Self-assembly of a peptide sequence, EKKE, composed of exclusively charged amino acids: Role of charge in morphology and lead binding.

The self-assembly of peptides is influenced by their amino acid sequence and other factors including pH, charge, temperature, and solvent. Herein, we explore whether a four-residue sequence, EKKE, consisting of exclusively charged amino acids shows the propensity to form self-assembled ordered nanostructures and whether the overall charge plays any role in morphological and functional properties. From a combination of experimental data provided by Thioflavin T fluorescence, Congo red absorbance, circular dichroism spectroscopy, dynamic light scattering, field emission-scanning electron microscopy, atomic force microscopy, and confocal microscopy, it is clear that the all-polar peptide and charged EKKE sequence shows a pH-dependent tendency to form amyloid-like structures, and the self-assembled entities under acidic, basic and neutral conditions exhibit morphological variation. Additionally, the ability of the self-assembled amyloid nanostructures to bind to the toxic metal, lead (Pb2+ ), was demonstrated from the analysis of the ultraviolet absorbance and X-ray photoelectron spectroscopy data. The modulation at the sequence level for the amyloid-forming EKKE scaffold can further extend its potential role not only in the remediation of other toxic metals but also towards biomedical applications.

DRGD-linked charged EKKE dimeric dodecapeptide: pH-based amyloid nanostructures and their application in lead and uranium binding.

Peptides have been reported to undergo self-assembly into diverse nanostructures, influenced by several parameters, including their amino acid sequence, pH, charge, solvent, and temperature. Inspired by natural systems, researchers have developed biomimetic peptides capable of self-assembling into supramolecular functional structures. The present study explored a newly designed peptide sequence, EKKEDRGDEKKE, where E = glutamic acid, K = lysine, D = aspartic acid, G = glycine, and R = arginine, with a metal binding DRGD sequence incorporated between the exclusively charged EKKE peptide. We investigated the formation and the potential of the EKKEDRGDEKKE peptide in retaining the structure and morphology adopted by the individual EKKE peptide. According to a combination of experimental techniques such as thioflavin T fluorescence, field emission-scanning electron microscopy, atomic force microscopy, and circular dichroism, it was evident that the EKKEDRGDEKKE peptide displayed a pH-dependent propensity to adopt amyloid-like structures. Furthermore, the self-assembled entities formed under acidic, basic, and neutral conditions exhibited morphological variations, which resembled that observed for the exclusively charged EKKE peptide. Furthermore, the incorporation of the functional DRGD motif resulted in promising binding to two toxic metal ions, lead (Pb) and uranium (U), as evidenced by a range of spectroscopic techniques, including UV-visible spectroscopy, atomic absorption spectroscopy, fluorescence spectroscopy, and X-ray photoelectron spectroscopy. The use of the amyloid-forming EKKEDRGDEKKE scaffold can also be extended to potential biomedical applications.

Physician behaviors associated with increased physician and nurse communication during bedside interdisciplinary rounds.

BACKGROUND: Effective team communication during interdisciplinary rounds (IDRs) is a hallmark of safe, efficient, patient-centered care. However, there is limited understanding of optimal IDR structures and procedures. OBJECTIVE: This study aimed to analyze direct observations of physician and nurse interactions during bedside IDR to identify behaviors associated with increased interprofessional communication. DESIGNS, SETTINGS AND PARTICIPANTS: Trained observers audited general medicine ward rounds at an academic medical center using a standardized tool to record physician and nurse behavior and communication in 1007 patient encounters in October 2019 to March 2020. RESULTS: There were significant differences in physician and nurse interaction time among physicians with different levels of training, with attendings demonstrating higher interaction time than residents (5.4 ± 4.6 vs. 4.3 ± 3.7 min, p = .02) and interns or medical students (3.0 ± 3.2 min, p = .002). Attendings were more likely to initiate a conversation about nurse concerns (76.9%) compared to residents (67.9%) and interns or medical students (59.3%, p = .03). Early nurse participation in bedside visits was associated with increased physician and nurse interaction time (5.0 ± 4.6 vs. 1.9 ± 1.7 min, p < .001) and physician initiative to ask about nurse concerns (74.8% vs. 64.3%, p = .04). In addition, physician initiative to ask the nurse for concerns rather than waiting for the nurse to offer concerns without being prompted was associated with a subsequent conversation about those concerns (74.5% vs. 61.8%, p < .001) and the physician asking about patient or family concerns (94.2% vs. 88.4%, p = .01). CONCLUSIONS: Implementing IDR structures and procedures that promote attending physician involvement, physician initiative, and early nurse participation could optimize interdisciplinary communication and quality of care.

Study on the SFRP4 gene polymorphism and expression in prostate cancer.

Prostate cancer is a heterogeneous disease and considered to be the most commonly diagnosed cancer. SFRP4 gene acts as Wnt antagonist in the Wnt signalling pathway, thereby playing an important role in carcinogenesis. The aim of the present study was to investigate two single-nucleotide polymorphisms: c.958 C>A (rs1802073) and c.1019 G>A (rs1802074) in the SFRP4 gene and its expression in prostate cancer. A sample size of 100 cases and 100 age-matched controls were recruited for the study. Statistical analysis revealed the heterozygous GA genotype of rs1802074 significantly increased in cases when compared to controls. Analysis of sFRP4 expression based on the genotypes showed a significantly increased expression for the heterozygous GA and homozygous AA genotypes in cases when compared to the controls. Fold change was calculated using 2-ΔΔCT method and the results showed that there were a 3.4 and 4.5 fold increase in the sFRP4 expression for GA and AA genotypes, respectively. Our results suggest that the rs1802074 polymorphism in SFRP4 gene may be associated with the risk of prostate cancer.

Induction of Short-Term Sensitization by an Aversive Chemical Stimulus in Zebrafish Larvae.

Larval zebrafish possess a number of molecular and genetic advantages for rigorous biological analyses of learning and memory. These advantages have motivated the search for novel forms of memory in these animals that can be exploited for understanding the cellular and molecular bases of vertebrate memory formation and consolidation. Here, we report a new form of behavioral sensitization in zebrafish larvae that is elicited by an aversive chemical stimulus [allyl isothiocyanate (AITC)] and that persists for ≥30 min. This form of sensitization is expressed as enhanced locomotion and thigmotaxis, as well as elevated heart rate. To characterize the neural basis of this nonassociative memory, we used transgenic zebrafish expressing the fluorescent calcium indicator GCaMP6 (Chen et al., 2013); because of the transparency of larval zebrafish, we could optically monitor neural activity in the brain of intact transgenic zebrafish before and after the induction of sensitization. We found a distinct brain area, previously linked to locomotion, that exhibited persistently enhanced neural activity following washout of AITC; this enhanced neural activity correlated with the behavioral sensitization. These results establish a novel form of memory in larval zebrafish and begin to unravel the neural basis of this memory.

The CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis.

Bone is one of the most common sites for metastasis across cancers. Cancer cells that travel through the vasculature and invade new tissues can remain in a non-proliferative dormant state for years before colonizing the metastatic site. Switching from dormancy to colonization is the rate-limiting step of bone metastasis. Here we develop an ex vivo co-culture method to grow cancer cells in mouse bones to assess cancer cell proliferation using healthy or cancer-primed bones. Profiling soluble factors from conditioned media identifies the chemokine CXCL5 as a candidate to induce metastatic colonization. Additional studies using CXCL5 recombinant protein suggest that CXCL5 is sufficient to promote breast cancer cell proliferation and colonization in bone, while inhibition of its receptor CXCR2 with an antagonist blocks proliferation of metastatic cancer cells. This study suggests that CXCL5 and CXCR2 inhibitors may have efficacy in treating metastatic bone tumors dependent on the CXCL5/CXCR2 axis.

Hodgkin-Huxley Neuron and FPAA Dynamics.

We present the experimental silicon results on the dynamics of a Hodgkin-Huxley neuron implemented on a reconfigurable platform. The circuit has been inspired by the similarity between biology and silicon, by modeling ion channels and their time constants. Another significant motivation behind this paper is to make the system available to circuit designers as well as users in the neuroscience community. The open-source tool infrastructure and a remote system ease the accessibility of our system to a number of users. We demonstrate the reproducibility of the results by replicating the dynamics across different boards along with responses from different inputs and with different parameters. The reconfigurability enables one to make use of a single primary design to obtain a variety of results. The measurements are taken from the system compiled on a field programmable analog array fabricated on a 350-nm process.