The mechanical effects of chemical stimuli on neurospheres.

The formulation of more accurate models to describe tissue mechanics necessitates the availability of tools and instruments that can precisely measure the mechanical response of tissues to physical loads and other stimuli. In this regard, neuroscience has trailed other life sciences owing to the unavailability of representative live tissue models and deficiency of experimentation tools. We previously addressed both challenges by employing a novel instrument called the cantilevered-capillary force apparatus (CCFA) to elucidate the mechanical properties of mouse neurospheres under compressive forces.

Design methodology for catadioptric zoom panoramic optical systems based on image plane bending matched correction.

Zoom panoramic optical systems incorporate a panoramic peripheral vision zoom imaging function, enabling swift wide-area coarse and localized precise detection. These systems find applicability in examining pipes and other internal structures. This study centers on the catadioptric zoom panoramic optical system and its associated optical design method.

A new instrument for interfacial dilational rheology.

We present a new design for an interfacial dilational rheometer that can generate oscillatory dilational strain on a planar air-liquid interface. The strain is generated by a pneumatic mechanism involving a deformable film, which forms a circular barrier that can contract or expand under different pressures. The interfacial stress is measured using a Wilhelmy rod.

Anti-tumor effects of an ID antagonist with no observed acquired resistance.

ID proteins are helix-loop-helix (HLH) transcriptional regulators frequently overexpressed in cancer. ID proteins inhibit basic-HLH transcription factors often blocking differentiation and sustaining proliferation. A small-molecule, AGX51, targets ID proteins for degradation and impairs ocular neovascularization in mouse models.

Histoplasmosis in an off-trail Hiker receiving ustekinumab: Implications for Preventive and diagnostic strategies for patients receiving anti-IL-12/23 therapy.

Ustekinumab, an IL-12/23 inhibitor, is an important agent in treatment of inflammatory bowel disease and psoriasis. Clinical trials have not demonstrated significantly increased infection risk with ustekinumab. We report a case of disseminated histoplasmosis in the setting of ustekinumab and methotrexate following a hike in the Catskill Mountains, a region not commonly associated with .

Development of a cardiac-and-piezoelectric hybrid system for application in drug screening.

In this paper, a cardiac-and-piezoelectric hybrid system is developed for drug screening. The core structure is a polyvinylidene-fluoride piezoelectric membrane that serves as a flexible structure to interact with hiPSC cardiomyocytes and that measures the contraction profile of cardiomyocytes. This design enables the capability of electrically monitoring cardiomyocytes without the aid of an optical system.

L1CAM defines the regenerative origin of metastasis-initiating cells in colorectal cancer.

Metastasis-initiating cells with stem-like properties drive cancer lethality, yet their origins and relationship to primary-tumor-initiating stem cells are not known. We show that L1CAM cells in human colorectal cancer (CRC) have metastasis-initiating capacity, and we define their relationship to tissue regeneration. L1CAM is not expressed in the homeostatic intestinal epithelium, but is induced and required for epithelial regeneration following colitis and in CRC organoid growth.

Publisher Correction: TGF-β orchestrates fibrogenic and developmental EMTs via the RAS effector RREB1.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

TGF-β orchestrates fibrogenic and developmental EMTs via the RAS effector RREB1.

Epithelial-to-mesenchymal transitions (EMTs) are phenotypic plasticity processes that confer migratory and invasive properties to epithelial cells during development, wound-healing, fibrosis and cancer. EMTs are driven by SNAIL, ZEB and TWIST transcription factors together with microRNAs that balance this regulatory network. Transforming growth factor β (TGF-β) is a potent inducer of developmental and fibrogenic EMTs.

ID1 Mediates Escape from TGFβ Tumor Suppression in Pancreatic Cancer.

TGFβ is an important tumor suppressor in pancreatic ductal adenocarcinoma (PDA), yet inactivation of TGFβ pathway components occurs in only half of PDA cases. TGFβ cooperates with oncogenic RAS signaling to trigger epithelial-to-mesenchymal transition (EMT) in premalignant pancreatic epithelial progenitors, which is coupled to apoptosis owing to an imbalance of SOX4 and KLF5 transcription factors. We report that PDAs that develop with the TGFβ pathway intact avert this apoptotic effect via ID1.

Flura-seq identifies organ-specific metabolic adaptations during early metastatic colonization.

Metastasis-initiating cells dynamically adapt to the distinct microenvironments of different organs, but these early adaptations are poorly understood due to the limited sensitivity of in situ transcriptomics. We developed fluorouracil-labeled RNA sequencing (Flura-seq) for in situ analysis with high sensitivity. Flura-seq utilizes cytosine deaminase (CD) to convert fluorocytosine to fluorouracil, metabolically labeling nascent RNA in rare cell populations in situ for purification and sequencing.

Design and analysis of a triple reflection grazing incidence x-ray telescope.

A triple reflection grazing incidence x-ray telescope is proposed and evaluated. This form of an optical system can detect x-ray energy that is close to the optical axis, which solves the problems encountered by traditional Wolter-type systems. In this paper, we also propose a new design method to ensure that the entire telescope structure is compact and integrated.

Identification of the Colicin V Bacteriocin Gene Cluster by Functional Screening of a Human Microbiome Metagenomic Library.

The forces that shape human microbial ecology are complex. It is likely that human microbiota, similarly to other microbiomes, use antibiotics as one way to establish an ecological niche. In this study, we use functional metagenomics to identify human microbial gene clusters that encode for antibiotic functions.

TGF-β Tumor Suppression through a Lethal EMT.

TGF-β signaling can be pro-tumorigenic or tumor suppressive. We investigated this duality in pancreatic ductal adenocarcinoma (PDA), which, with other gastrointestinal cancers, exhibits frequent inactivation of the TGF-β mediator Smad4. We show that TGF-β induces an epithelial-mesenchymal transition (EMT), generally considered a pro-tumorigenic event.

Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist.

The trillions of bacteria that make up the human microbiome are believed to encode functions that are important to human health; however, little is known about the specific effectors that commensal bacteria use to interact with the human host. Functional metagenomics provides a systematic means of surveying commensal DNA for genes that encode effector functions. Here, we examine 3,000 Mb of metagenomic DNA cloned from three phenotypically distinct patients for effectors that activate NF-κB, a transcription factor known to play a central role in mediating responses to environmental stimuli.

Development and utilization of a web-based application as a robust radiology teaching tool (radstax) for medical student anatomy teaching.

Rationale and Objectives: The primary role of radiology in the preclinical setting is the use of imaging to improve students' understanding of anatomy. Many currently available Web-based anatomy programs include either suboptimal or overwhelming levels of detail for medical students.Our objective was to develop a user-friendly software program that anatomy instructors can completely tailor to match the desired level of detail for their curriculum, meets the unique needs of the first- and the second-year medical students, and is compatible with most Internet browsers and tablets.

A systematic analysis of the PARP protein family identifies new functions critical for cell physiology.

The poly(ADP-ribose) polymerase (PARP) family of proteins use NAD(+) as their substrate to modify acceptor proteins with ADP-ribose modifications. The function of most PARPs under physiological conditions is unknown. Here, to better understand this protein family, we systematically analyse the cell cycle localization of each PARP and of poly(ADP-ribose), a product of PARP activity, then identify the knockdown phenotype of each protein and perform secondary assays to elucidate function.

Gene patents: a broken incentives system.

The proliferation of patents on human genes has raised important ethical questions centered on the conflict of patient rights and intellectual property rights. With the Supreme Court's June 2013 decision that altered the patent eligibility of genetic material, it is important to reexamine the ethical implications of gene patents as a concept. Such patents suggest an ownership of genetic material that may hinder access to healthcare and inhibit medical progress.