The cylindrical chaperonin GroEL and its lid-shaped cofactor GroES of Escherichia coli have an essential role in assisting protein folding by transiently encapsulating non-native substrate in an ...ATP-regulated mechanism. It remains controversial whether the chaperonin system functions solely as an infinite dilution chamber, preventing off-pathway aggregation, or actively enhances folding kinetics by modulating the folding energy landscape. Here we developed single-molecule approaches to distinguish between passive and active chaperonin mechanisms. Using low protein concentrations (100pM) to exclude aggregation, we measured the spontaneous and GroEL/ES-assisted folding of double-mutant maltose binding protein (DM-MBP) by single-pair fluorescence resonance energy transfer and fluorescence correlation spectroscopy. We find that GroEL/ES accelerates folding of DM-MBP up to 8-fold over the spontaneous folding rate. Accelerated folding is achieved by encapsulation of folding intermediate in the GroEL/ES cage, independent of repetitive cycles of protein binding and release from GroEL. Moreover, photoinduced electron transfer experiments provided direct physical evidence that the confining environment of the chaperonin restricts polypeptide chain dynamics. This effect is mediated by the net-negatively charged wall of the GroEL/ES cavity, as shown using the GroEL mutant EL(KKK2) in which the net-negative charge is removed. EL(KKK2)/ES functions as a passive cage in which folding occurs at the slow spontaneous rate. Taken together our findings suggest that protein encapsulation can accelerate folding by entropically destabilizing folding intermediates, in strong support of an active chaperonin mechanism in the folding of some proteins. Accelerated folding is biologically significant as it adjusts folding rates relative to the speed of protein synthesis.
Hypoxia, a characteristic trait of Glioblastoma (GBM), is known to cause resistance to chemo-radiation treatment and is linked with poor survival. There is hence an urgent need to non-invasively ...characterize tumor hypoxia to improve GBM management. We hypothesized that (a) radiomic texture descriptors can capture tumor heterogeneity manifested as a result of molecular variations in tumor hypoxia, on routine treatment naïve MRI, and (b) these imaging based texture surrogate markers of hypoxia can discriminate GBM patients as short-term (STS), mid-term (MTS), and long-term survivors (LTS). 115 studies (33 STS, 41 MTS, 41 LTS) with gadolinium-enhanced T1-weighted MRI (Gd-T1w) and T2-weighted (T2w) and FLAIR MRI protocols and the corresponding RNA sequences were obtained. After expert segmentation of necrotic, enhancing, and edematous/nonenhancing tumor regions for every study, 30 radiomic texture descriptors were extracted from every region across every MRI protocol. Using the expression profile of 21 hypoxia-associated genes, a hypoxia enrichment score (HES) was obtained for the training cohort of 85 cases. Mutual information score was used to identify a subset of radiomic features that were most informative of HES within 3-fold cross-validation to categorize studies as STS, MTS, and LTS. When validated on an additional cohort of 30 studies (11 STS, 9 MTS, 10 LTS), our results revealed that the most discriminative features of HES were also able to distinguish STS from LTS (p = 0.003).
Microfluidic-based manipulation of particles is of great interest due to the insight it provides into the physics of hydrodynamic forces. Here, we study a particle-size-dependent phenomenon based on ...differential inertial focusing that utilizes the flow characteristics of curved, low aspect ratio (channel width ≫ height), microfluidic channels. We report the emergence of two focusing points along the height of the channel (z-plane), where different sized particles are focused and ordered in evenly spaced trains at correspondingly different lateral positions within the channel cross-section. We applied the system for continuous ordering and separation of suspension particles.
The study was undertaken to assess the phytoremediation potential of four plants (
Sida acuta, Ricinus communis, Calotropis procera, Cassia fistula) growing at a tannery sludge disposal site. Results ...showed that maximum amount of K, Fe and Ni was associated with residual fraction, whereas, Zn, Mn, Cr, Pb, Cd and Co was found in Fe–Mn oxide fraction. Cu and Na were mostly associated with organic matter and carbonate fraction, respectively. The results demonstrated that the levels of accumulation of metals was found high in all the studied plants and followed the order;
C. procera
>
S. acuta
>
R. communis
=
C. fistula. The principal components analysis (PCA) revealed that translocation behavior of Cu, Zn and Mn, Cr were found similar in the plants. Correlation analysis between metal accumulation in the plants with DTPA extractable metals emphasized that
S. acuta and
C. fistula provide better value of correlation for most of the tested metals. The values of transfer factor were also found high for most of the tested metals in the plants of
S. acuta. Overall, the plants of
S. acuta and
C. fistula were found suitable for the decontamination of most of the metals from tannery waste contaminated sites.
Abstract
Background
There are many ways that students and trainees learn to talk about patients. The way trainees and physicians use language during clinical care is important, as labeling patients ...can have adverse effects on patient safety. Communication is considered a core competency by The Accreditation Council on Graduate Medical Education (ACGME). Past research has shown that participants in narrative medicine curricula report developing stronger communication skills however it is not clear how these workshops motivated trainees to use language differently during patient care. To explore this, we interviewed second-year residents in academic year 19–20 about their experiences both in participating in narrative medicine workshops and giving patient care.
Methods
The framing context for this constructivist thematic analysis is a series of narrative medicine workshops facilitated for interns in an internal medicine residency program at a large academic medical center during the 18–19 academic year. We developed a semi-structured interview study that allowed residents to reflect on their experiences in these workshops. Eighteen out of 60 residents (30%) were interviewed.
Results
We found that sessions regarding language use in patient care shaped how interns thought about and used language during clinical work, a finding that arose spontaneously during interviews.
Conclusions
Our research suggests that workshops aimed specifically at addressing the use of language in healthcare can have meaningful impact on trainees. Our study makes a unique contribution to the scholarship by suggesting that training in narrative medicine can lead to a change in the way that trainees use language during their clinical work.
Podocyte injury is an early feature of diabetic nephropathy (DN). Recently, urinary exosomal Wilm's tumor-1 protein (WT1), shed by renal epithelial cells, has been proposed as a novel biomarker for ...podocyte injury. However, its usefulness as biomarker for early diabetic nephropathy has not been verified yet. We investigated urinary exosomal WT1 in type-1 diabetic patients to confirm its role as a non-invasive biomarker for predicting early renal function decline.
The expression of WT1 protein in urinary exosomes from spot urine samples of type-1 diabetes mellitus patients (n = 48) and healthy controls (n = 25) were analyzed. Patients were divided based on their urinary albumin excretion, ACR (mg/g creatinine) into non- proteinuria group (ACR<30 mg/g, n = 30) and proteinuria group (ACR>30 mg/g, n = 18). Regression analysis was used to assess the association between urinary exosomal levels of WT1 with parameters for renal function. Receiver Operating Characteristic (ROC) curve analysis was used to determine the diagnostic performance of exosomal WT-1.
WT1 protein was detected in 33 out of 48 diabetic patients and in only 1 healthy control. The levels of urinary exosomal WT1 protein is significantly higher (p = 0.001) in patients with proteinuria than in those without proteinuria. In addition, all the patients with proteinuria but only half of the patients without proteinuria were positive for exosomal WT1. We found that the level of exosomal WT1 were associated with a significant increase in urine protein-to-creatinine ratio, albumin-to-creatinine ratio, and serum creatinine as well as a decline in eGFR. Furthermore, patients exhibiting WT1-positive urinary exosomes had decreased renal function compared to WT1-negative patients. ROC analysis shows that WT-1 effectively predict GFR<60 ml. min-1/1.73 m(2).
The predominant presence of WT1 protein in urinary exosomes of diabetic patients and increase in its expression level with decline in renal function suggest that it could be useful as early non-invasive marker for diabetic nephropathy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Introduction Most common type of hair loss is androgenetic alopecia. Orentreich's donor dominance theory and the definition of safe donor area are the theoretical foundation of modern hair ...transplantation. In safe donor area no progression of permanent hair loss occurs. Its knowledge is important to prevent loss of transplanted hair. Estimation is not tailored to every patient, also in early stages, the margins are assumed to be free from future hair loss. Our study is an attempt to find and establish a relationship between safe zone dimensions and other standard scalp dimensions, and effectively predict the complete safe zone in early stages of hair loss. Materials and Methods From July to December 2022, the first 100 patients with Norwood IV onwards of hair loss were included. Then, the distance between the vertex and the point of change in occipital hair quality and density was measured, and from this point till occipital protuberance were taken. The ratio between the two was taken. In the next 100 patients of Norwood II to IVa, the applicability of the new ratio to assess the permanent zone was used. Results Ratio method takes into account the patient's measurements, that is, permanent zone and total distance from vertex occiput. The ratio range we got is: Permanent zone: total distance from vertex to occiput: 0.43–0.53 Therefore, the permanent zone would be equal to = total distance from vertex to occiput × 0.43–0.53. With the lower limit being the occiput. Over 90% of the patients did not have significant reduction in density of transplanted hair. Conclusion The authors suggest the use of this ratio method to determine the dimensions of the permanent zone especially in patients with early grades of hair loss as per the Norwood scale. It is a simple, effective, and easily applicable concept that can ensure long-lasting results in patients undergoing hair transplants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Gallbladder cancer (GBC) is a lethal disease with surgical resection as the only curative treatment. However, many patients are ineligible for surgery, and current adjuvant treatments exhibit limited ...effectiveness. Next-generation sequencing has improved our understanding of molecular pathways in cancer, sparking interest in microRNA-based gene regulation. The aim of the study is to identify dysregulated miRNAs in GBC and investigate their potential as therapeutic tools for effective and targeted treatment strategies. GBC and control tissue samples were sequenced for miRNA expression using the Illumina HiSeq platform. Biological processes and related pathways were determined using the Panther and Gene Ontology databases. 439 significantly differentially expressed miRNAs were identified; 19 of them were upregulated and 29 were downregulated. Key enriched biological processes included immune cell apoptosis, endoplasmic reticulum (ER) overload response, and negative regulation of the androgen receptor (AR) signaling pathway. Panther analysis revealed the insulin-like growth factor (IGF)-mitogen activated protein kinases (MAPK) cascade, p38 MAPK pathway, p53 pathway, and FAS (a subgroup of the tumor necrosis factor receptor) signaling pathway as highly enriched among dysregulated miRNAs. Kirsten rat sarcoma virus (KRAS), AR, and interferon gamma (IFN-γ) pathways were identified among the key pathways potentially amenable to targeted therapy. We concluded that a combination approach involving miRNA-based interventions could enhance therapeutic outcomes. Our research emphasizes the importance of precision medicine, targeting pathways using sense and anti-sense miRNAs as potential therapies in GBC.
Electroencephalogram (EEG) signals are progressively growing data widely known as biomedical big data, which is applied in biomedical and healthcare research. The measurement and processing of EEG ...signal result in the probability of signal contamination through artifacts which can obstruct the important features and information quality existing in the signal. To diagnose the human neurological diseases like epilepsy, tumors, and problems associated with trauma, these artifacts must be properly pruned assuring that there is no loss of the main attributes of EEG signals. In this paper, the latest and updated information in terms of important key features are arranged and tabulated extensively by considering the 60 published technical research papers based on EEG artifact removal method. Moreover, the paper is a review vision about the works in the area of EEG applied to healthcare and summarizes the challenges, research gaps, and opportunities to improve the EEG big data artifacts removal more precisely.
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