The Raf/LIN-45 C-terminal distal tail segment negatively regulates signaling in Caenorhabditis elegans.

Raf protein kinases act as Ras-GTP sensing components of the ERK signal transduction pathway in animal cells, influencing cell proliferation, differentiation, and survival. In humans, somatic and germline mutations in the genes BRAF and RAF1 are associated with malignancies and developmental disorders. Recent studies shed light on the structure of activated Raf, a heterotetramer consisting of Raf and 14-3-3 dimers, and raised the possibility that a Raf C-terminal distal tail segment (DTS) regulates activation.

The Caenorhabditis elegans protein SOC-3 permits an alternative mode of signal transduction by the EGL-15 FGF receptor.

Fibroblast Growth Factors and their receptors (FGFRs) comprise a cell signaling module that can stimulate signaling by Ras and the kinases Raf, MEK, and ERK to regulate animal development and homeostatic functions. In Caenorhabditis elegans, the sole FGFR ortholog EGL-15 acts with the GRB2 ortholog SEM-5 to promote chemoattraction and migration by the sex myoblasts (SMs) and fluid homeostasis by the hypodermis (Hyp7). Cell-specific differences in EGL-15 signaling were suggested by the phenotypes caused by egl-15(n1457), an allele that removes a region of its C-terminal domain (CTD) known to bind SEM-5.

The Raf/LIN-45 C-terminal distal tail segment negatively regulates signaling in .

Raf protein kinases act as Ras-GTP sensing components of the ERK signal transduction pathway in animal cells, influencing cell proliferation, differentiation, and survival. In humans, somatic and germline mutations in the genes and are associated with malignancies and developmental disorders. Recent studies shed light on the structure of activated Raf, a heterotetramer consisting of Raf and 14-3-3 dimers, and raised the possibility that a Raf C-terminal distal tail segment (DTS) regulates activation.

The Drosophila tumor necrosis factor Eiger promotes Myc supercompetition independent of canonical Jun N-terminal kinase signaling.

Numerous factors have been implicated in the cell-cell interactions that lead to elimination of cells via cell competition, a context-dependent process of cell selection in somatic tissues that is based on comparisons of cellular fitness. Here, we use a series of genetic tests in Drosophila to explore the relative contribution of the pleiotropic cytokine tumor necrosis factor α (TNFα) in Myc-mediated cell competition (also known as Myc supercompetition or Myc cell competition). We find that the sole Drosophila TNF, Eiger (Egr), its receptor Grindelwald (Grnd/TNF receptor), and the adaptor proteins Traf4 and Traf6 are required to eliminate wild-type "loser" cells during Myc cell competition.

Ethical futures in biological anthropology: Research, teaching, community engagement, and curation involving deceased individuals.

Although ethical reforms in biological anthropology have gained ground in recent years, there is still a scarcity of ethical standards for work involving historical documented collections (HDCs) at US museums and universities. These collections of deceased individuals were created in the late 19th to mid-20th centuries under anatomy laws that targeted socially marginalized communities and allowed for the dissection of these individuals without their consent. Due to the extensive information associated with the individuals and made available to researchers, these collections have served as foundational resources for theory and methods development in biological anthropology into the 21st century.

The Highs and Lows of FBXW7: New Insights into Substrate Affinity in Disease and Development.

FBXW7 is a critical regulator of cell cycle, cell signaling, and development. A highly conserved F-box protein and component of the SKP1-Cullin-F-box (SCF) complex, FBXW7 functions as a recognition subunit within a Cullin-RING E3 ubiquitin ligase responsible for ubiquitinating substrate proteins and targeting them for proteasome-mediated degradation. In human cells, FBXW7 promotes degradation of a large number of substrate proteins, including many that impact disease, such as NOTCH1, Cyclin E, MYC, and BRAF.

Structural violence and institutionalized individuals: A paleopathological perspective on a continuing issue.

Past and present institutions (e.g., state and public hospitals, assisted living facilities, public nursing homes) have struggled with structural issues tied to patient care and neglect, which often manifests in the form of fracture trauma, and may explain why institutionalized individuals are at higher risk for this injury.

The E3/E4 ubiquitin ligase UFD-2 suppresses normal and oncogenic signaling mediated by a Raf ortholog in .

Signaling by the kinase cascade composed of Raf, MEK, and ERK is critical for animal development and is often inappropriately activated in human malignancies. We sought to identify factors that control signaling mediated by the Raf ortholog LIN-45. A genetic screen showed that the degradation of LIN-45 required the E3/E4 ubiquitin ligase UFD-2.

Twenty-first century bioarchaeology: Taking stock and moving forward.

This article presents outcomes from a Workshop entitled "Bioarchaeology: Taking Stock and Moving Forward," which was held at Arizona State University (ASU) on March 6-8, 2020. Funded by the National Science Foundation (NSF), the School of Human Evolution and Social Change (ASU), and the Center for Bioarchaeological Research (CBR, ASU), the Workshop's overall goal was to explore reasons why research proposals submitted by bioarchaeologists, both graduate students and established scholars, fared disproportionately poorly within recent NSF Anthropology Program competitions and to offer advice for increasing success. Therefore, this Workshop comprised 43 international scholars and four advanced graduate students with a history of successful grant acquisition, primarily from the United States.

The prognostic role of fatigue, depression and anxiety on postoperative outcomes after pancreatectomy for pancreatic cancer. A prospective observational study (FAT-PRO study).

Objectives: This study aims to assess the prevalence of preoperative fatigue, depression and anxiety among patients undergoing pancreatic surgery for pancreatic cancer (PC), and possible relationship with postoperative outcomes.

Methods: Prospective data from 162 consecutive patients undergoing pancreatectomy for PC at a third-level referral centers for pancreatic surgery were collected. All patients preoperatively completed four questionnaires assessing depression (PHQ-9), anxiety (STAI-Y2), chronic illness fatigue (FACIT-F) and cancer therapy fatigue (FACT-G).

Paving the Way for a Green Transition in the Design of Sensors and Biosensors for the Detection of Volatile Organic Compounds (VOCs).

The efficient and selective detection of volatile organic compounds (VOCs) provides key information for various purposes ranging from the toxicological analysis of indoor/outdoor environments to the diagnosis of diseases or to the investigation of biological processes. In the last decade, different sensors and biosensors providing reliable, rapid, and economic responses in the detection of VOCs have been successfully conceived and applied in numerous practical cases; however, the global necessity of a sustainable development, has driven the design of devices for the detection of VOCs to greener methods. In this review, the most recent and innovative VOC sensors and biosensors with sustainable features are presented.

Intersectionality and trauma analysis in bioarchaeology.

Intersectionality, the theory named by Kimberlé Crenshaw, outlines how multiple elements of an individual's social identity overlap to create and preserve societal inequalities and discrimination. Recently bioarchaeology's engagement with intersectionality has become increasingly explicit, as the field recognizes the lived experience of multiple axes of an individual's identity. Evidence of trauma can remain observable in an individual's skeleton for years, making it an ideal subject of study for intersectional analyses in bioarchaeology.

Negative feedback by conserved kinases patterns the degradation of Raf in vulval fate patterning.

Activation of a canonical EGFR-Ras-Raf-ERK cascade initiates patterning of multipotent vulval precursor cells (VPCs) of We have previously shown that this pathway includes a negative-feedback component in which MPK-1/ERK activity targets the upstream kinase LIN-45/Raf for degradation by the SEL-10/FBXW7 E3 ubiquitin ligase. This regulation requires a Cdc4 phosphodegron (CPD) in LIN-45 that is conserved in BRAF. Here, we identify and characterize the minimal degron that encompasses the CPD and is sufficient for SEL-10-mediated, MPK-1-dependent protein degradation.

Widely Used Mutants of , Encoding the Tumor Necrosis Factor, Carry Additional Mutations in the NimrodC1 Phagocytosis Receptor.

The process of apoptosis in epithelia involves activation of caspases, delamination of cells, and degradation of cellular components. Corpses and cellular debris are then rapidly cleared from the tissue by phagocytic blood cells. In studies of the TNF, Eiger (Egr) and cell death in wing imaginal discs, the epithelial primordia of fly wings, we noticed that dying cells appeared to transiently accumulate in mutant wing discs, raising the possibility that their phagocytic engulfment by hemocytes was impaired.

Osteoporosis, osteomalacia, and hip fracture: A case study from the Terry collection.

Objective: This case study describes a perimortem hip fracture in a documented individual from the Robert J. Terry Skeletal Collection. The purpose of this paper is to comprehend how co-occurring conditions contributed to fracture risk and to understand the effect of the injury on this individual.

Perimortem fracture manifestations and mortality after hip fracture in a documented skeletal series.

Objective: Unhealed hip fractures are underrepresented in the archaeological record, suggesting that better identification criteria are required. This paper evaluates whether a sample of documented perimortem hip fractures displayed classic perimortem features and which features may facilitate better identification of such fractures in the archaeological record.

Materials: Ten individuals from the Robert J.

Technology and Process Design for Phenols Recovery from Industrial Chicory () Leftovers.

Vegetal leftovers from the agro-food industry represent a huge source of primary and secondary metabolites, vitamin, mineral salts and soluble as well as insoluble fibers. Economic reports on the growth in the polyphenol market have driven us to focus our investigation on chicory ( L.), which is one of the most popular horticultural plants in the world and a rich source of phenolic compounds.

Synergistic Effects of Active Sites' Nature and Hydrophilicity on the Oxygen Reduction Reaction Activity of Pt-Free Catalysts.

This work highlights the importance of the hydrophilicity of a catalyst's active sites on an oxygen reduction reaction (ORR) through an electrochemical and physico-chemical study on catalysts based on nitrogen-modified carbon doped with different metals (Fe, Cu, and a mixture of them). BET, X-ray Powder Diffraction (XRPD), micro-Raman, X-ray Photoelectron Spectroscopy (XPS), Scanning Electron Microscopy (SEM), Scanning Transmission Electron Microscopy (STEM), and hydrophilicity measurements were performed. All synthesized catalysts are characterized not only by a porous structure, with the porosity distribution centered in the mesoporosity range, but also by the presence of carbon nanostructures.

A Real-Time Biosensor for ERK Activity Reveals Signaling Dynamics during C. elegans Cell Fate Specification.

Kinase translocation reporters (KTRs) are genetically encoded fluorescent activity sensors that convert kinase activity into a nucleocytoplasmic shuttling equilibrium for visualizing single-cell signaling dynamics. Here, we adapt the first-generation KTR for extracellular signal-regulated kinase (ERK) to allow easy implementation in vivo. This sensor, "ERK-nKTR," allows quantitative and qualitative assessment of ERK activity by analysis of individual nuclei and faithfully reports ERK activity during development and neural function in diverse cell contexts in Caenorhabditis elegans.

Treatment of branch-duct intraductal papillary mucinous neoplasms of the pancreas: state of the art.

The diagnosis of branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) has been dramatically increased. BD-IPMNs are frequently discovered as incidental findings in asymptomatic individuals, mainly in elderly patients. An accurate evaluation of BD-IPMNs with high-resolution imaging techniques and endoscopic ultrasound is necessary.

An ancient defense system eliminates unfit cells from developing tissues during cell competition.

Developing tissues that contain mutant or compromised cells present risks to animal health. Accordingly, the appearance of a population of suboptimal cells in a tissue elicits cellular interactions that prevent their contribution to the adult. Here we report that this quality control process, cell competition, uses specific components of the evolutionarily ancient and conserved innate immune system to eliminate Drosophila cells perceived as unfit.

Supercompetitor status of Drosophila Myc cells requires p53 as a fitness sensor to reprogram metabolism and promote viability.

In growing tissues, cell fitness disparities can provoke interactions that promote stronger cells at the expense of the weaker in a process called cell competition. The mechanistic definition of cell fitness is not understood, nor is it understood how fitness differences are recognized. Drosophila cells with extra Myc activity acquire "supercompetitor" status upon confrontation with wild-type (WT) cells, prompting the latter's elimination via apoptosis.

Stem cell therapy for neonatal diseases associated with preterm birth.

In the last decades, the prevention and treatment of neonatal respiratory distress syndrome with antenatal steroids and surfactant replacement allowed the survival of infants born at extremely low gestational ages. These extremely preterm infants are highly vulnerable to the detrimental effects of oxidative stress and infection, and are prone to develop lung and brain diseases that eventually evolve in severe sequelae: The so-called new bronchopulmonary dysplasia (BPD) and the noncystic, diffuse form of periventricular leukomalacia (PVL). Tissue simplification and developmental arrest (larger and fewer alveoli and hypomyelination in the lungs and brain, respectively) appears to be the hallmark of these emerging sequelae, while fibrosis is usually mild and contributes to a lesser extent to their pathogenesis.