Access to genetically encoded data depends on the dynamics of DNA-binding proteins searching for specific target sites in the genome. This search process is thought to occur by facilitated ...diffusion—a combination of three-dimensional diffusion and one-dimensional sliding. Although facilitated diffusion is capable of significantly speeding up the search in vitro, the importance of this mechanism in vivo remains unclear. We use numeric simulations and analytical theory to model the target-search dynamics of DNA-binding proteins under a wide range of conditions. Our models reproduce experimental measurements of search-rate enhancement within bulk in vitro experiments, as well as the target search time for transcription factors measured in vivo. We find that facilitated diffusion can accelerate the search process only for a limited range of parameters and only under dilute DNA conditions. We address the role of DNA configuration and confinement, demonstrating that facilitated diffusion does not speed up the search on coiled versus straight DNA. Furthermore, we show that, under in vivo conditions, the search process becomes effectively diffusive and is independent of DNA configuration. We believe our results cast in a new light the role of facilitated diffusion in DNA targeting kinetics within the cell.
Hyaluronic Acid (HA)-based dermal formulations have rapidly gained a large consensus in aesthetic medicine and dermatology. HA, highly expressed in the Extracellular Matrix (ECM), acts as an ...activator of biological cascades, stimulating cell migration and proliferation, and operating as a regulator of the skin immune surveillance, through specific interactions with its receptors. HA may be used in topical formulations, as dermal inducer, for wound healing. Moreover, intradermal HA formulations (injectable HA) provide an attractive tool to counteract skin aging (e.g., facial wrinkles, dryness, and loss of elasticity) and restore normal dermal functions, through simple and minimally invasive procedures. Biological activity of a commercially available hyaluronic acid, Profhilo®, based on NAHYCO™ technology, was compared to H-HA or L-HA alone. The formation of hybrid cooperative complexes was confirmed by the sudden drop in η0 values in the rheological measurements. Besides, hybrid cooperative complexes proved stable to hyaluronidase (BTH) digestion. Using in vitro assays, based on keratinocytes, fibroblasts cells and on the Phenion® Full Thickness Skin Model 3D, hybrid cooperative complexes were compared to H-HA, widely used in biorevitalization procedures, and to L-HA, recently proposed as the most active fraction modulating the inflammatory response. Quantitative real-time PCR analyses were accomplished for the transcript quantification of collagens and elastin. Finally immunofluorescence staining permitted to evaluate the complete biosynthesis of all the molecules investigated. An increase in the expression levels of type I and type III collagen in fibroblasts and type IV and VII collagen in keratinocytes were found with the hybrid cooperative complexes, compared to untreated cells (CTR) and to the H-HA and L-HA treatments. The increase in elastin expression found in both cellular model and in the Phenion® Full Thickness Skin Model 3D also at longer time (up to 7 days), supports the clinically observed improvement of skin elasticity. The biomarkers analyzed suggest an increase of tissue remodeling in the presence of Profhilo®, probably due to the long lasting release and the concurrent action of the two HA components.
Gene regulatory proteins find their target sites on DNA remarkably quickly; the experimental binding rate for lac repressor is orders-of-magnitude higher than predicted by free diffusion alone. It ...has been proposed that nonspecific binding aids the search by allowing proteins to slide and hop along DNA. We develop a reaction-diffusion theory of protein translocation that accounts for transport both on and off the strand and incorporates the physical conformation of DNA. For linear DNA modeled as a wormlike chain, the distribution of hops available to a protein exhibits long, power-law tails that make the long-time displacement along the strand superdiffusive. Our analysis predicts effective superdiffusion coefficients for given nonspecific binding and unbinding rate parameters. Translocation rate exhibits a maximum at intermediate values of the binding rate constant, while search efficiency is optimized at larger binding rate constant values. Thus, our theory predicts a region of values of the nonspecific binding and unbinding rate parameters that balance the protein translocation rate and the efficiency of the search. Published data for several proteins falls within this predicted region of parameter values.
Background/Aims: Adipose-derived Stem Cells (ASCs) are used in Regenerative Medicine, including fat grafting, recovery from local tissue ischemia and scar remodeling. The aim of this study was to ...evaluate hyaluronan based gel effects on ASCs differentiation and proliferation. Methods: Comparative analyses using high (H) and low (L) molecular weight hyaluronans (HA), hyaluronan hybrid cooperative complexes (HCCs), and high and medium cross-linked hyaluronan based dermal fillers were performed. Human ASCs were characterized by flow cytometry using CD90, CD34, CD105, CD29, CD31, CD45 and CD14 markers. Then, cells were treated for 7, 14 and 21 days with hyaluronans. Adipogenic differentiation was evaluated using Oil red-O staining and expression of leptin, PPAR-γ, LPL and adiponectin using qRT-PCR. Adiponectin was analyzed by immunofluorescence, PPAR-γ and adiponectin were analyzed using western blotting. ELISA assays for adiponectin and leptin were performed. Results: HCCs highly affected ASCs differentiation by up-regulating adipogenic genes and related proteins, that were also secreted in the culture medium. H-HA and L-HA induced a lower level of ASCs differentiation. Conclusion: HCCs-based formulations clearly enhance adipogenic differentiation and proliferation, when compared with linear HA and cross-linked hyaluronans. Injection of HCCs in subdermal fat compartment may recruit and differentiate stem cells in adipocytes, and considerably improving fat tissue renewal.
•Findings revealed overall declines in pre- to post-immigration alcohol use.•Gender, income, and national origin were associated with distinct drinking patterns.•Results inform future alcohol ...intervention research on Latinx immigrants early in the immigration process.
Despite important research advances on the alcohol use behaviors of Latinx immigrants, the bulk of existing evidence has focused on alcohol use patterns after immigrant’s arrival to the US. The present study examines pre- to post immigration alcohol use trajectories among Latinx immigrants of diverse national origins throughout their first decade in the United States.
Data for this longitudinal study was collected between 2007 and 2017. At baseline, retrospective pre-immigration alcohol use data was collected on 527 Cuban, South American and Central American participants ages 18–34 who immigrated to the US less than one year prior. Three subsequent follow-up assessments over the past 10 years have collected data on post-immigration alcohol use.
Overall decreases in pre- to post-immigration alcohol use were found. Gender, income, and national origin were associated with distinct drinking patterns after immigration.
Findings underscore the importance of examining pre-immigration experiences among Latinx immigrants, in addition to longitudinal alcohol use patterns after immigration. This knowledge is important not only from an epidemiological perspective, but for the development of effective culturally relevant alcohol interventions targeting Latinx immigrants early in the immigration process.
Marianismo is a Latino cultural value that describes both positive and negative aspects of traditional Latina femininity. Marianismo emphasizes culturally valued qualities such as interpersonal ...harmony, inner strength, self-sacrifice, and morality. Endorsement of marianismo is hypothesized to correlate with individual economic, educational, and personal variables. Marianismo also is theorized to potentially influence attitudes about, experiences of, and responses to intimate partner violence (IPV) among Latina women. The present study examined whether endorsement of marianismo beliefs mitigated or exacerbated psychological distress after experiences of IPV in a sample of 205 recently immigrated Latina women, aged 18 to 23 years. Latina women experiencing higher levels of IPV and endorsing greater marianismo beliefs were hypothesized to indicate greater psychological distress. Unexpectedly, women who endorsed more Subordinate to Others/Self-Silencing to Maintain Harmony marianismo beliefs indicated more psychological distress (p = .05), greater symptoms of psychological distress (p = .01), and greater average distress (p = .03) when they also reported less IPV than peers. Implications for understanding Latinas’ responses to and reporting of IPV, as well as for culturally tailored counseling interventions for this underserved and understudied population, are discussed.
We measured the distance between fluorescent-labeled DNA loci of various interloci contour lengths in Caulobacter crescentus swarmer cells to determine the in vivo configuration of the chromosome. ...For DNA segments less than about 300 kb, the mean interloci distances, 〈 r 〉, scale as n ⁰.²², where n is the contour length, and cell-to-cell distribution of the interloci distance r is a universal function of r/n ⁰.²² with broad cell-to-cell variability. For DNA segments greater than about 300 kb, the mean interloci distances scale as n , in agreement with previous observations. The 0.22 value of the scaling exponent for short DNA segments is consistent with theoretical predictions for a branched DNA polymer structure. Predictions from Brownian dynamics simulations of the packing of supercoiled DNA polymers in an elongated cell-like confinement are also consistent with a branched DNA structure, and simulated interloci distance distributions predict that confinement leads to “freezing” of the supercoiled configuration. Lateral positions of labeled loci at comparable positions along the length of the cell are strongly correlated when the longitudinal locus positions differ by <0.16 μm. We conclude that the chromosome structure is supercoiled locally and elongated at large length scales and that substantial cell-to-cell variability in the interloci distances indicates that in vivo crowding prevents the chromosome from reaching an equilibrium arrangement. We suggest that the force causing rapid transport of loci remote from the parS centromere to the distal cell pole may arise from the release at the polar region of potential energy within the supercoiled DNA.
Pluronic P105 micelles are potential candidates as chemotherapy drug delivery vehicles using ultrasonic stimulation as a release trigger. Acoustic power has been previously shown to release two ...anthracycline agents from these polymeric carriers. In this study, an ultrasonic exposure chamber with fluorescence detection was used to examine the mechanism of doxorubicin release from P105 micelles. Acoustic spectra were collected and analyzed, at the same spatial position as fluorescence data, to probe the role of cavitation in drug release. Our study showed a strong correlation between percent drug release and subharmonic acoustic emissions, and we attribute the drug release to collapse cavitation that perturbs the structure of the micelle and releases drug.
Socio-cultural factors, such as familismo, social support, machismo, and multigroup ethnic identity, are strongly associated with Latina/o immigrants’ alcohol misuse and depressive symptoms. However, ...research has rarely explored whether unobserved groups of Latina/o immigrants with similar socio-cultural factors exist. Latent Profile analysis can illuminate which subgroups to target, or which socio-cultural factors need to be supported, to have an impact on the prevention and treatment of alcohol use and/or depression in the Latina/o immigrant population. Cross sectional data from on ongoing longitudinal investigation was utilized (N = 518 Latina/o adults living in Miami-Dade County, Florida and have immigrated to the US within one year prior to assessment). Latent Profile Analyses (LPA) were conducted utilizing validated measures of familismo, social support, neighborhood collective efficacy, ethnic identity, machismo, caballerismo, and marianismo. The LPA revealed three, significantly different profiles: (1) low socio-cultural protection (n = 155, 29.98 %), (2) high socio-cultural protection (n = 21, 4.06 %), and (3) high socio-, low-cultural protection (n = 341, 65.96 %). Profile membership was associated significantly with immigrant documentation status, education level, and past family history of substance use. Results indicate that Latina/o immigrants in the low socio-cultural protection group had significantly higher alcohol use compared to high socio-, low cultural protection group. No significant differences were found for depressive symptoms. We discuss implications of our findings and encourage researchers to continue to unpack the complexities associated with socio-cultural factors and Latina/o mental and behavioral health. Specifically, research should focus on socio-cultural factors can provide protection from negative health outcomes and increase resiliency among this population.
Objective
Identifying and understanding determinants of alcohol use behavior among Hispanic immigrants is an increasingly significant public health concern. Although prior research has examined ...associations of cultural stressors with alcohol use among Hispanics, few studies have tested these associations among recent adult immigrants. As such, this study aimed to examine (a) the association of immigration stress on alcohol use severity among recently immigrated Hispanic adults (≤ 1 year in the United States) and (b) the moderating effects of gender, immigration status, and social support.
Method
A hierarchical multiple regression and moderation analyses were conducted on a sample of 527 participants in South Florida.
Results
Results indicated that, after controlling for demographic variables, preimmigration drinking behavior, and dimensions of social support, the association of higher immigration stress with higher alcohol use severity was statistically significant. Moderation analyses indicated that immigration stress had a statistically significant association with alcohol use severity among men, but not women. Also, dimensions of social support consistently reduced the deleterious effect of immigration stress on alcohol use severity.
Conclusion
This study adds to the scarce literature on cultural stressors and alcohol use among recent Hispanic immigrants. Findings suggest that it may be important to design gender‐specific interventions and that increasing levels of social support may offset the effects of immigration stress on alcohol use.
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