Climate Change and Biosphere Response: Unlocking the Collections Vault

Natural history collections (NHCs) are an important source of the long-term data needed to understand how biota respond to ongoing anthropogenic climate change. These include taxon occurrence data for ecological modeling, as well as information that can be used to reconstruct mechanisms through which biota respond to changing climates. The full potential of NHCs for climate change research cannot be fully realized until high-quality data sets are conveniently accessible for research, but this requires that higher priority be placed on digitizing the holdings most useful for climate change research (e.g., whole-biota studies, time series, records of intensively sampled common taxa). Natural history collections must not neglect the proliferation of new information from efforts to understand how present-day ecosystems are responding to environmental change. These new directions require a strategic realignment for many NHC holders to complement their existing focus on taxonomy and systematics. To set these new priorities, we need strong partnerships between NHC holders and global change biologists

HSP90 Inhibitor, NVP-AUY922, Improves Myelination in Vitro and Supports the Maintenance of Myelinated Axons in Neuropathic Mice.

Hereditary demyelinating neuropathies linked to peripheral myelin protein 22 (PMP22) involve the disruption of normal protein trafficking and are therefore relevant targets for chaperone therapy. Using a small molecule HSP90 inhibitor, EC137, in cell culture models, we previously validated the chaperone pathway as a viable target for therapy development. Here, we tested five commercially available inhibitors of HSP90 and identified BIIB021 and AUY922 to support Schwann cell viability and enhance chaperone expression. AUY922 showed higher efficacy, compared to BIIB021, in enhancing myelin synthesis in dorsal root ganglion explant cultures from neuropathic mice. For in vivo testing, we randomly assigned 2-3 month old C22 and 6 week old Trembler J (TrJ) mice to receive two weekly injections of either vehicle or AUY922 (2 mg/kg). By the intraperitoneal (i.p.) route, the drug was well-tolerated by all mice over the 5 month long study, without influence on body weight or general grooming behavior. AUY922 improved the maintenance of myelinated nerves of both neuropathic models and attenuated the decline in rotarod performance and peak muscle force production in C22 mice. These studies highlight the significance of proteostasis in neuromuscular function and further validate the HSP90 pathway as a therapeutic target for hereditary neuropathies

The Splenic Injury Outcomes Trial: An American Association For the Surgery of Trauma Multi-Institutional Study

BACKGROUND: Delayed splenic hemorrhage after nonoperative management (NOM) of blunt splenic injury (BSI) is a feared complication, particularly in the outpatient setting. Significant resources, including angiography (ANGIO), are used in an effort to prevent delayed splenectomy (DS). No prospective, long-term data exist to determine the actual risk of splenectomy. The purposes of this trial were to ascertain the 180-day risk of splenectomy after 24 hours of NOM of BSI and to determine factors related to splenectomy. METHODS: Eleven Level I trauma centers participated in this prospective observational study. Adult patients achieving 24 hours of NOM of their BSI were eligible. Patients were followed up for 180 days. Demographic, physiologic, radiographic, injury-related information, and spleen-related interventions were recorded. Bivariate and multivariable analyses were used to determine factors associated with DS. RESULTS: A total of 383 patients were enrolled. Twelve patients (3.1%) underwent in-hospital splenectomy between 24 hours and 9 days after injury. Of 366 discharged with a spleen, 1 (0.27%) required readmission for DS on postinjury Day 12. No Grade I injuries experienced DS. The splenectomy rate after 24 hours of NOM was 1.5 per 1,000 patient-days. Only extravasation from the spleen at time of admission (ADMIT-BLUSH) was associated with splenectomy (odds ratio, 3.6; 95% confidence interval, 1.4–12.4). Of patients with ADMIT-BLUSH (n = 49), 17 (34.7%) did not have ANGIO with embolization (EMBO), and 2 of those (11.8%) underwent splenectomy; 32 (65.3%) underwent ANGIO with EMBO, and 2 of those (6.3%, p = 0.6020 compared with no ANGIO with EMBO) required splenectomy. CONCLUSION: Splenectomy after 24 hours of NOM is rare. After the initial 24 hours, no additional interventions are warranted for patients with Grade I injuries. For Grades II to V, close observation as an inpatient or outpatient is indicated for 10 days to 14 days. ADMIT-BLUSH is a strong predictor of DS and should lead to close observation or earlier surgical intervention. LEVEL OF EVIDENCE: Prognostic/epidemiological study, level III; therapeutic study, level IV

Teaching Instrumental Science Globally Using a Collaborative Electronic Laboratory Notebook

In the higher education sector there is a strong push to improve the synergy between research and teaching. To achieve this there is a need to introduce into the undergraduate curriculum the new technologies that support research practice and process. There is no doubt that future scientific practice will increasingly involve collaborations around data and information that is delivered via the web. Our students must be trained in these new developments, and our staff must have access to tools that will facilitate their ability to teach it. New technologies, such as the Electronic Laboratory Notebook (ELN) developed at Southampton University in the UK, exploits the Web2.0 environment and offer the advantages of 1) being able to more readily share research resources, 2) as a digital record of experimental events and 3) a secure archive of data and metadata. We will discuss our initiative to extend the science curriculum in undergraduate chemistry through the introduction of an electronic laboratory notebook where instruments, experiments and data can be shared globally. The ELN is presently being implemented at UNSW, and the proposed project (funded by the Australian Learning and Teaching Council) will allow a multi-university (three in Australia, one in Thailand and one in the UK) exemplar of the ELN. By its nature, the project the outcomes will be available worldwide for tertiary science training. Keywords: electron laboratory notebook, science education, eResearch, eLearnin

Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity

Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson\u27s disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50 – 70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN − and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10 – 12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson\u27s disease

AAV-mediated delivery of an anti-BACE1 VHH alleviates pathology in an Alzheimer's disease model

Single domain antibodies (VHHs) are potentially disruptive therapeutics, with important biological value for treatment of several diseases, including neurological disorders. However, VHHs have not been widely used in the central nervous system (CNS), largely because of their restricted blood–brain barrier (BBB) penetration. Here, we propose a gene transfer strategy based on BBB-crossing adeno-associated virus (AAV)-based vectors to deliver VHH directly into the CNS. As a proof-of-concept, we explored the potential of AAV-delivered VHH to inhibit BACE1, a well-characterized target in Alzheimer’s disease. First, we generated a panel of VHHs targeting BACE1, one of which, VHH-B9, shows high selectivity for BACE1 and efficacy in lowering BACE1 activity in vitro. We further demonstrate that a single systemic dose of AAV-VHH-B9 produces positive long-term (12 months plus) effects on amyloid load, neuroinflammation, synaptic function, and cognitive performance, in the AppNL-G-F Alzheimer’s mouse model. These results constitute a novel therapeutic approach for neurodegenerative diseases, which is applicable to a range of CNS disease targets

The Close Binary Fraction as a Function of Stellar Parameters in APOGEE:A Strong Anti-Correlation With α Abundances

We use observations from the APOGEE survey to explore the relationship between stellar parameters and multiplicity. We combine high-resolution repeat spectroscopy for 41,363 dwarf and subgiant stars with abundance measurements from the APOGEE pipeline and distances and stellar parameters derived using \textit{Gaia} DR2 parallaxes from \cite{Sanders2018} to identify and characterise stellar multiples with periods below 30 years, corresponding to \drvm$\gtrsim$ 3 \kms, where \drvm\ is the maximum APOGEE-detected shift in the radial velocities. Chemical composition is responsible for most of the variation in the close binary fraction in our sample, with stellar parameters like mass and age playing a secondary role. In addition to the previously identified strong anti-correlation between the close binary fraction and \feh\, we find that high abundances of $\alpha$ elements also suppress multiplicity at most values of \feh\ sampled by APOGEE. The anti-correlation between $\alpha$ abundances and multiplicity is substantially steeper than that observed for Fe, suggesting C, O, and Si in the form of dust and ices dominate the opacity of primordial protostellar disks and their propensity for fragmentation via gravitational stability. Near \feh{} = 0 dex, the bias-corrected close binary fraction ($a<10$ au) decreases from $\approx$ 100 per cent at \alh{} = $-$0.2 dex to $\approx$ 15 per cent near \alh{} = 0.08 dex, with a suggestive turn-up to $\approx$20 per cent near \alh{} = 0.2. We conclude that the relationship between stellar multiplicity and chemical composition for sun-like dwarf stars in the field of the Milky Way is complex, and that this complexity should be accounted for in future studies of interacting binaries.Comment: 15 pages, 10 figures, plus appendices; accepted to MNRA