Continuous Theta Rhythm During Spatial Working Memory Task in Rodent Models of Streptozotocin-induced Type 2 Diabetes

Alzheimer’s disease is a neurodegenerative disorder altering memory loss thought to be due to neuropathological symptoms such as the buildup of beta amyloid plaques (Ab) and neurofibrillary tangles (NFT). The etiology of Alzheimer’s is still unknown; however, potential risk factors such as diabetes may lead to its development. The most common form of diabetes is type 2 diabetes known for persistent insulin resistance leading to a state of hyperglycemia. Insulin resistance has been shown to affect cognitive abilities such as learning, memory and also alters synaptic plasticity. Neural connections between the hippocampus (HC) and anterior cingulate cortex (ACC) are known to be very important for learning and memory and are highly plastic, making them an intriguing target that could be altered by hyperglycemia. We hypothesize that hyperglycemic rodents will exhibit spatial memory deficits that may be associated with cognitively linked interactions between the HC and ACC. Minimal doses of streptozotocin (STZ), which is toxic to insulin producing beta cells, were given for 9-10 weeks. Using a spatial working memory task known as delayed alternation we found significant differences between control and experimental rats in working memory accuracy. This task places strong working memory demands on subjects which may be compromised by a hyperglycemic state. We measured EEG recordings from the HC and ACC during task performance and found that hyperglycemic rats had nearly continuous theta rhythm during the 30-minute session. Control rats however, displayed normal transitions between theta and lower frequency delta. Neural connectivity may be altered due to a change in frequency activity between the HC and ACC due to diabetes which is a risk factor in the development of AD impairments. These results show that hyperglycemia leads to changes along the circuit critical for learning and memory

Linear Self-Motion Cues Support the Spatial Distribution and Stability of Hippocampal Place Cells

The vestibular system provides a crucial component of place-cell and head-direction cell activity [1-7]. Otolith signals are necessary for head-direction signal stability and associated behavior [8, 9], and the head-direction signal's contribution to parahippocampal spatial representations [10-14] suggests that place cells may also require otolithic information. Here, we demonstrate that self-movement information from the otolith organs is necessary for the development of stable place fields within and across sessions. Place cells in otoconia-deficient tilted mice showed reduced spatial coherence and formed place fields that were located closer to environmental boundaries, relative to those of control mice. These differences reveal an important otolithic contribution to place-cell functioning and provide insight into the cognitive deficits associated with otolith dysfunction

The effect of sampling density and study area size on landscape genetics inferences for the Mississippi slimy salamander (Plethodon mississippi)

In landscape genetics, it is largely unknown how choices regarding sampling density and study area size impact inferences upon which habitat features impede vs. facilitate gene flow. While it is recommended that sampling locations be spaced no further apart than the average individual\u27s dispersal distance, for low-mobility species, this could lead to a challenging number of sampling locations, or an unrepresentative study area. We assessed the effects of sampling density and study area size on landscape genetic inferences for a dispersal-limited amphibian, Plethodon mississippi, via analysis of nested datasets. Microsatellite-based genetic distances among individuals were divided into three datasets representing sparse sampling across a large study area, dense sampling across a small study area, or sparse sampling across the same small study area. These datasets were a proxy for gene flow (i.e., the response variable) in maximum-likelihood population effects models that assessed the nature and strength of their relationship with each of five land-use classes (i.e., potential predictor variables). Comparisons of outcomes were based on the rank order of effect, sign of effect (i.e., gene flow resistance vs. facilitation), spatial scale of effect, and functional relationship with gene flow. The best-fit model for each dataset had the same sign of effect for hardwood forests, manmade structures, and pine forests, indicating the impacts of these land-use classes on dispersal and gene flow in P. mississippi are robust to sampling scheme. Contrasting sampling densities led to a different inferred functional relationship between agricultural areas and gene flow. Study area size appeared to influence the scale of effect of manmade structures and the sign of effect of pine forests. Our findings provided evidence for an influence of sampling density, study area size, and sampling effort upon inferences. Accordingly, we recommend iterative subsampling of empirical datasets and continued investigation into the sensitivities of landscape genetic analyses using simulations

Novel antiinflammatory biologics shaped by parasite-host coevolution

Parasitic helminth infections, while a major cause of neglected tropical disease burden, negatively correlate with the incidence of immune-mediated inflammatory diseases such as inflammatory bowel diseases (IBD). To evade expulsion, helminths have developed sophisticated mechanisms to regulate their host\u27s immune responses. Controlled experimental human helminth infections have been assessed clinically for treating inflammatory conditions; however, such a radical therapeutic modality has challenges. An alternative approach is to harness the immunomodulatory properties within the worm\u27s excretory-secretory (ES) complement, its secretome. Here, we report a biologics discovery and validation pipeline to generate and screen in vivo a recombinant cell-free secretome library of helminth-derived immunomodulatory proteins. We successfully expressed 78 recombinant ES proteins from gastrointestinal hookworms and screened the crude in vitro translation reactions for anti-IBD properties in a mouse model of acute colitis. After statistical filtering and ranking, 20 proteins conferred significant protection against various parameters of colitis. Lead candidates from distinct protein families, including annexins, transthyretins, nematode-specific retinol-binding proteins, and SCP/TAPS were identified. Representative proteins were produced in mammalian cells and further validated, including ex vivo suppression of inflammatory cytokine secretion by T cells from IBD patient colon biopsies. Proteins identified herein offer promise as novel, safe, and mechanistically differentiated biologics for treating the globally increasing burden of inflammatory diseases

An Optical and Infrared Time-Domain Study of the Supergiant Fast X-ray Transient Candidate IC 10 X-2

We present an optical and infrared (IR) study of IC 10 X-2, a high-mass X-ray binary in the galaxy IC 10. Previous optical and X-ray studies suggest X-2 is a Supergiant Fast X-ray Transient: a large-amplitude (factor of $\sim$ 100), short-duration (hours to weeks) X-ray outburst on 2010 May 21. We analyze R- and g-band light curves of X-2 from the intermediate Palomar Transient Factory taken between 2013 July 15 and 2017 Feb 14 show high-amplitude ($\gtrsim$ 1 mag), short-duration ($\lesssim8$ d) flares and dips ($\gtrsim$ 0.5 mag). Near-IR spectroscopy of X-2 from Palomar/TripleSpec show He I, Paschen-$\gamma$, and Paschen-$\beta$ emission lines with similar shapes and amplitudes as those of luminous blue variables (LBVs) and LBV candidates (LBVc). Mid-IR colors and magnitudes from Spitzer/IRAC photometry of X-2 resemble those of known LBV/LBVcs. We suggest that the stellar companion in X-2 is an LBV/LBVc and discuss possible origins of the optical flares. Dips in the optical light curve are indicative of eclipses from optically thick clumps formed in the winds of the stellar counterpart. Given the constraints on the flare duration ($0.02 - 0.8$ d) and the time between flares ($15.1\pm7.8$ d), we estimate the clump volume filling factor in the stellar winds, $f_V$, to be $0.01 < f_V < 0.71$, which overlaps with values measured from massive star winds. In X-2, we interpret the origin of the optical flares as the accretion of clumps formed in the winds of an LBV/LBVc onto the compact object.Comment: 15 pages, 4 figures. Submitted to ApJ on Sep 26 201

Presynchronizing PGF2α and GnRH injections before timed artificial insemination CO-Synch + CIDR program

Fixed-time artificial insemination is an effective management tool that reduces the labor associated with more conventional artificial insemination programs requiring detection of estrus. The 7-day CO-Synch + controlled internal drug release (CIDR) insert protocol has been shown to effectively initiate estrus and ovulation in cycling and non-cycling suckled beef cows, producing pregnancy rates at or greater than 50% in beef cows. The gonadotropin-releasing hormone (GnRH) injection that begins the CO-Synch + CIDR program initiates ovulation in a large proportion of cows, particularly anestrous cows. The CIDR, which releases progesterone intravaginally, prevents short estrous cycles that usually follow the first postpartum ovulation in beef cows. Our hypothesis was that inducing estrus with a prostaglandin injection followed 3 days later with a GnRH injection, 7 days before applying the 7-day CO-Synch + CIDR protocol, might increase the percentage of cycling cows that would exhibit synchronous follicular waves after the onset of the CO-Synch + CIDR protocol. We also hypothesized that the additional GnRH injection would increase the percentage of anestrous cows that would ovulate, thereby increasing pregnancy outcomes

Simple Models Outperform More Complex Big-Leaf Models of Daily Transpiration in Forested Biomes

Transpiration makes up the bulk of total evaporation in forested environments yet remains challenging to predict at landscape-to-global scales. We harnessed independent estimates of daily transpiration derived from co-located sap flow and eddy-covariance measurement systems and applied the triple collocation technique to evaluate predictions from big leaf models requiring no calibration. In total, four models in 608 unique configurations were evaluated at 21 forested sites spanning a wide diversity of biophysical attributes and environmental backgrounds. We found that simpler models that neither explicitly represented aerodynamic forcing nor canopy conductance achieved higher accuracy and signal-to-noise levels when optimally configured (rRMSE = 20%; R2 = 0.89). Irrespective of model type, optimal configurations were those making use of key plant functional type dependent parameters, daily LAI, and constraints based on atmospheric moisture demand over soil moisture supply. Our findings have implications for more informed water resource management based on hydrological modeling and remote sensing.publishedVersio

Boron Difluoride Adducts of a Flexidentate Pyridine-Substituted Formazanate Ligand: Property Modulation via Protonation and Coordination Chemistry

The synthesis and characterization of a flexidentate pyridine-substituted formazanate ligand and its boron difluoride adducts, formed via two different coordination modes of the title ligand, are described. The first adduct adopted a structure that was typical of other boron difluoride adducts of triarylformazanate ligands and contained a free pyridine subsituent, while the second was formed via chelation of nitrogen atoms from the formazanate backbone and the pyridine substituent. Stepwise protonation of the pydridine-functionalized adduct, which is essentially non-emissive, resulted in a significant increase in the fluorescence quantum yield up to a maximum of 18%, prompting study of this adduct as a pH sensor. The coordination chemistry of each adduct was explored through reactions with nickel(II) bromide [NiBr2(CH3CN)2], triflate [Ni(OTf)2] and 1,1,1,4,4,4-hexafluoroacetylacetonate [Ni(hfac)2(H2O)2] salts. Coordination to nickel(II) ions altered the physical properties of the boron difluoride formazanate adducts, including red-shifted absorption maxima and less negative reduction potentials. Together, these studies have demonstrated that the physical and electronic properties of boron difluoride adducts of formazanate ligands can be readily modulated through protonation and coordination chemistry