An Animal Model of Alzheimer\u27s Disease: Behavioral and Histological Assessment Following Bilateral Intrahippocampal Injections of B-Amyloid (25-35)

Pathologically, Alzheimer\u27s disease (AD) is characterized by deposits of neuritic plaques (NP) and neurofibrillary tangles (NFT) typically found in the cerebral cortex, hippocampus, and basal forebrain. Increasing evidence suggests that the major constituent of NP, a B-amyloid protein(BAP) composed of 39-42 amino acids, possesses neurotoxic properties. It has been reputed that the neurotoxic properties of BAP(1-40) may be dependent on the aggregational state of the peptide. Recent studies have demonstrated in vitro that a fragment of the B-amyloid protein, BAP(25-35), disrupts intracellular calcium homeostasis, decreases neuronal survival, and potentiates the toxicity of excitatory amino acids (EAA). While some evidence supports the direct in vivo toxicity of BAP, the extent of neuronal damage has not been compared with standard lesions made by EAAs. Moreover, currently the effects of intracerebral injections of BAP(2535) on learning and memory in the rat is unknown. Therefore, in this study a comparative behavioral and histological assessment was conducted following bilateral intrahippocampal injections of BAP(25-35), ibotenic acid (IBO), BAP(25-35)+IBO, and incubated BAP(25-35) (1 week at 37 C). A radial arm maze and Morris water maze were utilized for comparative learning and memory assessment. Preliminary results indicate that there is a clear disruption of learning performance in animals co-injected with low doses of BAP(25-35) (4nmol/ul) + IBO (lug/ul) while identical doses injected separately had no effect. The deficits in learning observed following injections of BAP(25-35)+IBO and the high does of IBO was not, however, due to disruptions in motor behavior as there was no difference found between groups on a treadmill test in those that ran the maze and those that did not. In support of the behavioral results, preliminary histological analyses revealed cytotoxic effects in the hippocampus following injections of BAP(25-35) \u27+ IBO or a high does of IBO. This study suggests that the injection of BAP (25-35) into the hippocampus promotes the vulnerability of neurons to excitotoxic damage in vivo and disrupts learning/memory in rats

Single-cell western blotting.

To measure cell-to-cell variation in protein-mediated functions, we developed an approach to conduct ∼10(3) concurrent single-cell western blots (scWesterns) in ∼4 h. A microscope slide supporting a 30-μm-thick photoactive polyacrylamide gel enables western blotting: settling of single cells into microwells, lysis in situ, gel electrophoresis, photoinitiated blotting to immobilize proteins and antibody probing. We applied this scWestern method to monitor single-cell differentiation of rat neural stem cells and responses to mitogen stimulation. The scWestern quantified target proteins even with off-target antibody binding, multiplexed to 11 protein targets per single cell with detection thresholds of <30,000 molecules, and supported analyses of low starting cell numbers (∼200) when integrated with FACS. The scWestern overcomes limitations of antibody fidelity and sensitivity in other single-cell protein analysis methods and constitutes a versatile tool for the study of complex cell populations at single-cell resolution

"Is the Pope Catholic?" Applying Chain-of-Thought Reasoning to Understanding Conversational Implicatures

Conversational implicatures are pragmatic inferences that require listeners to deduce the intended meaning conveyed by a speaker from their explicit utterances. Although such inferential reasoning is fundamental to human communication, recent research indicates that large language models struggle to comprehend these implicatures as effectively as the average human. This paper demonstrates that by incorporating Grice's Four Maxims into the model through chain-of-thought prompting, we can significantly enhance its performance, surpassing even the average human performance on this task

Role of appetitive phenotype trajectory groups on child body weight during a family-based treatment for children with overweight or obesity.

ObjectiveEmerging evidence suggests that individual appetitive traits may usefully explain patterns of weight loss in behavioral weight loss treatments for children. The objective of this study was to identify trajectories of child appetitive traits and the impact on child weight changes over time.MethodsSecondary data analyses of a randomized noninferiority trial conducted between 2011 and 2015 evaluated children's appetitive traits and weight loss. Children with overweight and obesity (mean age = 10.4; mean BMI z = 2.0; 67% girls; 32% Hispanic) and their parent (mean age = 42.9; mean BMI = 31.9; 87% women; 31% Hispanic) participated in weight loss programs and completed assessments at baseline, 3, 6,12, and 24 months. Repeated assessments of child appetitive traits, including satiety responsiveness, food responsiveness and emotional eating, were used to identify parsimonious grouping of change trajectories. Linear mixed-effects models were used to identify the impact of group trajectory on child BMIz change over time.ResultsOne hundred fifty children and their parent enrolled in the study. The three-group trajectory model was the most parsimonious and included a high satiety responsive group (HighSR; 47.4%), a high food responsive group (HighFR; 34.6%), and a high emotional eating group (HighEE; 18.0%). Children in all trajectories lost weight at approximately the same rate during treatment, however, only the HighSR group maintained their weight loss during follow-ups, while the HighFR and HighEE groups regained weight (adjusted p-value < 0.05).ConclusionsDistinct trajectories of child appetitive traits were associated with differential weight loss maintenance. Identified high-risk subgroups may suggest opportunities for targeted intervention and maintenance programs

The iFat1 transgene permits conditional endogenous n-3 PUFA enrichment both in vitro and in vivo

Fat-1 transgenic mice, which endogenously convert n-6 PUFA to n-3 PUFA, are a useful tool in health research; however with this model timing of n-3 PUFA enrichment cannot be directly controlled. To add such capability, the novel Cre-recombinase inducible fat-1 (iFat1) transgenic mouse has been developed. The aim of this study was to characterize the utility of the iFat1 transgene as a model of Cre-inducible endogenous n-3 PUFA enrichment. Functionality of the iFat1 transgene was screened both in vitro and in vivo. In the presence of Cre, the iFat1 transgene resulted in a balancing (p < 0.01) of the n-6/n-3 PUFA ratio within phospholipids in the human embryonic kidney 293T cell line. For in vivo analysis, iFat1 transgenic mice were crossed with the R26-Cre-ERT2 (Tam-Cre) mouse line, a tamoxifen inducible Cre-expression model. Tam-Cre/iFat1 double hybrids were transiently treated with tamoxifen at 6–7 weeks, then terminated 3 weeks later. Tamoxifen treated mice had increased (p < 0.05) tissue n-3 PUFA and ≥two-fold reduction (p < 0.05) in the n-6/n-3 PUFA ratio of liver, kidney and muscle phospholipids relative to vehicle treated controls. Collectively these findings suggest that the iFat1 transgenic mouse may be a promising tool to help elucidate the temporal effects through which n-3 PUFA impacts health related outcomes

Precise Radial Velocities of Polaris: Detection of Amplitude Growth

We present a first results from a long-term program of a radial velocity study of Cepheid Polaris (F7 Ib) aimed to find amplitude and period of pulsations and nature of secondary periodicities. 264 new precise radial velocity measurements were obtained during 2004-2007 with the fiber-fed echelle spectrograph Bohyunsan Observatory Echelle Spectrograph (BOES) of 1.8m telescope at Bohyunsan Optical Astronomy Observatory (BOAO) in Korea. We find a pulsational radial velocity amplitude and period of Polaris for three seasons of 2005.183, 2006.360, and 2007.349 as 2K = 2.210 +/- 0.048 km/s, 2K = 2.080 +/- 0.042 km/s, and 2K = 2.406 +/- 0.018 km/s respectively, indicating that the pulsational amplitudes of Polaris that had decayed during the last century is now increasing rapidly. The pulsational period was found to be increasing too. This is the first detection of a historical turnaround of pulsational amplitude change in Cepheids. We clearly find the presence of additional radial velocity variations on a time scale of about 119 days and an amplitude of about +/- 138 m/s, that is quasi-periodic rather than strictly periodic. We do not confirm the presence in our data the variation on a time scale 34-45 days found in earlier radial velocity data obtained in 80's and 90's. We assume that both the 119 day quasi-periodic, noncoherent variations found in our data as well as 34-45 day variations found before can be caused by the 119 day rotation periods of Polaris and by surface inhomogeneities such as single or multiple spot configuration varying with the time.Comment: 15 pages, 7 figures, Accepted for publication in The Astronomical Journa