Changing gears to neutral in a polymorph of one-dimensional arrays of cogwheel-like pairs of molecular rotors

We report on a polymorph (2) of an amphidynamic crystal of molecular rods with two helical 1,4-bis(ethynyl)bicyclo[2.2.2]octane rotators where half of the rod-like molecules appear to be shifted with respect to their closest neighbours. This translation takes cogwheel-like pairs of rotators apart in the lattice in such a way that their motion becomes uncorrelated. This property is to be contrasted with the highly correlated motion found to govern the rotators in a recently-published polymorph 1 of the same material. As with polymorph 1, this motion is shown to take place independently of mutations in the handedness of the rotators and of the ‘mutamer’-induced second harmonic generation

Static Modulation Wave of Arrays of Halogen Interactions Transduced to a Hierarchy of Nanoscale Change Stimuli of Crystalline Rotors Dynamics

Here we present a study where what can be seen as a static modulation wave encompassing four successive arrays of interacting iodine atoms in cryst. 1,​4-​Bis((4\u27-​(iodoethynyl)​phenyl) ethynyl)​bicyclo[2,​2,​2]​octane rotors changes the structure from one-​half mol. to three-​and-​a-​half mols. in the asym. unit below a phase transition at 105 K.  The remarkable finding is that the total 1H spin-​lattice relaxation rate, T1-​1, of unprecedented complexity to date in mol. rotors, is the weighted sum of the relaxation rates of the four contributing rotors relaxation rates, each with distinguishable exchange frequencies reflecting Arrhenius parameters with different activation barriers (Ea) and attempt frequencies (τo-​1)​.  This allows us to show in tandem with rotor-​environment interaction energy calcns. how the dynamics of mol. rotors are able to decode structural information from their surroundings with remarkable nanoscale precision

On the possibility of magneto-structural correlations: detailed studies of di-nickel carboxylate complexes

A series of water-bridged dinickel complexes of the general formula [Ni<sub>2</sub>(μ<sub>2</sub>-OH<sub>2</sub>)(μ2- O<sub>2</sub>C<sup>t</sup>Bu)<sub>2</sub>(O<sub>2</sub>C<sup>t</sup>Bu)2(L)(L0)] (L = HO<sub>2</sub>C<sup>t</sup>Bu, L0 = HO<sub>2</sub>C<sup>t</sup>Bu (1), pyridine (2), 3-methylpyridine (4); L = L0 = pyridine (3), 3-methylpyridine (5)) has been synthesized and structurally characterized by X-ray crystallography. The magnetic properties have been probed by magnetometry and EPR spectroscopy, and detailed measurements show that the axial zero-field splitting, D, of the nickel(ii) ions is on the same order as the isotropic exchange interaction, J, between the nickel sites. The isotropic exchange interaction can be related to the angle between the nickel centers and the bridging water molecule, while the magnitude of D can be related to the coordination sphere at the nickel sites

Synaptic phosphorylated a-synuclein in dementia with Lewy bodies

Dementia with Lewy bodies is characterized by the accumulation of Lewy bodies and Lewy neurites in the CNS, both of which are composed mainly of aggregated a-synuclein phosphorylated at Ser129. Although phosphorylated a-synuclein is believed to exert toxic effects at the synapse in dementia with Lewy bodies and other a-synucleinopathies, direct evidence for the precise synaptic localization has been difficult to achieve due to the lack of adequate optical microscopic resolution to study human synapses. In the present study we applied array tomography, a microscopy technique that combines ultrathin sectioning of tissue with immunofluorescence allowing precise identification of small structures, to quantitatively investigate the synaptic phosphorylated a-synuclein pathology in dementia with Lewy bodies. We performed array tomography on human brain samples from five patients with dementia with Lewy bodies, five patients with Alzheimer’s disease and five healthy control subjects to analyse the presence of phosphorylated a-synuclein immunoreactivity at the synapse and their relationship with synapse size. Main analyses were performed in blocks from cingulate cortex and confirmed in blocks from the striatum of cases with dementia with Lewy bodies. A total of 1 318 700 single pre- or post-synaptic terminals were analysed. We found that phosphorylated a-synuclein is present exclusively in dementia with Lewy bodies cases, where it can be identified in the form of Lewy bodies, Lewy neurites and small aggregates (50.16 mm3). Between 19% and 25% of phosphorylated a-synuclein deposits were found in presynaptic terminals mainly in the form of small aggregates. Synaptic terminals that co-localized with small aggregates of phosphorylated a-synuclein were significantly larger than those that did not. Finally, a gradient of phosphorylated a-synuclein aggregation in synapses (pre4pre + post4post-synaptic) was observed. These results indicate that phosphorylated a-synuclein is found at the presynaptic terminals of dementia with Lewy bodies cases mainly in the form of small phosphorylated a-synuclein aggregates that are associated with changes in synaptic morphology. Overall, our data support the notion that pathological phosphorylated a-synuclein may disrupt the structure and function of the synapse in dementia with Lewy bodies.Peer ReviewedPostprint (author's final draft

The Behavioral and Psychological Symptoms of Dementia in Down Syndrome (BPSD-DS) Scale:Comprehensive Assessment of Psychopathology in Down Syndrome

People with Down syndrome (DS) are prone to develop Alzheimer's disease (AD). Behavioral and psychological symptoms of dementia (BPSD) are core features, but have not been comprehensively evaluated in DS. In a European multidisciplinary study, the novel Behavioral and Psychological Symptoms of Dementia in Down Syndrome (BPSD-DS) scale was developed to identify frequency and severity of behavioral changes taking account of life-long characteristic behavior. 83 behavioral items in 12 clinically defined sections were evaluated. The central aim was to identify items that change in relation to the dementia status, and thus may differentiate between diagnostic groups. Structured interviews were conducted with informants of persons with DS without dementia (DS, n = 149), with questionable dementia (DS+Q, n = 65), and with diagnosed dementia (DS+AD, n = 67). First exploratory data suggest promising interrater, test-retest, and internal consistency reliability measures. Concerning item relevance, group comparisons revealed pronounced increases in frequency and severity in items of anxiety, sleep disturbances, agitation & stereotypical behavior, aggression, apathy, depressive symptoms, and eating/drinking behavior. The proportion of individuals presenting an increase was highest in DS+AD, intermediate in DS+Q, and lowest in DS. Interestingly, among DS+Q individuals, a substantial proportion already presented increased anxiety, sleep disturbances, apathy, and depressive symptoms, suggesting that these changes occur early in the course of AD. Future efforts should optimize the scale based on current results and clinical experiences, and further study applicability, reliability, and validity. Future application of the scale in daily care may aid caregivers to understand changes, and contribute to timely interventions and adaptation of caregiving

Mechanisms Involved in Epileptogenesis in Alzheimer's Disease and Their Therapeutic Implications

Altres ajuts: Fondo de Investigaciones Sanitario (FIS); National Institutes of Health (1R01AG056850-01A1, R21AG056974, R01AG061566); Fundació La Marató de TV3 (20141210); Sociedad Catalana de Neurología (SCN-2020 to MCI); Fundació Catalana Síndrome de Down; Fundació Víctor Grífols i Luca; Fundación Tatiana Pérez de Guzmán el Bueno.Epilepsy and Alzheimer's disease (AD) incidence increases with age. There are recip-rocal relationships between epilepsy and AD. Epilepsy is a risk factor for AD and, in turn, AD is an independent risk factor for developing epilepsy in old age, and abnormal AD biomarkers in PET and/or CSF are frequently found in late-onset epilepsies of unknown etiology. Accordingly, epilepsy and AD share pathophysiological processes, including neuronal hyperexcitability and an early excitatory-inhibitory dysregulation, leading to dysfunction in the inhibitory GABAergic and excitatory glutamatergic systems. Moreover, both β-amyloid and tau protein aggregates, the anato-mopathological hallmarks of AD, have proepileptic effects. Finally, these aggregates have been found in the resection material of refractory temporal lobe epilepsies, suggesting that epilepsy leads to amyloid and tau aggregates. Some epileptic syndromes, such as medial temporal lobe epilepsy, share structural and functional neuroimaging findings with AD, leading to overlapping symptomatology, such as episodic memory deficits and toxic synergistic effects. In this respect, the existence of epilepti-form activity and electroclinical seizures in AD appears to accelerate the progression of cognitive decline, and the presence of cognitive decline is much more prevalent in epileptic patients than in elderly patients without epilepsy. Notwithstanding their clinical significance, the diagnosis of clinical seizures in AD is a challenge. Most are focal and manifest with an altered level of consciousness without motor symptoms, and are often interpreted as cognitive fluctuations. Finally, despite the frequent association of epilepsy and AD dementia, there is a lack of clinical trials to guide the use of antiseizure medications (ASMs). There is also a potential role for ASMs to be used as disease-modifying drugs in AD

On the chronological structure of the solutrean in Southern Iberia

The Solutrean techno-complex has gained particular significance over time for representing a clear demographic and techno-typological deviation from the developments occurred during the course of the Upper Paleolithic in Western Europe. Some of Solutrean's most relevant features are the diversity and techno-typological characteristics of the lithic armatures. These have been recurrently used as pivotal elements in numerous Solutrean-related debates, including the chronological organization of the techno-complex across Iberia and Southwestern France. In Southern Iberia, patterns of presence and/or absence of specific point types in stratified sequences tend to validate the classical ordering of the techno-complex into Lower, Middle and Upper phases, although some evidence, namely radiocarbon determinations, have not always been corroborative. Here we present the first comprehensive analysis of the currently available radiocarbon data for the Solutrean in Southern Iberia. We use a Bayesian statistical approach from 13 stratified sequences to compare the duration, and the start and end moments of each classic Solutrean phase across sites. We conclude that, based on the current data, the traditional organization of the Solutrean cannot be unquestionably confirmed for Southern Iberia, calling into doubt the status of the classically defined type-fossils as precise temporal markers.Fundacao para a Ciencia e Tecnologia [PTDC/HAH/64184/2006, PTDC/HIS-ARQ/117540/2010, SFRH/BD/65527/2009, SFRH/BPD/96277/2013]; National Geographic Society [8045-06]; Wenner-Gren Foundation for Anthropological Research [8290

SILEX: A fast and inexpensive high-quality DNA extraction method suitable for multiple sequencing platforms and recalcitrant plant species

Background: The use of sequencing and genotyping platforms has undergone dramatic improvements, enabling the generation of a wealth of genomic information. Despite this progress, the availability of high-quality genomic DNA (gDNA) in sufficient concentrations is often a main limitation, especially for third-generation sequencing platforms. A variety of DNA extraction methods and commercial kits are available. However, many of these are costly and frequently give either low yield or low-quality DNA, inappropriate for next generation sequencing (NGS) platforms. Here, we describe a fast and inexpensive DNA extraction method (SILEX) applicable to a wide range of plant species and tissues. Results: SILEX is a high-throughput DNA extraction protocol, based on the standard CTAB method with a DNA silica matrix recovery, which allows obtaining NGS-quality high molecular weight genomic plant DNA free of inhibitory compounds. SILEX was compared with a standard CTAB extraction protocol and a common commercial extraction kit in a variety of species, including recalcitrant ones, from different families. In comparison with the other methods, SILEX yielded DNA in higher concentrations and of higher quality. Manual extraction of 48 samples can be done in 96 min by one person at a cost of 0.12 €/sample of reagents and consumables. Hundreds of tomato gDNA samples obtained with either SILEX or the commercial kit were successfully genotyped with Single Primer Enrichment Technology (SPET) with the Illumina HiSeq 2500 platform. Furthermore, DNA extracted from Solanum elaeagnifolium using this protocol was assessed by Pulsed-field gel electrophoresis (PFGE), obtaining a suitable size ranges for most sequencing platforms that required high-molecular-weight DNA such as Nanopore or PacBio. Conclusions: A high-throughput, fast and inexpensive DNA extraction protocol was developed and validated for a wide variety of plants and tissues. SILEX offers an easy, scalable, efficient and inexpensive way to extract DNA for various next-generation sequencing applications including SPET and Nanopore among others

A Crystalline Hybrid of Paddlewheel Copper(II) Dimers and Molecular Rotors: Singlet-triplet Dynamics Revealed by Variable-temperature Proton Spin-lattice Relaxation

10.1002/zaac.20130062