Modeling the influence of Peromyscus leucopus body mass, sex, and habitat on immature Dermacentor variabilis burden

mmature (larvae and nymph) tick burden on rodents is an important determinant of adult tick population size and understanding infectious disease dynamics. The objective of this research was to build a descriptive model for immature Dermacentor variabilis burden on Peromyscus leucopus. Mice were live-trapped on two permanent grids in an old field and an early successional forest every other month between April and October, 2006-2009. Negative binomial regression was used to examine the association between immature D. variabilis burden and the host related variables of host habitat, body mass, and/or sex. The model containing all three variables had the lowest Akaike\u27s Information Criterion (AIC), corrected AIC (AICc), and greatest AICc weight. Immature D. variabilis burden was positively associated with mice with higher body mass, male mice, and those captured in the field habitat. These data are consistent with studies from other tick-rodent systems and suggest that single factor models do not describe host burden. Variables other than those that are related to the host may also be important in describing the tick burden on rodents. The next step is to examine variables that affect tick development rate and questing behavior. © 2012 The Society for Vector Ecology

Dissociable Effects of Salience on Attention and Goal-Directed Action

SummaryEveryday behavior frequently involves encounters with multiple objects that compete for selection. For example, driving a car requires constant shifts of attention between oncoming traffic, rearview mirrors, and traffic signs and signals, among other objects. Behavioral goals often drive this selection process [1, 2]; however, they are not the sole determinant of selection. Physically salient objects, such as flashing, brightly colored hazard signs, or objects that are salient by virtue of learned associations with reward, such as pictures of food on a billboard, often capture attention regardless of the individual’s goals [3–6]. It is typically thought that strongly salient distractor objects capture more attention and are more disruptive than weakly salient distractors [7, 8]. Counterintuitively, though, we found that this is true for perception, but not for goal-directed action. In a visually guided reaching task [9–11], we required participants to reach to a shape-defined target while trying to ignore salient distractors. We observed that strongly salient distractors produced less disruption in goal-directed action than weakly salient distractors. Thus, a strongly salient distractor triggers suppression during goal-directed action, resulting in enhanced efficiency and accuracy of target selection relative to when weakly salient distractors are present. In contrast, in a task requiring no goal-directed action, we found greater attentional interference from strongly salient distractors. Thus, while highly salient stimuli interfere strongly with perceptual processing, increased physical salience or associated value attenuates action-related interference

Graduate Training in Educational Measurement and Psychometrics: A Curriculum Review of Graduate Programs in the U.S.

This mixed-methods study included a curriculum review of 118 graduate (masters & doctoral) programs in educational measurement, assessment, evaluation, psychometrics, and/or quantitative psychology in the United States to examine both the content and skills prioritized in graduate training. In addition to required content, programs/program curricula were coded with respect to intellectual home (psychology v. education departments), level of program (M.A. v. EdD or PhD), total credits, and number and rank of faculty. Patterns with respect to content variation are presented. To supplement these data, interviews were conducted with measurement professionals – working in industry, government, and the academy- to determine what skills and content knowledge they believe to be critical for success in the field and to evaluate any disconnects between content knowledge thought to be important to practitioners and the actual content knowledge taught

Proteomic analysis of Bifidobacterium longum subsp. infantis reveals the metabolic insight on consumption of prebiotics and host glycans.

Bifidobacterium longum subsp. infantis is a common member of the intestinal microbiota in breast-fed infants and capable of metabolizing human milk oligosaccharides (HMO). To investigate the bacterial response to different prebiotics, we analyzed both cell wall associated and whole cell proteins in B. infantis. Proteins were identified by LC-MS/MS followed by comparative proteomics to deduce the protein localization within the cell. Enzymes involved in the metabolism of lactose, glucose, galactooligosaccharides, fructooligosaccharides and HMO were constitutively expressed exhibiting less than two-fold change regardless of the sugar used. In contrast, enzymes in N-Acetylglucosamine and sucrose catabolism were induced by HMO and fructans, respectively. Galactose-metabolizing enzymes phosphoglucomutase, UDP-glucose 4-epimerase and UTP glucose-1-P uridylytransferase were expressed constitutively, while galactokinase and galactose-1-phosphate uridylyltransferase, increased their expression three fold when HMO and lactose were used as substrates for cell growth. Cell wall-associated proteomics also revealed ATP-dependent sugar transport systems associated with consumption of different prebiotics. In addition, the expression of 16 glycosyl hydrolases revealed the complete metabolic route for each substrate. Mucin, which possesses O-glycans that are structurally similar to HMO did not induced the expression of transport proteins, hydrolysis or sugar metabolic pathway indicating B. infantis do not utilize these glycoconjugates

Interactions Between Spermine-Derivatized Tentacle Porphyrins And The Human Telomeric DNA G-Quadruplex

G-rich DNA sequences have the potential to fold into non-canonical G-Quadruplex (GQ) structures implicated in aging and human diseases, notably cancers. Because stabilization of GQs at telomeres and oncogene promoters may prevent cancer, there is an interest in developing small molecules that selectively target GQs. Herein, we investigate the interactions of meso-tetrakis-(4-carboxysperminephenyl)porphyrin (TCPPSpm4) and its Zn(II) derivative (ZnTCPPSpm4) with human telomeric DNA (Tel22) via UV-Vis, circular dichroism (CD), and fluorescence spectroscopies, resonance light scattering (RLS), and fluorescence resonance energy transfer (FRET) assays. UV-Vis titrations reveal binding constants of 4.7 × 10⁶ and 1.4 × 10⁷ M⁻¹ and binding stoichiometry of 2–4:1 and 10–12:1 for TCPPSpm4 and ZnTCPPSpm4, respectively. High stoichiometry is supported by the Job plot data, CD titrations, and RLS data. FRET melting indicates that TCPPSpm4 stabilizes Tel22 by 36 ± 2 °C at 7.5 eq., and that ZnTCPPSpm4 stabilizes Tel22 by 33 ± 2 °C at ~20 eq.; at least 8 eq. of ZnTCPPSpm4 are required to achieve significant stabilization of Tel22, in agreement with its high binding stoichiometry. FRET competition studies show that both porphyrins are mildly selective for human telomeric GQ vs duplex DNA. Spectroscopic studies, combined, point to end-stacking and porphyrin self-association as major binding modes. This work advances our understanding of ligand interactions with GQ DNA

Role of Ghrelin Receptor in Sarcopenia: Involvement of Redox Signaling and RANKL.

Sarcopenia is aging-induced debilitating loss of skeletal muscle strength and function. Evidence from aging research suggests an integration of disrupted mechanotransduction and oxidative stress elevation that leads to muscle atrophy. Ghrelin is a 28 amino acid peptide hormone circulating in both acylated (AG) and unacylated (UAG) forms that acts as a nutrient sensor and metabolic regulator. Acylated ghrelin then binds to the growth hormone secretagogue receptor (GHS-R) or the “ghrelin receptor.” Emerging evidence indicates that GHS-R knockout may hold greater promise in protecting against sarcopenia and fasting-induced atrophy (Wu 2020, Sun 2020). Furthermore, ghrelin can promote the elevation of nNOS, which is important as nNOS is critical to the preservation of the morphology and strength of the skeletal muscle (Lawler, 2021). Ghrelin can also stimulate protective proteins (e.g., HSP70, SIRT1), which attenuate Nox2 and ROS production. In our laboratory, recent preliminary data demonstrated positive feedback between Nox2 and RANKL that amplifies pathology and attenuates ca2+ overload, damage, and inflammation in dystrophic skeletal muscle. However, this feedback between RANKL and Nox2, and the redox regulation in sarcopenia is unknown. PURPOSE: Thus, we propose that GHS-R-dependent ghrelin pathways attenuate the markers of damage, inflammation, and redox regulation that mitigate the RANKL/Nox2 feedback and fibrosis in the aged muscles-induced sarcopenia. METHODS: Two different age C57Bl/6 mice were divided into four different groups (n = 6/group): (a) 11 months middle age wildtype, (b) Middle age WT + GHS-R -/-, (c) 23 months old age wildtype, (d) old age WT + GHS-R -/-. At the end of the experiments, gastrocnemius muscles were dissected and snap-frozen for further analysis. RESULTS: Data of protein abundance by western blotting revealed that elevated Nox2 complex marker (p67 phox), and Nox4 are decreased in the GHSR -/- groups in both middle and old-age mice. RANKL levels are significantly increased in the old group compared to the middle age. Furthermore, knocking out the GHSR mitigate the elevated RANKL levels. Markers for the damage, inflammation, Ca2+ overload, and sarcopenia-related sarcolemma-DGC dysregulation are currently being investigated. CONCLUSION: In conclusion, we demonstrate the contribution of RANKL, Nox2, and Nox4 in aging-induced sarcopenia. GHSR-dependent ghrelin pathway knockout shows a promising mechanism to mitigate oxidative stress, damage, and inflammation in sarcopenia. Further analysis will be performed to fully understand these underlying mechanisms

Structural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45

CD45 is the prototypic member of transmembrane receptor-like protein tyrosine phosphatases (RPTPs) and has essential roles in immune functions. The cytoplasmic region of CD45, like many other RPTPs, contains two homologous protein tyrosine phosphatase domains, active domain 1 (D1) and catalytically impaired domain 2 (D2). Here, we report crystal structure of the cytoplasmic D1D2 segment of human CD45 in native and phosphotyrosyl peptide-bound forms. The tertiary structures of D1 and D2 are very similar, but doubly phosphorylated CD3ζ immunoreceptor tyrosine-based activation motif peptide binds only the D1 active site. The D2 “active site” deviates from the other active sites significantly to the extent that excludes any possibility of catalytic activity. The relative orientation of D1 and D2 is very similar to that observed in leukocyte common antigen–related protein with both active sites in an open conformation and is restrained through an extensive network of hydrophobic interactions, hydrogen bonds, and salt bridges. This crystal structure is incompatible with the wedge model previously suggested for CD45 regulation

Intramolecular interactions of the regulatory domains of the Bcr–Abl kinase reveal a novel control mechanism

AbstractBackground The Abl nonreceptor tyrosine kinase is implicated in a range of cellular processes and its transforming variants are involved in human leukemias. The N-terminal regulatory region of the Abl protein contains Src homology domains SH2 and SH3 which have been shown to be important for the regulation of its activity in vivo. These domains are often found together in the same protein and biochemical data suggest that the functions of one domain can be influenced by the other.Results We have determined the crystal structure of the Abl regulatory region containing the SH3 and SH2 domains. In general, the individual domains are very similar to those of previously solved structures, although the Abl SH2 domain contains a loop which is extended so that one side of the resulting phosphotyrosine-binding pocket is open. In our structure the protein exists as a monomer with no intermolecular contacts to which a biological function may be attributed. However, there is a significant intramolecular contact between a loop of the SH3 domain and the extended loop of the SH2 domain. This contact surface includes the SH2 loop segment that is responsible for binding the phosphate moiety of phosphotyrosine-containing proteins and is therefore critical for orienting peptide interactions.Conclusions The crystal structure of the composite Abl SH3–SH2 domain provides the first indication of how SH2 and SH3 domains communicate with each other within the same molecule and why the presence of one directly influences the activity of the other. This is the first clear evidence that these two domains are in contact with each other. The results suggest that this direct interaction between the two domains may affect the ligand binding properties of the SH2 domain, thus providing an explanation for biochemical and functional data concerning the Bcr–Abl kinase

Prevalence of sarcopenia and sarcopenic obesity in Korean adults: The Korean Sarcopenic Obesity Study (KSOS)

*Context:* Sarcopenic obesity (SO), a combination of excess weight and reduced muscle mass and/or strength, is suggested to be associated with an increased risk of adverse health outcomes. 
*Objectives:* To examine the prevalence and characteristics of Sarcopenic and SO defined by using different indices such as Appendicular Skeletal muscle Mass (ASM)/height^2^ and Skeletal Muscle Index (SMI (%): skeletal muscle mass (kg)/weight (kg) × 100) for Korean adults. 
*Methods:* 591 participants were recruited from the Korean Sarcopenic Obesity Study (KSOS) which is an ongoing prospective observational cohort study. Analysis was conducted in 526 participants (328 women, 198 men) who had complete data on body composition using Dual X-ray absorptiometry and computed tomography. 
*Results:* The prevalence of sarcopenia and SO increases with aging. Using two or more standard deviations (SD) of ASM/height^2^ below reference values from young, healthy adults as a definition of sarcopenia, the prevalence of sarcopenia and SO was 6.3% and 1.3% in men and 4.1% and 1.7% in women over 60 years of age. However, using two or more SD of SMI, the prevalence of sarcopenia and SO was 5.1% and 5.1% respectively in men and 14.2% and 12.5% respectively in women. As defined by SMI, subjects with SO had 3 times the risk of metabolic syndrome (OR = 3.03, 95% confidence interval (CI) = 1.26-7.26) and subjects with non-sarcopenic obesity had approximately 2 times the risk of metabolic syndrome (OR = 1.89, 95% CI = 1.18-3.02) compared with normal subjects. 
*Conclusion:* Obese subjects with relative sarcopenia were associated with a greater likelihood for metabolic syndrome. As Koreans were more obese and aging, the prevalence of SO and its impact on health outcomes are estimated to be rapidly grow. Further research is requested to establish the definition, cause and consequences of SO.
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