Large-scale dependency and drug screens characterize the therapeutic vulnerabilities of Multiple Myeloma with 1q.

The development of targeted therapy for patients with multiple myeloma (MM) is hampered by the low frequency of actionable genetic abnormalities. Gain or amplification of chromosome 1q (1q+) is the most frequent arm-level copy number gain in patients with MM and is associated with higher risk of progression and death despite recent therapeutic advances. Thus, developing targeted therapy for MM patients with 1q+ stands to benefit a large portion of patients in need of more effective management.

Specific and potent inhibition of steroid hormone pre-receptor regulator AKR1C2 by perfluorooctanoic acid: Implications for androgen metabolism.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental pollutants that are highly stable synthetic organofluorine compounds. One congener perfluorooctanoic acid (PFOA) can be detected in nearly all humans and is recognized as an endocrine disrupting chemical (EDC). EDCs disrupt hormone synthesis and metabolism and receptor function.

Understanding Polysulfide-Mediated Papain Inhibition and Differentiating between Disulfide vs Persulfide Formation.

Protein cysteine residues are sensitive to redox-regulating molecules, including reactive sulfur species (RSS). As an important member of the RSS family, polysulfides are known to react with protein cysteines to form persulfides and disulfides, both affecting protein functions. In this work, we studied how polysulfides could impact cysteine proteases through careful mechanistic and kinetic studies.

Harnessing Nature-Inspired Catechol Amino Acid to Engineer Sticky Proteins and Bacteria.

3,4-Dihydroxy-L-phenylalanine (DOPA) serves as a post-translational modification amino acid present in mussel foot proteins. Mussels exploit the exceptional adhesive properties of DOPA to adhere to a wide range of surfaces. This study presents the development of sticky proteins and bacteria through the site-specific incorporation of DOPA using Genetic Code Expansion Technology.

The interferon/STAT1 signaling axis is a common feature of tumor-initiating cells in breast cancer.

Unlabelled: A tumor cell subpopulation of tumor-initiating cells (TIC), or "cancer stem cells", are associated with therapeutic resistance, as well as both local and distant recurrence. Enriched populations of TIC are identified by markers including aldehyde dehydrogenase (ALDH1) activity, the cell surface marker combination CD44 /CD24 , or fluorescent reporters for signaling pathways that regulate TIC function. We showed previously that S ignal T ransducer and A ctivator of T ranscription (STAT)-mediated transcription allows enrichment for TIC in claudin-low models of human triple-negative breast cancer using a STAT-responsive reporter.

Unleashing the potential of noncanonical amino acid biosynthesis to create cells with precision tyrosine sulfation.

Despite the great promise of genetic code expansion technology to modulate structures and functions of proteins, external addition of ncAAs is required in most cases and it often limits the utility of genetic code expansion technology, especially to noncanonical amino acids (ncAAs) with poor membrane internalization. Here, we report the creation of autonomous cells, both prokaryotic and eukaryotic, with the ability to biosynthesize and genetically encode sulfotyrosine (sTyr), an important protein post-translational modification with low membrane permeability. These engineered cells can produce site-specifically sulfated proteins at a higher yield than cells fed exogenously with the highest level of sTyr reported in the literature.

Biosynthesis and Genetic Incorporation of 3,4-Dihydroxy-L-Phenylalanine into Proteins in Escherichia coli.

While 20 canonical amino acids are used by most organisms for protein synthesis, the creation of cells that can use noncanonical amino acids (ncAAs) as additional protein building blocks holds great promise for preparing novel medicines and for studying complex questions in biological systems. However, only a small number of biosynthetic pathways for ncAAs have been reported to date, greatly restricting our ability to generate cells with ncAA building blocks. In this study, we report the creation of a completely autonomous bacterium that utilizes 3,4-dihydroxy-L-phenylalanine (DOPA) as its 21st amino acid building block.

Effect of wetland plants and bacterial inoculation on dissipation of phenanthrene.

This study attempts to evaluate the capacity of wetland plants' ability to dissipate phenanthrene (PHE) under waterlogged conditions. The results indicate that Typha latifolia and Vetiveria zizanioides may efficiently degrade PHE, and were much more effective when under combined plant cultivation with the inoculation of Pseudomonas frederiksbergensis (ATCC BAA-257) . Concentrations of PHE declined from 200 to less than 52 mg kg in all treatments with plant cultivation.

Intermittent vibration protects aged muscle from mechanical and oxidative damage under prolonged compression.

Deep tissue pressure ulcers, a serious clinical challenge originating in the muscle layer, are hardly detectable at the beginning. The challenge apparently occurs in aged subjects more frequently. As the ulcer propagates to the skin surface, it becomes very difficult to manage and can lead to fatal complications.

Cortisol in human milk predicts child BMI.

Objective: Breastfeeding has been linked to lower rates of childhood obesity. Human milk contains cortisol, known to regulate glucose storage and metabolism. The aim of this study was to to test the hypothesis that early exposure to cortisol in human breast milk helps to modulate infant body mass index (BMI) trajectories over the first 2 years of life.

Histone deacetylase 6-mediated selective autophagy regulates COPD-associated cilia dysfunction.

Chronic obstructive pulmonary disease (COPD) involves aberrant airway inflammatory responses to cigarette smoke (CS) that are associated with epithelial cell dysfunction, cilia shortening, and mucociliary clearance disruption. Exposure to CS reduced cilia length and induced autophagy in vivo and in differentiated mouse tracheal epithelial cells (MTECs). Autophagy-impaired (Becn1+/- or Map1lc3B-/-) mice and MTECs resisted CS-induced cilia shortening.

Root exudates of wetland plants influenced by nutrient status and types of plant cultivation.

The present study investigated the amounts of root exudates and composition of organic acids released from two wetland plants (Typha latifolia and Vetiver zizanioides) under two nutrient treatments: low level (0.786 mM N and 0.032 mM P) and high level (7.

Reliability of the Chinese version of the perceived family burden scale.

The study examined reliability of the 24-item Chinese version of the perceived family burden scale (CPFBS), which is a measure of behaviors associated with Chinese people with schizophrenia and the impacts of these behaviors on caregivers and relatives. Many patients with mental illness are returning to the community and living with families. Unfortunately, family members who have to live with the patients experience a sense of burden.