Objective:
To investigate in vivo the impact of age on nigrostriatal dopamine dysfunction in Parkinson's disease (PD).
Methods:
PD patients (n = 78) and healthy control subjects (n = 35) underwent ...longitudinal positron emission tomography assessments using 3 presynaptic dopamine markers: (1) 11C(±)dihydrotetrabenazine (DTBZ), to estimate the density of the vesicular monoamine transporter type 2; (2) 11Cd‐threo‐methylphenidate, to estimate the density of the plasma membrane dopamine transporter; and (3) 6‐18F‐fluoro‐L‐dopa, to estimate the activity of the enzyme dopa‐decarboxylase.
Results:
The study comprised 438 PD scans and 241 control scans (679 scans in total). At symptom onset, the loss of putamen DTBZ binding was substantially greater in younger compared to older PD patients (p = 0.015). Remarkably, however, the rate of progression of DTBZ binding loss was significantly slower in younger patients (p < 0.05). The estimated presymptomatic phase of the disease spanned more than 2 decades in younger patients, compared to 1 decade in older patients.
Interpretation:
Our results suggest that, compared to older patients, younger PD patients progress more slowly and are able to endure more damage to the dopaminergic system before the first motor symptoms appear. These observations suggest that younger PD patients have more efficient compensatory mechanisms. Ann Neurol 2011;
Summary The genus Anaplasmais one of four distinct genera in the family Anaplasmataceae, which are obligate intracellular pathogens vectored by ticks and found exclusively within parasitophorous ...vacuoles in the host cell cytoplasm. The 2001 reclassification of the order Rickettsiales expanded the genus Anaplasma, which previously contained pathogens that were host specific for ruminants (A. marginale, A. centrale and A. bovis), by adding A. phagocytophilum, a unification of three organisms previously classified as Ehrlichia (E. equi, E. phagocytophila and the unnamed agent of human granulocytic ehrlichiosis). Also included in the genus Anaplasma were A. bovis (formerly E. bovis), A. platys (formerly E. platys) and Aegyptianella pullorum. Despite the genomic relatedness of the regrouped organisms, many aspects of their biology are diverse, including their host specificity, host cell preferences, major surface proteins (MSPs) and tick vectors. This review focuses on the two most important pathogens: A. marginale, which causes bovine anaplasmosis, and A. phagocytophilum, the aetiologic agent of tick-borne fever in sheep and human granulocytic anaplasmosis, an emerging tick-borne disease of humans. For both pathogens, strain diversity is much greater than previously recognised. While MSPs were found to be useful in phylogenetic studies and strain identification, highly conserved MSPs were found to affect the specificity of serologic tests. Comparison of these two important pathogens highlights the challenges and insight derived from reclassification and molecular analysis, both of which have implications for the development and evaluation of diagnosis and control strategies.
The cooling and drying associated with the so-called '8.2 ka event' have long been hypothesized as having sweeping implications for human societies in the Early Holocene, including some of the last ...Mesolithic hunter-gatherers in Atlantic Europe. Nevertheless, detailed 'on-site' records with which the impacts of broader climate changes on human-relevant environments can be explored have been lacking. Here, we reconstruct sea surface temperatures (SST) from δ
O values measured on subfossil topshells Phorcus lineatus exploited by the Mesolithic human groups that lived at El Mazo cave (N Spain) between 9 and 7.4 ka. Bayesian modelling of 65 radiocarbon dates, in combination with this δ
O data, provide a high-resolution seasonal record of SST, revealing that colder SST during the 8.2 ka event led to changes in the availability of different shellfish species. Intensification in the exploitation of molluscs by humans indicates demographic growth in these Atlantic coastal settings which acted as refugia during this cold event.
The effect of the diameter of multiwalled carbon nanotubes for the incorporation of N and Fe and the consequences for the oxygen reduction reaction in acid medium has been studied. For this, a series ...of multiwalled carbon nanotubes with mean diameters of 10, 20 and 60 nm have been thermally treated in acid media and modified by addition of N- and Fe-groups by means of thermal treatments under inert atmosphere. The chemically treated nanotubes and the FeN-CNTs have been thoroughly characterized by N2 adsorption/desorption isotherms, Raman spectroscopy, X-ray photoelectron spectroscopy, elemental analysis, thermogravimetric analysis and X-ray diffraction. The performance of the FeN-CNTs for the oxygen reduction reaction (ORR) in acid medium has been evaluated by means of electrochemical techniques. We have found that the amount of nitrogen actually incorporated onto the multiwalled carbon nanotubes, which ranges between 2 and 3 wt.%, can be directly related with the number of defects of the chemically treated multiwalled nanotubes. On the other hand, the BET specific surface area of the FeN-CNTs increases with the decreasing diameter of the CNTs. A direct relationship between the nitrogen external surface area and the ORR performance has been observed.
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•Fe/N centres have been created onto chemically treated MWCNT with different mean diameters.•The amount of N incorporated onto the MWCNT increases with their mean diameter.•Fe/N/CNTS are very active electrocatalysts for the ORR in acid medium.•N-sites located at the external surface area are the most actives for the ORR.
ABSTRACT
We present an observational and numerical study of the borderline hyperbolic comet C/2021 O3 (PANSTARRS) performed during its recent passage through the inner Solar system. Our observations ...were carried out at OASI and SOAR between 2021 October and 2022 January, and reveal a low level of activity relative to which was measured for other long-period comets. In addition, we observed a decrease in brightness as the comet got closer to the Sun. Our photometric data, obtained as C/2021 O3 approached perihelion on 2022 April 21, show that the comet was much less active than what is usually expected in the cases of long-period comets, with Afρ values more in line with those of short-period comets (specifically, the Jupiter-family comets). On the other hand, the observed increase in the value of the spectral slope as the amount of dust in the coma decreased could indicate that the smaller dust particles were being dispersed from the coma by radiation pressure faster than they were injected by possible sublimation jets. The analysis of its orbital evolution suggests that C/2021 O3 could be a dynamically old comet, or perhaps a new one masquerading as a dynamically old comet, with a likely origin in the Solar system.
Highlights • Cattle were vaccinated with tick proteins involved in vector–pathogen interactions. • Recombinant TROSPA, SILK, Subolesin (SUB) and Q38 were used for vaccination. • Vaccination with ...SILK, SUB and Q38 reduced tick infestations and oviposition. • Vaccination with Q38, TROSPA and SUB reduced B. bigemina DNA in ticks. • Vaccination with SILK and SUB reduced A. marginal e DNA in ticks.
Accelerating growth and global expansion of antimicrobial resistance has deepened the need for discovery of novel antimicrobial agents. Antimicrobial peptides have clear advantages over conventional ...antibiotics which include slower emergence of resistance, broad-spectrum antibiofilm activity, and the ability to favourably modulate the host immune response. Broad bacterial susceptibility to antimicrobial peptides offers an additional tool to expand knowledge about the evolution of antimicrobial resistance. Structural and functional limitations, combined with a stricter regulatory environment, have hampered the clinical translation of antimicrobial peptides as potential therapeutic agents. Existing computational and experimental tools attempt to ease the preclinical and clinical development of antimicrobial peptides as novel therapeutics. This Review identifies the benefits, challenges, and opportunities of using antimicrobial peptides against multidrug-resistant pathogens, highlights advances in the deployment of novel promising antimicrobial peptides, and underlines the needs and priorities in designing focused development strategies taking into account the most advanced tools available.
As bacterial biofilms are often refractory to conventional antimicrobials, the need for alternative and/or novel strategies for the treatment of biofilm related infections has become of paramount ...importance. Herein, we report the synthesis of novel hybrid molecules comprised of two different hindered nitroxides linked to the piperazinyl secondary amine of ciprofloxacin via a tertiary amine linker achieved utilising reductive amination. The corresponding methoxyamine derivatives were prepared alongside their radical-containing counterparts as controls. Subsequent biological evaluation of the hybrid compounds on preformed P. aeruginosa flow cell biofilms divulged significant dispersal and eradication abilities for ciprofloxacin-nitroxide hybrid compound 10 (up to 95% eradication of mature biofilms at 40 μM). Importantly, these hybrids represent the first dual-action antimicrobial-nitroxide agents, which harness the dispersal properties of the nitroxide moiety to circumvent the well-known resistance of biofilms to treatment with antimicrobial agents.
Neurodegenerative diseases of the central nervous system (CNS) are characterized by progressive neuronal death and neurological dysfunction, leading to increased disability and a loss of cognitive or ...motor functions. Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis have neurodegeneration as a primary feature. However, in other CNS diseases such as multiple sclerosis, stroke, traumatic brain injury, and spinal cord injury, neurodegeneration follows another insult, such as demyelination or ischaemia. Although there are different primary causes to these diseases, they all share a hallmark of neuroinflammation. Neuroinflammation can occur through the activation of resident immune cells such as microglia, cells of the innate and adaptive peripheral immune system, meningeal inflammation and autoantibodies directed toward components of the CNS. Despite chronic inflammation being pathogenic in these diseases, local inflammation after insult can also promote endogenous regenerative processes in the CNS, which are key to slowing disease progression. The normal aging process in the healthy brain is associated with a decline in physiological function, a steady increase in levels of neuroinflammation, brain shrinkage, and memory deficits. Likewise, aging is also a key contributor to the progression and exacerbation of neurodegenerative diseases. As there are associated co-morbidities within an aging population, pinpointing the precise relationship between aging and neurodegenerative disease progression can be a challenge. The CNS has historically been considered an isolated, "immune privileged" site, however, there is mounting evidence that adaptive immune cells are present in the CNS of both healthy individuals and diseased patients. Adaptive immune cells have also been implicated in both the degeneration and regeneration of the CNS. In this review, we will discuss the key role of the adaptive immune system in CNS degeneration and regeneration, with a focus on how aging influences this crosstalk.
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