Event Begins: Thursday, November 14, 2024 1:00pm
Location:
Organized By: University Career Center

Looking for an internship? The Environmental Protection Agency is hiring!Join the U.S. Environmental Protection Agency (EPA) for a virtual hiring webinar on November 14th, at 1 p.m. ET. You’ll hearfrom EPA executives (who started as interns at EPA!), hiring specialists, and current interns at the event.RSVP on Handshake for the eventlink. ASL and CART services will be provided. This event will be recorded.Never applied for a federal job before? No problem! You will learnhow to navigate the federal job application process and unique hiring pathways for students and recent graduates. There will be a Q&A portion where you can ask our panel of hiring specialists questions about the federal hiring process.There has never been a more critical moment to join our team. From tackling the climate crisis to advancing environmental justice, what happens here helps change our world.This event is open to the public. If you have any questions, please contact the Careers Team by emailing careers@epa.gov.You can do so much impactful work at EPA. Be the one who protects human health and the environment. Be EPA. For more information about EPA, visit epa.gov/careers.

In the next 4 episodes, Andrew gets very practical on ways to find our way out of addiction. Part 1 asks "How Do We Live?" Read a transcript HERE.

Andrew tells us that will power and relying on ourselves is an ineffective strategy for dealing with addiction to pornography. Read the transcript HERE.

Today Andrew continues his practical advise for freeing ourselves from addiction by offering St. Theophan's four spiritual weapons for our contimplation . Read the transcript HERE.

St Theophan tells us that “the four weapons of which we have spoken receive their power from the forces and gifts of grace, obtained for us by the blood of Christ.” And the mystery of holy communion “is Christ’s blood itself, and His flesh itself, in which Christ is Himself present as God.” Find the transcript HERE.

Fr. Philip LeMasters reminds us that our Orthodox faith does not require us to abandon or condemn any dimension of life, but instead to offer all that we are and do for fulfillment and blessing and healing.

Aim/Purpose: This study builds upon existing research by investigating the elements contributing to or buffering the onset of burnout symptoms. We examine the relationship between empowering leadership and burnout, considering the concurrent mediation effects of interpersonal workplace conflict, work-home conflict, and support from coworkers. Background: Burnout is a phenomenon that has been widely considered in the scientific literature due to its negative effect on individual and organizational well-being, as well as implications for leadership, coworker support, and conflict resolution. A deeper understanding of burnout prevention strategies across various professional contexts is paramount for enhancing productivity and job satisfaction. Methodology: Using a survey-based cross-sectional design, we employed a combination of Structural Equation Modelling (SEM) and Artificial Neural Network (ANN) to investigate the direct and indirect influences of empowering leadership on four dimensions of employee burnout, mediated by coworker support, interpersonal conflict at work, and work-home conflict. Contribution: This study provides initial insights into the direct and indirect influences of empowering leadership on various dimensions of burnout, highlighting the complex interplay with coworker support, work-home conflict, and workplace interpersonal conflicts. Ultimately, the study provides a comprehensive approach to understanding and mitigating burnout. Findings: Empowering leadership and coworker support can significantly reduce burnout symptoms, while high levels of work-home conflict and interpersonal conflict at work can exacerbate them. Our findings underscore the paramount role of interpersonal conflict in predicting burnout, urging organizations to prioritize resolving such issues for burnout prevention. Recommendation for Researchers: Following our findings, organizations should (a) promote empowering leadership styles, (b) foster coworker support and work-life balance, and (c) address interpersonal conflicts to reduce the likelihood of employee burnout while ensuring that these strategies are tailored to the specific context and culture of the workplace. Future Research: Future research should broaden the exploration of leadership styles’ effects on burnout, identify additional mediators and moderators, expand studies across sectors and cultures, examine differential impacts on burnout dimensions, leverage advanced analytical models, and investigate the nuanced relationship between work contract types and burnout.

The 4th EU BON roundtable will take place on Thursday, 17 November 2016 at the premises of the Museum fuer Naturkunde in Berlin with the motto "Pathways to sustainability for EU BONs network of collaborators and technical infrastructure".  

One of the key questions will be how to achieve sustainability for the many different products of EU BON, such as tools, software, models and infrastructure after the project ends. It should be discussed how a European Biodiversity Observation Network and its essential components could be sustained after the project will end in May 2017, by which institutions or networks and how the products can be used in the best way for European policy and research needs.  

How can hazardous chemicals enter the human body? What should safety professionals know about each avenue of entry?

David Gross, executive director, INSTALL, shares his experience, how he came to land in a union organization and provides next steps for flooring installers who are interested in moving into another role within the flooring industry.

New models for studying the human brain — human neural organoids, transplants, and chimeras — show promise for advancing understanding of the brain and laying the groundwork for new therapeutic approaches to brain diseases that have so far proved hard to treat, says a new report from the National Academies of Sciences, Engineering, and Medicine.

To meet its diversity and inclusion goals for competed mission leadership, NASA should invest in STEM career pathways, partner with historically Black colleges and universities and minority-serving institutions, and expand training and mentorship opportunities, among other actions.

 Helping Clinicians automate workflows for better patient outcomes

The partnership aims to offer professionals who are currently in job transition affordable short-term learning pathways aligned with today's in-demand jobs.

Introducing LearnKey's Upskill Academy, enabling youths and adults to get upskilled and certified in ninety (90) days or less.

Event Begins: Wednesday, November 13, 2024 12:00pm
Location:
Organized By: University Career Center

Upcoming or recent graduates, please tune in on November 13th to learn all about the Science Policy Fellowship! In thispanel discussion we’ll be joined by both the Science Policy Fellowship program director as well as current and former fellows. Lisa, Rebecca, Kush and Irina will share their own unique career journeys – plus perspectives on how the Science Policy Fellowship has shaped where they are today. Additionally, our panel will provide insights into project work, skills development, and tips on applying to the program. Learn how you can put your education to work while making a tangible impact in thescience and technology policy arena at a Federally Funded Research and Development Center (FFRDC).We’ll also share background on IDA's culture and the mission behind the work we do.The Science Policy Fellowship is a two-year program from the Science and Technology Policy Institute – one of the Institute for Defense Analyses’ three FFRDCs. The fellowship provides recent bachelor’s or master’s degree recipients with aunique opportunity to use their critical thinking and analytic skills to work on a diverse set of challenges in science and technology policy areas, including energy and the environment, space sciences, innovation and competitiveness, evaluation, life sciences, information technologies, national security, and STEM education. Fellows will be involved in collaborative research for leaders in the Office of Science and Technology Policy (OSTP) in the Executive Office of the President and other Federal Government organizations, such as the National Science Foundation and the National Institutes of Health.Innovative, analytical self-starters who are able to work well in teams are encouraged to apply. Previous policy experience is not required. Ideal candidates will have at leasta BS/BA degree conferred between May 2023 and July 2025. MA/MS-degree candidates and recipients are also encouraged to apply, provided their bachelor’s degrees are within the May 2022 – July 2024 timeframe. Have specific questions for our panelists? Email us at employment@ida.org and we’ll answer them duringthe session. You’ll also have the chance to ask questions live during the panel. Tune in via Zoom on November, 13th at 12pmEST for this virtual opportunity! https://ida-org.zoomgov.com/j/1615153527Webinar Passcode: 369321 

Proteomics of mouse brain endothelium uncovers dysregulation of vesicular transport pathways during aging  Nature.com

Resilient pathways: the adaptation of the ICT sector to climate change

The human cardiovascular system has adapted to function optimally in Earth's 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1. Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47phox, and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities.

Robert W. Mahley
Jan 1, 1999; 40:1-16
Reviews

The two branches of the Kennedy pathways (CDP-choline and CDP-ethanolamine) are the predominant pathways responsible for the synthesis of the most abundant phospholipids, phosphatidylcholine and phosphatidylethanolamine, respectively, in mammalian membranes. Recently, hereditary diseases associated with single gene mutations in the Kennedy pathways have been identified. Interestingly, genetic diseases within the same pathway vary greatly, ranging from muscular dystrophy to spastic paraplegia to a childhood blinding disorder to bone deformations. Indeed, different point mutations in the same gene (PCYT1; CCTα) result in at least three distinct diseases. In this review, we will summarize and review the genetic diseases associated with mutations in genes of the Kennedy pathway for phospholipid synthesis. These single-gene disorders provide insight, indeed direct genotype-phenotype relationships, into the biological functions of specific enzymes of the Kennedy pathway. We discuss potential mechanisms of how mutations within the same pathway can cause disparate disease.

Juntuo Zhou
Nov 30, 2020; 0:RA120.002384v1-mcp.RA120.002384
Research

Elevated levels of fasting insulin release and insufficient glucose-stimulated insulin secretion (GSIS) are hallmarks of diabetes. Studies have established cross-talk between integrin signaling and insulin activity, but more details of how integrin-dependent signaling impacts the pathophysiology of diabetes are needed. Here, we dissected integrin-dependent signaling pathways involved in the regulation of insulin secretion in β-cells and studied their link to the still debated autocrine regulation of insulin secretion by insulin/insulin-like growth factor (IGF) 2–AKT signaling. We observed for the first time a cooperation between different AKT isoforms and focal adhesion kinase (FAK)–dependent adhesion signaling, which either controlled GSIS or prevented insulin secretion under fasting conditions. Indeed, β-cells form integrin-containing adhesions, which provide anchorage to the pancreatic extracellular matrix and are the origin of intracellular signaling via FAK and paxillin. Under low-glucose conditions, β-cells adopt a starved adhesion phenotype consisting of actin stress fibers and large peripheral focal adhesion. In contrast, glucose stimulation induces cell spreading, actin remodeling, and point-like adhesions that contain phospho-FAK and phosphopaxillin, located in small protrusions. Rat primary β-cells and mouse insulinomas showed an adhesion remodeling during GSIS resulting from autocrine insulin/IGF2 and AKT1 signaling. However, under starving conditions, the maintenance of stress fibers and the large adhesion phenotype required autocrine IGF2-IGF1 receptor signaling mediated by AKT2 and elevated FAK-kinase activity and ROCK-RhoA levels but low levels of paxillin phosphorylation. This starved adhesion phenotype prevented excessive insulin granule release to maintain low insulin secretion during fasting. Thus, deregulation of the IGF2 and adhesion-mediated signaling may explain dysfunctions observed in diabetes.

Kinases are critical components of intracellular signaling pathways and have been extensively investigated with regard to their roles in cancer. p21-activated kinase-1 (PAK1) is a serine/threonine kinase that has been previously implicated in numerous biological processes, such as cell migration, cell cycle progression, cell motility, invasion, and angiogenesis, in glioma and other cancers. However, the signaling network linked to PAK1 is not fully defined. We previously reported a large-scale yeast genetic interaction screen using toxicity as a readout to identify candidate PAK1 genetic interactions. En masse transformation of the PAK1 gene into 4,653 homozygous diploid Saccharomyces cerevisiae yeast deletion mutants identified ∼400 candidates that suppressed yeast toxicity. Here we selected 19 candidate PAK1 genetic interactions that had human orthologs and were expressed in glioma for further examination in mammalian cells, brain slice cultures, and orthotopic glioma models. RNAi and pharmacological inhibition of potential PAK1 interactors confirmed that DPP4, KIF11, mTOR, PKM2, SGPP1, TTK, and YWHAE regulate PAK1-induced cell migration and revealed the importance of genes related to the mitotic spindle, proteolysis, autophagy, and metabolism in PAK1-mediated glioma cell migration, drug resistance, and proliferation. AKT1 was further identified as a downstream mediator of the PAK1-TTK genetic interaction. Taken together, these data provide a global view of PAK1-mediated signal transduction pathways and point to potential new drug targets for glioma therapy.

Montgomery Blencowe
Dec 23, 2020; 0:jlr.RA120000713v1-jlr.RA120000713
Research Articles

Genome-wide association studies (GWAS) have implicated ~380 genetic loci for plasma lipid regulation. However, these loci only explain 17-27% of the trait variance and a comprehensive understanding of the molecular mechanisms has not been achieved. In this study, we utilized an integrative genomics approach leveraging diverse genomic data from human populations to investigate whether genetic variants associated with various plasma lipid traits, namely total cholesterol (TC), high and low density lipoprotein cholesterol (HDL and LDL), and triglycerides (TG), from GWAS were concentrated on specific parts of tissue-specific gene regulatory networks. In addition to the expected lipid metabolism pathways, gene subnetworks involved in ‘interferon signaling’, ‘autoimmune/immune activation’, ‘visual transduction’, and ‘protein catabolism’ were significantly associated with all lipid traits. Additionally, we detected trait-specific subnetworks, including cadherin-associated subnetworks for LDL, glutathione metabolism for HDL, valine, leucine and isoleucine biosynthesis for TC, and insulin signaling and complement pathways for TG. Finally, utilizing gene-gene relations revealed by tissue-specific gene regulatory networks, we detected both known (e.g. APOH, APOA4, and ABCA1) and novel (e.g. F2 in adipose tissue) key regulator genes in these lipid-associated subnetworks. Knockdown of the F2 gene (Coagulation Factor II, Thrombin) in 3T3-L1 and C3H10T1/2 adipocytes reduced gene expression of Abcb11, Apoa5, Apof, Fabp1, Lipc, and Cd36, reduced intracellular adipocyte lipid content, and increased extracellular lipid content, supporting a link between adipose thrombin and lipid regulation. Our results shed light on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation and lipid-associated diseases.

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The histopathological subtype of lung adenocarcinoma (LUAD) is closely associated with prognosis. Micropapillary or solid predominant LUAD tends to relapse after surgery at an early stage, whereas lepidic pattern shows a favorable outcome. However, the molecular mechanism underlying this phenomenon remains unknown. Here, we recruited 31 lepidic predominant LUADs (LR: low-risk subtype group) and 28 micropapillary or solid predominant LUADs (HR: high-risk subtype group). Tissues of these cases were obtained and label-free quantitative proteomic and bioinformatic analyses were performed. Additionally, prognostic impact of targeted proteins was validated using The Cancer Genome Atlas databases (n=492) and tissue microarrays composed of early-stage LUADs (n=228). A total of 192 differentially expressed proteins were identified between tumor tissues of LR and HR and three clusters were identified via hierarchical clustering excluding eight proteins. Cluster 1 (65 proteins) showed a sequential decrease in expression from normal tissues to tumor tissues of LR and then to HR and was predominantly enriched in pathways such as tyrosine metabolism and ECM-receptor interaction, and increased matched mRNA expression of 18 proteins from this cluster predicted favorable prognosis. Cluster 2 (70 proteins) demonstrated a sequential increase in expression from normal tissues to tumor tissues of LR and then to HR and was mainly enriched in pathways such as extracellular organization, DNA replication and cell cycle, and high matched mRNA expression of 25 proteins indicated poor prognosis. Cluster 3 (49 proteins) showed high expression only in LR, with high matched mRNA expression of 20 proteins in this cluster indicating favorable prognosis. Furthermore, high expression of ERO1A and FEN1 at protein level predicted poor prognosis in early-stage LUAD, supporting the mRNA results. In conclusion, we discovered key differentially expressed proteins and pathways between low-risk and high-risk subtypes of early-stage LUAD. Some of these proteins could serve as potential biomarkers in prognostic evaluation.

A statewide initiative aims to enroll half the state's high school students into career pathways to close a "skills gap."

At a new park in Bosnia and Herzegovina, two dozen gardeners have spent years replicating the Dutch artist's masterpiece using the land as their canvas

A new book by a College of Education professor offers insights into how educators can empower low-income students of color.

Plan would improve Delaware’s efforts to connect educators and employers, and expand work-based learning WILMINGTON, Del. – The Delaware Pathways Steering Committee presented its Strategic Plan to Governor John Carney on Wednesday – including priorities designed to more effectively connect Delaware educators and employers, create additional work-based learning opportunities for Delaware middle and high school […]

Pathways provides high school and postsecondary students with the opportunity to gain work-based learning experiences for in-demand careers WILMINGTON, Del. – Governor John Carney on Friday announced a $3.25 million grant from Bloomberg Philanthropies to expand access to economic opportunity for Delaware students. Funding will help bolster the Delaware Pathways program, which provides high school […]

The orexigenic gut peptide ghrelin is an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHSR1a). Systemic ghrelin administration has previously been shown to increase gastric motility and emptying. While these effects are known to be mediated by the vagus nerve, the cellular mechanism underlying these effects remains unclear. Therefore, the purpose of the present study was to investigate the signaling mechanism by which GHSR1a inhibits voltage-gated Ca²⁺ channels in isolated rat gastric vagal afferent neurons using whole-cell patch-clamp electrophysiology. The ghrelin pharmacological profile indicated that Ca²⁺ currents were inhibited with a log (Ic₅₀) = –2.10 ± 0.44 and a maximal inhibition of 42.8 ± 5.0%. Exposure to the GHSR1a receptor antagonist (D-Lys3)-GHRP-6 reduced ghrelin-mediated Ca²⁺ channel inhibition (29.4 ± 16.7% vs. 1.9 ± 2.5%, n = 6, P = 0.0064). Interestingly, we observed that activation of GHSR1a inhibited Ca²⁺ currents through both voltage-dependent and voltage-independent pathways. We also treated the gastric neurons with either pertussis toxin (PTX) or YM-254890 to examine whether the Ca²⁺ current inhibition was mediated by the Gα_i/o or Gα_q/11 family of subunits. Treatment with both PTX (Ca²⁺ current inhibition = 15.7 ± 10.6%, n = 8, P = 0.0327) and YM-254890 (15.2 ± 11.9%, n = 8, P = 0.0269) blocked ghrelin’s effects on Ca²⁺ currents, as compared with control neurons (34.3 ± 18.9%, n = 8). These results indicate GHSR1a can couple to both Gα_i/o and Gα_q/11 in gastric vagal afferent neurons. Overall, our findings suggest GHSR1a-mediated inhibition of Ca²⁺ currents occurs through two distinct pathways, offering necessary insights into the cellular mechanisms underlying ghrelin’s regulation of gastric vagal afferents.

Although acute inflammation serves essential functions in maintaining tissue homeostasis, chronic inflammation is causally linked to many diseases. Macrophages are a major cell type that orchestrates inflammatory processes. During inflammation, macrophages undergo polarization and activation, thereby mobilizing pro-inflammatory and anti-inflammatory transcriptional programs that regulate ensuing macrophage functions. Fatty acid binding protein 5 (FABP5) is a lipid chaperone highly expressed in macrophages. FABP5 deletion is implicated in driving macrophages toward an anti-inflammatory phenotype, yet signaling pathways regulated by macrophage-FABP5 have not been systematically profiled. We leveraged proteomic and phosphoproteomic approaches to characterize pathways modulated by FABP5 in M1 and M2 polarized bone marrow-derived macrophages (BMDMs). Stable isotope labeling by amino acids-based analysis of M1 and M2 polarized wild-type and FABP5 knockout BMDMs revealed numerous differentially regulated proteins and phosphoproteins. FABP5 deletion impacted downstream pathways associated with inflammation, cytokine production, oxidative stress, and kinase activity. Toll-like receptor 2 (TLR2) emerged as a novel target of FABP5 and pharmacological FABP5 inhibition blunted TLR2-mediated activation of downstream pathways, ascribing a novel role for FABP5 in TLR2 signaling. This study represents a comprehensive characterization of the impact of FABP5 deletion on the proteomic and phosphoproteomic landscape of M1 and M2 polarized BMDMs. Loss of FABP5 altered pathways implicated in inflammatory responses, macrophage function, and TLR2 signaling. This work provides a foundation for future studies seeking to investigate the therapeutic potential of FABP5 inhibition in pathophysiological states resulting from dysregulated inflammatory signaling.

Jun 28, 2024

Ensuring that space remains a domain for peaceful exploration and mutual benefit rather than a new frontier for conflict will significantly depend on the global community's ability to navigate the complex interplay of technological advancements, regulatory frameworks, economic opportunities, and geopolitical challenges. 

This paper was written for the final assignment of IGA-250, a Harvard Kennedy School course on emerging technology: security, strategy, and risk.

Amjad Jamal discusses IWMI's significant role in Pakistan’s water sector, including key opportunities and potential strategies for overcoming the water crisis.

The post Navigating water challenges: Pathways to sustainability in Pakistan first appeared on International Water Management Institute (IWMI).

medlinkCancer/medlink-causing mutations in prostate cancer hyperactivate PI3K signaling, leading to cancer cell growth. PLEKHS1, a largely unknown

A newly identified gene pathway involving zinc in mice brings us one step closer to using zinc-based supplements to treat people with the rare disorder

Announcement Number: SE-18-BUS-INTERN
Closing Date: 12 April 2018

Announcement Number: TN-19-EI-BUS-INTERN
Closing Date: 20 February 2019

Announcement Number: SE-18-STEM-INTERN
Closing Date: 12 April 2018

Announcement Number: TN-19-EI-STEM-INTERN
Closing Date: 20 February 2019