Biodegradable bacterial nanocellulose (BNC) is a highly in-demand but expensive polymer, and the reduction of its production cost is an important task. The present study aimed to biosynthesize BNC on ...biologically high-quality hydrolyzate media prepared from miscanthus and oat hulls, and to explore the properties of the resultant BNC depending on the microbial producer used. In this study, three microbial producers were utilized for the biosynthesis of BNC: individual strains Komagataeibacter xylinus B-12429 and Komagataeibacter xylinus B-12431, and symbiotic Medusomyces gisevii Sa-12. The use of symbiotic Medusomyces gisevii Sa-12 was found to have technological benefits: nutrient media require no mineral salts or growth factors, and pasteurization is sufficient for the nutrient medium instead of sterilization. The yield of BNCs produced by the symbiotic culture turned out to be 44–65% higher than that for the individual strains. The physicochemical properties of BNC, such as nanofibril width, degree of polymerization, elastic modulus, Iα allomorph content and crystallinity index, are most notably dependent on the microbial producer type rather than the nutrient medium composition. This is the first study in which we investigated the biosynthesis of BNC on hydrolyzate media prepared from miscanthus and oat hulls under the same conditions but using different microbial producers, and showed that it is advisable to use the symbiotic culture. The choice of a microbial producer is grounded on the yield, production process simplification and properties. The BNC production from technical raw materials would cover considerable demands of BNC for technical purposes without competing with food resources.
Biased signaling, in which different ligands that bind to the same G protein-coupled receptor preferentially trigger distinct signaling pathways, holds great promise for the design of safer and more ...effective drugs. Its structural mechanism remains unclear, however, hampering efforts to design drugs with desired signaling profiles. Here, we use extensive atomic-level molecular dynamics simulations to determine how arrestin bias and G protein bias arise at the angiotensin II type 1 receptor. The receptor adopts two major signaling conformations, one of which couples almost exclusively to arrestin, whereas the other also couples effectively to a G protein. A long-range allosteric network allows ligands in the extracellular binding pocket to favor either of the two intracellular conformations. Guided by this computationally determined mechanism, we designed ligands with desired signaling profiles.
Biased agonists of G protein-coupled receptors (GPCRs) preferentially activate a subset of downstream signaling pathways. In this work, we present crystal structures of angiotensin II type 1 receptor ...(AT1R) (2.7 to 2.9 angstroms) bound to three ligands with divergent bias profiles: the balanced endogenous agonist angiotensin II (AngII) and two strongly β-arrestin-biased analogs. Compared with other ligands, AngII promotes more-substantial rearrangements not only at the bottom of the ligand-binding pocket but also in a key polar network in the receptor core, which forms a sodium-binding site in most GPCRs. Divergences from the family consensus in this region, which appears to act as a biased signaling switch, may predispose the AT1R and certain other GPCRs (such as chemokine receptors) to adopt conformations that are capable of activating β-arrestin but not heterotrimeric G
protein signaling.
Chemistry of a Unique Polyketide-like Synthase Chun, Stephanie W; Hinze, Meagan E; Skiba, Meredith A ...
Journal of the American Chemical Society,
02/2018, Letnik:
140, Številka:
7
Journal Article
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Like many complex natural products, the intricate architecture of saxitoxin (STX) has hindered full exploration of this scaffold’s utility as a tool for studying voltage-gated sodium ion channels and ...as a pharmaceutical agent. Established chemical strategies can provide access to the natural product; however, a chemoenzymatic route to saxitoxin that could provide expedited access to related compounds has not been devised. The first step toward realizing a chemoenzymatic approach toward this class of molecules is the elucidation of the saxitoxin biosynthetic pathway. To date, a biochemical link between STX and its putative biosynthetic enzymes has not been demonstrated. Herein, we report the first biochemical characterization of any enzyme involved in STX biosynthesis. Specifically, the chemical functions of a polyketide-like synthase, SxtA, from the cyanobacteria Cylindrospermopsis raciborskii T3 are elucidated. This unique megasynthase is comprised of four domains: methyltransferase (MT), GCN5-related N-acetyltransferase (GNAT), acyl carrier protein (ACP), and the first example of an 8-amino-7-oxononanoate synthase (AONS) associated with a multidomain synthase. We have established that this single polypeptide carries out the formation of two carbon–carbon bonds, two decarboxylation events and a stereospecific protonation to afford the linear biosynthetic precursor to STX (4). The synthetic utility of the SxtA AONS is demonstrated by the synthesis of a suite of α-amino ketones from the corresponding α-amino acid in a single step.
Unlike the interface between two immiscible electrolyte solutions (ITIES) formed between water and polar solvents, molecular understanding of the liquid-liquid interface formed for aqueous biphasic ...systems (ABSs) is relatively limited and mostly relies on surface tension measurements and thermodynamic models. Here, high-resolution Raman imaging is used to provide spatial and chemical resolution of the interface of lithium chloride - lithium bis(trifluoromethanesulfonyl)imide - water (LiCl-LiTFSI-water) and HCl-LiTFSI-water, prototypical salt-salt ABSs found in a range of electrochemical applications. The concentration profiles of both TFSI anions and water are found to be sigmoidal thus not showing any signs of a positive adsorption for both salts and solvent. More striking, however, is the length at which the concentration profiles extend, ranging from 11 to 2 µm with increasing concentrations, compared to a few nanometers for ITIES. We thus reveal that unlike ITIES, salt-salt ABSs do not have a molecularly sharp interface but rather form an interphase with a gradual change of environment from one phase to the other. This knowledge represents a major stepping-stone in the understanding of aqueous interfaces, key for mastering ion or electron transfer dynamics in a wide range of biological and technological settings including novel battery technologies such as membraneless redox flow and dual-ion batteries.
•The stability limits of a lab scale, premixed annular combustor were assessed.•The flame experienced a sequence of transition when approaching lean blow-off.•Close to blow-off, it was found a ...pattern of detachment and re-attachment of the flame.•Stability decreases when increasing bulk velocity or reducing inter-burner distance.•The behaviour strongly differs from a single burner system.
The behaviour of the flame in an annular combustor with multiple bluff-body injectors with swirl was investigated to provide insights into lean blow-off (LBO) mechanisms when flames interact. Two different configurations, with 12 and 18 burners, and various bulk velocities and equivalence ratios were tested. Flame shape and main features were studied by means of 5 kHz OH∗ chemiluminescence imaging and the stability limits were identified and compiled into stability regime diagrams. As the equivalence ratio of the mixture was reduced the individual flames would first exhibit a transition from a stable “W-shape” state to a stable “V-shape” state before becoming unstable close to extinction. In the 18-burner configuration LBO was characterised by random detachment and re-stabilisation of the flames over multiple burners across the chamber, until complete lift-off. In the 12-burner configuration the flame anchors on a few burners in azimuthally symmetric locations, making the overall flame less prone to global extinction. Finally, the stability curves were computed using a correlation based on the Damkhöler (Da) number and compared to single burner configurations. The beginning of the blow-off transient was found to be similar to the LBO condition for a single burner in the 12-burner setup, while the 18-burner configuration was less stable for all the conditions investigated. However, it was found that correlations based on single burner extinction data do not fully work for the extinction of interacting flames. The results provide insights into the blow-off of realistic gas turbine engines and can be used for validating models of such processes.
Antibodies are essential biological research tools and important therapeutic agents, but some exhibit non-specific binding to off-target proteins and other biomolecules. Such polyreactive antibodies ...compromise screening pipelines, lead to incorrect and irreproducible experimental results, and are generally intractable for clinical development. Here, we design a set of experiments using a diverse naïve synthetic camelid antibody fragment (nanobody) library to enable machine learning models to accurately assess polyreactivity from protein sequence (AUC > 0.8). Moreover, our models provide quantitative scoring metrics that predict the effect of amino acid substitutions on polyreactivity. We experimentally test our models' performance on three independent nanobody scaffolds, where over 90% of predicted substitutions successfully reduced polyreactivity. Importantly, the models allow us to diminish the polyreactivity of an angiotensin II type I receptor antagonist nanobody, without compromising its functional properties. We provide a companion web-server that offers a straightforward means of predicting polyreactivity and polyreactivity-reducing mutations for any given nanobody sequence.
The ability to rapidly process speech sounds is integral not only for processing other's speech, but also for auditory processing of one's own speech, which allows for maintenance of speech accuracy. ...Deficits in rapid auditory processing have been demonstrated in autistic individuals, particularly those with language impairment. We examined rapid auditory processing for speech sounds in relation to performance on a battery of verbal communication measures to determine which aspects of verbal communication were associated with cortical auditory processing in a sample of individuals with autism.
Participants were 57 children and adolescents (40 male and 17 female) ages 5-18 who were diagnosed with an Autism Spectrum Disorder (ASD). Rapid auditory processing of speech sounds was measured via a magnetoencephalographic (MEG) index of the quality of the auditory evoked response to the second of two differing speech sounds ("Ga" / "Da") presented in rapid succession. Verbal communication abilities were assessed on standardized clinical measures of overall expressive and receptive language, vocabulary, articulation, and phonological processing. Associations between cortical measures of left- and right-hemisphere rapid auditory processing and verbal communication measures were examined.
Rapid auditory processing of speech sounds was significantly associated with speech articulation bilaterally (
= 0.463,
= 0.001 for left hemisphere and
= 0.328,
= 0.020 for right hemisphere). In addition, rapid auditory processing in the left hemisphere was significantly associated with overall expressive language abilities (
= 0.354,
= 0.013); expressive (
= 0.384,
= 0.005) vocabulary; and phonological memory (
= 0.325,
= 0.024). Phonological memory was found to mediate the relationship between rapid cortical processing and receptive language.
These results demonstrate that impaired rapid auditory processing for speech sounds is associated with dysfunction in verbal communication in ASD. The data also indicate that intact rapid auditory processing may be necessary for even basic communication skills that support speech production, such as phonological memory and articulatory control.
Throughout this paper, all groups are finite.
σ
=
{
σ
i
∣
i
∈
I
}
is some partition of the set of all primes
P
, and
σ
(
n
)
=
{
σ
i
∣
σ
i
∩
π
(
n
)
≠
∅
}
for any
n
∈
N
. The natural numbers
n
and
m
...are called
σ
-coprime if
σ
(
n
)
∩
σ
(
m
)
=
∅
.
Let
t
> 1 be a natural number and let
F
be a class of groups. Then we say that
F
is
Γ
t
σ
-
closed
(respectively
weakly
Γ
t
σ
-
closed
) provided
F
contains each finite group
G
which satisfies the following conditions:
G
has subgroups
A
1
,
…
,
A
t
∈
F
such that
G
=
A
i
A
j
for all
i
≠
j
;
The indices
|
G
:
N
G
(
A
1
)
|
,
…
,
|
G
:
N
G
(
A
t
)
|
(respectively the indices
|
G
:
A
1
|
,
…
,
|
G
:
A
t
-
1
|
,
|
G
:
N
G
(
A
t
)
|
) are pairwise
σ
-
coprime
.
We study properties and some applications of (weakly)
Γ
t
σ
-closed classes of finite groups.
Miscanthus is a valuable renewable feedstock and has a significant potential for the manufacture of diverse biotechnology products based on macromolecules such as cellulose, hemicelluloses and ...lignin. Herein, we overviewed the state-of-the art of research on the conversion of miscanthus polymers into biotechnology products comprising low-molecular compounds and macromolecules: bioethanol, biogas, bacterial cellulose, enzymes (cellulases, laccases), lactic acid, lipids, fumaric acid and polyhydroxyalkanoates. The present review aims to assess the potential of converting miscanthus polymers in order to develop sustainable technologies.
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