No Child Left Behind's Supplemental Educational Services: A Case Study of Participant Experiences in an Urban Afterschool Program in the District of Columbia

The enactment of No Child Left Behind's (NCLB) Supplemental Educational Services (SES) provision shifted new attention to the ability of afterschool programs to increase students' achievement levels and help close the pervasive achievement gap between Students of Color and their white counterparts. Though studies of supplemental education programs in general have shown their potential to successfully augment traditional classroom instruction, reports thus far on indicate that states, districts, providers, and families have faced numerous challenges in the execution of the SES model. The scant research that exists on SES primarily has focused on national, state, and district-level investigations of implementation. With the upcoming reauthorization of NCLB, information in needed on the ground-level implementation of SES, and the lived experiences of participants within SES Provider organizations, particularly those in urban areas that face significant social and economic challenges. This purpose of this study was to include the voices of SES program participants in the dialogue surrounding the provision's redesign and to understand their individual perceptions of the opportunities and challenges of involvement within one SES Provider program in the District of Columbia. Participant stories revealed that, despite some challenges, the program of study was beneficial and fostered the academic, social, and personal development of student participants, including increases in grades, test scores, and attendance, as well as in self-esteem and confidence. Tutors and staff reported experiencing personal growth and development. Participant narratives also uncovered a number of challenges that exist in the implementation of SES policy within the District of Columbia Public School System (DCPS), including issues with timing, communication, and district expectations. Participant experiences within the DCPS and subsequent policy recommendations may help to inform SES policy moving forward to aid in the development of policy that truly works to the benefit of the individuals it was intended to serve

Restricted Rotational Flexibility of the C5α-Methyl-Substituted Carbapenem NA-1-157 Leads to Potent Inhibition of the GES-5 Carbapenemase

Carbapenem antibiotics are used as a last-resort treatment for infections caused by multidrug-resistant bacteria. The wide spread of carbapenemases in Gram-negative bacteria has severely compromised the utility of these drugs and represents a serious public health threat. To combat carbapenemase-mediated resistance, new antimicrobials and inhibitors of these enzymes are urgently needed. Here, we describe the interaction of the atypically C5α-methyl-substituted carbapenem, NA-1-157, with the GES-5 carbapenemase. MICs of this compound against Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii producing the enzyme were reduced 4–16-fold when compared to MICs of the commercial carbapenems, reaching clinically sensitive breakpoints. When NA-1-157 was combined with meropenem, a strong synergistic effect was observed. Kinetic and ESI-LC/MS studies demonstrated that NA-1-157 is a potent inhibitor of GES-5, with a high inactivation efficiency of (2.9 ± 0.9) × 105 M–1 s–1. Acylation of GES-5 by NA-1-157 was biphasic, with the fast phase completing within seconds, and the slow phase taking several hours and likely proceeding through a reversible tetrahedral intermediate. Deacylation was extremely slow (k3 = (2.4 ± 0.3) × 10–7 s–1), resulting in a residence time of 48 ± 6 days. MD simulation of the GES-5-meropenem and GES-5-NA-1-157 acyl-enzyme complexes revealed that the C5α-methyl group in NA-1-157 sterically restricts rotation of the 6α-hydroxyethyl group preventing ingress of the deacylating water into the vicinity of the scissile bond of the acyl-enzyme intermediate. These data demonstrate that NA-1-157 is a potent irreversible inhibitor of the GES-5 carbapenemase

Investments in Building Citywide Out-of-School-Time Systems: A Six-City Study

This report is the last in a series funded by The Wallace Foundation and developed by P/PV and The Finance Project to document the costs of out-of-school-time (OST) programs and the city-level systems that support them. The report examines the development of OST systems in six cities across the country and summarizes the strategies and activities commonly pursued, their associated investments and options for financing such system-building efforts. These findings can provide OST stakeholders with critical information to help guide their investments in system planning, start-up and ongoing operations. The report serves as a companion to two previous resources: The Cost of Quality Out-of-School-Time Programs, which provides information on both the average out-of-pocket expenditures and the average full cost of a wide range of quality OST programs; and an online cost calculator that enables users to generate tailored cost estimates for many different types of OST programs

The Effect of Dietary Carbohydrate and Fat Manipulation on the Metabolome and Markers of Glucose and Insulin Metabolism: A Randomised Parallel Trial.

From Europe PMC via Jisc Publications RouterHistory: ppub 2022-09-01, epub 2022-09-07Publication status: PublishedHigh carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, <50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p < 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p < 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation

Locomotor conditioning by amphetamine requires cyclin-dependent kinase 5 signaling in the nucleus accumbens

Intermittent systemic exposure to psychostimulants such as amphetamine leads to several forms of long-lasting behavioral plasticity including non-associative sensitization and associative conditioning. In the nucleus accumbens (NAcc), the protein serine/threonine kinase cyclin-dependent kinase 5 (Cdk5) and its phosphorylation target, the guanine-nucleotide exchange factor kalirin-7 (Kal7), may contribute to the neuroadaptations underlying each of these forms of plasticity. Pharmacological inhibition of Cdk5 in the NAcc prevents the increases in dendritic spine density in this site and enhances the locomotor sensitization normally observed following repeated cocaine. Mice lacking the Kal7 gene display similar phenotypes suggesting that locomotor sensitization and increased NAcc spine density need not be positively correlated. As increases in spine density may relate to the formation of associative memories and both Cdk5 and Kal7 regulate the generation of spines following repeated drug exposure, we hypothesized that either inhibiting Cdk5 or preventing its phosphorylation of Kal7 in the NAcc may prevent the induction of drug conditioning. In the present experiments, blockade in rats of NAcc Cdk5 activity with roscovitine (40 nmol/0.5µl/side) prior to each of 4 injections of amphetamine (1.5 mg/kg; i.p.) prevented the accrual of contextual locomotor conditioning but spared the induction of locomotor sensitization as revealed on tests conducted one week later. Similarly, transient viral expression in the NAcc exclusively during amphetamine exposure of a threonine-alanine mutant form of Kal7 [mKal7(T1590A)] that is not phosphorylated by Cdk5 also prevented the accrual of contextual conditioning and spared the induction of sensitization. These results indicate that Cdk5 phosphorylation of Kal7 in the NAcc is necessary for the formation of context-drug associations potentially through the modulation of dendritic spine dynamics in this site

Genomic characterization of the Yersinia genus

Comparative Yersinia genomics identifies features responsible for the colonization of specific host habitats and the horizontal transfer of virulence determinants

The Effect of Dietary Carbohydrate and Fat Manipulation on the Metabolome and Markers of Glucose and Insulin Metabolism: A Randomised Parallel Trial

From MDPI via Jisc Publications RouterHistory: received 2022-07-22, accepted 2022-08-24, collection 2022-09, epub 2022-09-07Peer reviewed: TrueArticle version: VoRPublication status: PublishedFunder: Liverpool John Moores UniversityHigh carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, <50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p < 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p < 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation

The interfacial bioscience grand challenge.

This report is broken down into the following 3 sections: (1) Chemical Cross-linking and Mass Spectrometry Applied to Determination of Protein Structure and Dynamics; (2) Computational Modeling of Membrane Protein Structure and Dynamics; and (3) Studies of Toxin-Membrane Interactions using Single Molecule Biophysical Methods

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival