Altered expression of Alzheimer's disease-related proteins in male hypogonadal mice

Age-related depletion of estrogens and androgens is associated with an increase in Alzheimer's disease (AD) brain pathology and diminished cognitive function. Here we investigated AD-associated molecular and cellular changes in brains of aged hypogonadal (hpg) male and female mice. hpg Mice have a spontaneous, inactivating genetic mutation in the GnRH gene resulting in lifelong deficiency of gonadotropins and gonadal sex hormones. Western blot analysis revealed low levels of amyloid precursor protein and high levels of presenilin 1, amyloid precursor protein C-terminal fragment, and beta-amyloid 42 in brains of aged male, but not female, hpg mice. Changes were confined to the hippocampus and were not evident in the cerebellum or other brain tissues. Male hpg mice tended to have lower levels of IL-1 beta protein than male littermate controls. Immunohistochemical staining of the basal forebrain revealed that male hpg mice had lower choline acetyltransferase levels per neuron compared with controls. These AD-like changes specific to male hpg mice supports a link between androgen depletion and the development of AD pathology

The state of Play with iPSCs and Spinal Cord Injury

The application of induced pluripotent stem cell (iPSC) technologies in cell based strategies, for the repair of the central nervous system (with particular focus on the spinal cord), is moving towards the potential use of clinical grade donor cells. The ability of iPSCs to generate donor neuronal, glial and astrocytic phenotypes for transplantation is highlighted here, and we review recent research using iPSCs in attempts to treat spinal cord injury in various animal models. Also discussed are issues relating to the production of clinical grade iPSCs, recent advances in transdifferentiation protocols for iPSC-derived donor cell populations, concerns about tumourogenicity, and whether iPSC technologies offer any advantages over previous donor cell candidates or tissues already in use as therapeutic tools in experimental spinal cord injury studies

In vivo oximetry of human bulbar conjunctival and episcleral microvasculature using snapshot multispectral imaging

A retinal-fundus camera fitted with a custom Image-Replicating Imaging Spectrometer was used to image the bulbar conjunctival and episcleral microvasculature in ten healthy human subjects at normoxia (21% Fraction of Inspired Oxygen [FiO2]) and acute mild hypoxia (15% FiO2) conditions. Eyelid closure was used to control oxygen diffusion between ambient air and the sclera surface. Four subjects were imaged for 30 seconds immediately following eyelid opening. Vessel diameter and Optical Density Ratio (ODR: a direct proxy for oxygen saturation) of vessels was computed automatically. Oximetry capability was validated using a simple phantom that mimicked the scleral vasculature. Acute mild hypoxia resulted in a decrease in blood oxygen saturation (SO2) (i.e. an increase in ODR) when compared with normoxia in both bulbar conjunctival (p < 0.001) and episcleral vessels (p = 0.03). Average episcleral diameter increased from 78.9 ± 8.7 μm (mean ± standard deviation) at normoxia to 97.6 ± 14.3 μm at hypoxia (p = 0.02). Diameters of bulbar conjunctival vessels showed no significant change from 80.1 ± 7.6 μm at normoxia to 80.6 ± 7.0 μm at hypoxia (p = 0.89). When exposed to ambient air, hypoxic bulbar conjunctival vessels rapidly reoxygenated due to oxygen diffusion from ambient air. Reoxygenation occured in an exponential manner, and SO2 reached normoxia baseline levels. The average ½ time to full reoxygenation was 3.4 ± 1.4 s. As a consequence of oxygen diffusion, bulbar conjunctival vessels will be highly oxygenated (i.e. close to 100% SO2) when exposed to ambient air. Episcleral vessels were not observed to undergo any significant oxygen diffusion, instead behaving similarly to pulse oximetry measurements. This is the first study to the image oxygen dynamics of bulbar conjunctival and episcleral microvasculature, and consequently, the first study to directly observe the rapid reoxygenation of hypoxic bulbar conjunctival vessels when exposed to ambient air. Oximetry of bulbar conjunctival vessels could potentially provide insight into conditions where oxygen dynamics of the microvasculature are not fully understood, such as diabetes, sickle-cell diseases, and dry-eye syndrome. Oximetry in the bulbar conjunctival and episcleral microvasculature could be complimentary or alternative to retinal oximetry

Millimeter-wave aperture synthesis radiometry for snow and ice mapping

An outline design for a dual-band mm-wave polarimetric SAIR has been presented and is considered to be tractable. The envisaged application is for snow and ice mapping and ocean wind vector measurement. The vastly increased complexity of the high-frequency waveband may not be justified by the scientific benefit and operation at an additional lower frequency such as 18 GHz may give improved classification, though with reduced spatial resolution. The authors describe the outline design for a polarimetric, mm-wave SAIR. One-dimensional aperture synthesis employs a hybrid technique in which a long linear array of real-aperture stick antennas form over-lapping fan beams on the ground and aperture synthesis within the fan beams enables synthesis of the mm-wave image. Critical aspects for building a high-resolution, mm-wave ESTAR are system calibration and the construction of stick antennas that will be 3 m long and about half a wavelength wide.Peer ReviewedPostprint (published version

The Partonic Nature of Instantons

In both Yang-Mills theories and sigma models, instantons are endowed with degrees of freedom associated to their scale size and orientation. It has long been conjectured that these degrees of freedom have a dual interpretation as the positions of partonic constituents of the instanton. These conjectures are usually framed in d=3+1 and d=1+1 dimensions respectively where the partons are supposed to be responsible for confinement and other strong coupling phenomena. We revisit this partonic interpretation of instantons in the context of d=4+1 and d=2+1 dimensions. Here the instantons are particle-like solitons and the theories are non-renormalizable. We present an explicit and calculable model in d=2+1 dimensions where the single soliton in the CP^N sigma-model can be shown to be a multi-particle state whose partons are identified with the ultra-violet degrees of freedom which render the theory well-defined at high energies. We introduce a number of methods which reveal the partons inside the soliton, including deforming the sigma model and a dual version of the Bogomolnyi equations. We conjecture that partons inside Yang-Mills instantons hold the key to understanding the ultra-violet completion of five-dimensional gauge theories.Comment: 28 pages. v3: extra references and comments. Mathematica notebooks for the figures can be downloaded from http://www.damtp.cam.ac.uk/user/dt281/parton.htm

Holographic Description of Gravitational Anomalies

The holographic duality can be extended to include quantum theories with broken coordinate invariance leading to the appearance of the gravitational anomalies. On the gravity side one adds the gravitational Chern-Simons term to the bulk action which gauge invariance is only up to the boundary terms. We analyze in detail how the gravitational anomalies originate from the modified Einstein equations in the bulk. As a side observation we find that the gravitational Chern-Simons functional has interesting conformal properties. It is invariant under conformal transformations. Moreover, its metric variation produces conformal tensor which is a generalization of the Cotton tensor to dimension $d+1=4k-1, k\in Z$. We calculate the modification of the holographic stress-energy tensor that is due to the Chern-Simons term and use the bulk Einstein equations to find its divergence and thus reproduce the gravitational anomaly. Explicit calculation of the anomaly is carried out in dimensions $d=2$ and $d=6$. The result of the holographic calculation is compared with that of the descent method and agreement is found. The gravitational Chern-Simons term originates by Kaluza-Klein mechanism from a one-loop modification of M-theory action. This modification is discussed in the context of the gravitational anomaly in six-dimensional $(2,0)$ theory. The agreement with earlier conjectured anomaly is found.Comment: 24 pages, Latex; presentation re-structured, new references adde

Moduli Stabilization from Fluxes in a Simple IIB Orientifold

We study novel type IIB compactifications on the T^6/Z_2 orientifold. This geometry arises in the T-dual description of Type I theory on T^6, and one normally introduces 16 space-filling D3-branes to cancel the RR tadpoles. Here, we cancel the RR tadpoles either partially or fully by turning on three-form flux in the compact geometry. The resulting (super)potential for moduli is calculable. We demonstrate that one can find many examples of N=1 supersymmetric vacua with greatly reduced numbers of moduli in this system. A few examples with N>1 supersymmetry or complete supersymmetry breaking are also discussed.Comment: 49 pages, harvmac big; v2, corrected some typo

I=3/2 KπK \pi Scattering in the Nonrelativisitic Quark Potential Model

We study $I=3/2$ elastic $K\pi$ scattering to Born order using nonrelativistic quark wavefunctions in a constituent-exchange model. This channel is ideal for the study of nonresonant meson-meson scattering amplitudes since s-channel resonances do not contribute significantly. Standard quark model parameters yield good agreement with the measured S- and P-wave phase shifts and with PCAC calculations of the scattering length. The P-wave phase shift is especially interesting because it is nonzero solely due to $SU(3)_f$ symmetry breaking effects, and is found to be in good agreement with experiment given conventional values for the strange and nonstrange constituent quark masses.Comment: 12 pages + 2 postscript figures, Revtex, MIT-CTP-210

Pain coping tools for children and young adults with a neurodevelopmental disability: A systematic review of measurement properties

First published: 16 September 2022. OnlinePublAim: To systematically identify and evaluate the measurement properties of patient-reported outcome measures (PROMs) and observer-reported outcome measures (parent proxy report) of pain coping tools that have been used with children and young adults (aged 0–24 years) with a neurodevelopmental disability. Method: A two-stage search using MEDLINE, Embase, CINAHL, Web of Science, and PsycInfo was conducted. Search 1 in August 2021 identified pain coping tools used in neurodevelopmental disability and search 2 in September 2021 located additional studies evaluating the measurement properties of these tools. Methodological quality was assessed using the COnsensus-based Standards for the Selection of Health Measurement INstruments (COSMIN) guidelines (PROSPERO protocol registration no. CRD42021273031). Results: Sixteen studies identified seven pain coping tools, all PROMs and observer-reported outcome measures (parent proxy report) versions. The measurement properties of the seven tools were appraised in 44 studies. No tool had high-quality evidence for any measurement property or evidence for all nine measurement properties as outlined by COSMIN. Only one tool had content validity for individuals with neurodevelopmental disability: the Cerebral Palsy Quality of Life tool. Interpretation: Pain coping assessment tools with self-report and parent proxy versions are available; however, measurement invariance has not been tested in young adults with a neurodevelopmental disability. This is an area for future research.Nadine L. Smith, Meredith G. Smith, Noula Gibson, Christine Imms, Ashleigh l. Thornton, Adrienne R. Harve