

Purpose: Respiratory motion causes uptake in positron emission tomography (PET) images of chest structures to spread out and misregister with the CT images. This misregistration can alter the attenuation correction and thus the quantisation of PET images. In this paper, we present the first clinical results for a respiratory-gated PET (RG-PET) processing method based on a single breath-hold CT (BH-CT) acquisition, which seeks to improve diagnostic accuracy via better PET-to-CT co-registration. We refer to this method as "CT-based" RG-PET processing., Methods: Thirteen lesions were studied. Patients underwent a standard clinical PET protocol and then the CT-based protocol, which consists of a 10-min List Mode RG-PET acquisition, followed by a shallow end-expiration BH-CT. The respective performances of the CT-based and clinical PET methods were evaluated by comparing the distances between the lesions' centroids on PET and CT images. SUV(MAX) and volume variations were also investigated., Results: The CT-based method showed significantly lower (p = 0.027) centroid distances (mean change relative to the clinical method = -49%; range = -100% to 0%). This led to higher SUV(MAX) (mean change = +33%; range = -4% to 69%). Lesion volumes were significantly lower (p = 0.022) in CT-based PET volumes (mean change = -39%: range = -74% to -1%) compared with clinical ones., Conclusions: A CT-based RG-PET processing method can be implemented in clinical practice with a small increase in radiation exposure. It improves PET-CT co-registration of lung lesions and should lead to more accurate attenuation correction and thus SUV measurement.

Purpose: We propose a respiratory-correlated PET data processing method (called "BH-CT-based") based on breath-hold CT acquisition to reduce the smearing effect and improve the attenuation correction. The resulting images are compared with the ungated PET images acquired using a standard, free-breathing clinical protocol., Methods: The BH-CT-based method consisted of a list-mode acquisition with simultaneous respiratory signal recording. An additional breath-hold CT acquisition was also performed in order to define a tissue position from which PET events can be selected. A phantom study featured a 0.5-ml sphere (filled with 18F-fluorodeoxyglucose ((18)F-FDG) solution) pushed onto a rubber balloon (filled with (18)F-FDG solution and iodinated contrast agent). The feasibility of the BH-CT-based method was also assessed in two patients., Results: In the phantom study, the contrast-to-noise ratios (CNRs) were -1.6 for the Ungated volume and 5.1 for the BH-CT-based volume. For patients, CNRs were higher for BH-CT-based volumes than those for Ungated volumes (17.3 vs. 6.3 and 7.3 vs. 3.8, for patients 1 and 2, respectively). Bias-variance measurements were performed and yielded bias reduction of 40% with BH-CT-based., Conclusion: The application of a BH-CT-based method decreases motion bias in PET images. This method resolves issues related to both PET-to-CT misregistration and erroneous attenuation correction and increases lesion detectability.

Purpose: To evaluate the contributions of phase-contrast magnetic resonance (PCMR) and transcranial color Doppler (TCCD) imaging in the investigation of cerebral hydrodynamics., Materials and Methods: A total of 13 healthy subjects were studied. Blood velocity measurements were performed with TCCD and gated PCMR imaging in major intracranial and extracranial arteries stages. Peak systolic velocity and end-diastolic velocity were extracted to establish correlations between TCCD and PCMR imaging. Cerebral blood flow (CBF) and intracranial volume change (IVC) during the cardiac cycle were calculated, taking into account cerebrospinal fluid (CSF) oscillations., Results: Despite an underestimation of velocities with PCMR imaging, significant correlations were observed for velocity measurements between the two modalities in extracranial vessels, but were poorly correlated in intracranial vessels. PCMR data processing gave a mean CBF of 690+/-90 mL/minute., Conclusion: PCMR imaging provides complementary information to TCCD to assess various intracranial parameters such as instantaneous velocities, blood and CSF flow distributions, volume variation, or pressure regulation mechanisms during cardiac cycles., (Copyright (c) 2006 Wiley-Liss, Inc.)

A computational fluid dynamics (CFD) method is presented to investigate the flow of cerebro-spinal fluid (CSF) in the cerebral aqueduct. In addition to former approaches exhibiting a rigid geometry, we propose a model which includes a deformable membrane as the wall of this flow channel. An anatomical shape of the aqueduct was computed from magnetic resonance images (MRI) and the resulting meshing was immersed in a marker-and-cell (MAC) staggered grid for to take into account fluid-structure interactions. The time derivatives were digitized using the Crank-Nicolson scheme. The equation of continuity was modified by introducing an artificial compressibility and digitized by a finite difference scheme. Calculations were validated with the simulation of laminar flow in a rigid tube. Then, comparisons were made between simulations of a rigid aqueduct and a deformable one. We found that the deformability of the walls has a strong influence on the pressure drop for a given flow.

Acetylcholinesterase (AChE) inhibitors are one of the most actively investigated classes of compounds in the search for an effective treatment of Alzheimer's disease. This work describes the synthesis, AChE inhibitory activity, and structure-activity relationships of some compounds related to a recently discovered series of AChE inhibitors: the omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxy xanthen-9-ones. The influence of structural variations on the inhibitory potency was carefully investigated by modifying different parts of the parent molecule, and a theoretical model of the binding of one representative compound to the enzyme was developed. The biological properties of the series were investigated in some detail by considering not only the activity on isolated enzyme but the selectivity with respect to butyrylcholinesterase (BuChE) and the in vitro inhibitory activity on rat cerebral cortex as well. Some of the newly synthesized derivatives, when tested on isolated and/or AChE-enriched rat brain cortex fraction, displayed a selective inhibitory activity and were more active than physostigmine. In particular, compound 13, an azaxanthone derivative, displayed the best rat cortex AChE inhibition (190-fold higher than physostigmine), as well as a high degree of enzyme selectivity (over 60-fold more selective for AChE than for BuChE). When tested in the isolated enzyme, compound 13 was less active, suggesting some differences either in drug availability/biotransformation or in the inhibitor-sensitive residues of the enzyme when biologically positioned in rat brain membranes.

The paper describes the use of crystal-violet and lysine containing media to detect yeast infection in brewing and to classify it. The crystal-violet containing medium helps to separate brewing yeast Saccharomyces cerevisiae and Saccharomyces carlsbergensis from wild yeast of the Saccharomyces genus, whereas the lysine containing medium--from wild yeast of the genera Candida, Debaryomyces, Brethanomyces, Pichia. The test has been used both on museum cultures and on yeast isolated from beer and non-alcoholic beverages.