Hydrogel crosslinking modulates macrophages, fibroblasts, and their communication, during wound healing.

Biomaterial wound dressings, such as hydrogels, interact with host cells to regulate tissue repair. This study investigates how crosslinking of gelatin-based hydrogels influences immune and stromal cell behavior and wound healing in female mice. We observe that softer, lightly crosslinked hydrogels promote greater cellular infiltration and result in smaller scars compared to stiffer, heavily crosslinked hydrogels.

Measurement of Atmospheric Mercury: Current Limitations and Suggestions for Paths Forward.

Mercury (Hg) researchers have made progress in understanding atmospheric Hg, especially with respect to oxidized Hg (Hg) that can represent 2 to 20% of Hg in the atmosphere. Knowledge developed over the past ∼10 years has pointed to existing challenges with current methods for measuring atmospheric Hg concentrations and the chemical composition of Hg compounds. Because of these challenges, atmospheric Hg experts met to discuss limitations of current methods and paths to overcome them considering ongoing research.

ROS-induced ribosome impairment underlies ZAKα-mediated metabolic decline in obesity and aging.

The ribotoxic stress response (RSR) is a signaling pathway in which the p38- and c-Jun N-terminal kinase (JNK)-activating mitogen-activated protein kinase kinase kinase (MAP3K) ZAKα senses stalling and/or collision of ribosomes. Here, we show that reactive oxygen species (ROS)-generating agents trigger ribosomal impairment and ZAKα activation. Conversely, zebrafish larvae deficient for ZAKα are protected from ROS-induced pathology.

Reporting reimbursement price decisions for onco-hematology drugs in Spain.

Introduction: Even using well-established technology assessment processes, the basis of the decisions on drug price and reimbursement are sometimes perceived as poorly informed and sometimes may be seen as disconnected from value. The literature remains inconclusive about how Health Technology Assessment Bodies (HTAb) should report the determinants of their decisions. This study evaluates the relationship between oncology and hematology drug list prices and structured value parameters at the time of reimbursement decision in Spain.

Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target.

The genomic landscape of colorectal cancer (CRC) is shaped by inactivating mutations in tumour suppressors such as APC, and oncogenic mutations such as mutant KRAS. Here we used genetically engineered mouse models, and multimodal mass spectrometry-based metabolomics to study the impact of common genetic drivers of CRC on the metabolic landscape of the intestine. We show that untargeted metabolic profiling can be applied to stratify intestinal tissues according to underlying genetic alterations, and use mass spectrometry imaging to identify tumour, stromal and normal adjacent tissues.

Comparison of Protein and Carbohydrate Consumption and Processing in Emerging Workers, Gynes and Males of the Wasp .

There is growing evidence that paper wasps' () fate as workers or reproductive females (gynes) is affected by cues that exist at the larval stage and during eclosion. The nutritional requirements for workers and gynes are different early in their adult lives. Males are short-lived and have different nutritional needs than females.

Ribosomal RNA 2'-O-methylation dynamics impact cell fate decisions.

Translational regulation impacts both pluripotency maintenance and cell differentiation. To what degree the ribosome exerts control over this process remains unanswered. Accumulating evidence has demonstrated heterogeneity in ribosome composition in various organisms.

β-Catenin Drives Butyrophilin-like Molecule Loss and γδ T-cell Exclusion in Colon Cancer.

Intraepithelial lymphocytes (IEL) expressing γδ T-cell receptors (γδTCR) play key roles in elimination of colon cancer. However, the precise mechanisms by which progressing cancer cells evade immunosurveillance by these innate T cells are unknown. Here, we investigated how loss of the Apc tumor suppressor in gut tissue could enable nascent cancer cells to escape immunosurveillance by cytotoxic γδIELs.

Dedifferentiation maintains melanocyte stem cells in a dynamic niche.

For unknow reasons, the melanocyte stem cell (McSC) system fails earlier than other adult stem cell populations, which leads to hair greying in most humans and mice. Current dogma states that McSCs are reserved in an undifferentiated state in the hair follicle niche, physically segregated from differentiated progeny that migrate away following cues of regenerative stimuli. Here we show that most McSCs toggle between transit-amplifying and stem cell states for both self-renewal and generation of mature progeny, a mechanism fundamentally distinct from those of other self-renewing systems.

The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic Options.

It is well established that mutations in the canonical WNT-signalling pathway play a major role in various cancers. Critical to developing new therapeutic strategies is understanding which cancers are driven by WNT pathway activation and at what level these mutations occur within the pathway. Some cancers harbour mutations in genes whose protein products operate at the receptor level of the WNT pathway.

The Correlation of Papanicolaou Smears and Clinical Features to Identify the Common Risk Factors for Cervical Cancer: A Retrospective and Descriptive Study from a Tertiary Care Hospital in Trinidad.

Cervical cancer, the fourth most frequent cancer in women, is associated with the human papillomavirus (HPV). This study identifies risk factors and clinical findings for abnormal cervical cytology and histopathology in the Trinidad and Tobago populations. Some risk factors include early age of first coitus, a high number of sexual partners, high parity, smoking, and using certain medications, such as oral contraception.

The Neuropilin-1/PKC axis promotes neuroendocrine differentiation and drug resistance of prostate cancer.

Background: Neuroendocrine prostate cancer (NEPC) is a multi-resistant variant of prostate cancer (PCa) that has become a major challenge in clinics. Understanding the neuroendocrine differentiation (NED) process at the molecular level is therefore critical to define therapeutic strategies that can prevent multi-drug resistance.

Methods: Using RNA expression profiling and immunohistochemistry, we have identified and characterised a gene expression signature associated with the emergence of NED in a large PCa cohort, including 169 hormone-naïve PCa (HNPC) and 48 castration-resistance PCa (CRPC) patients.

Microvascular anatomy suggests varying aerobic activity levels in the adipose tissues of diving tetrapods.

Adipose tissue has many important functions including metabolic energy storage, endocrine functions, thermoregulation and structural support. Given these varied functions, the microvascular characteristics within the tissue will have important roles in determining rates/limits of exchange of nutrients, waste, gases and molecular signaling molecules between adipose tissue and blood. Studies on skeletal muscle have suggested that tissues with higher aerobic capacity contain higher microvascular density (MVD) with lower diffusion distances (DD) than less aerobically active tissues.

Expert Consensus on the Use of Teprotumumab for the Management of Thyroid Eye Disease Using a Modified-Delphi Approach.

Background: Teprotumumab is the first treatment for thyroid eye disease (TED), a debilitating autoinflammatory condition, approved by the Food and Drug Administration in the United States, which reduces proptosis and improves quality of life. In the absence of guidelines, clinical recommendations were developed for using teprotumumab in patients with TED in the United States.

Methods: A 3-round modified-Delphi panel was conducted between October 2020 and February 2021 with experts in the management of patients with TED.

Mammals adjust diel activity across gradients of urbanization.

Time is a fundamental component of ecological processes. How animal behavior changes over time has been explored through well-known ecological theories like niche partitioning and predator-prey dynamics. Yet, changes in animal behavior within the shorter 24-hr light-dark cycle have largely gone unstudied.

mutation suppresses colorectal cancer by promoting eEF2 phosphorylation via eEF2K.

Increased protein synthesis supports the rapid cell proliferation associated with cancer. The mutant mouse reduces the expression of the ribosomal protein RPL24 and has been used to suppress translation and limit tumorigenesis in multiple mouse models of cancer. Here, we show that also suppresses tumorigenesis and proliferation in a model of colorectal cancer (CRC) with two common patient mutations, and .

Translational control through ribosome heterogeneity and functional specialization.

The conceptual origins of ribosome specialization can be traced back to the earliest days of molecular biology. Yet, this field has only recently begun to gather momentum, with numerous studies identifying distinct heterogeneous ribosome populations across multiple species and model systems. It is proposed that some of these compositionally distinct ribosomes may be functionally specialized and able to regulate the translation of specific mRNAs.

A RAC-GEF network critical for early intestinal tumourigenesis.

RAC1 activity is critical for intestinal homeostasis, and is required for hyperproliferation driven by loss of the tumour suppressor gene Apc in the murine intestine. To avoid the impact of direct targeting upon homeostasis, we reasoned that indirect targeting of RAC1 via RAC-GEFs might be effective. Transcriptional profiling of Apc deficient intestinal tissue identified Vav3 and Tiam1 as key targets.

Potential sources, scavenging processes, and source regions of mercury in the wet deposition of South Korea.

In this study, the potential sources, scavenging processes, and emission regions for Hg in wet deposition were investigated in rural (Jeju), suburban (Gwangju), and urban sites (Incheon and Seoul) of South Korea. The annual volume-weighted mean concentrations of Hg in wet deposition were four to five times higher in Incheon (16.6 ng L) and Seoul (22.

Age-associated mitochondrial DNA mutations cause metabolic remodelling that contributes to accelerated intestinal tumorigenesis.

Oxidative phosphorylation (OXPHOS) defects caused by somatic mitochondrial DNA (mtDNA) mutations increase with age in human colorectal epithelium and are prevalent in colorectal tumours, but whether they actively contribute to tumorigenesis remains unknown. Here we demonstrate that mtDNA mutations causing OXPHOS defects are enriched during the human adenoma/carcinoma sequence, suggesting they may confer a metabolic advantage. To test this we deleted the tumour suppressor Apc in OXPHOS deficient intestinal stem cells in mice.

What do you do if your relief comes to work intoxicated: An Impaired Provider Scenario.

Audience: The primary audience for this simulation exercise is emergency medicine (EM) residents, although it could be more broadly applied to all provider groups, including medical students, advanced practice providers, and faculty physicians.

Introduction: Over the course of their professional careers, approximately 10-15% of physicians will misuse or abuse alcohol or drugs.1 Unfortunately, Emergency Physicians (EPs) are not immune to this phenomenon, and although EPs make up only 4.

A New Monitoring Effort for Asia: The Asia Pacific Mercury Monitoring Network (APMMN).

The Asia Pacific Mercury Monitoring Network (APMMN) cooperatively measures mercury in precipitation in a network of sites operating in Asia and the Western Pacific region. The network addresses significant data gaps in a region where mercury emission estimates are the highest globally, and available measurement data are limited. The reduction of mercury emissions under the Minamata Convention on Mercury also justifies the need for continent-wide and consistent observations that can help determine the magnitude of the problem and assess the efficacy of reductions over time.