The Art of Dermatology: Lessons Learned from Master Morphologist, Dr. Irwin Braverman.

In dermatology, the art and skill of morphologic assessment is key to generating logical differential diagnoses and understanding disease pathogenesis. Dr. Irwin M.

Cancer-cell derived S100A11 promotes macrophage recruitment in ER+ breast cancer.

Macrophages are pivotal in driving breast tumor development, progression, and resistance to treatment, particularly in estrogen receptor-positive (ER+) tumors, where they infiltrate the tumor microenvironment (TME) influenced by cancer cell-secreted factors. By analyzing single-cell RNA sequencing data from 25 ER+ tumors, we elucidated interactions between cancer cells and macrophages, correlating macrophage density with epithelial cancer cell density. We identified that S100A11, a previously unexplored factor in macrophage-cancer crosstalk, predicts high macrophage density and poor outcomes in ER+ tumors.

Rational Design of HER2-Targeted Combination Therapies to Reverse Drug Resistance in Fibroblast-Protected HER2+ Breast Cancer Cells.

Introduction: Fibroblasts, an abundant cell type in the breast tumor microenvironment, interact with cancer cells and orchestrate tumor progression and drug resistance. However, the mechanisms by which fibroblast-derived factors impact drug sensitivity remain poorly understood. Here, we develop rational combination therapies that are informed by proteomic profiling to overcome fibroblast-mediated therapeutic resistance in HER2+ breast cancer cells.

CAR T cell infiltration and cytotoxic killing within the core of 3D breast cancer spheroids under the control of antigen sensing in microwell arrays.

The success of chimeric antigen receptor (CAR) T cells in blood cancers has intensified efforts to develop CAR T therapies for solid cancers. In the solid tumor microenvironment, CAR T cell trafficking and suppression of cytotoxic killing represent limiting factors for therapeutic efficacy. Here, we present a microwell platform to study CAR T cell interactions with 3D breast tumor spheroids and determine predictors of anti-tumor CAR T cell function.

Ontogenetic biomechanics of tufted (Sapajus) and untufted (Cebus) capuchin mandibles.

Objectives: Cortical bone geometry is commonly used to investigate biomechanical properties of primate mandibles. However, the ontogeny of these properties is less understood. Here we investigate changes in cortical bone cross-sectional properties throughout capuchin ontogeny and compare captive versus wild, semi-provisioned groups.

Mitochondrial metabolism regulation and epigenetics in hypoxia.

The complex and dynamic interaction between cellular energy control and gene expression modulation is shown by the intersection between mitochondrial metabolism and epigenetics in hypoxic environments. Poor oxygen delivery to tissues, or hypoxia, is a basic physiological stressor that sets off a series of reactions in cells to adapt and endure oxygen-starved environments. Often called the "powerhouse of the cell," mitochondria are essential to cellular metabolism, especially regarding producing energy through oxidative phosphorylation.

Rational design of HER2-targeted combination therapies to reverse drug resistance in fibroblast-protected HER2+ breast cancer cells.

Introduction: Fibroblasts, an abundant cell type in the breast tumor microenvironment, interact with cancer cells and orchestrate tumor progression and drug resistance. However, the mechanisms by which fibroblast-derived factors impact drug sensitivity remain poorly understood. Here, we develop rational combination therapies that are informed by proteomic profiling to overcome fibroblast-mediated therapeutic resistance in HER2+ breast cancer cells.

Defining and Measuring the Scope of Atopic Dermatitis.

Atopic dermatitis (AD) has no definitive diagnostic test and has a large range of phenotypes, making it a difficult disease to assess and define. However, an agreed-upon definition of AD is important for clinical trials, population-based studies, and clinical practice. Several diagnostic criteria systems have been proposed to fill these needs, with none considered the gold standard.

Tradeoffs between bite force and gape in Eulemur and Varecia.

In 1974, Sue Herring described the relationship between two important performance variables in the feeding system, bite force and gape. These variables are inversely related, such that, without specific muscular adaptations, most animals cannot produce high bite forces at large gapes for a given sized muscle. Despite the importance of these variables for feeding biomechanics and functional ecology, the paucity of in vivo bite force data in primates has led to bite forces largely being estimated through ex vivo methods.

Ontogenetic changes in jaw leverage and skull shape in tufted and untufted capuchins.

The ontogeny of feeding is characterized by shifting functional demands concurrent with changes in craniofacial anatomy; relationships between these factors will look different in primates with disparate feeding behaviors during development. This study examines the ontogeny of skull morphology and jaw leverage in tufted (Sapajus) and untufted (Cebus) capuchin monkeys. Unlike Cebus, Sapajus have a mechanically challenging diet and behavioral observations of juvenile Sapajus suggest these foods are exploited early in development.

CAR T cell infiltration and cytotoxic killing within the core of 3D breast cancer spheroids under control of antigen sensing in microwell arrays.

The success of chimeric antigen receptor (CAR) T cells in blood cancers has intensified efforts to develop CAR T therapies for solid cancers. In the solid tumor microenvironment, CAR T cell trafficking and suppression of cytotoxic killing represent limiting factors for therapeutic efficacy. Here, we present a microwell platform to study CAR T cell interactions with 3D tumor spheroids and determine predictors of anti-tumor CAR T cell function.

Utilizing targeted integration CHO pools to potentially accelerate the GMP manufacturing of monoclonal and bispecific antibodies.

Monoclonal antibodies (mAbs) are effective therapeutic agents against many acute infectious diseases including COVID-19, Ebola, RSV, Clostridium difficile, and Anthrax. mAbs can therefore help combat a future pandemic. Unfortunately, mAb development typically takes years, limiting its potential to save lives during a pandemic.

The admixed brushtail possum genome reveals invasion history in New Zealand and novel imprinted genes.

Combining genome assembly with population and functional genomics can provide valuable insights to development and evolution, as well as tools for species management. Here, we present a chromosome-level genome assembly of the common brushtail possum (Trichosurus vulpecula), a model marsupial threatened in parts of their native range in Australia, but also a major introduced pest in New Zealand. Functional genomics reveals post-natal activation of chemosensory and metabolic genes, reflecting unique adaptations to altricial birth and delayed weaning, a hallmark of marsupial development.

Introduction: food processing and nutritional assimilation in animals.

How animals process and absorb nutrients from their food is a fundamental question in biology. Despite the continuity and interaction between intraoral food processing and post-oesophageal nutritional extraction, these topics have largely been studied separately. At present, we lack a synthesis of how pre- and post-oesophageal mechanisms of food processing shape the ability of various taxa to effectively assimilate nutrients from their diet.

Energetic costs of feeding in 12 species of small-bodied primates.

There are no comparative, empirical studies of the energetic costs of feeding in mammals. As a result, we lack physiological data to better understand the selection pressures on the mammalian feeding apparatus and the influence of variables such as food geometric and material properties. This study investigates interspecific scaling of the net energetic costs of feeding in relation to body size, jaw-adductor muscle mass and food properties in a sample of 12 non-human primate species ranging in size from 0.

Gape drives regional variation in temporalis architectural dynamics in tufted capuchins.

Dynamic changes in jaw movements and bite forces depend on muscle architectural and neural factors that have rarely been compared within the same muscle. Here we investigate how regional muscle architecture dynamics-fascicle rotation, shortening, lengthening and architectural gear ratio (AGR)-vary during chewing across a functionally heterogeneous muscle. We evaluate whether timing in architecture dynamics relates to gape, food material properties and/or muscle activation.

Thiol-Disulfide Exchange Kinetics and Redox Potential of the Coenzyme M and Coenzyme B Heterodisulfide, an Electron Acceptor Coupled to Energy Conservation in Methanogenic Archaea.

Methanogenic and methanotrophic archaea play important roles in the global carbon cycle by interconverting CO and methane. To conserve energy from these metabolic pathways that happen close to the thermodynamic equilibrium, specific electron carriers have evolved to balance the redox potentials between key steps. Reduced ferredoxins required to activate CO are provided by energetical coupling to the reduction of the high-potential heterodisulfide (HDS) of coenzyme M (2-mercaptoethanesulfonate) and coenzyme B (7-mercaptoheptanoylthreonine phosphate).

Hypoxia-induced cancer cell reprogramming: a review on how cancer stem cells arise.

Cancer stem cells are a subset of cells within the tumor that possess the ability to self-renew as well as differentiate into different cancer cell lineages. The exact mechanisms by which cancer stem cells arise is still not completely understood. However, current research suggests that cancer stem cells may originate from normal stem cells that have undergone genetic mutations or epigenetic changes.

Ontogenetic changes in bite force and gape in tufted capuchins.

Bite force and gape are two important performance metrics of the feeding system, and these metrics are inversely related for a given muscle size because of fundamental constraints in sarcomere length-tension relationships. How these competing performance metrics change in developing primates is largely unknown. Here, we quantified in vivo bite forces and gapes across ontogeny and examined these data in relation to body mass and cranial measurements in captive tufted capuchins, Sapajus spp.

Organosilica nanoparticles containing sodium borocaptate (BSH) provide new prospects for boron neutron capture therapy (BNCT): efficient cellular uptake and enhanced BNCT efficacy.

Boron neutron capture therapy (BNCT), a method based on the fission of boron-10 upon neutron irradiation, has emerged as an attractive option for radiation therapy. To date, the main drugs used in BNCT are 4-boronophenylalanine (BPA) and sodium borocaptate (BSH). While BPA has been extensively tested in clinical trials, the use of BSH has been limited, mainly due to its poor cellular uptake.

Socs3b regulates the development and function of innate immune cells in zebrafish.

Introduction: Suppressor of cytokine signaling 3 (SOCS3) is a critical component of the negative feedback regulation that controls signaling by cytokines and other factors thereby ensuring that important processes such as hematopoiesis and inflammation occur at appropriate levels.

Methods: To gain further insights into SOCS3 function, the zebrafish gene was investigated through analysis of a knockout line generated using CRISPR/Cas9-mediated genome editing.

Results: Zebrafish knockout embryos displayed elevated numbers of neutrophils during primitive and definitive hematopoiesis but macrophage numbers were not altered.

Navigating a New Normal: Perceptions and Experiences of an Online Exercise Program for Older Adults During COVID-19.

Online exercise programming has surged in popularity; however, little is known about older adults' perceptions and experiences of online exercise. The purpose of this study was to qualitatively examine older adults' (aged 59-82 years) experiences and perceptions of an online exercise program during the COVID-19 pandemic. Nineteen individuals (individuals who used the online exercise program and those who did not) completed a semistructured interview.

FAM193A is a positive regulator of p53 activity.

Inactivation of the p53 tumor suppressor, either by mutations or through hyperactivation of repressors such as MDM2 and MDM4, is a hallmark of cancer. Although many inhibitors of the p53-MDM2/4 interaction have been developed, such as Nutlin, their therapeutic value is limited by highly heterogeneous cellular responses. We report here a multi-omics investigation of the cellular response to MDM2/4 inhibitors, leading to identification of FAM193A as a widespread regulator of p53 function.

Sagittal suture strain in capuchin monkeys (Sapajus and Cebus) during feeding.

Objectives: Morphological variation in cranial sutures is used to infer aspects of primate feeding behavior, including diet, but strain regimes across sutures are not well documented. Our aim is to test hypotheses about sagittal suture morphology, strain regime, feeding behavior, and muscle activity relationships in robust Sapajus and gracile Cebus capuchin primates.

Materials And Methods: Morphometrics of sinuosity in three regions of the sagittal suture were compared among museum specimens of Sapajus and Cebus, as well as in robust and gracile lab specimens.