Secreted frizzled related-protein 2 is prognostic for human pancreatic cancer patient survival and is associated with fibrosis.

Pancreatic adenocarcinoma (PDAC) is one of the deadliest cancers, with five-year survival rates of 9%. We hypothesized that secreted frizzled-related protein 2 (SFRP2) may influence stromal growth in pancreatic cancer, since it increases fibrosis and collagen production in non-neoplastic pathologies. We assessed SFRP2 value as a biomarker and assessed its function in PDAC. SFRP2 gene expression in patients with PDAC was analyzed using TCGA data. Disease free survival (DFS) was analyzed using Kaplan Meier test. The effect of KRAS inhibition on SFRP2 expression in PDAC cells was assessed. The associations of stromal content with SFPR2 mRNA and protein with fibrosis were analyzed. The role of SFRP2 in mesenchymal transformation was assessed by western blot in fibroblasts. Of all cancers in TCGA, SFRP2 levels were highest in PDAC, and higher in PDAC than normal tissues (n= 234, p= 0.0003). High SFRP2 levels correlated with decreased DFS (p= 0.0097). KRAS inhibition reduced SFRP2 levels. Spearman correlation was 0.81 between stromal RNA and SFRP2 in human PDAC, and 0.75 between fibrosis and SFRP2 levels in PDAC tumors. SFRP2-treated fibroblasts displayed mesenchymal characteristics. SFRP2 is prognostic for PDAC survival, regulated by KRAS, and associated with PDAC fibrosis.

Peptide Self-Assembly Controlled Photoligation of Polymers.

Highly efficient chemical ligations that operate in water under mild conditions are the foundation of bioorthogonal chemistry. However, the toolbox of suitable reactions is limited. Conventional approaches to expand this toolbox aim at altering the inherent reactivity of functional groups to design new reactions that meet the required benchmarks. Inspired by controlled reaction environments that enzymes provide, we report a fundamentally different approach that makes inefficient reactions highly efficient within defined local environments. Contrasting enzymatically catalyzed reactions, the reactivity controlling self-assembled environment is brought about by the ligation targets themselves─avoiding the use of a catalyst. Targeting [2 + 2] photocycloadditions, which are inefficient at low concentrations and readily quenched by oxygen, short ß-sheet encoded peptide sequences are inserted between a hydrophobic photoreactive styrylpyrene unit and a hydrophilic polymer. In water, electrostatic repulsion of deprotonated amino acid residues governs the formation of small self-assembled structures, which enable a highly efficient photoligation of the polymer, reaching ∼90% ligation within 2 min (0.034 mM). Upon protonation at low pH, the self-assembly changes into 1D fibers, altering photophysical properties and shutting down the photocycloaddition reaction. Using the reversible morphology change, it is possible to switch the photoligation "ON" or "OFF" under constant irradiation simply by varying the pH. Importantly, in dimethylformamide, the photoligation reaction did not occur even at 10-fold higher concentrations (0.34 mM). The self-assembly into a specific architecture, encoded into the polymer ligation target, enables a highly efficient ligation that overcomes the concentration limitations and high oxygen sensitivity of [2 + 2] photocycloadditions.

The Importance of General Surgery Residency Program's Online Presence Varies Among Applicant Groups.

INTRODUCTION: The COVID-19 pandemic necessitated an exclusively virtual 2021 residency application cycle. We hypothesized that residency programs' online presence would have increased utility and influence for applicants. METHODS: Substantial surgery residency website modifications were undertaken in the summer of 2020. Page views were gathered by our institution's information technology office for comparison across years and programs. An anonymous, voluntary, online survey was sent to all interviewed applicants for our 2021 general surgery program match. Five-point Likert-scale questions evaluated applicants' perspective on the online experience. RESULTS: Our residency website received 10,650 page views in 2019 and 12,688 in 2020 (P = 0.14). Page views increased with a greater margin compared to a different specialty residency program's (P < 0.01). From 108 interviewees, 75 completed the survey (69.4%). Respondents indicated our website was satisfactory or very satisfactory compared to other programs (83.9%), and none found it unsatisfactory. Applicants overall stated our institution's online presence impacted their decision to interview (51.6%). Programs' online presence impacted the decision to interview for nonWhite applicants (68%) but significantly less for white applicants (31%, P < 0.03). We observed a trend that those with fewer than this cohort's median interviews (17 or less) put more weight on online presence (65%), compared to those with 18 or greater interviews (35%). CONCLUSIONS: Applicants utilized program websites more during the 2021 virtual application cycle; our data show most applicants depend on institutions' websites to supplement their decision-making; however, there are subgroup differences in the influence online presence has on applicant decisions. Efforts to enhance residency webpages and online resources for candidates may positively influence prospective surgical trainees, and especially those underrepresented in medicine, to decide to interview.

Embedding Peptides into Synthetic Polymers: Radical Ring-Opening Copolymerization of Cyclic Peptides.

Biopolymers such as proteins and nucleic acids are the key building blocks of life. Synthetic polymers have nevertheless revolutionized our everyday life through their robust synthetic accessibility. Combining the unmatched functionality of biopolymers with the robustness of tailorable synthetic polymers holds the promise to create materials that can be designed ad hoc for a wide array of applications. Radical polymerization is the most widely applied polymerization technique in both fundamental science and industrial polymer production. While this polymerization technique is robust and well controlled, it generally yields unfunctional all-carbon backbones. Combinations of natural polymers such as peptides, with synthetic polymers, are thus limited to tethering peptides onto the side chains or chain ends of the latter. This synthetic limitation is a critical restraint, considering that the function of biopolymers is programmed into the sequence of their main chain (i.e., primary structure). Here, we report the radical copolymerization of peptides and synthetic comonomers yielding synthetic polymers with defined peptide sequences embedded into their main chain. Key was the development of a solid-phase peptide synthesis (SPPS) approach to generate synthetic access to peptide conjugates containing allylic sulfides. Following cyclization, the obtained peptide monomers can be readily copolymerized with N,N-dimethylacrylamide (DMA)─controlled by reversible addition-fragmentation chain transfer (RAFT). Importantly, the developed synthetic strategy is compatible with all 20 standard amino acids and uses exclusively standard SPPS chemicals or chemicals accessible in one-step synthesis─prerequisite for widespread and universal application.

Genetics and nutrition impacts on herd productivity in the Northern Australian beef cattle production cycle.

Genetics and nutrition drive herd productivity due to significant impacts on all components of the beef cattle production cycle. In northern Australia, the beef production system is largely extensive and relies heavily on tropical cattle grazing low quality, phosphorus-deficient pastures with seasonal variations in nutritive value. The existing feedlots are predominantly grain-based; providing high-energy rations, faster turn-off and finishing of backgrounded cattle to meet market specifications. This review focusses on the beef cattle production cycle components of maternal nutrition, foetal development, bull fertility, post-natal to weaning, backgrounding, feedlotting, rumen microbes and carcass quality as influenced by genetics and nutrition. This student-driven review identified the following knowledge gaps in the published literature on northern Australian beef cattle production cycle: 1. Long-term benefits and effects of maternal supplementation to alter foetal enzymes on the performance and productivity of beef cattle; 2. Exogenous fibrolytic enzymes to increase nutrient availability from the cell wall and better utilisation of fibrous and phosphorus deficient pasture feedbase during backgrounding; 3. Supplementation with novel encapsulated calcium butyrate and probiotics to stimulate the early development of rumen papillae and enhance early weaning of calves; 4. The use of single nucleotide polymorphisms as genetic markers for the early selection of tropical beef cattle for carcass and meat eating quality traits prior to feedlotting; The review concludes by recommending future research in whole genome sequencing to target specific genes associated with meat quality characteristics in order to explore the development of breeds with superior genes more suited to the North Australian beef industry. Further research into diverse nutritional strategies of phosphorus supplementation and fortifying tropically adapted grasses with protein-rich legumes and forages for backgrounding and supplementing lot-fed beef cattle with omega-3 oil of plant origin will ensure sustainable production of beef with a healthy composition, tenderness, taste and eating quality.