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Lifestyle choices leading to obesity, hypertension and diabetes in mid-life contribute directly to the risk of late-life Alzheimer's disease (AD). However, in late-life or in late-stage AD conditions, obesity reduces the risk of AD and disease progression. To examine the mechanisms underlying this paradox, TgF344-AD rats were fed a varied high-carbohydrate, high-fat (HCHF) diet to induce obesity from nine months of age representing early stages of AD to twelve months of age in which rats exhibit the full spectrum of AD symptomology. We hypothesized regions primarily composed of gray matter, such as the somatosensory cortex (SSC), would be differentially affected compared to regions primarily composed of white matter, such as the striatum. We found increased myelin and oligodendrocytes in the somatosensory cortex of rats fed the HCHF diet with an absence of neuronal loss. We observed decreased inflammation in the somatosensory cortex despite increased AD pathology. Compared to the somatosensory cortex, the striatum had fewer changes. Overall, our results suggest that the interaction between diet and AD progression affects myelination in a brain region specific manner such that regions with a lower density of white matter are preferentially affected. Our results offer a possible mechanistic explanation for the obesity paradox., (© 2024. The Author(s).)

Strong evidence demonstrates a significant association between cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). For this reason, interest in understanding the underlying vascular pathologies that contribute to AD remain. CAA research has primarily focused on arterioles and capillaries, overlooking the draining venules. Therefore, this study sought to examine venular amyloid pathology and its relationship to arteriolar amyloidosis throughout AD progression in the TgF344-AD rat model. Antibodies targeting the amyloid-beta peptide (Aβ) sequence suggest morphological differences between arteriolar and venular amyloid. Mass spectrometric analyses of isolated cortical parenchymal plaques, arteriolar and venular amyloid demonstrated presence of Aβ in all three samples, as well as proteins known to be associated with AD. Histopathological analysis indicates a significant age effect for both arteriolar and venular amyloid accumulation, with accumulation initiated in the somatosensory cortex followed by the motor and cingulate cortex. Lastly, significant arteriolar amyloid accumulates relative to venular amyloid deposition in AD progression. Overall, understanding venular and arteriolar amyloid pathology provides insight into the complex connection between CAA and AD., (© 2022. The Author(s).)

NASA's Parker Solar Probe mission 1 recently plunged through the inner heliosphere of the Sun to its perihelia, about 24 million kilometres from the Sun. Previous studies farther from the Sun (performed mostly at a distance of 1 astronomical unit) indicate that solar energetic particles are accelerated from a few kiloelectronvolts up to near-relativistic energies via at least two processes: 'impulsive' events, which are usually associated with magnetic reconnection in solar flares and are typically enriched in electrons, helium-3 and heavier ions 2 , and 'gradual' events 3,4 , which are typically associated with large coronal-mass-ejection-driven shocks and compressions moving through the corona and inner solar wind and are the dominant source of protons with energies between 1 and 10 megaelectronvolts. However, some events show aspects of both processes and the electron-proton ratio is not bimodally distributed, as would be expected if there were only two possible processes 5 . These processes have been very difficult to resolve from prior observations, owing to the various transport effects that affect the energetic particle population en route to more distant spacecraft 6 . Here we report observations of the near-Sun energetic particle radiation environment over the first two orbits of the probe. We find a variety of energetic particle events accelerated both locally and remotely including by corotating interaction regions, impulsive events driven by acceleration near the Sun, and an event related to a coronal mass ejection. We provide direct observations of the energetic particle radiation environment in the region just above the corona of the Sun and directly explore the physics of particle acceleration and transport.

Over a two-year period, Voyager 1 observed a gradual slowing-down of radial plasma flow in the heliosheath to near-zero velocity after April 2010 at a distance of 113.5 astronomical units from the Sun (1 astronomical unit equals 1.5 × 10(8) kilometres). Voyager 1 was then about 20 astronomical units beyond the shock that terminates the free expansion of the solar wind and was immersed in the heated non-thermal plasma region called the heliosheath. The expectation from contemporary simulations was that the heliosheath plasma would be deflected from radial flow to meridional flow (in solar heliospheric coordinates), which at Voyager 1 would lie mainly on the (locally spherical) surface called the heliopause. This surface is supposed to separate the heliosheath plasma, which is of solar origin, from the interstellar plasma, which is of local Galactic origin. In 2011, the Voyager project began occasional temporary re-orientations of the spacecraft (totalling about 10-25 hours every 2 months) to re-align the Low-Energy Charged Particle instrument on board Voyager 1 so that it could measure meridional flow. Here we report that, contrary to expectations, these observations yielded a meridional flow velocity of +3 ± 11 km s(-1), that is, one consistent with zero within statistical uncertainties.

Voyager 1 has been in the reservoir of energetic ions and electrons that constitutes the heliosheath since it crossed the solar wind termination shock on 16 December 2004 at a distance from the Sun of 94 astronomical units (1 AU = 1.5 × 10(8) km). It is now ∼22 AU past the termination shock crossing. The bulk velocity of the plasma in the radial-transverse plane has been determined using measurements of the anisotropy of the convected energetic ion distribution. Here we report that the radial component of the velocity has been decreasing almost linearly over the past three years, from ∼70 km s(-1) to ∼0 km s(-1), where it has remained for the past eight months. It now seems that Voyager 1 has entered a finite transition layer of zero-radial-velocity plasma flow, indicating that the spacecraft may be close to the heliopause, the border between the heliosheath and the interstellar plasma. The existence of a flow transition layer in the heliosheath contradicts current predictions--generally assumed by conceptual models--of a sharp discontinuity at the heliopause.

Broad regions on both sides of the solar wind termination shock are populated by high intensities of non-thermal ions and electrons. The pre-shock particles in the solar wind have been measured by the spacecraft Voyager 1 (refs 1-5) and Voyager 2 (refs 3, 6). The post-shock particles in the heliosheath have also been measured by Voyager 1 (refs 3-5). It was not clear, however, what effect these particles might have on the physics of the shock transition until Voyager 2 crossed the shock on 31 August-1 September 2007 (refs 7-9). Unlike Voyager 1, Voyager 2 is making plasma measurements. Data from the plasma and magnetic field instruments on Voyager 2 indicate that non-thermal ion distributions probably have key roles in mediating dynamical processes at the termination shock and in the heliosheath. Here we report that intensities of low-energy ions measured by Voyager 2 produce non-thermal partial ion pressures in the heliosheath that are comparable to (or exceed) both the thermal plasma pressures and the scalar magnetic field pressures. We conclude that these ions are the >0.028 MeV portion of the non-thermal ion distribution that determines the termination shock structure and the acceleration of which extracts a large fraction of bulk-flow kinetic energy from the incident solar wind.

The outer limit of the Solar System is often considered to be at the distance from the Sun where the solar wind changes from supersonic to subsonic flow. Theory predicts that a termination shock marks this boundary, with locations ranging from a few to over 100 au (1 Au approximately 1.5 x 10(8) km, the distance from Earth to the Sun). 'Pick-up ions' that originate as interstellar neutral atoms should be accelerated to tens of MeV at the termination shock, generating anomalous cosmic rays. Here we report a large increase in the intensity of energetic particles in the outer heliosphere, as measured by an instrument on the Voyager 1 spacecraft. We argue that the spacecraft exited the supersonic solar wind and passed into the subsonic region (possibly beyond the termination shock) on about 1 August 2002 at a distance of approximately 85 Au (heliolatitude approximately 34 degrees N), then re-entered the supersonic solar wind about 200 days later at approximately 87 au from the Sun. We show that the composition of the ions accelerated at the putative termination shock is that of anomalous cosmic rays and of interstellar pick-up ions.

A library of 50,000 recombinants representative of the human X chromosome has been constructed. Human X chromosomes were physically separated using a fluorescence-activated cell sorter. The DNA was purified from the chromosomes, digested to completion with the restriction enzyme EcoRI and cloned into the phage lambda gtWES.lambda B. The X-derived nature of the recombinants was confirmed by hybridization to rodent/human cell line DNA containing only the human X chromosome. Such libraries will be particularly useful for the investigation of genetic diseases such as Duchenne muscular dystrophy, where the basic defect has not been elucidated, and of neoplasia, where several specific chromosomal anomalies, particularly for the leukaemias, have been identified.