Callophycoic acids and callophycols from the Fijian red alga Callophycus serratus

Callophycoic acids A−H (1−8) and callophycols A and B (9 and 10) were isolated from extracts of the Fijian red alga Callophycus serratus, and identified by NMR, X-ray, and mass spectral analyses. These natural products represent four novel carbon skeletons, providing the first examples of diterpene−benzoic acids and diterpene−phenols in macroalgae. Compounds 1−10 exhibited antibacterial, antimalarial, and anticancer activity, although they are less bioactive than diterpene-benzoate macrolides previously isolated from this red alga

Brain regions showing white matter loss in Huntington's Disease are enriched for synaptic and metabolic genes

Background The earliest white matter changes in Huntington’s disease are seen before disease onset in the premanifest stage around the striatum, within the corpus callosum, and in posterior white matter tracts. While experimental evidence suggests that these changes may be related to abnormal gene transcription, we lack an understanding of the biological processes driving this regional vulnerability. Methods Here, we investigate the relationship between regional transcription in the healthy brain, using the Allen Institute for Brain Science transcriptome atlas, and regional white matter connectivity loss at three time points over 24 months in subjects with premanifest Huntington’s disease relative to control participants. The baseline cohort included 72 premanifest Huntington’s disease participants and 85 healthy control participants. Results We show that loss of corticostriatal, interhemispheric, and intrahemispheric white matter connections at baseline and over 24 months in premanifest Huntington’s disease is associated with gene expression profiles enriched for synaptic genes and metabolic genes. Corticostriatal gene expression profiles are predominately associated with motor, parietal, and occipital regions, while interhemispheric expression profiles are associated with frontotemporal regions. We also show that genes with known abnormal transcription in human Huntington’s disease and animal models are overrepresented in synaptic gene expression profiles, but not in metabolic gene expression profiles. Conclusions These findings suggest a dual mechanism of white matter vulnerability in Huntington’s disease, in which abnormal transcription of synaptic genes and metabolic disturbance not related to transcription may drive white matter loss

Apathy Associated With Impaired Recognition of Happy Facial Expressions in Huntington's Disease.

OBJECTIVES: Previous research has demonstrated an association between emotion recognition and apathy in several neurological conditions involving fronto-striatal pathology, including Parkinson's disease and brain injury. In line with these findings, we aimed to determine whether apathetic participants with early Huntington's disease (HD) were more impaired on an emotion recognition task compared to non-apathetic participants and healthy controls. METHODS: We included 43 participants from the TRACK-HD study who reported apathy on the Problem Behaviours Assessment - short version (PBA-S), 67 participants who reported no apathy, and 107 controls matched for age, sex, and level of education. During their baseline TRACK-HD visit, participants completed a battery of cognitive and psychological tests including an emotion recognition task, the Hospital Depression and Anxiety Scale (HADS) and were assessed on the PBA-S. RESULTS: Compared to the non-apathetic group and the control group, the apathetic group were impaired on the recognition of happy facial expressions, after controlling for depression symptomology on the HADS and general disease progression (Unified Huntington's Disease Rating Scale total motor score). This was despite no difference between the apathetic and non-apathetic group on overall cognitive functioning assessed by a cognitive composite score. CONCLUSIONS: Impairment of the recognition of happy expressions may be part of the clinical picture of apathy in HD. While shared reliance on frontostriatal pathways may broadly explain associations between emotion recognition and apathy found across several patient groups, further work is needed to determine what relationships exist between recognition of specific emotions, distinct subtypes of apathy and underlying neuropathology. (JINS, 2019, 25, 453-461)

Design and evaluation of a simulation environment for evaluating departure scheduling algorithms

To meet traffic demand predictions, the global air traffic management (ATM) system needs to be changed. Several visions on future ATM operations exist. A commonality between the different visions is 4D Trajectory management. This function enables plan-based operation as opposed to the state-based approach of the present system. Plan-based operation enables the optimization of traffic flows by generating 4D trajectories. A part of the traffic flow generation process is scheduling. The research presented in this thesis focuses on these scheduling opportunities. In this research the scheduling opportunities for departure traffic at a runway are investigated. A study of the existing literature showed that the most common scheduling algorithms currently available can be divided into four categories: first come first served, brand-and-bound, greedy search and genetic algorithms. A simulation environment is designed for evaluation of the departure scheduling algorithms using various input parameters like traffic situation, airport map and algorithm. The four algorithm categories are evaluated on output aspects like delay and robustness of the schedule and are compared with the current method of traffic scheduling. The evaluation of the scheduling algorithms shows that the performance of the current method of scheduling departure traffic performs well in comparison with the tested algorithms. In case of no disturbances the genetic algorithm performs slightly better than the current method, but the other algorithms do not have a better performance. When disturbances are taken into account, a bigger performance increase can be obtained by using scheduling algorithms.Group of Microwave Technology and Systems for Radar (MTSR)TelecommunicationsElectrical Engineering, Mathematics and Computer Scienc

Unusual antimalarial meroditerpenes from tropical red macroalgae

Three antimalarial meroditerpenes have been isolated from two Fijian red macroalgae. The absolute stereochemistry of callophycolide A (1), a unique macrolide from Callophycus serratus, was determined using a combination of Mosher’s ester analysis, circular dichroism analysis with a dimolybdenum tetraacetate complex, and conformational analysis using NOEs. In addition, two known tocopherols, β-tocopherylhydroquinone (4) and δ-tocopherylhydroquinone (5), were isolated from Amphiroa crassa. By oxidizing 5 to the corresponding δ-tocopherylquinone (6), antimalarial activity against the human malaria parasite Plasmodium falciparum was increased by more than 20-fold

Antimalarial bromophycolides J-Q from the Fijian red alga Callophycus serratus

Bromophycolides J−Q (1−8) were isolated from extracts of the Fijian red alga Callophycus serratus and identified with 1D and 2D NMR spectroscopy and mass spectral analyses. These diterpene−benzoate macrolides represent two novel carbon skeletons and add to the 10 previously reported bromophycolides (9−18) from this alga. Among these 18 bromophycolides, several exhibited activities in the low micromolar range against the human malaria parasite Plasmodium falciparum

Antibacterial Neurymenolides from the Fijian red alga Neurymenia fraxinifolia

Two novel α-pyrone macrolides, neurymenolides A (1) and B (2), were isolated from the Fijian red alga Neurymenia fraxinifolia and characterized using a combination of NMR and mass spectral analyses. These molecules represent only the second example of α-pyrone macrolides, with 1 existing as interchanging atropisomers due to restricted rotation about the α-pyrone ring system. Neurymenolide A (1) displayed moderately potent activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistantEnterococcus faecium (VREF)

Magnetization Transfer Imaging in Premanifest and Manifest Huntington Disease: A 2-Year Follow-Up

Neurological Motor Disorder