Illinois State University

Characterizing how organisms respond to transient temperatures may further our understanding of their susceptibility to climate change. Past studies in the freshwater turtle, Trachemys scripta, have demonstrated that the timing and duration of heat waves can have major implications for the response of genes involved in gonadal development and the production of female hatchlings. Yet, no study has considered how the response of these genes to transient cold snap exposure may affect gonadal development and the production of males. We investigated how cold snap timing affects gonadal gene expression in T. scripta embryos and how the duration of an early cold snap influences the resulting hatchling sex ratios. Results show that responsiveness to cold changes rapidly across development, such that genes that responded when exposure began on incubation day 14 responded differently when exposure occurred just four or eight days later. Sex ratio data revealed that embryos experiencing an early cold snap also require a long exposure (>20 days) before most commit to testis development, suggesting that warm baseline temperatures may lower their sensitivity to later cold snap exposures. These results highlight how individual responses to incubation temperature can change rapidly across development in turtles and have important effects on sex ratios.

In this study, we explored the intricate relationship between Pannexin 1 (PANX1) and the Hippo signaling pathway effector, Yes‐associated protein (YAP). Analysis of The Cancer Genome Atlas (TCGA) data revealed a significant positive correlation between PANX1 mRNA and core Hippo components, Yes‐associated protein 1 [YAP], Transcriptional coactivator with PDZ‐binding motif [TAZ], and Hippo scaffold, Ras GTPase‐activating‐like protein IQGAP1 [IQGAP1], in invasive cutaneous melanoma and breast carcinoma. Furthermore, we demonstrated that PANX1 expression is upregulated in invasive melanoma cell lines and is associated with increased YAP protein levels. Notably, our investigations uncovered a previously unrecognized interaction between endogenous PANX1 and the Hippo scaffold protein IQGAP1 in melanoma cells. Moreover, our findings revealed that IQGAP1 exhibits differential expression in melanoma cells and plays a regulatory role in cellular morphology. Functional studies involving PANX1 knockdown provided compelling evidence that PANX1 modulates YAP protein levels and its cotranscriptional activity in melanoma and breast carcinoma cells. Importantly, our study highlights the potential therapeutic significance of targeting PANX1. Pharmacological inhibition of PANX1 using selective FDA‐approved inhibitors or PANX1 knockdown reduced YAP levels in melanoma cells. Furthermore, our Clariom™ S analysis unveiled key genes implicated in cell proliferation, such as neuroglin1 (NRG1), β‐galactoside binding protein and galectin‐3 (LGALS3), that are affected in PANX1‐deficient cells. In summary, our investigation delves into the intricate interplay between PANX1 and YAP in the context of invasive melanoma, offering valuable insights into potential therapeutic strategies for effective treatment.

Protein degradation is pivotal for all biochemical aspects of cellular function. In mammalian cells, protein degradation is mediated mainly by the ubiquitin proteasome system (UPS) and the autophagic‐lysosomal system (ALS). Over the last two decades, different types of targeted protein degradation approaches have been developed including proteolysis targeting chimeras (PROTACs) and lysosome targeting chimeras (LYTACs), which employ the UPS to degrade intracellular proteins and the ALS to degrade extracellular and membrane proteins respectively. Nevertheless, Current targeted membrane protein degradation approaches face some inherent challenges including limited target protein degradation efficacy and cell type specific applicability. Herein, we highlight some recent developments of novel targeted membrane protein degradation modalities that exhibit wide‐applicability and high protein degradation efficiency. These novel membrane protein degraders hold tremendous promise as new pharmacological and biochemical tools in targeting membrane and secretory proteins for lysosomal degradation.

Many oncoproteins are important therapeutic targets because of their critical role in inducing rapid cell proliferation, which represents one of the salient hallmarks of cancer. Chronic Myeloid Leukemia (CML) is a cancer of hematopoietic stem cells that is caused by the oncogene BCR-ABL1. BCR-ABL1 encodes a constitutively active tyrosine kinase protein that leads to the uncontrolled proliferation of myeloid cells, which is a hallmark of CML. A current therapeutic approach for the treatment of CML, Tyrosine Kinase Inhibitors (TKIs), effectively inactivates BCR-ABL1 kinase activity; however, drug resistance to TKIs limits the long-term potential for this treatment. Proteolysis Targeting Chimera (PROTAC) has emerged as a promising pharmacological approach for degrading, rather than inhibiting, targeted proteins by harnessing the ubiquitin-proteosome system. This process involves tagging a Protein of Interest (POI) with ubiquitin by the E3 ubiquitin ligases, which subsequently target the protein for proteasomal degradation. The N-end rule or the N-degron concept describes the correlation between the metabolic stability of a protein and the biochemical identity of its N-terminal amino acid. A recent work unveiled that N-degron PROTACs could offer a potential treatment for CML by targeting and degrading BCR-ABL1 proteins. Herein, we present the molecular and biochemical implications for targeting chronic myeloid leukemia.

The content of 39 metals and metalloids (MMs) in submicron road dust (PM1 fraction) was studied in the traffic zone, residential courtyards with parking lots, and on pedestrian roads in parks in Moscow. The geochemical profiles of PM1 vary slightly between different types of roads and courtyards but differ significantly from those in parks. In Moscow, compared to other cities worldwide, submicron road dust contains less As, Sb, Mo, Cr, Cd, Sn, Tl, Ca, Rb, La, Y, U, but more Cu, Zn, Co, Fe, Mn, Ti, Zr, Al, V. Relative to the upper continental crust, PM1 is highly enriched in Sb, Zn, Cd, Cu, W, Sn, Bi, Mo, Pb. In the courtyards, where contact between pollutants and the population is most frequent and occurs over an extended period, the level of PM1 pollution with MMs (from strong to extreme) is comparable to that on large roads. Source identification was conducted using correlations, elemental ratios, and absolute principal component analysis with multiple linear regression (APCA-MLR). In the traffic zone, non-exhaust and exhaust vehicle emissions contribute significantly to the MM concentrations in PM1 (especially for Bi, Sb, Sn, V, Fe, Cu, W, Mo); soil particles, abrasion of steel surfaces, industrial emissions, tire and road wear with carbonate dust resuspension contribute less. In the courtyards, the contribution of the road wear with carbonate dust resuspension and soil particles increases by up to 16% due to the poor condition of the road surface, frequent construction works, and large contact areas of roads with soils. In parks, the contribution of anthropogenic sources sharply decreases by 20–48% due to the increased soil resuspension rate. The spatial distribution pattern of MMs in submicron road dust should aid in the development of more effective road surface washing strategies, ultimately minimizing the risk to public health.

In this study, we examined the differences in reading comprehension processes between students with and without reading difficulties. A total of 72 third- and fourth-grade students in South Korea participated in the study; of these, 28 were identified as having reading difficulties and 44 were not. Multiple types of tasks were administered to evaluate the participants’ eye-movement behaviors, including reading different types of texts and answering questions. Nonparametric tests were conducted on the students’ responses, and the results indicated that students with reading difficulties fixated significantly longer and more frequently on both narrative and expository texts than those without such difficulties. Students without reading difficulties demonstrated significantly decreased reading comprehension processing times after a question-answering activity for all types of texts, whereas students with reading difficulties experienced decreased processing times only for a whole passage reading of narrative text. These results suggest that educators should be aware of differences in comprehension processes among students and develop differentiated instructional plans for students who struggle with reading.

This paper addresses the problem of distributed optimization with uncertainties for multiagent systems. We propose a new distributed consensus scenario approach, handling uncertainties through a scenario program method. An approximate solution is developed, followed by a distributed estimation algorithm to manage large data volumes without a centralized approach. Our design inherently offers robustness against adversarial attacks and preserves data privacy. We provide rigorous convergence analysis and demonstrate the effectiveness of our approach through application examples in regression and robust internal model control. This work presents a significant step towards holistic solutions for optimization in safety-critical multiagent systems.

This work aims to address key issues in the ballistic performance of ceramic-based composite armor, particularly at the joints of spliced bulletproof panels. The edge structure of C/C-SiC ceramic plates and ultra-high molecular weight polyethylene is redesigned to superimpose the joint areas. These structurally optimized composite pads are examined by numerical simulation of impact dynamics to understand their anti-penetration performance whose accuracy is then validated by live fire tests. The results reveal that (1) the ceramic plates with improved edge design enhance the anti-penetration efficiency, (2) the established dynamic constitutive model of penetration resistance effectively predicts the ballistic performance of the armor pad, and (3) inability to penetrate high-speed real bullets through the armor suggests that the ballistic performance fully meets the protection requirements of the MIL-A-46103EIII Class 2 A standard. In this regard, structural regulation of the shape of the ceramic-based composite plates allows for the design of lightweight armor with improved bulletproof capability. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-80752-0.

“The most important issue confronting educators and educational theorists is the choice of ends for the educational process. Without clear and rational educational goals, it becomes impossible to decide which educational programs achieve objectives of general import and which teach incidental facts and attitudes of dubious worth.” (Kohlberg & Mayer, 1972, p. 449)

This chapter provides a rationale and guidelines for quality birth-to-3 early intervention services for children with cochlear implants and their families. It outlines the positive benefit of early intervention for children with hearing loss and their families if the child is enrolled soon after diagnosis in an intervention program, if intervention services are provided by qualified and experienced professionals, and if the services the family and child receive are designed to maximize listening, language, and literacy development which will carry over to the child’s daily home and community environments. A framework for designing and delivering therapy content across a continuum of chronological and listening ages is shared, including strategies that enhance listening, language, and literacy and activities professionals can utilize with parents and their children who are pre- and post-cochlear implantation. Included are therapy needs for the child and parent both pre- and post-implant, and guidelines for the interventionist and recommendations for carryover activities that parents and their child can engage in at home during daily routines.

This paper reviews the recent literature on business sustainability. While it is almost impossible to give a universally agreeable definition of “sustainability” due to its scope, depth, and inclusive nature, this paper reviews a fairly large set of research efforts, both empirical and normative, that examine the sustainability issue in regards to the theoretical development, the interface between business and society, the interrelationships among firms, markets, and the public interest, sustainability measurement and assessment, as well as the changes, developments, and evolution in recent years along those lines. The uniqueness of the study is to review the literature by following the developmental and evolutionary sequences in business sustainability in order to shed light on how the concept of corporate sustainability has evolved from the traditional shareholders-focused neoclassical view and how it is advanced from the ideas of environmentalism, stakeholder theory, and CSR.

At the time of my internship, I knew I would focus on the vampire archetype in literature and pop-culture remediations based on how prevalent the monster is and the likelihood of students having at least some foundational information about the creatures. My research and data collection were predicated on literacy development for an interdisciplinary, general education course, IDS121: Texts & Contexts. The aim of the course is to examine one specific genre of literary archetypes and trace its trajectory across cultures, mediums, and ecologies. Students learn to identify key elements of the vampire that define its parameters and explore how those elements are challenged or reinforced as the archetype moves through multimodal spaces. In the end, students would be able to quantify what those changes are but also articulate what they mean within a given social lens, such as feminism or elitism. This chapter involves the specific changes implemented in light of the research conducted regarding the global gothic, onomastic, and non-verbal components which not only corrected what I view as failings of the initial course but more broadly improved the multicultural aspects, making it a more diverse and inclusive experience.

Leishmaniasis is a parasitic disease caused by the protozoa Leishmania. These organisms secrete acid phosphatases during their growth cycle as an important part of cell targeting to host macrophage cells thus allowing for a successful infection. Secreted acid phosphatases (SAP) are reported to play a significant role in the survival of Leishmania cells, thus evaluation of these enzymes is of interest. The inhibition of SAP can be the focus of a new drug therapy. We tested for SAP activity from Leishmania tarentolae following the addition of a series of vanadium complexes including decavanadate. Cell cultures at different stages in their growth curve were harvested by centrifugation and supernatant was collected. The SAP activity in the supernatant was assayed with the artificial substrate p-nitrophenylphosphate (pNPP). Incubation with orthovanadate resulted in a decrease in activity of 18% ± 1 relative to the control, in comparison to decavanadate, which resulted in a 35% ± 4 decrease in activity. Other vanadium complexes showed smaller inhibitory effects than orthovanadate. Some vanadium complexes appeared to have an effect on reducing cell clumping when compared to control cells. The SAP was partially isolated through anion exchange chromatography and results indicate that SAP isozyme forms are present in the supernatant from cells. Future work is focused on obtaining recombinant enzyme which can be more completely characterized for inhibition by vanadium complexes.

Sulfonamide drugs were the original class of antibiotics, demonstrating the antibacterial potential of dithiocarbazate and thiosemicarbazone Schiff base derivatives of syringaldehyde and 4-hydroxy-3,5-dimethylbenzaldehyde. We synthesized unique Schiff bases via the condensation of the aldehydes with hydrazine derivatives, which allows for the easy synthesis of several related compounds. These Schiff base derivatives were tested for antileishmanial properties against the parasitic protozoan Leishmania tarentolae. The inhibitory properties of these sulfur compounds were tested using a series of cell viability and secreted acid phosphatase (SAP) assays. The results demonstrated that compounds ZZ1-04 and ZZ1-20 had potent inhibitory effects on parasite cell viability and SAP, an enzyme that may play a role in infectivity. These results increase our understanding of the role of sulfur in inhibiting Leishmania, providing more knowledge of the structural activity relationships that may prove critical for their development into possible antileishmanial treatments.