The Current Structure of Intellect Remediation Lab as an Intervention for Deficient Readers in Grades 3, 4, and 5

Problem. Educational testing procedures focus on identification and classification of students rather than on remediation for their abilities. The Structure of Intellect (SOI) model proposes a multidimensional view of intelligence with a focus on remediation for underdeveloped or nonexistent abilities as they relate to school achievement. Purpose. The purposes of this study were to determine if participation in the SOI remediation lab had a measurable effect on reading achievement with third-, fourth-, and fifth-grade students, and to describe SOI learning profiles of students with below grade reading skills. Methodology. The subjects for this quasi-experimental study were third-, fourth-, and fifth-graders from two public schools. Eleven subtests from the SOI Learning Abilities Tests, Forms CR and L, purportedly related to reading, were used as pre- and post-test measures. ANCOVA was used to analyze data from these 11 subtests. The Burns & Roe Informal Reading Inventory was a pre/post measure of reading. Chi-square was used to analyze the pro-portions of students making gains in reading achievement. The SOI learning profiles were analyzed descriptively. Findings and conclusions. The results supported the SOI Intervention lab as a useful intervention for remedial reading. Students who participated in the SOI remediation labshowed significant increases in reading achievement. The 11 subtests proposed as prerequisite skills for reading and comprehension did not uniformly increase as did the reading levels. Gains were only noted on 4 of the 11 subtests. There were no discernable patterns of SOI learning profiles that predicted below grade level reading skills. It appears that the SOI remediation lab could serve as an effective intervention for students with deficient reading skills in grades three though five. The lack of discernable distinct learning profiles limits the Forms CR and L of the Structure of Intellect Learning Abilities tests as a possible option for identification

Cell-penetrating peptide conjugates of peptide nucleic acids (PNA) as inhibitors of HIV-1 Tat-dependent trans-activation in cells

The trans-activation response (TAR) RNA stem–loop that occurs at the 5′ end of HIV RNA transcripts is an important antiviral target and is the site of interaction of the HIV-1 Tat protein together with host cellular factors. Oligonucleotides and their analogues targeted to TAR are potential antiviral candidates. We have investigated a range of cell penetrating peptide (CPP) conjugates of a 16mer peptide nucleic acid (PNA) analogue targeted to the apical stem–loop of TAR and show that disulfide-linked PNA conjugates of two types of CPP (Transportan or a novel chimeric peptide R(6)-Penetratin) exhibit dose-dependent inhibition of Tat-dependent trans-activation in a HeLa cell assay when incubated for 24 h. Activity is reached within 6 h if the lysosomotropic reagent chloroquine is co-administered. Fluorescein-labelled stably-linked conjugates of Tat, Transportan or Transportan TP10 with PNA were inactive when delivered alone, but attained trans-activation inhibition in the presence of chloroquine. Confocal microscopy showed that such fluorescently labelled CPP–PNA conjugates were sequestered in endosomal or membrane-bound compartments of HeLa cells, which varied in appearance depending on the CPP type. Co-administration of chloroquine was seen in some cases to release fluorescence from such compartments into the nucleus, but with different patterns depending on the CPP. The results show that CPP–PNA conjugates of different types can inhibit Tat-dependent trans-activation in HeLa cells and have potential for development as antiviral agents. Endosomal or membrane release is a major factor limiting nuclear delivery and trans-activation inhibition

Production of Reactive Oxygen Species by Multipotent Stromal Cells/Mesenchymal Stem Cells Upon Exposure to Fas Ligand

Multipotent stromal cells (MSCs) can be differentiated into osteoblasts and chondrocytes, making these cells candidates to regenerate cranio-facial injuries and lesions in long bones. A major problem with cell replacement therapy, however, is the loss of transplanted MSCs at the site of graft. Reactive oxygen species (ROS) and nonspecific inflammation generated at the ischemic site have been hypothesized to lead to MSCs loss; studies in vitro show MSCs dying both in the presence of ROS or cytokines like FasL. We questioned whether MSCs themselves may be the source of these death inducers, specifically whether MSCs produce ROS under cytokine challenge. On treating MSCs with FasL, we observed increased ROS production within 2 h, leading to apoptotic death after 6 h of exposure to the cytokine. N-acetyl cysteine, an antioxidant, is able to protect MSCs from FasL-induced ROS production and subsequent ROS-dependent apoptosis, though the MSCs eventually succumb to ROS-independent death signaling. Epidermal growth factor (EGF), a cell survival factor, is able to protect cells from FasL-induced ROS production initially; however, the protective effect wanes with continued FasL exposure. In parallel, FasL induces upregulation of the uncoupling protein UCP2, the main uncoupling protein in MSCs, which is not abrogated by EGF; however, the production of ROS is followed by a delayed apoptotic cell death despite moderation by UCP2. FasL-induced ROS activates the stress-induced MAPK pathways JNK and p38MAPK as well as ERK, along with the activation of Bad, a proapoptotic protein, and suppression of survivin, an antiapoptotic protein; the latter two key modulators of the mitochondrial death pathway. FasL by itself also activates its canonical extrinsic death pathway noted by a time-dependent degradation of c-FLIP and activation of caspase 8. These data suggest that MSCs participate in their own demise due to nonspecific inflammation, holding implications for replacement therapies.National Institute of General Medical Sciences (U.S.) (GM069668)National Institute of Dental and Craniofacial Research (U.S.) (DE019523

Faculty and Staff Perspectives

University of Dayton is an employer across all sorts of levels. We are citizens of the University in lots of ways, and what we contribute as faculty and staff creates the place. We have longevity that students do not have. We hope that this will develop into a deeper dive into the University of Dayton\u27s past and thinking about the lives of Black faculty and staff. This isn’t the culmination of a project but rather a beginning of thinking about learning from and remembering that past because if we don’t cultivate these things, we lose them. This is what we’re doing today. We’re going to feature the voices of Black faculty and staff who have contributed to the life of our University, many of whom keep the University running and going. These proceedings are available free for download but also available for purchase in print for $6 plus tax and shipping.https://ecommons.udayton.edu/global_voices_4/1012/thumbnail.jp

Efficient splicing correction by PNA conjugation to an R6-Penetratin delivery peptide

Sequence-specific interference with the nuclear pre-mRNA splicing machinery has received increased attention as an analytical tool and for development of therapeutics. It requires sequence-specific and high affinity binding of RNaseH-incompetent DNA mimics to pre-mRNA. Peptide nucleic acids (PNA) or phosphoramidate morpholino oligonucleotides (PMO) are particularly suited as steric block oligonucleotides in this respect. However, splicing correction by PNA or PMO conjugated to cell penetrating peptides (CPP), such as Tat or Penetratin, has required high concentrations (5–10 μM) of such conjugates, unless an endosomolytic agent was added to increase escape from endocytic vesicles. We have focused on the modification of existing CPPs to search for peptides able to deliver more efficiently splice correcting PNA or PMO to the nucleus in the absence of endosomolytic agents. We describe here R6-Penetratin (in which arginine-residues were added to the N-terminus of Penetratin) as the most active of all CPPs tested so far in a splicing correction assay in which masking of a cryptic splice site allows expression of a luciferase reporter gene. Efficient and sequence-specific correction occurs at 1 μM concentration of the R6Pen–PNA705 conjugate as monitored by luciferase luminescence and by RT-PCR. Some aspects of the R6Pen–PNA705 structure–function relationship have also been evaluated

Distribution and Compartmentalization of Human Circulating and Tissue-Resident Memory T Cell Subsets

SummaryKnowledge of human T cells derives chiefly from studies of peripheral blood, whereas their distribution and function in tissues remains largely unknown. Here, we present a unique analysis of human T cells in lymphoid and mucosal tissues obtained from individual organ donors, revealing tissue-intrinsic compartmentalization of naive, effector, and memory subsets conserved between diverse individuals. Effector memory CD4+ T cells producing IL-2 predominated in mucosal tissues and accumulated as central memory subsets in lymphoid tissue, whereas CD8+ T cells were maintained as naive subsets in lymphoid tissues and IFN-γ-producing effector memory CD8+ T cells in mucosal sites. The T cell activation marker CD69 was constitutively expressed by memory T cells in all tissues, distinguishing them from circulating subsets, with mucosal memory T cells exhibiting additional distinct phenotypic and functional properties. Our results provide an assessment of human T cell compartmentalization as a new baseline for understanding human adaptive immunity

Audit of Helicobacter pylori Testing in Microbiology Laboratories in England: To Inform Compliance with NICE Guidance and the Feasibility of Routine Antimicrobial Resistance Surveillance.

Introduction. The National Institute for Health and Clinical Excellence (NICE) guidance recommends that dyspeptic patients are tested for Helicobacter pylori using a urea breath test, stool antigen test, or serology. Antibiotic resistance in H. pylori is globally increasing, but treatment in England is rarely guided by susceptibility testing or surveillance. Aims. To determine compliance of microbiology laboratories in England with NICE guidance and whether laboratories perform culture and antibiotic susceptibility testing (AST). Methods. In 2015, 170 accredited English microbiology laboratories were surveyed, by email. Results. 121/170 (71%) laboratories responded; 96% provided H. pylori testing (78% on site). 94% provided H. pylori diagnosis using stool antigen; only four provided serology as their noninvasive test; 3/4 of these encouraged urea breath tests in their acute trusts. Only 22/94 (23%) of the laboratories performed H. pylori cultures from gastric biopsies on site; 9/22 performed AST, but the vast majority processed less than one specimen/week. Conclusions. Only five laboratories in England do not comply with NICE guidance; these will need the guidance reinforced. National surveillance needs to be implemented; culture-based AST would need to be centralised. Moving forward, detection of resistance in H. pylori from stool specimens using molecular methods (PCR) needs to be explored