Divergent iron regulatory states contribute to heterogeneity in breast cancer aggressiveness.

Contact with dense collagen I (Col1) can induce collective invasion of triple negative breast cancer (TNBC) cells and transcriptional signatures linked to poor patient prognosis. However, this response is heterogeneous and not well understood. Using phenotype-guided sequencing analysis of invasive vs.

A senescence restriction point acting on chromatin integrates oncogenic signals.

We identify a senescence restriction point (SeRP) as a critical event for cells to commit to senescence. The SeRP integrates the intensity and duration of oncogenic stress, keeps a memory of previous stresses, and combines oncogenic signals acting on different pathways by modulating chromatin accessibility. Chromatin regions opened upon commitment to senescence are enriched in nucleolar-associated domains, which are gene-poor regions enriched in repeated sequences.

Targeting ribosome biogenesis reinforces ERK-dependent senescence in pancreatic cancer.

Pancreatic adenocarcinomas (PDAC) often possess mutations in K-Ras that stimulate the ERK pathway. Aberrantly high ERK activation triggers oncogene-induced senescence, which halts tumor progression. Here we report that low-grade pancreatic intraepithelial neoplasia displays very high levels of phospho-ERK consistent with a senescence response.

Divergent iron-regulatory states contribute to heterogeneity in breast cancer aggressiveness.

Primary tumors with similar mutational profiles can progress to vastly different outcomes where transcriptional state, rather than mutational profile, predicts prognosis. A key challenge is to understand how distinct tumor cell states are induced and maintained. In triple negative breast cancer cells, invasive behaviors and aggressive transcriptional signatures linked to poor patient prognosis can emerge in response to contact with collagen type I.

The consistency of exploration behaviours across life stages in a native Australian rodent, the fawn-footed mosaic-tailed rat Melomys cervinipes.

Many species show inter-individual variation in exploratory behaviours that are consistent over time, reflecting a personality. Differences in exploration can affect how individuals acquire resources and use their environment. However, few studies have considered whether exploratory behaviours are consistent across developmental life stages, such as when individuals disperse out the natal territory or when they become sexually mature.

The NAMPT Inhibitor FK866 Increases Metformin Sensitivity in Pancreatic Cancer Cells.

Pancreatic cancer (pancreatic ductal adenocarcinoma: PDAC) is one of the most aggressive neoplastic diseases. Metformin use has been associated with reduced pancreatic cancer incidence and better survival in diabetics. Metformin has been shown to inhibit PDAC cells growth and survival, both in vitro and in vivo.

Both age and experience are important for successful problem solving in juvenile fawn-footed mosaic-tailed rats Melomys cervinipes.

Problem solving ability is affected by many factors, including physiology, personality, and cognition. However, how age and experience influence problem-solving ability during development is harder to untangle. We tested how age and experience affected problem solving in a native Australian rodent, the fawn-footed mosaic-tailed rat Melomys cervinipes.

Problem solving in fawn-footed mosaic-tailed rats Melomys cervinipes is not significantly influenced by maternal care or genetic effects.

Innovative problem solving is thought to be a flexible trait that allows animals to adjust to changing or challenging environmental conditions. However, it is not known how problem solving develops during an animal's early life, or whether it may have a heritable component. We investigated whether maternal genetic and nongenetic effects influenced problem-solving ability in a native Australian rodent, the fawn-footed mosaic-tailed rat Melomys cervinipes.

Corticosterone Metabolite Concentration Is Not Related to Problem Solving in the Fawn-Footed Mosaic-Tailed Rat .

Animals can respond physiologically, such as by adjusting glucocorticoid hormone concentrations, to sudden environmental challenges. These physiological changes can then affect behavioural and cognitive responses. While the relationships between adrenocortical activity and behaviour and cognition are well documented, results are equivocal, suggesting species-specific responses.

A hydride transfer complex reprograms NAD metabolism and bypasses senescence.

Metabolic rewiring and redox balance play pivotal roles in cancer. Cellular senescence is a barrier for tumorigenesis circumvented in cancer cells by poorly understood mechanisms. We report a multi-enzymatic complex that reprograms NAD metabolism by transferring reducing equivalents from NADH to NADP.

Memory enhances problem solving in the fawn-footed mosaic-tailed rat Melomys cervinipes.

Problem solving is important for survival, allowing animals to access novel food resources or escape from predators. It was originally thought to rely on an animal's intelligence; however, studies examining the relationship between individual cognitive ability and problem solving performance show mixed results, and studies are often restricted to only one cognitive and one problem solving task. We investigated the relationship between general cognitive ability and problem solving across multiple tasks in the fawn-footed mosaic-tailed rat Melomys cervinipes.

Phenylethynylbenzyl-modified biguanides inhibit pancreatic cancer tumor growth.

We present the design and synthesis of a small library of substituted biguanidium salts and their capacity to inhibit the growth of pancreatic cancer cells. We first present their in vitro and membrane activity, before we address their mechanism of action in living cells and in vivo activity. We show that phenylethynyl biguanidium salts possess higher ability to cross hydrophobic barriers, improve mitochondrial accumulation and anticancer activity.

Problem Solving in Animals: Proposal for an Ontogenetic Perspective.

Problem solving, the act of overcoming an obstacle to obtain an incentive, has been studied in a wide variety of taxa, and is often based on simple strategies such as trial-and-error learning, instead of higher-order cognitive processes, such as insight. There are large variations in problem solving abilities between species, populations and individuals, and this variation could arise due to differences in development, and other intrinsic (genetic, neuroendocrine and aging) and extrinsic (environmental) factors. However, experimental studies investigating the ontogeny of problem solving are lacking.

Characteristics and outcomes of COVID-19 patients in New York City's public hospital system.

Background: New York City (NYC) bore the greatest burden of COVID-19 in the United States early in the pandemic. In this case series, we describe characteristics and outcomes of racially and ethnically diverse patients tested for and hospitalized with COVID-19 in New York City's public hospital system.

Methods: We reviewed the electronic health records of all patients who received a SARS-CoV-2 test between March 5 and April 9, 2020, with follow up through April 16, 2020.

Characteristics and Outcomes of COVID-19 Patients in New York City's Public Hospital System.

Background New York City (NYC) has borne the greatest burden of COVID-19 in the United States, but information about characteristics and outcomes of racially/ethnically diverse individuals tested and hospitalized for COVID-19 remains limited. In this case series, we describe characteristics and outcomes of patients tested for and hospitalized with COVID-19 in New York City's public hospital system. Methods We reviewed the electronic health records of all patients who received a SARS-CoV-2 test between March 5 and April 9, 2020, with follow up through April 16, 2020.

A Phone Call Away: New York's Hotline And Public Health In The Rapidly Changing COVID-19 Pandemic.

In early March 2020 an outbreak of coronavirus disease 2019 (COVID-19) in New York City exerted sudden and extreme pressures on emergency medical services and quickly changed public health policy and clinical guidance. Recognizing this, New York City Health + Hospitals established a clinician-staffed COVID-19 hotline for all New Yorkers. The hotline underwent three phases as the health crisis evolved.

Innovation in a native Australian rodent, the fawn-footed mosaic-tailed rat (Melomys cervinipes).

Innovation is the ability to use a new behaviour, or use an existing behaviour in a new context. Innovation, as an aspect of behavioural flexibility, could be important for allowing animals to cope with rapid environmental changes. Surprisingly, few studies have focused on how innovation ability is affected by task complexity.

Phosphorylation of SOCS1 Inhibits the SOCS1-p53 Tumor Suppressor Axis.

Expression of the suppressor of cytokine signaling-1 (SOCS1) is inactivated in hematopoietic and solid cancers by promoter methylation, miRNA-mediated silencing, and mutations. Paradoxically, SOCS1 is also overexpressed in many human cancers. We report here that the ability of SOCS1 to interact with p53 and regulate cellular senescence depends on a structural motif that includes tyrosine (Y)80 in the SH2 domain of SOCS1.

Ribosomal protein RPL22/eL22 regulates the cell cycle by acting as an inhibitor of the CDK4-cyclin D complex.

Senescence is a tumor suppressor program characterized by a stable growth arrest while maintaining cell viability. Senescence-associated ribogenesis defects (SARD) have been shown to regulate senescence through the ability of the ribosomal protein S14 (RPS14 or uS11) to bind and inhibit the cyclin-dependent kinase 4 (CDK4). Here we report another ribosomal protein that binds and inhibits CDK4 in senescent cells: L22 (RPL22 or eL22).

The senescence-associated secretory phenotype and its regulation.

The senescence-associated secretory phenotype (SASP) defines the ability of senescent cells to express and secrete a variety of extracellular modulators that includes cytokines, chemokines, proteases, growth factors and bioactive lipids. The role of the SASP depends on the context. The SASP reinforces the senescent cell cycle arrest, stimulates the immune-mediated clearance of potentially tumorigenic cells, limits fibrosis and promotes wound healing and tissue regeneration.

Circumventing senescence is associated with stem cell properties and metformin sensitivity.

Most cancers arise in old individuals, which also accumulate senescent cells. Cellular senescence can be experimentally induced by expression of oncogenes or telomere shortening during serial passage in culture. In vivo, precursor lesions of several cancer types accumulate senescent cells, which are thought to represent a barrier to malignant progression and a response to the aberrant activation of growth signaling pathways by oncogenes (oncogene toxicity).

Senescence-associated ribosome biogenesis defects contributes to cell cycle arrest through the Rb pathway.

Cellular senescence is a tumour suppressor programme characterized by a stable cell cycle arrest. Here we report that cellular senescence triggered by a variety of stimuli leads to diminished ribosome biogenesis and the accumulation of both rRNA precursors and ribosomal proteins. These defects were associated with reduced expression of several ribosome biogenesis factors, the knockdown of which was also sufficient to induce senescence.

How Should We Judge the Ethics of Illustrations in Graphic Medicine Novels?

This essay argues that we should judge the illustrations in a graphic novel (often a memoir) in the context of the entire work. Judging a work on its emotive effects and the values it expresses, we can consider the ways a graphic novel represents the experience of illness, disability, or injury.

Orchidopexy in children with Prader-Willi syndrome: Results of a long-term follow-up study.

Introduction: Prader-Willi syndrome (PWS) is a rare (1:20.000) genetic condition affecting both males and females. Among other features, in boys, the syndrome is characterized by cryptorchidism in 86-100% of cases, hypogonadism, delayed puberty and infertility.