Unidirectional single-file transport of full-length proteins through a nanopore.

The electrical current blockade of a peptide or protein threading through a nanopore can be used as a fingerprint of the molecule in biosensor applications. However, threading of full-length proteins has only been achieved using enzymatic unfolding and translocation. Here we describe an enzyme-free approach for unidirectional, slow transport of full-length proteins through nanopores. We show that the combination of a chemically resistant biological nanopore, α-hemolysin (narrowest part is ~1.4 nm in diameter), and a high concentration guanidinium chloride buffer enables unidirectional, single-file protein transport propelled by an electroosmotic effect. We show that the mean protein translocation velocity depends linearly on the applied voltage and translocation times depend linearly on length, resembling the translocation dynamics of ssDNA. Using a supervised machine-learning classifier, we demonstrate that single-translocation events contain sufficient information to distinguish their threading orientation and identity with accuracies larger than 90%. Capture rates of protein are increased substantially when either a genetically encoded charged peptide tail or a DNA tag is added to a protein.

Blood plasma supply chain planning to respond COVID-19 pandemic: a case study.

The COVID-19 pandemic causes a severe threat to human lives worldwide. Convalescent plasma as supportive care for COVID-19 is critical in reducing the death rate and staying in hospitals. Designing an efficient supply chain network capable of managing convalescent plasma in this situation seems necessary. Although many researchers investigated supply chains of blood products, no research was conducted on the planning of convalescent plasma in the supply chain framework with specific features of COVID-19. This gap is covered in the current work by simultaneous regular and convalescent plasma flow in a supply chain network. Besides, due to the growing importance of environmental problems, the resulting carbon emission from transportation activities is viewed to provide a green network. In other words, this study aims to plan the integrated green supply chain network of regular and convalescent plasma in the pandemic outbreak of COVID-19 for the first time. The presented mixed-integer multi-objective optimization model determines optimal network decisions while minimizing the total cost and total carbon emission. The Epsilon constraint method is used to handle the considered objectives. The model is applied to a real case study from the capital of Iran. Sensitivity analyses are carried out, and managerial insights are drawn. Based on the obtained results, product demand impacts the objective functions significantly. Moreover, the systems' total carbon emission is highly dependent on the flow of regular plasma. The results also reveal that changing transportation emission unit causes significant variation in the total emission while the total cost remains fixed.

Designing a sustainable reverse supply chain network for COVID-19 vaccine waste under uncertainty.

The vast nationwide COVID-19 vaccination programs are implemented in many countries worldwide. Mass vaccination is causing a rapid increase in infectious and non-infectious vaccine wastes, potentially posing a severe threat if there is no well-organized management plan. This paper develops a mixed-integer mathematical programming model to design a COVID-19 vaccine waste reverse supply chain (CVWRSC) for the first time. The presented problem is based on minimizing the system's total cost and carbon emission. The uncertainty in the tendency rate of vaccination is considered, and a robust optimization approach is used to deal with it, where an interactive fuzzy approach converts the model into a single objective problem. Additionally, a Lagrangian relaxation (LR) algorithm is utilized to deal with the computational difficulty of the large-scale CVWRSC network. The model's practicality is investigated by solving a real-life case study. The results show the gain of the developed integrated network, where the presented framework performs better than the disintegrated vaccine and waste supply chain models. According to the results, vaccination operations and transportation of non-infectious wastes are responsible for a large portion of total cost and emission, respectively. Autoclaving technology plays a vital role in treating infectious wastes. Moreover, the sensitivity analyses demonstrate that the vaccination tendency rate significantly impacts both objective functions. The case study results prove the model's robustness under different realization scenarios, where the average objective function of the robust model is less than the deterministic model ones' in all scenarios. Finally, some insights are given based on the obtained results.

Discrimination of RNA fiber structures using solid-state nanopores.

RNA fibers are a class of biomaterials that can be assembled using HIV-like kissing loop interactions. Because of the programmability of molecular design and low immunorecognition, these structures present an interesting opportunity to solve problems in nanobiotechnology and synthetic biology. However, the experimental tools to fully characterize and discriminate among different fiber structures in solution are limited. Herein, we utilize solid-state nanopore experiments and Brownian dynamics simulations to characterize and distinguish several RNA fiber structures that differ in their degrees of branching. We found that, regardless of the electrolyte type and concentration, fiber structures that have more branches produce longer and deeper ionic current blockades in comparison to the unbranched fibers. Experiments carried out at temperatures ranging from 20-60 °C revealed almost identical distributions of current blockade amplitudes, suggesting that the kissing loop interactions in fibers are resistant to heating within this range.

Alteration in cardiac uncoupling proteins and eNOS gene expression following high-intensity interval training in favor of increasing mechanical efficiency.

OBJECTIVES: High-intensity interval training (HIIT) increases energy expenditure and mechanical energy efficiency. Although both uncoupling proteins (UCPs) and endothelial nitric oxide synthase (eNOS) affect the mechanical efficiency and antioxidant capacity, their effects are inverse. The aim of this study was to determine whether the alterations of cardiac UCP2, UCP3, and eNOS mRNA expression following HIIT are in favor of increased mechanical efficiency or decreased oxidative stress. MATERIALS AND METHODS: Wistar rats were divided into five groups: control group (n=12), HIIT for an acute bout (AT1), short term HIIT for 3 and 5 sessions (ST3 and ST5), long-term training for 8 weeks (LT) (6 in each group). The rats of the training groups were made to run on a treadmill for 60 min in three stages: 6 min running for warm-up, 7 intervals of 7 min running on treadmill with a slope of 5° to 20° (4 min with an intensity of 80-110% VO2max and 3 min at 50-60% VO2max), and 5-min running for cool-down. The control group did not participate in any exercise program. Rats were sacrificed and the hearts were extracted to analyze the levels of UCP2, UCP3 and eNOS mRNA by RT-PCR. RESULTS: UCP3 expression was increased significantly following an acute training bout. Repeated HIIT for 8 weeks resulted in a significant decrease in UCPs mRNA and a significant increase in eNOS expression in cardiac muscle. CONCLUSION: This study indicates that Long term HIIT through decreasing UCPs mRNA and increasing eNOS mRNA expression may enhance energy efficiency and physical performance.

Candida species in cutaneous candidiasis patients in the Guilan province in Iran; identified by PCR-RFLP method.

Due to the epidemiological alteration in distribution of Candida species as well as significant increasing trend of either intrinsic or acquired in resistance of some of these fungi, the precise identification of Candida species is necessary for effective antifungal therapy and also for prevention of nosocomial infections. PCR-RFLP method is indicated to be a reliable, rapid and simple technique which is able to differentiate the Candida species. In the present study, we applied this method to evaluate the distribution of Candida species in patients affected with cutaneous candidiasis in the Guilan province. 896 clinical cutaneous samples were collected from different parts of skin and nail of suspected patients referred to clinical centers all over the Guilan province during 24 months. Samples were examined directly with 15% KOH and cultured on fungal specific media. Genomic DNA was extracted and the restriction enzyme Msp1 was applied for polymorphism analysis. Totally, 47 yeast strains were successfully isolated from different clinical samples and identified by conventional as well as PCR-RFLP methods. The results indicated that Candida albicans (36.17%) was the most frequent species followed by C. parapsilosis (25.53%), C. tropicalis (19.14%), C. guilliermondii (14.89%), C. famata (2.12%) and C. krusei (2.12%). Female finger nails were the most common location to be affected by Candida species. In conclusion, PCR-RFLP method was successfully used for recognition of clinical Candida species within the Guilan province and obtained results revealed C. albicans as the predominant causative agent of cutaneous candidiasis. However, distribution of other Candida species did not completely consist with the reported distribution of Candida species in other parts of Iran with different climate to the Guilan province.

Down-regulation of the ALS3 gene as a consequent effect of RNA-mediated silencing of the EFG1 gene in Candida albicans.

BACKGROUND: The most important virulence factor which plays a central role in Candida albicans pathogenesis is the ability of this yeast to alternate between unicellular yeast and filamentous hyphal forms. Efg1 protein is thought to be the main positive regulating transcription factor, which is responsible for regulating hyphal-specific gene expression under most conditions. ALS3 is one of the Efg1-associated genes encoding a multi-functional adhesive polypeptide, which mediates adherence to diverse host substrates. In this study, the EFG1 gene was knocked down by using synthetic siRNA in C. albicans and the regulation in ALS3 as one of the Efg1-dependent genes was investigated. METHOD: The 19-nucleotide siRNA was designed based on cDNA sequence of EFG1 gene in C. albicans. Transfection was performed using modified- plyethylen glycol/LiAc method. To quantify the level of EFG1 and the hyphal-specific ALS3 gene expression, the cognate EFG1 and ALS3 mRNA were measured in C. albicans by quantitative real-time RT-PCR. RESULTS: Fluorescent microscopy pictures indicated that transfection was performed successfully. Also, according to relative expression software tool, expression of EFG1 gene was decreased significantly with 500 nM siRNA as well as 1 µM siRNA (P<0.05). However, more significant down-regulations were observed in the expression of ALS3 in both concentrations of 500 nM and 1 µM siRNA (P<0.05). CONCLUSION: In conclusion, we demonstrated the down-regulation of ALS3 gene as a consequent of applying EFG1-specific siRNA in C. albicans. This may lead us to design anti-fungal-specific agents in order to face with C. albicans-associated infections.

A case report of tinea pedis caused by Trichosporon faecale in Iran.

Trichosporon species are known as the causative agents of cutaneous infections and are involved in systemic, localized, as well as disseminated mycoses particularly in immunocompromised patients. Here we report a case of tinea pedis infection caused by Trichosporon faecale in a healthy 29-year-old woman in the north of Iran. Macroscopic and microscopic characteristics using direct examination as well as culture method revealed the causative agent as Trichosporon species. Molecular analysis of the internal transcribed spacer region validated the initial result and indicated that this case of tinea pedis was caused by T. faecale. The patient was recovered after treatment with topical myconazole accompanied with oral fluconazole.

A case of fungus ball type pansinusitis caused by Schizophillum commune.

Schizophillum commune has been increasingly reported from allergic bronchopulmonary mycosis (ABPM) as well as fungus ball, brain abscess and several cases of maxillary or allergic fungal sinusitis. In the present study, we reported a case of fungus ball type pansinusitis from a 32-year-old woman in Iran. According to computed tomography (CT) scan, fungus ball type pan-sinusitis was likely to be the first diagnosis. Mycological examination revealed hyaline hyphae with small projection and also clamp connection structures on PDA medium. To identify the obtained isolate properly, molecular analysis of the internal transcribed spacer region was performed and indicated that the causing agent of the infection is surely Schizophillum commune. The patient completely recovered after surgical endoscopic operation and consequent post-operation MRI revealed clearance of sinuses.

The effect of hand dimensions, hand shape and some anthropometric characteristics on handgrip strength in male grip athletes and non-athletes.

It has been suggested that athletes with longer fingers and larger hand surfaces enjoy stronger grip power. Therefore, some researchers have examined a number of factors and anthropometric variables that explain this issue. To our knowledge, the data is scarce. Thus, the aim of this study was to investigate the effect of hand dimensions, hand shape and some anthropometric characteristics on handgrip strength in male grip athletes and non-athletes. 80 subjects aged between 19 and 29 participated in this study in two groups including: national and collegian grip athletes (n=40), and non-athletes (n=40). Body height and mass were measured to calculate body mass index. The shape of the dominant hand was drawn on a piece of paper with a thin marker so that finger spans, finger lengths, and perimeters of the hand could be measured. The hand shape was estimated as the ratio of the hand width to hand length. Handgrip strength was measured in the dominant and non-dominant hand using a standard dynamometer. Descriptive statistics were used for each variable and independent t test was used to analyze the differences between the two groups. The Pearson correlation coefficient test was used to evaluate the correlation between studied variables. Also, to predict important variables in handgrip strength, the linear trend was assessed using a linear regression analysis. There was a significant difference between the two groups in absolute handgrip strength (p<0.001) and handgrip/height ratio (p<0.001). The indices of body height, body mass, lean body mass and body fat content (p<0.001) were significantly greater in grip athletes. All hand variables except FS1-4 (p>0.05) were significantly different between the groups (p<0.001). After controlling body mass all hand anthropometric characteristics except thumb length (r=0.240, p= 0.135), hand shape (r=-0.029, p=0.858), middle finger length (r=0.305, p=0.056) and forearm circumference (r=0.162, p=0.319) significantly correlated with handgrip strength in grip athletes, but not in non-athletes, except for forearm circumference (r=0.406, p=0.010). The results showed that handgrip strength and some of the hand dimensions may be different in athletes who have handgrip movements with an object or opponent in comparison to non-athletes. Also, there was a significant positive correlation between handgrip strength and most of the hand dimensions in grip athletes. Therefore, these can be used in talent identification in handgrip-related sports and in clinical settings as well.