25 research outputs found
Toward a Designable Extracellular Matrix: Molecular Dynamics Simulations of an Engineered Laminin-mimetic, Elastin-like Fusion Protein
Native extracellular matrices (ECMs), such as those of the human brain and
other neural tissues, exhibit networks of molecular interactions between
specific matrix proteins and other tissue components. Guided by these naturally
self-assembling supramolecular systems, we have designed a matrix-derived
protein chimera that contains a laminin globular-like (LG) domain fused to an
elastin-like polypeptide (ELP). All-atom, classical molecular dynamics
simulations of our designed laminin-elastin fusion protein reveal
temperature-dependent conformational changes, in terms of secondary structure
composition, solvent accessible surface area, hydrogen bonding, and surface
hydration. These properties illuminate the phase behavior of this fusion
protein, via the emergence of -sheet character in
physiologically-relevant temperature ranges.Comment: 53 pages, 7 figures in the main text; Supporting Information contains
1 table, 12 figures, 4 trajectory animations (videos
ΠΠΈΠ½Π°ΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ΅Π½Π΄Π΅Π½ΡΠΈΠΈ Π² ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΈΠΈ ΠΏΡΠ΅Π΄ΠΌΠ΅ΡΠ° Π»ΠΈΠ½Π³Π²ΠΎΡΠΊΠΎΠ»ΠΎΠ³ΠΈΠΈ
ΠΠΊΠΎΠ»ΠΎΠ³ΠΈΠ·Π°ΡΠΈΡ Π²ΡΠ΅Ρ
ΡΡΠ΅Ρ ΠΎΠ±ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΆΠΈΠ·Π½ΠΈ ΠΈ ΡΠ°ΠΌΠΎΠ³ΠΎ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° ΡΠΈΡΠΎΠΊΠΎ ΠΎΠ±ΡΡΠΆΠ΄Π°Π΅ΡΡΡ Π²ΠΎ ΠΌΠ½ΠΎΠ³ΠΈΡ
Π½Π°ΡΠΊΠ°, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΈ Π² ΠΎΠ±Π»Π°ΡΡΠΈ ΡΠ·ΡΠΊΠ°. ΠΠΎ ΠΌΠ½ΠΎΠ³ΠΈΡ
ΡΠ°Π±ΠΎΡΠ°Ρ
Π»ΠΈΠ½Π³Π²ΠΈΡΡΠΎΠ² ΡΠΊΠΎΠ»ΠΎΠ³ΠΈΡ ΡΠ·ΡΠΊΠ° ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ΅ΡΡΡ ΠΊΠ°ΠΊ Π½Π°ΡΠΊΠ° ΠΎ
Π²Π·Π°ΠΈΠΌΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡΡ
ΠΌΠ΅ΠΆΠ΄Ρ ΡΠ·ΡΠΊΠΎΠΌ ΠΈ Π΅Π³ΠΎ ΠΎΠΊΡΡΠΆΠ΅Π½ΠΈΠ΅ΠΌ, ΡΠ°ΠΊ ΠΊΠ°ΠΊ ΡΠ·ΡΠΊ ΡΡΡΠ΅ΡΡΠ²ΡΠ΅Ρ Π½Π΅ ΡΠΎΠ»ΡΠΊΠΎ Π² ΡΠΎΠ·Π½Π°Π½ΠΈΠΈ Π³ΠΎΠ²ΠΎΡΡΡΠΈΡ
Π½Π° Π½Π΅ΠΌ ΠΈ ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΡΠ΅Ρ ΡΠΎΠ»ΡΠΊΠΎ ΠΏΡΠΈ Π²Π·Π°ΠΈΠΌΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡΡ
Ρ Π΄ΡΡΠ³ΠΈΠΌΠΈ ΠΊΠΎΠΌΠΌΡΠ½ΠΈΠΊΠ°Π½ΡΠ°ΠΌΠΈ ΠΈ Ρ ΠΈΡ
ΡΠΎΡΠΈΠ°Π»ΡΠ½ΡΠΌ ΠΈ ΠΏΡΠΈΡΠΎΠ΄Π½ΡΠΌ ΠΎΠΊΡΡΠΆΠ΅Π½ΠΈΠ΅ΠΌ. Π ΡΡΠΎΠΌ ΠΊΠΎΠ½ΡΠ΅ΠΊΡΡΠ΅ ΠΏΠΎΠ½ΡΡΠΈΠ΅ Β«ΡΠ·ΡΠΊΠΎΠ²ΠΎΠ΅ ΡΠΎΠ·Π½Π°Π½ΠΈΠ΅Β» ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅Ρ ΡΠΎΠ±ΠΎΠΉ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΡΡ ΠΊΠ°ΡΡΠΈΠ½Ρ Π²Π·Π°ΠΈΠΌΠΎΡΠ²ΡΠ·ΠΈ ΠΊΡΠ»ΡΡΡΡΡ ΠΈ ΠΎΠ±ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΆΠΈΠ·Π½ΠΈ ΡΠΎΡΠΈΡΠΌΠ°, ΠΊΠΎΡΠΎΡΠ°Ρ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ΅Ρ Π΅Π³ΠΎ ΠΏΡΠΈΡ
ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΡΠ²ΠΎΠ΅ΠΎΠ±ΡΠ°Π·ΠΈΠ΅ ΠΈ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ΅ΡΡΡ Π΄Π°Π½Π½ΠΎΠ³ΠΎ ΡΠ·ΡΠΊΠ°
Does Glycine max leaves or Garcinia Cambogia promote weight-loss or lower plasma cholesterol in overweight individuals: a randomized control trial
<p>Abstract</p> <p>Background</p> <p>Natural food supplements with high flavonoid content are often claimed to promote weight-loss and lower plasma cholesterol in animal studies, but human studies have been more equivocal. The aim of this study was firstly to determine the effectiveness of natural food supplements containing <it>Glycine max </it>leaves extract (EGML) or <it>Garcinia cambogia </it>extract (GCE) to promote weight-loss and lower plasma cholesterol. Secondly to examine whether these supplements have any beneficial effect on lipid, adipocytokine or antioxidant profiles.</p> <p>Methods</p> <p>Eighty-six overweight subjects (Male:Female = 46:40, age: 20~50 yr, BMI > 23 < 29) were randomly assigned to three groups and administered tablets containing EGML (2 g/day), GCE (2 g/day) or placebo (starch, 2 g/day) for 10 weeks. At baseline and after 10 weeks, body composition, plasma cholesterol and diet were assessed. Blood analysis was also conducted to examine plasma lipoproteins, triglycerides, adipocytokines and antioxidants.</p> <p>Results</p> <p>EGML and GCE supplementation failed to promote weight-loss or any clinically significant change in %body fat. The EGML group had lower total cholesterol after 10 weeks compared to the placebo group (p < 0.05). EGML and GCE had no effect on triglycerides, non-HDL-C, adipocytokines or antioxidants when compared to placebo supplementation. However, HDL-C was higher in the EGML group (p < 0.001) after 10 weeks compared to the placebo group.</p> <p>Conclusions</p> <p>Ten weeks of EGML or GCE supplementation did not promote weight-loss or lower total cholesterol in overweight individuals consuming their habitual diet. Although, EGML did increase plasma HDL-C levels which is associated with a lower risk of atherosclerosis.</p
Crime among irregular immigrants and the influence of internal border control
Both the number of crime suspects without legal status and the number of irregular or undocumented immigrants held in detention facilities increased substantially in theNetherlands between 1997 and 2003. In this period, theDutch state increasingly attempted to exclude irregular immigrants from the formal labour market and public provisions. At the same time the registered crime among irregular migrants rose. The 'marginalisation thesis' asserts that a larger number of migrants have become involved in crime in response to a decrease in conventional life chances. Using police and administrative data, the present study takes four alternative interpretations into consideration based on: 1) reclassification of immigrant statuses by the state and redefinition of the law, 2) criminal migration and crossborder crime, 3) changes in policing, and 4) demographic changes. A combination of factors is found to have caused the rise in crime, but the marginalisation thesis still accounts for at least 28%. These findings accentuate the need for a more thorough discussion on the intended and unintended consequences of border control for immigrant crime
Climate change effects on agriculture: Economic responses to biophysical shocks
Agricultural production is sensitive to weather and thus directly affected by climate change. Plausible estimates of these climate change impacts require combined use of climate, crop, and economic models. Results from previous studies vary substantially due to differences in models, scenarios, and data. This paper is part of a collective effort to systematically integrate these three types of models. We focus on the economic component of the assessment, investigating how nine global economic models of agriculture represent endogenous responses to seven standardized climate change scenarios produced by two climate and five crop models. These responses include adjustments in yields, area, consumption, and international trade. We apply biophysical shocks derived from the Intergovernmental Panel on Climate Change's representative concentration pathway with end-of-century radiative forcing of 8.5 W/m2. The mean biophysical yield effect with no incremental CO2 fertilization is a 17% reduction globally by 2050 relative to a scenario with unchanging climate. Endogenous economic responses reduce yield loss to 11%, increase area of major crops by 11%, and reduce consumption by 3%. Agricultural production, cropland area, trade, and prices show the greatest degree of variability in response to climate change, and consumption the lowest. The sources of these differences include model structure and specification; in particular, model assumptions about ease of land use conversion, intensification, and trade. This study identifies where models disagree on the relative responses to climate shocks and highlights research activities needed to improve the representation of agricultural adaptation responses to climate change
Microscale Architecture in Biomaterial Scaffolds for Spatial Control of Neural Cell Behavior
Biomaterial scaffolds mimic aspects of the native central nervous system (CNS) extracellular matrix (ECM) and have been extensively utilized to influence neural cell (NC) behavior in in vitro and in vivo settings. These biomimetic scaffolds support NC cultures, can direct the differentiation of NCs, and have recapitulated some native NC behavior in an in vitro setting. However, NC transplant therapies and treatments used in animal models of CNS disease and injury have not fully restored functionality. The observed lack of functional recovery occurs despite improvements in transplanted NC viability when incorporating biomaterial scaffolds and the potential of NC to replace damaged native cells. The behavior of NCs within biomaterial scaffolds must be directed in order to improve the efficacy of transplant therapies and treatments. Biomaterial scaffold topography and imbedded bioactive cues, designed at the microscale level, can alter NC phenotype, direct migration, and differentiation. Microscale patterning in biomaterial scaffolds for spatial control of NC behavior has enhanced the capabilities of in vitro models to capture properties of the native CNS tissue ECM. Patterning techniques such as lithography, electrospinning and three-dimensional (3D) bioprinting can be employed to design the microscale architecture of biomaterial scaffolds. Here, the progress and challenges of the prevalent biomaterial patterning techniques of lithography, electrospinning, and 3D bioprinting are reported. This review analyzes NC behavioral response to specific microscale topographical patterns and spatially organized bioactive cues
Oligodendrocyte Precursor Cell Viability, Proliferation, and Morphology is Dependent on Mesh Size and Storage Modulus in 3D Poly(ethylene glycol)-Based Hydrogels
Oligodendrocytes
in the central nervous system (CNS) are responsible
for generating myelin, an electrically insulating layer around neuronal
axons. When myelin is damaged, neurons are incapable of sustaining
normal communications, which can manifest in patients as pain and
loss of mobility and vision. A plethora of research has used biomaterials
to promote neuronal regeneration, but despite the wide implications
of a disrupted myelin sheath, very little is known about how biomaterial
environments impact proliferation of oligodendrocyte precursor cells
(OPCs) or their differentiation into myelinating oligodendrocytes.
This work investigates how the storage modulus and mesh size of a
polyethylene glycol (PEG)-based hydrogel, varied via two different
mechanisms, directly affect the proliferation of two OPC lines encapsulated
and cultured in 3D. Viability and proliferation of both OPC lines
was dependent on hydrogel swelling and stiffness, where the concentration
of ATP increased more in the more compliant gels. OPCs multiplied
in the 3D hydrogels, creating significantly larger spheroids in the
less cross-linked conditions. Stiffer, more highly cross-linked materials
lead to greater expression of PDGFRΞ±, an OPC receptor, indicating
that fewer cells were committed to the oligodendrocyte lineage or
had dedifferentiated in compliant materials. Laminin incorporation
in the 3D matrix was found to have little effect on viability or proliferation.
These findings provide valuable information on how mesh size and stiffness
affect OPCs where more compliant materials favor proliferation of
OPCs with less commitment to a mature oligodendrocyte lineage. Such
information will be useful in the development of translational biomaterials
to stimulate oligodendrocyte maturation for neural regeneration
Tetrakis(hydroxymethyl) Phosphonium Chloride as a Covalent Cross-Linking Agent for Cell Encapsulation within Protein-Based Hydrogels
Native tissues provide cells with complex, three-dimensional
(3D)
environments comprised of hydrated networks of extracellular matrix
proteins and sugars. By mimicking the dimensionality of native tissue
while deconstructing the effects of environmental parameters, protein-based
hydrogels serve as attractive, in vitro platforms to investigate cellβmatrix
interactions. For cell encapsulation, the process of hydrogel formation
through physical or covalent cross-linking must be mild and cell compatible.
While many chemical cross-linkers are commercially available for hydrogel
formation, only a subset are cytocompatible; therefore, the identification
of new and reliable cytocompatible cross-linkers allows for greater
flexibility of hydrogel design for cell encapsulation applications.
Here, we introduce tetrakisΒ(hydroxymethyl) phosphonium chloride (THPC)
as an inexpensive, amine-reactive, aqueous cross-linker for 3D cell
encapsulation in protein-based hydrogels. We characterize the THPC-amine
reaction by demonstrating THPC's ability to react with primary and
secondary amines of various amino acids. In addition, we demonstrate
the utility of THPC to tune hydrogel gelation time (6.7 Β± 0.2
to 27 Β± 1.2 min) and mechanical properties (storage moduli βΌ250
Pa to βΌ2200 Pa) with a recombinant elastin-like protein. Lastly,
we show cytocompatibility of THPC for cell encapsulation with two
cell types, embryonic stem cells and neuronal cells, where cells exhibited
the ability to differentiate and grow in elastin-like protein hydrogels.
The primary goal of this communication is to report the identification
and utility of tetrakisΒ(hydroxymethyl) phosphonium chloride
(THPC) as an inexpensive but widely applicable cross-linker for protein-based
materials