Specificity of Membrane-Associated J-Domain Protein, Caj1, in Amphotericin B Tolerance in Budding Yeast.

Hsp70:J-domain protein (JDP) machineries play pivotal roles in maintaining cellular proteostasis and governing various aspects of fungal physiology. While Hsp70 is known for its involvement in conferring tolerance to diverse antifungal drugs, the specific contribution of JDPs remains unclear. In this study, we examined the sensitivity of cytosolic JDP deletion strains of budding yeast to amphotericin B (AmB), a polyene antifungal agent widely utilized in fungal disease treatment due to its ability to disrupt the fungal plasma membrane (PM). Deleting Caj1, a PM-associated class II JDP, heightened susceptibility to AmB, and the protection conferred by Caj1 against AmB necessitated both its N-terminal J-domain and C-terminal lipid binding domain. Moreover, Caj1 deficiency compromised PM integrity as evidenced by increased phosphate efflux and exacerbated AmB sensitivity, particularly at elevated temperatures. Notably, phytosphingosine (PHS) addition as well as overexpression of PMP3, a positive PM integrity regulator, significantly rescued AmB sensitivity of caj1Δ cells. Our results align with the notion that Caj1 associates with the PM and cooperates with Hsp70 to regulate PM proteostasis, thereby influencing PM integrity in budding yeast. Loss of Caj1 function at the PM compromises PM protein quality control, thereby rendering yeast cells more susceptible to AmB.

Liquid state theory of the structure of model polymerized ionic liquids.

We employ polymer integral equation theory to study a simplified model of semiflexible polymerized ionic liquids (PolyILs) that interact via hard core repulsions and short range screened Coulomb interactions. The multi-scale structure in real and Fourier space of PolyILs (ions chosen to mimic Li, Na, K, Br, PF6, and TFSI) are determined as a function of melt density, Coulomb interaction strength, and ion size. Comparisons with a homopolymer melt, a neutral polymer-solvent-like athermal mixture, and an atomic ionic liquid are carried out to elucidate the distinct manner that ions mediate changes of polymer packing, the role of excluded volume effects, and the influence of chain connectivity, respectively. The effect of Coulomb strength depends in a rich manner on ion size and density, reflecting the interplay of steric packing, ion adsorption, and charge layering. Ion-mediated bridging of monomers is found, which intensifies for larger ions. Intermediate range charge layering correlations are characterized by a many-body screening length that grows with PolyIL density, cooling, and Coulomb strength, in disagreement with Debye-Hückel theory, but in accord with experiments. Qualitative differences in the collective structure, including an ion-size-dependent bifurcation of the polymer structure factor peak and pair correlation function, are predicted. The monomer cage order parameter increases significantly, but its collective ion counterpart decreases, as ions become smaller. Such behaviors allow one to categorize PolyILs into two broad classes of small and large ions. Dynamical implications of the predicted structural results are qualitatively discussed.

Perceptions, Experiences, and Patterns of Cannabis Use in Individuals with Mood and Anxiety Disorders in the Context of Cannabis Legalization and Medical Cannabis Program in Canada - A Qualitative Study.

INTRODUCTION: Perceptions of cannabis as a potential medical treatment for mood and anxiety disorders have been increasing in the context of legalizations, availability, and medical cannabis programs, though current evidence predominately indicates risks and negative effects of cannabis use (CU) on mental health outcomes. This study aims to understand motivations, perceptions, effects, and patterns of CU in individuals with mood and anxiety disorders. METHODS: Thirty-six adult patients diagnosed with mood or anxiety disorders, obsessive-compulsive disorder, or posttraumatic stress disorder who were currently using cannabis completed an in-depth qualitative interview on individual motivations, perceptions, experiences, effects, and patterns of their CU. The thematic analysis focused on phases of CU and sources of cannabis products and information. RESULTS: Reported motivations for initiation of CU included curiosity, peer pressure, and dissatisfaction with conventional treatments. Factors such as psychotropic effects and coping with mental health symptoms and insomnia contributed to the continuation of CU. More negative effects, including cognitive dysfunction, worsening of mood, and anxiety symptoms, were acknowledged with ongoing CU. Concerning findings included common initiation of CU before age 18, combined medical and recreational CU, rare consultation of medical professionals on CU, and potential effects and harms. DISCUSSION: Findings indicate individual complexity of motivations, perceptions, and patterns of CU in the study population. The reported potential beneficial effects of specific cannabis products should be further investigated. Findings emphasize patient-provider dialogue on both CU and conventional treatments. Information from this study can contribute to and inform the development of education, prevention, and intervention strategies.

The more the better? Integration of vertebral pelvic angles (VPA) PJK thresholds to existing alignment schemas for prevention of mechanical complications after adult spinal deformity surgery.

PURPOSE: While existing adult spinal deformity (ASD) alignment schemas acknowledge the dynamic relationship between the pelvis and spine, consideration of vertebral pelvic angles (VPA) thresholds for PJK may provide further insight into the relationship of each individual vertebra to the pelvis, which may allow for greater individualization of operative targets. Herein, we examine VPA's utility in preventing mechanical complications and its possible unification with prevalent scoring systems. METHODS: In a retrospective cohort study of a prospectively collected database, operative ASD patients ≥ 18 years with complete baseline (BL) and two-year (Y) operative, radiographic, and health-related quality of life data were included. Descriptive analyses, means comparison, and logistic regression tests were applied to explore demographic and surgical differences, as well as the impact of alignment goals on outcomes. Cohorts were grouped as patients who met VPA non-PJK thresholds, as defined by Duvvuri et al. 2023 alone versus traditional GAP/SAAS alignment matching versus combined VPA + SAAS + GAP. The Non-PJK VPA validated mean for L1PA was 10.4 ± 7.0 and T9PA 8.9 ± 7.5. RESULTS: 398 patients met inclusion criteria (mean age 61 ± 14 years, 78% female, BL BMI 27 ± 6, BL CCI 2 ± 2). At baseline, mean vertebral pelvic angles were as follows: T1PA: 24 ± 14; T4PA 20 ± 13, T9PA 15 ± 12, L1PA 11 ± 10, L4PA 11 ± 6. Mean vertebral pelvic angles at 6 W postoperatively: T1PA 16 ± 10, T4PA 12 ± 10, T9PA 8 ± 9, L1PA 9 ± 8, L4PA 11 ± 5. 240 (60%) patients attained optimal L1PA, while 104 patients (26.1%) reached non-PJK mean for T9PA. 89 patients (22%) were optimal by both VPA standards. VPA-Optimal group demonstrated significantly lower rates of 1Y PJK (17% v 83%, p = 0.042) and PJF by 2Y (7% v. 93%, p = 0.038). When patients attained VPA goals in addition to GAP/SAAS goals at 6 W, they demonstrated significantly lower rates of Y1 PJK (p = 0.026) and Y1 and Y2 PJF. Those with optimal VPA registered greater SRS-22 scores across multiple domains (p < 0.02) as well as a greater rate of normal neurological examination at 6 W (p = 0.048). CONCLUSIONS: Vertebral pelvic angles are a reliable measure of global alignment, and respecting certain targets may help prevent development of PJK/PJF. The value of VPA can be augmented through integration with GAP/SAAS frameworks to prevent complications and improve quality of life.

Diversity trends in traumatic brain injury clinical trials in the United States.

BACKGROUND: This study aims to understand the demographic representation of patients in Traumatic Brain Injury (TBI) clinical trials by evaluating the proportions of patients from various demographic categories amongst completed TBI clinical trials in the United States. METHODS: ClinicalTrials.gov was queried for active TBI clinical trials. One hundred and eight completed trials in the United States were selected based on inclusion criteria, and information regarding intervention, setting, age, sex, race, and ethnicity was extracted. 2002-2006 TBI incidence data was obtained from the CDC. Chi-squared testing was applied to analyze the relationship between distributions of race and sex in the collected clinical trials and the national TBI data, and logistic regression was conducted to identify variables that may predict reporting of race or ethnicity. RESULTS: About 53.7% of selected clinical trials reported racial data and 34.3% reported ethnicity data. Logistic regression identified that clinical trials in defined phases were more likely to report racial data (p = 0.047 [1.015, 9.603]). CONCLUSION: Current TBI trials do not consistently report race or ethnicity data. Future efforts to ensure equitable representation in clinical trials may involve reform of recruitment processes and accountability measures implemented within the grant application process to ensure proper racial and ethnicity data reporting.

Point-of-care impedimetric aptasensor to detect the luteinizing hormone.

Luteinizing hormone (LH) is a useful biomarker for identifying ovulation events in the cows to predict the time of ovulation to achieve a high success rate of conception following artificial insemination. Although antibody-based radioimmunoassay and enzyme-linked immunosorbent assay are being used for LH measurement, these techniques are expensive, time-consuming, and require expertise and sophisticated laboratory facilities. So, there is a need for a field-applicable, affordable, easy-to-use method for LH detection. For developing such a specific, quantitative, and inexpensive system, an aptamer-based smartphone-enabled aptasensor has been investigated. The aptamer was used instead of the antibody as a biorecognition element due to its comparative stability at ambient temperature, ease of synthesis, and cost-effectiveness. Electrochemical impedance spectroscopy has been used to obtain label-free detection of LH within 20 min in ~ 20 µL sample volume. The screen-printed gold electrode is compatible with a smartphone-enabled miniaturized device (Sensit Smart; Palmsens BV, The Netherlands) and was fabricated with the aptamer to detect LH in biological fluids (limit of detection 0.80 and 0.61 ng/mL in buffer and undiluted/unprocessed serum, respectively, with the dynamic range of detection of 0.01 to 50 ng/mL). All the data were obtained in the 10 kHz to 0.10 Hz frequency range at a bias potential of 0.30 V with an alternating potential of 10 mV. The clinical relevance of the sensor was evaluated in 10 serum samples collected from dairy animals which established a high correlation with standard LH-ELISA (κ > 0.87). The aptasensor can be stored at room temperature for 30 days without any significant loss in electrochemical sensing ability.

Designing Site Specificity in the Mechanochemical Cargo Release of Small Molecules.

Mechanical force can trigger the predictable and precise release of small molecules from macromolecular carriers. In this article, based on mechanochemical simulations, we show that norborn-2-en-7-one (NEO), I, and its derivatives can selectively release CO, N2, and SO2 and produce two distinctly different products, A ((3E,5Z,7E)-dimethyl-5,6-diphenyldeca-3,5,7-triene-1,10-diyl bis(2-bromo-2-methylpropanoate)) and B (4',5'-dimethyl-4',5'-dihydro-[1,1':2',1''-terphenyl]-3',6'-diyl)bis(ethane-2,1-diyl) bis(2-bromo-2-methylpropanoate). Site-specific design in the pulling points (PP) ensures that by changing the regioselectivity, either A or B can be exclusively generated. Controlling the rigidity of the NEO scaffold by replacing a 6-membered ring with an 8-membered ring and concomitantly tuning the pulling groups makes it mechanolabile toward the selective formation of B. The diradical intermediate formed during I → A is predicted to be persistent for ∼150 fs. The structural design holds the key to the trade-off between mechanochemical rigidity and lability.

Frailty as a Superior Predictor of Dysphagia and Surgically Placed Feeding Tube Requirement After Anterior Cervical Discectomy and Fusion Relative to Age.

Frailty is a measure of physiological reserve that has been demonstrated to be a discriminative predictor of worse outcomes across multiple surgical subspecialties. Anterior cervical discectomy and fusion (ACDF) is one of the most common neurosurgical procedures in the United States and has a high incidence of postoperative dysphagia. To determine the association between frailty and dysphagia after ACDF and compare the predictive value of frailty and age. 155,300 patients with cervical stenosis (CS) who received ACDF were selected from the 2016-2019 National Inpatient Sample (NIS) utilizing International Classification of Disease, tenth edition (ICD-10) codes. The 11-point modified frailty index (mFI-11) was used to stratify patients based on frailty: mFI-11 = 0 was robust, mFI-11 = 1 was prefrail, mFI-11 = 2 was frail, and mFI-11 = 3 + was characterized as severely frail. Demographics, complications, and outcomes were compared between frailty groups. A total of 155,300 patients undergoing ACDF for CS were identified, 33,475 (21.6%) of whom were frail. Dysphagia occurred in 11,065 (7.1%) of all patients, and its incidence was significantly higher for frail patients (OR 1.569, p < 0.001). Frailty was a risk factor for postoperative complications (OR 1.681, p < 0.001). Increasing frailty and undergoing multilevel ACDF were significant independent predictors of negative postoperative outcomes, including dysphagia, surgically placed feeding tube (SPFT), prolonged LOS, non-home discharge, inpatient death, and increased total charges (p < 0.001 for all). Increasing mFI-11 score has better prognostic value than patient age in predicting postoperative dysphagia and SPFT after ACDF.

Comparison of Characteristics, Inpatient Outcomes, and Trends in Percutaneous Versus Open Placement of Spinal Cord Stimulators.

OBJECTIVES: Spinal cord stimulation (SCS) is an effective treatment modality for chronic pain conditions for which other treatment modalities have failed to provide relief. Ample prospective studies exist supporting its indications for use and overall efficacy. However, less is known about how SCS is used at the population level. Our objective is to understand the demographics, clinical characteristics, and utilization patterns of open and percutaneous SCS procedures. MATERIALS AND METHODS: The Nationwide Inpatient Sample data base of 2016-2019 was queried for cases of percutaneous or open placement (through laminotomy/laminectomy) of SCS (excluding SCS trials) using International Classification of Disease (ICD), 10th revision, procedure coding system. Baseline demographic characteristics, complications, ICD-Clinical Modification, Diagnosis Related Group, length of stay (LOS), and yearly implementation data were collected. Complications and outcomes were evaluated in total and between the open and percutaneous SCS groups. RESULTS: A total of 2455 inpatients had an SCS placed, of whom 1970 (80.2%) received SCS through open placement. Placement of open SCS was associated with Caucasian race (odds ratio [OR] = 1.671, p < 0.001), private insurance (OR = 1.332, p = 0.02), and age more than 65 years (OR = 1.25, p = 0.034). The most common diagnosis was failed back surgery syndrome (23.8%). Patients with percutaneous SCS were more likely to have a hospital stay of < 1 day (OR = 2.318; 95% CI, 1.586-3.387; p < 0.001). Implant complications during the inpatient stay were positively associated with open SCS placement and reported in 9.4% of these cases (OR = 3.247, p < 0.001). CONCLUSIONS: Patients who underwent open SCS placement were more likely to be older, Caucasian, and privately insured. Open SCS placement showed greater LOS and implant-related complications during their hospital stay. These findings highlight both potential socioeconomic disparities in health care access for chronic pain relief and the importance of increasing age and medical comorbidities as important factors that can influence SCS implants in the inpatient setting.

Frailty and outcomes in lacunar stroke.

BACKGROUND: Lacunar strokes (LS) are ischemic strokes of the small perforating arteries of deep gray and white matter of the brain. Frailty has been associated with greater mortality and attenuated response to treatment after stroke. However, the effect of frailty on patients with LS has not been previously described. OBJECTIVE: To analyze the association between frailty and outcomes in LS. METHODS: Patients with LS were selected from the National Inpatient Sample (NIS) 2016-2019 using the International Classification of Disease, 10th edition (ICD-10) diagnosis codes. The 11-point modified frailty scale (mFI-11) was used to group patients into severely frail and non-severely frail cohorts. Demographics, clinical characteristics, and complications were defined. Health care resource utilization (HRU) was evaluated by comparing total hospital charges and length of stay (LOS). Other outcomes studied were discharge disposition and inpatient death. RESULTS: Of 48,980 patients with LS, 10,830 (22.1%) were severely frail. Severely frail patients were more likely to be older, have comorbidities, and pertain to lower socioeconomic status categories. Severely frail patients with LS had worse clinical stroke severity and increased rates of complications such as urinary tract infection (UTI) and pneumonia (PNA). Additionally, severe frailty was associated with unfavorable outcomes and increased HRU. CONCLUSION: Severe frailty in LS patients is associated with higher rates of complications and increased HRU. Risk stratification based on frailty may allow for individualized treatments to help mitigate adverse outcomes in the setting of LS.

Prevalence of Ectopic Canine in Different Sagittal and Vertical Skeletal Patterns.

AIM: The present investigation aims to find out the prevalence of ectopic canines among skeletal class I, II, and III malocclusions and to evaluate its variability among different genders and their growth patterns. MATERIAL AND METHODS: The study sample included orthopantomograms (OPGs), lateral skull views, and study models of 999 patients collected from departmental archives. Among the selected samples, 258 were males and 738 were females. They were divided into skeletal class I, II, and III malocclusions sagittally and hypodivergent, normodivergent, and hyperdivergent groups according to their angle formed between point A-Nasion - point B (ANB) and angle formed between the Sella-Nasion (SN) plane and Gonion (Go) - Gnathion (Gn) plane (SnGoGn) values respectively. RESULTS: Of the 999 samples, 738 (73.9%) were female and 260 (25.8%) were male patients. When compared to men, females had a higher proportion of ectopic canines. An estimated 62.3% of skeletal class I, 29.1% of skeletal class II, and 8.6% of skeletal class III cases were found to have ectopic canines. An estimated 720 (72.1%) patients were found to have maxillary ectopic canines and out of the available sample, 474 patients have horizontal growth patterns, 335 have average growth patterns and 190 patients have vertical growth patterns. Labial impaction was the commonest (65.4%) followed by palatal (24.8%). Bilateral impaction was comparatively more (51.1%) than unilateral impaction (48.2%). Maxilla was more prevalent (72.1%) as compared to the mandible (16.3%) and for both the arches it was (11.6%). Ectopic canines were identified in a total of 62.3% of cases with skeletal class I, 29.1% of cases with skeletal class II, and 8.6% of cases with skeletal class III. CONCLUSION: The bilateral ectopic canine was mostly seen in skeletal class I and class III malocclusions, whereas, a unilateral presentation was mostly seen in skeletal class II malocclusions. CLINICAL SIGNIFICANCE: Knowing the likelihood of a maxillary canine erupting ectopically will aid clinicians in starting with interceptive therapy since this condition necessitates complex orthodontic mechanics.

N-Heterocyclic Olefins on a Silicon Surface.

The adsorption of N-heterocyclic olefins (NHOs) on silicon is investigated in a combined scanning tunneling microscopy, X-ray photoelectron spectroscopy, and density functional theory study. We find that both of the studied NHOs bind covalently, with ylidic character, to the silicon adatoms of the substrate and exhibit good thermal stability. The adsorption geometry strongly depends on the N-substituents: for large N-substituents, an upright adsorption geometry is favored, while a flat-lying geometry is found for the NHO with smaller wingtips. These different geometries strongly influence the quality and properties of the obtained monolayers. The upright geometry leads to the formation of ordered monolayers, whereas the flat-lying NHOs yield a mostly disordered, but denser, monolayer. The obtained monolayers both show large work function reductions, as the higher density of the flat-lying monolayer is found to compensate for the smaller vertical dipole moments. Our findings offer new prospects in the design of tailor-made ligand structures in organic electronics and optoelectronics, catalysis, and material science.

The role of TNFRSF11B in development of osteoarthritic cartilage.

OBJECTIVES: OA is a complex genetic disease with different risk factors contributing to its development. One of the genes, TNFRSF11B, previously identified with gain-of-function mutation in a family with early-onset OA with chondrocalcinosis, is among the highest upregulated genes in lesioned OA cartilage (RAAK-study). Here, we determined the role of TNFRSF11B overexpression in development of OA. METHODS: Human primary articular chondrocytes (9 donors RAAK study) were transduced using lentiviral particles with or without TNFRSF11B. Cells were cultured for 1 week in a 3 D in-vitro chondrogenic model. TNFRSF11B overexpression was confirmed by RT-qPCR, immunohistochemistry and ELISA. Effects of TNFRSF11B overexpression on cartilage matrix deposition, matrix mineralization, and genes highly correlated to TNFRSF11B in RNA-sequencing dataset (r >0.75) were determined by RT-qPCR. Additionally, glycosaminoglycans and collagen deposition were visualized with Alcian blue staining and immunohistochemistry (COL1 and COL2). RESULTS: Overexpression of TNFRSF11B resulted in strong upregulation of MMP13, COL2A1 and COL1A1. Likewise, mineralization and osteoblast characteristic markers RUNX2, ASPN and OGN showed a consistent increase. Among 30 genes highly correlated to TNFRSF11B, expression of only eight changed significantly, with BMP6 showing the highest increase (9-fold) while expression of RANK and RANKL remained unchanged indicating previously unknown downstream pathways of TNFRSF11B in cartilage. CONCLUSION: Results of our 3D in vitro chondrogenesis model indicate that upregulation of TNFRSF11B in lesioned OA cartilage may act as a direct driving factor for chondrocyte to osteoblast transition observed in OA pathophysiology. This transition does not appear to act via the OPG/RANK/RANKL triad common in bone remodeling.

Control of Chemical Reaction Pathways by Light-Matter Coupling.

Because plasmonic metal nanostructures combine strong light absorption with catalytically active surfaces, they have become platforms for the light-assisted catalysis of chemical reactions. The enhancement of reaction rates by plasmonic excitation has been extensively discussed. This review focuses on a less discussed aspect: the induction of new reaction pathways by light excitation. Through commentary on seminal reports, we describe the principles behind the optical modulation of chemical reactivity and selectivity on plasmonic metal nanostructures. Central to these phenomena are excited charge carriers generated by plasmonic excitation, which modify the energy landscape available to surface reactive species and unlock pathways not conventionally available in thermal catalysis. Photogenerated carriers can trigger bond dissociation or desorption in an adsorbate-selective manner, drive charge transfer and multielectron redox reactions, and generate radical intermediates. Through one or more of these mechanisms, a specific pathway becomes favored under light. By improved control over these mechanisms, light-assisted catalysis can be transformational for chemical synthesis and energy conversion.

Comparative evaluation of proliferative potential and replicative senescence associated changes in mesenchymal stem cells derived from dental pulp and umbilical cord.

Mesenchymal stem cells (MSC) have been widely studied for tissue regeneration and cell-based therapy. MSC can be isolated from different body tissues while several biological waste sources like dental pulp, umbilical cord, cord derived blood, amniotic fluid or urine have also emerged as potential sources of MSCs. Specifically, isolation of MSCs from such non-conventional sources show promising outcomes due to the non-invasiveness of the extraction process and high proliferation capacity of the isolated MSC. However, these stem cells also exhibit the limitation of replicative senescence in long-term culture condition. Inter-cellular reactive oxygen species is an important contributor for inducing cellular senescence under long-term culture conditions. For translational application, it becomes imperative to compare the stem cells isolated from these sources for their senescence and proliferative properties. In this study, MSC were extracted from two different sources of biological waste materials-dental pulp and umbilical cord, and compared for their proliferation capacity and replicative senescence at different passage numbers (i.e. P2 and P6). Intracellular ROS production was significantly (p < 0.001) less in dental pulp stem cells culture in comparison to umbilical cord-derived stem cells at P6. The ß-gal expression also showed significantly (p < 0.001) low expression in DPSC culture compared to that of UCSC at P6. The study indicates the source of stem cells influences the proliferation capacity as well as replicative senescence of MSCs. This study will thus pave the path of future research in selecting appropriate stem cell source for regenerative medicine application.

Chromium/Photoredox Dual Catalyzed Synthesis of α-Benzylic Alcohols, Isochromanones, 1,2-Oxy Alcohols and 1,2-Thio Alcohols.

Herein, a Cr/Photoredox-catalyzed general synthetic strategy to access α-benzylic alcohols, isochromanones, oxy alcohols and thio alcohols is unveiled. Alkylation of aldehydes being a crucial C-C bond forming reaction, designing competent catalytic systems would render an attractive and decorated set of diverse alcohol motifs. Considering the challenges associated with classical organometallic chemistry, the strategy of dual catalysis is applied here to generate diverse alcohol motifs in a mild and efficient manner. The amalgamation of photocatalysis with chromium chemistry is chosen for this purpose to generate an environment with low basicity and thus, high chemoselectivity. With alkyl silanes as preferred coupling partners, this catalytic setup produces a broad substrate scope with an excellent functional group tolerance and displays a facile scale-up as well. Its application towards biologically relevant molecules and product diversification contributes to the synthetic utility of this method.

Depletion of S-adenosylmethionine pool and promoter hypermethylation of Arsenite methyltransferase in arsenic-induced skin lesion individuals: A case-control study from West Bengal, India.

Methylation of arsenic compounds in the human body occurs following a series of biochemical reactions in the presence of methyl donor S-adenosylmethionine (SAM) and catalyzed by arsenite methyltransferase (AS3MT). However, the extent and pattern of methylation differs among the arsenic exposed individuals leading to differential susceptibility. The mechanism for such inter-individual difference is enigmatic. In the present case-control study we recruited exposed individuals with and without arsenic induced skin lesion (WSL and WOSL), and an unexposed cohort, each having 120 individuals. Using ELISA, we observed a reduction in SAM levels (p < 0.05) in WSL compared to WOSL. Linear regression analysis revealed a negative correlation between urinary arsenic concentration and SAM concentration between the study groups. qRT-PCR revealed a significant down-regulation (p < 0.01) of key regulatory genes like MTHFR, MTR, MAT2A and MAT2B of SAM biogenesis pathway in WSL cohort. Methylation-specific PCR revealed significant promoter hypermethylation of AS3MT (WSL vs. WOSL: p < 0.01) which resulted in its subsequent transcriptional repression (WSL vs. WOSL: p < 0.001). Linear regression analysis also showed a negative correlation between SAM concentration and percentage of promoter methylation. Taken together, these results indicate that reduction in SAM biogenesis along with a higher utilization of SAM results in a decreased availability of methyl donor. These along with epigenetic down-regulation of AS3MT may be responsible for higher susceptibility in arsenic exposed individuals.

Frequency-dependent specific heat in quantum supercooled liquids: A mode-coupling study.

Frequency-dependence of specific heat in supercooled hard sphere liquid is computed using quantum mode-coupling theory (QMCT). Mode-coupling equations are solved using a recently proposed perturbative method that allows us to study relaxation in the moderate quantum regime where quantum effects assist liquid to glass transition. Zwanzig's formulation is used to compute the frequency-dependent specific heat in the supercooled state using dynamical information from QMCT. Specific heat shows strong variation as the quantumness of the liquid is changed, which becomes more significant as density is increased. It is found that, near the transition point, different dynamical modes contribute to specific heat in classical and quantum liquids.

Structural relaxation in quantum supercooled liquids: A mode-coupling approach.

We study supercooled dynamics in a quantum hard-sphere liquid using quantum mode-coupling formulation. In the moderate quantum regime, classical cage effects lead to slower dynamics compared to the strongly quantum regime, where tunneling overcomes classical caging, leading to faster relaxation. As a result, the glass transition critical density can become significantly higher than for the classical liquids. A perturbative approach is used to solve time dependent quantum mode-coupling equations to study in detail the dynamics of the supercooled liquid in the moderate quantum regime. Similar to the classical case, the relaxation time shows the power-law increase with the increase in the density in the supercooled regime. However, the power-law exponent is found to be dependent on the quantumness; it increases linearly as the quantumness is increased in the moderate quantum regime.

Tuning the Morphology of Protein-Inorganic Calcium-Phosphate Supraparticles via Directed Assembly.

Understanding the phenomena that govern complex interfacial and directed assemblies is essential for both control and scale-up of particle syntheses. The present work describes an effort to understand, control, and tune the formation of protein-inorganic calcium-phosphate supraparticles that are produced at an oscillating air-water interface created by end-over-end rotation of the synthesis solution. Supraparticles were synthesized under an array of different conditions that varied reagent concentration, the presence of additives, tube size, and rotational speed. Paired with a fluid mechanics model of the end-over-end rotation and dimensional analysis, the sensitivity of the synthesis to physicochemical and mechanical parameters was determined. Surface tension and bubble formation were found to be important criteria for changing the size distribution of supraparticles. Thresholds for the values of the Froude, Iribarren, and rotational Reynolds numbers were identified for narrowing particle size distribution. These results both guide the specific protein-inorganic supraparticle synthesis described here and inform future manipulation and scale-up of other complex interfacial colloidal assemblies.