Structured illumination microscopy for cancer identification in diagnostic breast biopsies.

Breast cancer is the second most common cancer diagnosed in women in the US with almost 280,000 new cases anticipated in 2023. Currently, on-site pathology for location guidance is not available during the collection of breast biopsies or during surgical intervention procedures. This shortcoming contributes to repeat biopsy and re-excision procedures, increasing the cost and patient discomfort during the cancer management process.

Regulators of male and female sexual development are critical for the transmission of a malaria parasite.

Malaria transmission to mosquitoes requires a developmental switch in asexually dividing blood-stage parasites to sexual reproduction. In Plasmodium berghei, the transcription factor AP2-G is required and sufficient for this switch, but how a particular sex is determined in a haploid parasite remains unknown. Using a global screen of barcoded mutants, we here identify genes essential for the formation of either male or female sexual forms and validate their importance for transmission.

Drug repurposing: Misconceptions, challenges, and opportunities for academic researchers.

Drug repurposing is promoted as a cost- and time-effective mechanism for providing new medicines. Often, however, there is insufficient consideration by academic researchers of the processes required to ensure that a repurposed drug can be used for a new indication. This may explain the inability of drug repurposing to fulfill its promise.

Evaluation of the binding affinity of E3 ubiquitin ligase ligands by cellular target engagement and in-cell ELISA assay.

The discovery of potent cell-permeable E3 ubiquitin ligase ligands can significantly facilitate the development of proteolysis targeting chimeras (PROTACs). Here, we present a protocol to determine the binding affinity of ligands toward CRBN E3 ubiquitin ligase, using a cellular target engagement mechanism and in-cell ELISA assay. This protocol is easy to establish, with relatively low cost and rapid time frame.

Experimentally Engineered Mutations in a Ubiquitin Hydrolase, UBP-1, Modulate Susceptibility to Artemisinin and Chloroquine in Plasmodium berghei.

As resistance to artemisinins (current frontline drugs in malaria treatment) emerges in Southeast Asia, there is an urgent need to identify the genetic determinants and understand the molecular mechanisms underpinning such resistance. Such insights could lead to prospective interventions to contain resistance and prevent the eventual spread to other regions where malaria is endemic. Reduced susceptibility to artemisinin in Southeast Asia has been primarily linked to mutations in the Kelch-13 gene, which is currently widely recognized as a molecular marker of artemisinin resistance.

Chemical Synthesis and Biological Application of Modified Oligonucleotides.

RNA plays a myriad of roles in the body including the coding, decoding, regulation, and expression of genes. RNA oligonucleotides have garnered significant interest as therapeutics via antisense oligonucleotides or small interfering RNA strategies for the treatment of diseases ranging from hyperlipidemia, HCV, and others. Additionally, the recently developed CRISPR-Cas9 mediated gene editing strategy also relies on Cas9-associated RNA strands.

Body Art Confounding a Case of Breast Cancer.

Background: Heavy metals in tattoo ink can be deposited in axillary lymph nodes, mimicking malignant calcifications. High-density foci in axillary lymph nodes can be the sequelae of a benign or malignant process.

Case Report: A 34-year-old female presented with left breast discomfort.

c-Src/Cav1-dependent activation of the EGFR by Dsg2.

The desmosomal cadherin, desmoglein 2 (Dsg2), is deregulated in a variety of human cancers including those of the skin. When ectopically expressed in the epidermis of transgenic mice, Dsg2 activates multiple mitogenic signaling pathways and increases susceptibility to tumorigenesis. However, the molecular mechanism responsible for Dsg2-mediated cellular signaling is poorly understood.

Palmitoylation of Desmoglein 2 Is a Regulator of Assembly Dynamics and Protein Turnover.

Desmosomes are prominent adhesive junctions present between many epithelial cells as well as cardiomyocytes. The mechanisms controlling desmosome assembly and remodeling in epithelial and cardiac tissue are poorly understood. We recently identified protein palmitoylation as a mechanism regulating desmosome dynamics.

Cell fate determination in cisplatin resistance and chemosensitization.

Understanding the determination of cell fate choices after cancer treatment will shed new light on cancer resistance. In this study, we quantitatively analyzed the individual cell fate choice in resistant UM-SCC-38 head and neck cancer cells exposed to cisplatin. Our study revealed a highly heterogeneous pattern of cell fate choices in UM-SCC-38 cells, in comparison to that of the control, non-tumorigenic keratinocyte HaCaT cells.

A novel member of the let-7 microRNA family is associated with developmental transitions in filarial nematode parasites.

Background: Filarial nematodes are important pathogens in the tropics transmitted to humans via the bite of blood sucking arthropod vectors. The molecular mechanisms underpinning survival and differentiation of these parasites following transmission are poorly understood. microRNAs are small non-coding RNA molecules that regulate target mRNAs and we set out to investigate whether they play a role in the infection event.

The carboxyl tail of connexin32 regulates gap junction assembly in human prostate and pancreatic cancer cells.

Connexins, the constituent proteins of gap junctions, are transmembrane proteins. A connexin (Cx) traverses the membrane four times and has one intracellular and two extracellular loops with the amino and carboxyl termini facing the cytoplasm. The transmembrane and the extracellular loop domains are highly conserved among different Cxs, whereas the carboxyl termini, often called the cytoplasmic tails, are highly divergent.

Palmitoylation of plakophilin is required for desmosome assembly.

Desmosomes are prominent adhesive junctions found in various epithelial tissues. The cytoplasmic domains of desmosomal cadherins interact with a host of desmosomal plaque proteins, including plakophilins, plakoglobin and desmoplakin, which, in turn, recruit the intermediate filament cytoskeleton to sites of cell-cell contact. Although the individual components of the desmosome are known, mechanisms regulating the assembly of this junction are poorly understood.

Novel expression of Haemonchus contortus vaccine candidate aminopeptidase H11 using the free-living nematode Caenorhabditis elegans.

With the problem of parasitic nematode drug resistance increasing, vaccine development offers an alternative sustainable control approach. For some parasitic nematodes, native extracts enriched for specific proteins are highly protective. However, recombinant forms of these proteins have failed to replicate this protection.

Stratifin (14-3-3 σ) limits plakophilin-3 exchange with the desmosomal plaque.

Desmosomes are prominent cell-cell adhesive junctions in stratified squamous epithelia and disruption of desmosomal adhesion has been shown to have dramatic effects on the function and integrity of these tissues. During normal physiologic processes, such as tissue development and wound healing, intercellular adhesion must be modified locally to allow coordinated cell movements. The mechanisms that control junction integrity and adhesive strength under these conditions are poorly understood.

Complications of liver resection: laparoscopic versus open procedures.

Background And Objective: Minimally invasive surgery for liver resection remains controversial. This study was designed to compare open versus laparoscopic surgical approaches to liver resection.

Methods: We performed a single-center retrospective chart review.

Characteristics of atrial tachycardia due to small vs large reentrant circuits after ablation of persistent atrial fibrillation.

Background: While macroreentrant atrial tachycardias (ATs) have been reasonably well described, little is known about small reentrant circuits.

Objective: To compare characteristics of large and small reentrant circuits after ablation of persistent atrial fibrillation.

Methods: Seventy-seven patients (age 61±10 years; left atrium 46±6 mm; ejection fraction 0.

Effect of radiation therapy on permanent pacemaker and implantable cardioverter-defibrillator function.

Background: Radiation therapy's (RT's) effects on cardiac implantable electronic devices (CIEDs) such as implantable cardioverter-defibrillators (ICDs) and pacemakers (PMs) are not well established, leading to device removal or relocation in preparation for RT.

Objective: To determine the effect of scattered RT on CIED performance.

Methods: We analyzed 69 patients--50 (72%) with PMs and 19 (28%) with ICDs--receiving RT at the University of Michigan.

Melanisation of Teladorsagia circumcincta larvae exposed to sunlight: a role for GTP-cyclohydrolase in nematode survival.

Trichostrongylid nematode parasites of livestock inhabit two very different niches during their life-cycle; within the host and free-living in the environment. UV radiation plays a significant role in the survival of free-living, pre-parasitic nematode larvae, with different species exhibiting differing levels of sensitivity. In many eukaryotes, melanisation is a key protective mechanism against UV damage, however there is little information about this process in parasitic nematodes.