Structures and mechanisms of tRNA methylation by METTL1-WDR4.

Specific, regulated modification of RNAs is important for proper gene expression1,2. tRNAs are rich with various chemical modifications that affect their stability and function3,4. 7-Methylguanosine (m7G) at tRNA position 46 is a conserved modification that modulates steady-state tRNA levels to affect cell growth5,6. The METTL1-WDR4 complex generates m7G46 in humans, and dysregulation of METTL1-WDR4 has been linked to brain malformation and multiple cancers7-22. Here we show how METTL1 and WDR4 cooperate to recognize RNA substrates and catalyse methylation. A crystal structure of METTL1-WDR4 and cryo-electron microscopy structures of METTL1-WDR4-tRNA show that the composite protein surface recognizes the tRNA elbow through shape complementarity. The cryo-electron microscopy structures of METTL1-WDR4-tRNA with S-adenosylmethionine or S-adenosylhomocysteine along with METTL1 crystal structures provide additional insights into the catalytic mechanism by revealing the active site in multiple states. The METTL1 N terminus couples cofactor binding with conformational changes in the tRNA, the catalytic loop and the WDR4 C terminus, acting as the switch to activate m7G methylation. Thus, our structural models explain how post-translational modifications of the METTL1 N terminus can regulate methylation. Together, our work elucidates the core and regulatory mechanisms underlying m7G modification by METTL1, providing the framework to understand its contribution to biology and disease.

Molecular Endotypes of Idiopathic Pulmonary Fibrosis: A Latent Class Analysis of Two Multicenter Observational Cohorts.

Rationale: Idiopathic pulmonary fibrosis (IPF) causes irreversible fibrosis of the lung parenchyma. While antifibrotic therapy can slow IPF progression, treatment response is variable. There exists a critical need to develop a precision medicine approach to IPF. Objective: To identify and validate biologically driven molecular endotypes of IPF. Methods: Latent class analysis (LCA) was independently performed in prospectively recruited discovery (n=875) and validation (n=347) cohorts. Twenty-five plasma biomarkers associated with fibrogenesis served as class-defining variables. The association between molecular endotype and 4-year transplant-free survival was tested using multivariable Cox regression adjusted for baseline confounders. Endotype-dependent differential treatment response to future antifibrotic exposure was then assessed in a pooled cohort of patients naïve to antifibrotic therapy at time of biomarker measurement (n=555). Results: LCA independently identified two latent classes in both cohorts (p<0.0001). WAP four-disulfide core domain protein 2 (WFDC2) was the most important determinant of class membership across cohorts. Membership in Class 2 was characterized by higher biomarker concentrations and higher risk of death or transplantation (discovery: HR 2.02 [95% CI 1.64-2.48]; p<0.001; validation: HR 1.95 [1.34-2.82]; p<0.001). In pooled analysis, significant heterogeneity in treatment effect was observed between endotypes (pinteraction=0.030), with a favorable antifibrotic response in Class 2 (HR 0.64 [0.45-0.93]; p=0.018) but not in Class 1 (HR 1.19 [0.77-1.84]; p=0.422). Conclusions: In this multicohort study, we identified two novel molecular endotypes of IPF with divergent clinical outcomes and response to antifibrotics. Pending further validation, these endotypes could enable a precision medicine approach for future IPF clinical trials.

A double-blind, placebo-controlled, randomized withdrawal trial of sarilumab for the treatment of glucocorticoid-dependent sarcoidosis.

OBJECTIVES: Effective steroid-sparing therapies for the treatment of sarcoidosis are lacking; interleukin-6 (IL-6) antagonists may reduce sarcoidosis disease activity. This study assessed the safety and efficacy of the IL-6 receptor antagonist, sarilumab, in subjects with glucocorticoid-dependent sarcoidosis. METHODS: This phase II, double-blind, placebo-controlled, randomized withdrawal trial enrolled 15 subjects with biopsy-proven sarcoidosis at Stanford University from November 2019 to September 2022. In Period 1, subjects were treated with open-label sarilumab 200mg subcutaneously every two weeks for 16 weeks, with predefined tapering of prednisone. Subjects who completed Period 1 without a sarcoidosis flare entered Period 2 and were randomized to continue sarilumab or to receive matching placebo for 12 weeks. Endpoints included flare-free survival, as well as changes in pulmonary function tests, chest imaging, patient reported outcomes, and laboratory values. RESULTS: Fifteen subjects were enrolled in the study (median age 57 years, 80% male, 73.3% White), and 10 subjects successfully completed Period 1. During Period 1, 4 of 15 subjects (26.7%) discontinued due to worsening of their sarcoidosis, and CT chest imaging worsened in 5 of 15 subjects (35.7%). During Period 2, 0 of 2 subjects in the sarilumab group and 1 of 8 subjects (12.5%) in the placebo group had a flare. Treatment with sarilumab 200 mg was generally well tolerated in subjects with sarcoidosis. CONCLUSION: In this double-blind, placebo-controlled, randomized withdrawal trial, a meaningful signal for improvement in subjects with sarcoidosis treated with sarilumab was not observed. Given the small numbers in this study, no definitive conclusions can be drawn. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04008069.

Lung function trajectories in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease characterised by decline in lung function. We evaluated trajectories of forced vital capacity (FVC) and diffusing capacity (DLco) in a cohort of patients with IPF. METHODS: Patients with IPF that was diagnosed or confirmed at the enrolling centre in the previous 6 months were enrolled into the IPF-PRO Registry between June 2014 and October 2018. Patients were followed prospectively, with lung function data collected as part of routine clinical care. Mean trajectories of FVC and DLco % predicted in all patients and in subgroups by characteristics assessed at enrolment were estimated using a joint model that accounted for factors such as disease severity and visit patterns. RESULTS: Of 1002 patients in the registry, 941 had ≥ 1 FVC and/or DLco measurement after enrolment. The median (Q1, Q3) follow-up period was 35.1 (18.9, 47.2) months. Overall, mean estimated declines in FVC and DLco % predicted were 2.8% and 2.9% per year, respectively. There was no evidence that the mean trajectories of FVC or DLco had a non-linear relationship with time at the population level. Patients who were male, white, had a family history of ILD, were using oxygen, or had prior/current use of antifibrotic therapy at enrolment had greater rates of decline in FVC % predicted. Patients who were male or white had greater rates of decline in DLco % predicted. CONCLUSIONS: Data from the IPF-PRO Registry suggest a constant rate of decline in lung function over a prolonged period, supporting the inexorably progressive nature of IPF. A graphical abstract summarising the data in this manuscript is available at: https://www.usscicomms.com/respiratory/IPF-PRORegistry_LungFunctionTrajectories . TRIAL REGISTRATION: NCT01915511.

Integrative multi-omics analysis reveals novel idiopathic pulmonary fibrosis endotypes associated with disease progression.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of extracellular matrix in the pulmonary interstitium and progressive functional decline. We hypothesized that integration of multi-omics data would identify clinically meaningful molecular endotypes of IPF. METHODS: The IPF-PRO Registry is a prospective registry of patients with IPF. Proteomic and transcriptomic (including total RNA [toRNA] and microRNA [miRNA]) analyses were performed using blood collected at enrollment. Molecular data were integrated using Similarity Network Fusion, followed by unsupervised spectral clustering to identify molecular subtypes. Cox proportional hazards models tested the relationship between these subtypes and progression-free and transplant-free survival. The molecular subtypes were compared to risk groups based on a previously described 52-gene (toRNA expression) signature. Biological characteristics of the molecular subtypes were evaluated via linear regression differential expression and canonical pathways (Ingenuity Pathway Analysis [IPA]) over-representation analyses. RESULTS: Among 232 subjects, two molecular subtypes were identified. Subtype 1 (n = 105, 45.3%) and Subtype 2 (n = 127, 54.7%) had similar distributions of age (70.1 +/- 8.1 vs. 69.3 +/- 7.6 years; p = 0.31) and sex (79.1% vs. 70.1% males, p = 0.16). Subtype 1 had more severe disease based on composite physiologic index (CPI) (55.8 vs. 51.2; p = 0.002). After adjusting for CPI and antifibrotic treatment at enrollment, subtype 1 experienced shorter progression-free survival (HR 1.79, 95% CI 1.28,2.56; p = 0.0008) and similar transplant-free survival (HR 1.30, 95% CI 0.87,1.96; p = 0.20) as subtype 2. There was little agreement in the distribution of subjects to the molecular subtypes and the risk groups based on 52-gene signature (kappa = 0.04, 95% CI= -0.08, 0.17), and the 52-gene signature risk groups were associated with differences in transplant-free but not progression-free survival. Based on heatmaps and differential expression analyses, proteins and miRNAs (but not toRNA) contributed to classification of subjects to the molecular subtypes. The IPA showed enrichment in pulmonary fibrosis-relevant pathways, including mTOR, VEGF, PDGF, and B-cell receptor signaling. CONCLUSIONS: Integration of transcriptomic and proteomic data from blood enabled identification of clinically meaningful molecular endotypes of IPF. If validated, these endotypes could facilitate identification of individuals likely to experience disease progression and enrichment of clinical trials. TRIAL REGISTRATION: NCT01915511.

Investigating the Vapor-Phase Adsorption of Aroma Molecules on the Water-Vapor Interface using Molecular Dynamics Simulations.

Surfactants are amphiphilic additives primarily used to reduce the surface tension of water and manipulate its wettability on various surfaces. Recent reports suggest that volatile surfactants, such as aroma molecules, diffuse more quickly to the interface from the vapor-phase than conventional surfactants typically used in the aqueous phase. The ability to adsorb from the vapor phase, in addition to their use as cosurfactants, expands the potential applications of volatile surfactants, particularly in situations where adding surfactants from the liquid phase is difficult. Here, we present a molecular level understanding of the adsorption kinetics of linalool, a common aroma molecule, on the water interface using molecular dynamics simulations. We note that the value of surface tension while adsorption from vapor and liquid phases is dependent only on the surface coverage. A minimum surface tension of 32 ± 1.8 mN/m is obtained in both cases at a maximum surface coverage of 4.88 µmol/m2 at 300 K. We observe the extent of decrease of the H-bonds between linalool-water and linalool-linalool molecules at various surface coverages to explain the mechanism of surface tension reduction. We solve Gibb's adsorption equation to establish a correlation between the surface coverage of linalool and the corresponding bulk concentration in experiments. We investigate the free energy profile of linalool's adsorption behavior at different surface coverages and temperatures. Our report suggests that linalool adsorption onto the water interface is an enthalpy-driven process primarily dependent on the strength of the interaction between the hydroxyl group of linalool and water molecules. These insights are crucial for selecting a suitable aroma molecule for various applications that target the vapor-phase adsorption mechanism.

Rapid and label-free detection of Aflatoxin-B1viamicrofluidic electrochemical biosensor based on manganese (III) oxide (Mn3O4) synthesized by co-precipitation route at room temperature.

Aflatoxin B1 (AFB1) is the most toxic mycotoxin, naturally occurring in food items, and it causes several types of lethal diseases. Therefore, a rapid and convenient detection method for AFB1 is the first step toward overcoming the effect of AFB1. The current work presents the development of an efficient microfluidic electrochemical-based biosensor using tri-manganese tetroxide nanoparticles (Mn3O4nps) for AFB1 detection. The Mn3O4nps were synthesized at room temperature through the co-precipitation route. Its phase purity, structural and morphological studies have been characterized through x-ray diffraction, Raman spectroscopy, energy-dispersive x-ray, Fourier transform infrared spectroscopy and transmission electron microscopy. The mask-less UV-lithography was carried out to fabricate the three-electrode chip and microfluidic channel of the microfluidic electrochemical biosensing system. The designed microfluidic immunosensor (BSA/Ab-AFB1/Mn3O4/ITO) was fabricated using the three-electrode chip, microfluidic channel in poly-dimethyl siloxane. The fabricated sensor exhibited the 3.4µA ml ng-1cm-2sensitivity and had the lowest lower detection limit of 0.295 pg ml-1with the detection range of 1 pg ml-1to 300 ng ml-1. Additionally, the spiked study was also performed with this immunoelectrode and a recovery rate was obtained of 108.2%.

An Update on the Management of Mixed Neuroendocrine-Non-neuroendocrine Neoplasms (MiNEN).

OPINION STATEMENT: The classification of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) is evolving, and no clear management guidelines are currently available. However, recent studies provide insight into factors affecting outcomes and could help develop treatment decisions for patients with these rare malignancies. The majority of MiNENs have a poorly differentiated neuroendocrine carcinoma (NEC) component which is associated with an aggressive clinical course and poor outcomes. Due to the paucity of clinical trials, strategies adopted in gastrointestinal cancers and NECs are used to manage MiNENs. It is also to be noted that the thoracic neuroendocrine neoplasm WHO 2021 classification does not recognize MiNEN terminology but suggests an equivalent terminology called "combined neuroendocrine non neuroendocrine neoplasm." Surgical management is appropriate in early-stage disease with a low threshold for addition of adjuvant chemotherapy. Multimodality treatment with chemotherapy offers a survival benefit in advanced disease or when surgical resection is not possible without significant morbidity. Chemotherapy should be directed at the more aggressive component which is often the NEC component. In addition, molecular testing should be employed to evaluate patients for enrollment in clinical trials and other targeted treatments. Being a rare disease with retrospective studies and case series providing the majority of data on treatment selection, it is essential to include more granular details of pathology (e.g., Ki-67, mitotic index, percentage of each component, staging information) and treatment modalities (e.g., type and duration, rationale, radiologic response, survival outcomes) in future studies to make systematic reviews possible and help derive meaningful conclusions.

Factors Affecting the Job Satisfaction of U.S. Adult Endocrinologists: A Nationwide Survey.

OBJECTIVE: Despite the increased demand and worsening burnout among U.S. endocrinologists, there is a paucity of data on job satisfaction and associated factors. This study examines the factors associated with job satisfaction among a nationally representative sample of U.S. endocrinologists. METHODS: We conducted a cross-sectional survey of 1700 U.S. adult endocrinologists on the Facebook group "Endocrinologists." The survey was conducted over 4 weeks using an anonymous online questionnaire. The 45-question survey assessed job and salary satisfaction scores on a 5-point Likert scale along with multiple job-related variables. Univariate and multivariate analyses were conducted to identify the factors affecting job satisfaction. RESULTS: Out of 1700, 654 adult endocrinologists (504 women and 139 men) completed the survey. The mean job satisfaction score was 3.72 ± 0.86, with 67.5% having high job satisfaction. Comparatively, 339 (52.1%) had high salary satisfaction. There was a statistically significant relationship between the job and salary satisfaction scores (P < .01). Factors significantly associated with the job satisfaction score (P < .05) included the practice region, gender, number of medical assistants per endocrinologist, self-performance of thyroid ultrasound, and number of patients in the hospital per week. Multivariate analysis showed that full-time employment, along with high salary satisfaction, seeing fewer new patients per day, performing thyroid ultrasounds, and fewer patients in the hospital were associated with the highest job satisfaction. CONCLUSION: This study found about one-third of endocrinologists to have lower job satisfaction and identified multiple modifiable factors associated with endocrinologists' job satisfaction. Interventions focused on these potentially modifiable factors may improve job satisfaction among U.S. endocrinologists.

Effects of Trauma and Anxiety on Adherence in Pediatric Type 1 Diabetes.

Background: Psychiatric factors such as depression, anxiety, and life stressors have been shown to negatively affect diabetes self-management and A1C in children and adolescents. However, less is known about how trauma exposure and symptoms of post-traumatic stress disorder (PTSD) may affect type 1 diabetes. Objectives: To determine the rates of trauma exposure and PTSD symptoms in patients aged 7-21 years with type 1 diabetes and to examine the relationships among trauma exposure, PTSD, anxiety, depression, and diabetes self-management. Methods: Patients underwent standardized psychiatric screening questionnaires during clinic visits. A1C at goal was defined as <7.0%, and behavioral adherence was defined as specific parameters of blood glucose monitoring. χ2 and Fisher exact tests were used to assess the relationships among trauma, PTSD, anxiety, and behavioral adherence. ANOVA was conducted to examine group differences between A1C and the presence of suicidal ideation. Results: Of the participants, 38.4% (n = 99, mean age 13.8 ± 3.5 years, 51.5% female) had trauma symptoms and functional impairment concerning for PTSD. Rates of trauma secondary to accidental injury, medical traumatic stress, natural disaster, and witness to family violence were 28.3, 22.2, 10.1, and 6.1%, respectively. Neither PTSD nor anxiety nor depression symptoms were associated with behavioral nonadherence (P = 0.546, P = 0.337, and P = 0.697, respectively), but the subscales for significant school avoidance and generalized anxiety disorders were associated with behavioral nonadherence (P = 0.023 and P = 0.032, respectively). Those who reported suicidal ideation had higher mean A1C than those who did not (A1C 8.9 vs. 8.3, P = 0.047). Conclusion: Although trauma was common among youth with type 1 diabetes, neither trauma nor PTSD was associated with changes to self-management. However, certain forms of anxiety and suicidal ideation were associated with poor self-management and higher A1C, respectively.

Structural and biochemical characteristics of two Staphylococcus epidermidis RNase J paralogs RNase J1 and RNase J2.

RNase J enzymes are metallohydrolases that are involved in RNA maturation and RNA recycling, govern gene expression in bacteria, and catalyze both exonuclease and endonuclease activity. The catalytic activity of RNase J is regulated by multiple mechanisms which include oligomerization, conformational changes to aid substrate recognition, and the metal cofactor at the active site. However, little is known of how RNase J paralogs differ in expression and activity. Here we describe structural and biochemical features of two Staphylococcus epidermidis RNase J paralogs, RNase J1 and RNase J2. RNase J1 is a homodimer with exonuclease activity aided by two metal cofactors at the active site. RNase J2, on the other hand, has endonuclease activity and one metal ion at the active site and is predominantly a monomer. We note that the expression levels of these enzymes vary across Staphylococcal strains. Together, these observations suggest that multiple interacting RNase J paralogs could provide a strategy for functional improvisation utilizing differences in intracellular concentration, quaternary structure, and distinct active site architecture despite overall structural similarity.

Cloaked Droplets on Lubricant-Infused Surfaces: Union of Constant Mean Curvature Interfaces Dictated by Thin-Film Tension.

It has been recently shown that small-volume droplets on lubricant-infused surfaces (LISs) can be analytically modeled using rotationally symmetric constant mean curvature (CMC) surfaces. While such an approach is available for noncloaked droplets, a similar approach is missing for cloaked droplets that are ubiquitous in a number of LIS-related applications. The presence of a thin cloaking film on the top spherical cap portion and its gradual transition to a bulk meniscus remain unaddressed for its implications on the interfacial profile of cloaked droplets. Here, we take into account the cloaking film tension and the disjoining pressure to present a mean curvature-based framework for modeling cloaked droplets on LISs. The transition of the bulk meniscus to a thin film is formulated as a transition regime, which is then modeled as a single imaginary point akin to the Neumann point of noncloaked droplets. We next show that the shape of a small droplet on a LIS essentially obeys a simple fundamental mean curvature relation that changes forms depending on the regimes of lubrication and whether the droplet is cloaked or noncloaked. We validate our framework with the droplet profiles recorded during the evaporation of cloaked droplets in our experiments, as well as those published in the literature. In addition, we also demonstrate the ability to model the shapes of floating droplets on LISs reported in the literature. In addition to quantifying the effect of disjoining pressure on interfacial profiles, we importantly unmask the behavior of the contact line, which is optically covered by the lubricant meniscus around the droplets on LISs.

Droplets on Lubricant-Infused Surfaces: Combination of Constant Mean Curvature Interfaces with Neumann Triangle Boundary Conditions.

Superior mobility of droplets on lubricant-infused surfaces (LIS) has recently attracted significant attention for designing liquid-repellent surfaces. Unlike sessile droplets on flat surfaces wherein the contact line is easily visible in experiments, the contact line on LIS is masked by the lubricant meniscus, and special imaging techniques are required to visualize the hidden droplet-lubricant interface. Moreover, the overall shape deviates significantly from the spherical cap geometry even at very low droplet volumes. These difficulties necessitate the need to model interfaces in order to assess the effect of surface and fluid properties on LIS. In this work, we first numerically simulate the droplet shapes to show that at very small volumes, droplet-air and droplet-lubricant interfaces are constant mean curvature (CMC) interfaces. Moreover, we elucidate that these mean curvatures are related by the ratio of interfacial tensions of the droplet-air and the droplet-lubricant interfaces. These insights reduce the modeling of LIS interfacial profiles to a simplified geometric problem, which is solved using the parametric equations of CMC surfaces along with the angles of the Neumann triangle as the boundary conditions. Predicted profiles of the droplet-air interface as a spherical cap, the droplet-lubricant interface as a nodoid, and the lubricant-air interface as a catenoid/nodoid show good agreement with experimental results in the literature. Importantly, we for the first time provide a framework, which accurately predicts the true contact angle at the hidden solid contact line by just using the information of the top spherical cap portion visible in experiments.

Leidenfrost phenomenon during quenching in aqueous solutions: effect of evaporation-induced concentration gradients.

The minimum temperature limit for a sustained vapor film on a hot surface defines the well-known Leidenfrost temperature (LFT). LFT for pure fluids is typically a strong function of the surface tension. However, the effect of surface tension on LFT of aqueous additive solutions is confusing with many complicated trends. For example, despite an insignificant increase of ≈1 mN m-1 in surface tension, a substantial increase in LFT of ≈50 °C with aqueous salt and sugar solutions has been reported in comparison to pure water. Conversely, no appreciable change in LFT (within ±2 °C) is observed despite a substantial drop of up to ≈30 mN m-1 in surface tension upon varying the concentration of surfactant additives in aqueous solutions. Here, we perform simultaneous thermal, visual, and acoustic characterization of pool quenching experiments with aqueous solutions of salt, sugar, surfactant, and ionic liquids. We model the evaporation-induced increase in the concentration of the non-volatile additives at the liquid-vapor interface using Fick's second law of diffusion. We show that the localized concentration buildup of additives at the liquid-vapor interface dramatically alters the surface tension values in comparison to the typical equilibrium values estimated otherwise. We use these modified surface tension values to correlate the diverse set of experimental LFT data reported in our work and in the literature using a unified framework. We believe that these clarifications regarding the Leidenfrost mechanism will encourage the use of additives in various applications, specifically those where surface modification strategies may not be practically feasible.

Sleep Patterns and Health Behaviors in Healthcare Students.

OBJECTIVES: Personal health behavior can influence the academic development of healthcare students. This study was designed to evaluate the personal health behavior, including sleep time, of healthcare students at a large health sciences center. METHODS: An anonymous online survey based on standardized questionnaires about sleep, insomnia, depression, alcohol use, and exercise was sent to all of the healthcare students (including medical, nursing, pharmacy, graduate biomedical science, and allied health students) in the Texas Tech University Health Sciences Center graduate education programs in Lubbock. RESULTS: In total, 412 students replied to this survey. Their mean sleep duration during the weekday was 7.5 ± 1.2 hours; 16.5% were short sleepers (<7 hours) during weekdays; 33% of the students woke up "feeling tired or worn out" >15 days during the last month. Many students were either moderately or severely bothered by "the lack of energy" because of poor sleep, and 56.6% of students rated their sleep as either fair or poor. Approximately 35% of students had drinking patterns that qualified as hazardous drinking, 6.3% of students smoked, and 23% of students did not do even mild exercise during the week. Eighty-nine percent of students reported stress in their life, including family stress, job stress, financial stress, legal stress, and other stress. Thirty-five percent of students considered their health as either poor or fair. Approximately 50% of students did not expect any change in their situation during the next 3 to 6 months. CONCLUSIONS: Although most healthcare students report adequate sleep times, more than half of them rate their sleep as fair or poor. In addition, some have poor health habits, including excessive alcohol use. Health science centers should introduce programs to promote healthy behaviors and reduce stress in healthcare students.

Effect of foamability on pool boiling critical heat flux with nanofluids.

Foaming, which is of significant importance to many industrial processes, is attributed to the reduced coalescence of bubbles due to the presence of stabilizing/foaming agents such as surfactants and nanoparticles. While foams have been extensively investigated for their rheological properties, their impact on the critical heat flux (CHF) during boiling is not well understood. The technical benefits of CHF enhancement with nanofluids are lost when surfactants are added to improve their stability. The actual mechanism of this decrease is unresolved, and thermal engineers are forced to look for alternative CHF enhancement solutions. Here, we showed that nucleating bubbles formed vapor-foam and crowded the heater surface to inhibit rewetting. Less frequent rewetting forces premature dryout, which is primarily responsible for the reported CHF deterioration. In this regime, strong foaming agents such as SDS mask the effect of nanoparticles on CHF. Using these insights, we presented a master curve that captured the effect of foamability on CHF and could be used to predict the value of CHF solely based on the foamability of the solution. We further showed that the CHF mechanism switched from the foamability regime to the conventional wettability regime upon lowering the surfactant concentration and/or with weakly foaming surfactants. In such cases, an increase in the nanoparticle concentration successfully increased CHF. We believe that the important clarifications regarding the CHF mechanism with nanofluids and the master curve of CHF versus foamability presented in this study will facilitate the design of energy-efficient boiling systems.

Characterization of Staphylococcus epidermidis Polynucleotide phosphorylase and its interactions with ribonucleases RNase J1 and RNase J2.

Polynucleotide phosphorylase catalyzes both 3'-5' exoribonuclease and polyadenylation reactions. The crystal structure of Staphylococcus epidermidis PNPase revealed a bound phosphate in the PH2 domain of each protomer coordinated by three adjacent serine residues. Mutational analysis suggests that phosphate coordination by these serine residues is essential to maintain the catalytic center in an active conformation. We note that PNPase forms a complex with RNase J1 and RNase J2 without substantially altering either exo-ribonuclease or polyadenylation activity of this enzyme. This decoupling of catalytic activity from protein-protein interactions suggests that association of these endo- or exo-ribonucleases with PNPase could be more relevant for cellular localization or concerted targeting of structured RNA for recycling.

Droplets on Microdecorated Surfaces: Evolution of the Polygonal Contact Line.

Interaction of liquids with surfaces is ubiquitous in our physical environment as well as many engineering applications. Recent advances on this topic have not only provided us with valuable insight into nature's design, but also enabled improved fluidic manipulation for liquid-based printing applications such as biomicroarrays for protein and DNA sequencing, multicolor polymer-based LED displays, inkjet printing, and solder droplet printing, among others. For example, droplet contact lines, which are typically circular on a smooth and homogeneous surface, when deposited on a microdecorated surface may take various common polygonal shapes such as squares, rectangles, hexagons, octagons and dodecagons. These polygonal contact line shapes are highly stable due to the local energy barriers associated with the anisotropy in depinning contact angles. In addition to the knowledge of the eventual contact line shapes, liquid-based printing applications would require accurate prediction of temporal evolution of contact line on these surfaces. In this work, we model and validate the evolution of droplets on microdecorated surfaces with microgoniometry experiments reported in the literature. We show that various metastable contact line shapes are formed in-between the well-known stable polygonal contact line shapes usually observed in experiments. We elucidate that the movement of the contact line between adjacent micropillars can primarily be categorized as primary zipping and transition zipping. Primary zipping occurs when the contact line moves radially outward to the next row of pillars, often resulting in the formation of a metastable contact line shape. Conversely, metastable droplet attains stable polygonal contact line shape via transition zipping wherein the contact line advances sideways. We believe that the current simulation approach can be effectively utilized for designing optimized textured surfaces for applications where control over liquid supply via surface design is required.