Growth Factor Binding Peptides in Poly (Ethylene Glycol) Diacrylate (PEGDA)-Based Hydrogels for an Improved Healing Response of Human Dermal Fibroblasts

Growth factors (GF) are critical cytokines in wound healing. However, the direct delivery of these biochemical cues into a wound site significantly increases the cost of wound dressings and can lead to a strong immunological response due to the introduction of a foreign source of GFs. To overcome this challenge, we designed a poly(ethylene glycol) diacrylate (PEGDA) hydrogel with the potential capacity to sequester autologous GFs directly from the wound site. We demonstrated that synthetic peptide sequences covalently tethered to PEGDA hydrogels physically retained human transforming growth factor beta 1 (hTGFβ1) and human vascular endothelial growth factor (hVEGF) at 3.2 and 0.6 ng/mm2, respectively. In addition, we demonstrated that retained hTGFβ1 and hVEGF enhanced human dermal fibroblasts (HDFa) average cell surface area and proliferation, respectively, and that exposure to both GFs resulted in up to 1.9-fold higher fraction of area covered relative to the control. After five days in culture, relative to the control surface, non-covalently bound hTGFβ1 significantly increased the expression of collagen type I and hTGFβ1 and downregulated vimentin and matrix metalloproteinase 1 expression. Cumulatively, the response of HDFa to hTGFβ1 aligns well with the expected response of fibroblasts during the early stages of wound healing

The Role of Gender Inequality and Health Expenditure on the Coverage of Demand for Family Planning Satisfied by Modern Contraceptives: A Multilevel Analysis of Cross-Sectional Studies in 14 LAC Countries

BACKGROUND: Despite international efforts to improve reproductive health indicators, little attention is paid to the contributions of contextual factors to modern contraceptive coverage, especially in the Latin America and the Caribbean (LAC) region. This study aimed to identify the association between country-level Gender Inequality and Health Expenditure with demand for family planning satisfied by modern contraceptive methods (DFPSm) in Latin American sexually active women. METHODS: Our analyses included data from the most recent (post-2010) Demographic and Health Survey or Multiple Indicator Cluster Survey from 14 LAC countries. Descriptive analyses and multilevel logistic regressions were performed. Six individual-level factors were included. The effect of the country-level factors Gender Inequality Index (GII) and Current Health Expenditure on DFPSm was investigated. FINDINGS: DFPSm ranged from 41.8% (95% CI: 40.2-43.5) in Haiti to 85.6% (95% CI: 84.9-86.3) in Colombia, with an overall median coverage of 77.8%. A direct association between the odds of DFPSm and woman\u27s education, wealth index, and the number of children was identified. Women from countries in the highest GII tertile were less likely (OR: 0.32, 95% CI: 0.13-0.76) to have DFPSm than those living in countries in the lowest tertile. INTERPRETATION: Understanding the contribution of country-level factors to modern contraception may allow macro-level actions focused on the population\u27s reproductive needs. In this sense, country-level gender inequalities play an important role, as well as individual factors such as wealth and education. FUNDING: Bill and Melinda Gates Foundation and Associação Brasileira de Saúde Coletiva (ABRASCO)

Structural basis of nuclear import of flap endonuclease 1 (FEN1)

Flap endonuclease 1 (FEN1) is a member of the nuclease family and is structurally conserved from bacteriophages to humans. This protein is involved in multiple DNA-processing pathways, including Okazaki fragment maturation, stalled replication-fork rescue, telomere maintenance, long-patch base-excision repair and apoptotic DNA fragmentation. FEN1 has three functional motifs that are responsible for its nuclease, PCNA-interaction and nuclear localization activities, respectively. It has been shown that the C-terminal nuclear localization sequence (NLS) facilitates nuclear localization of the enzyme during the S phase of the cell cycle and in response to DNA damage. To determine the structural basis of the recognition of FEN1 by the nuclear import receptor importin alpha, the crystal structure of the complex of importin alpha with a peptide corresponding to the FEN1 NLS was solved. Structural studies confirmed the binding of the FEN1 NLS as a classical bipartite NLS; however, in contrast to the previously proposed (KRKX8KKK367)-K-354 sequence, it is the (354)KRX(10)KKAK(369) sequence that binds to importin alpha. This result explains the incomplete inhibition of localization that was observed on mutating residues (KKK367)-K-365. Acidic and polar residues in the X-10 linker region close to the basic clusters play an important role in binding to importin alpha. These results suggest that the basic residues in the N-terminal basic cluster of bipartite NLSs may play roles that are more critical than those of the many basic residues in the C-terminal basic cluster

High-velocity outflows in massive post-starburst galaxies at z > 1

We investigate the prevalence of galactic-scale outflows in post-starburst (PSB) galaxies at high redshift (1 1010M⊙⁠) PSBs at z > 1, there is clear evidence for a strong blue-shifted component to the Mg ii absorption feature, indicative of high-velocity outflows (⁠vout∼1150±160kms−1⁠) in the interstellar medium. We conclude that such outflows are typical in massive PSBs at this epoch, and potentially represent the residual signature of a feedback process that quenched these galaxies. Using full spectral fitting, we also obtain a typical stellar velocity dispersion σ* for these PSBs of ∼200kms−1⁠, which confirms they are intrinsically massive in nature (dynamical mass Md∼1011M⊙⁠). Given that these high-z PSBs are also exceptionally compact (re ∼ 1–2kpc⁠) and spheroidal (Sérsic index n ∼ 3), we propose that the outflowing winds may have been launched during a recent compaction event (e.g. major merger or disc collapse) that triggered either a centralized starburst or active galactic nuclei (AGN) activity. Finally, we find no evidence for AGN signatures in the optical spectra of these PSBs, suggesting they were either quenched by stellar feedback from the starburst itself, or that if AGN feedback is responsible, the AGN episode that triggered quenching does not linger into the post-starburst phase.Publisher PDFPeer reviewe

Prenylated flavonoid-enriched fraction from maclura tinctoria shows biological activity against Staphylococcus aureus and protects galleria mellonella larvae from bacterial infection.

Background: The Atlantic Forest biome extends along the entire Brazilian coast and is home to approximately 20,000 plant species, many of which are endemic; it is considered one of the hotspot regions of the planet. Several of these species are sources of natural products with biological activities that are still unknown. In this study, we evaluated the antimicrobial activity of 90 extracts derived from native Atlantic Forest tree species against Staphylococcus aureus, an important human and veterinary pathogen. Methods: Extracts from native Atlantic Forest tree species were evaluated for their antimicrobial activity against S. aureus by in vitro standard methods. Phytochemical fractionation of the extract from Maclura tinctoria was performed by liquid-liquid partitioning. LC-DAD-ESI-MS was used for identification of constituents in the most active fraction. Damage of cells and alterations in the permeability of cell membrane were determined by atomic force microscopy (AFM) and crystal violet uptake assay, respectively. In vivo antimicrobial activity was evaluated using Galleria mellonella larvae infected with S. aureus with survival data collected using the Kaplan-Meier method. Results: Among the organic or aqueous extracts tested here, 26 showed biological activity. Eight species showed relevant results, with a minimum inhibitory concentration (MIC) below 1?mg/mL. Antibacterial activity was registered for three species for the first time. An organic extract from Maclura tinctoria leaves showed the lowest MIC (0.08?mg/mL). Fractionation of this extract by liquid-liquid partitioning led to obtaining fraction 11FO d with a MIC of 0.04?mg/mL. This fraction showed strong activity against veterinary S. aureus isolates and contributed to the increased survival of Galleria mellonella larvae infected with S. aureus ATCC 29213. The bacterial surface was not altered by the presence of 11FO d, and no cell membrane damage was detected. The LC-DAD-ESI/MS analyses identified prenylated flavonoids as the major constituents responsible for the antibacterial activity of this active extract. Conclusion: A fraction enriched in prenylated isoflavones and flavanones from M. tinctoria showed in vitro and in vivo efficacy as antistaphylococcal agents. These findings justify the need for further research to elucidate the mechanisms of action of these compounds

Elliptic flow of charged particles in Pb-Pb collisions at 2.76 TeV

We report the first measurement of charged particle elliptic flow in Pb-Pb collisions at 2.76 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurement is performed in the central pseudorapidity region (|$\eta$|<0.8) and transverse momentum range 0.2< $p_{\rm T}$< 5.0 GeV/$c$. The elliptic flow signal v$_2$, measured using the 4-particle correlation method, averaged over transverse momentum and pseudorapidity is 0.087 $\pm$ 0.002 (stat) $\pm$ 0.004 (syst) in the 40-50% centrality class. The differential elliptic flow v$_2(p_{\rm T})$ reaches a maximum of 0.2 near $p_{\rm T}$ = 3 GeV/$c$. Compared to RHIC Au-Au collisions at 200 GeV, the elliptic flow increases by about 30%. Some hydrodynamic model predictions which include viscous corrections are in agreement with the observed increase.Comment: 10 pages, 4 captioned figures, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/389

Estrogenic Plant Extracts Reverse Weight Gain and Fat Accumulation without Causing Mammary Gland or Uterine Proliferation

Long-term estrogen deficiency increases the risk of obesity, diabetes and metabolic syndrome in postmenopausal women. Menopausal hormone therapy containing estrogens might prevent these conditions, but its prolonged use increases the risk of breast cancer, as wells as endometrial cancer if used without progestins. Animal studies indicate that beneficial effects of estrogens in adipose tissue and adverse effects on mammary gland and uterus are mediated by estrogen receptor alpha (ERα). One strategy to improve the safety of estrogens to prevent/treat obesity, diabetes and metabolic syndrome is to develop estrogens that act as agonists in adipose tissue, but not in mammary gland and uterus. We considered plant extracts, which have been the source of many pharmaceuticals, as a source of tissue selective estrogens. Extracts from two plants, Glycyrrhiza uralensis (RG) and Pueraria montana var. lobata (RP) bound to ERα, activated ERα responsive reporters, and reversed weight gain and fat accumulation comparable to estradiol in ovariectomized obese mice maintained on a high fat diet. Unlike estradiol, RG and RP did not induce proliferative effects on mammary gland and uterus. Gene expression profiling demonstrated that RG and RP induced estradiol-like regulation of genes in abdominal fat, but not in mammary gland and uterus. The compounds in extracts from RG and RP might constitute a new class of tissue selective estrogens to reverse weight gain, fat accumulation and metabolic syndrome in postmenopausal women