Crystallization of Adenylylsulfate Reductase from Desulfovibrio gigas: A Strategy Based on Controlled Protein Oligomerization

Adenylylsulfate reductase (adenosine 5′-phosphosulfate reductase, APS reductase or APSR, E.C.1.8.99.2) catalyzes the conversion of APS to sulfite in dissimilatory sulfate reduction. APSR was isolated and purified directly from massive anaerobically grown Desulfovibrio gigas, a strict anaerobe, for structure and function investigation. Oligomerization of APSR to form dimers–α_2β_2, tetramers–α_4β_4, hexamers–α_6β_6, and larger oligomers was observed during purification of the protein. Dynamic light scattering and ultracentrifugation revealed that the addition of adenosine monophosphate (AMP) or adenosine 5′-phosphosulfate (APS) disrupts the oligomerization, indicating that AMP or APS binding to the APSR dissociates the inactive hexamers into functional dimers. Treatment of APSR with β-mercaptoethanol decreased the enzyme size from a hexamer to a dimer, probably by disrupting the disulfide Cys156—Cys162 toward the C-terminus of the β-subunit. Alignment of the APSR sequences from D. gigas and A. fulgidus revealed the largest differences in this region of the β-subunit, with the D. gigas APSR containing 16 additional amino acids with the Cys156—Cys162 disulfide. Studies in a pH gradient showed that the diameter of the APSR decreased progressively with acidic pH. To crystallize the APSR for structure determination, we optimized conditions to generate a homogeneous and stable form of APSR by combining dynamic light scattering, ultracentrifugation, and electron paramagnetic resonance methods to analyze the various oligomeric states of the enzyme in varied environments

Human mobility variations in response to restriction policies during the COVID-19 pandemic: An analysis from the Virus Watch community cohort in England, UK

Objective: Since the outbreak of COVID-19, public health and social measures to contain its transmission (e.g., social distancing and lockdowns) have dramatically changed people's lives in rural and urban areas globally. To facilitate future management of the pandemic, it is important to understand how different socio-demographic groups adhere to such demands. This study aims to evaluate the influences of restriction policies on human mobility variations associated with socio-demographic groups in England, UK. Methods: Using mobile phone global positioning system (GPS) trajectory data, we measured variations in human mobility across socio-demographic groups during different restriction periods from Oct 14, 2020 to Sep 15, 2021. The six restriction periods which varied in degree of mobility restriction policies, denoted as "Three-tier Restriction," "Second National Lockdown," "Four-tier Restriction," "Third National Lockdown," "Steps out of Lockdown," and "Post-restriction," respectively. Individual human mobility was measured with respect to the time period people stayed at home, visited places outside the home, and traveled long distances. We compared these indicators across the six restriction periods and across socio-demographic groups. Results: All human mobility indicators significantly differed across the six restriction periods, and the influences of restriction policies on individual mobility behaviors are correlated with socio-demographic groups. In particular, influences relating to mobility behaviors are stronger in younger and low-income groups in the second and third national lockdowns. Conclusions: This study enhances our understanding of the influences of COVID-19 pandemic restriction policies on human mobility behaviors within different social groups in England. The findings can be usefully extended to support policy-making by investigating human mobility and differences in policy effects across not only age and income groups, but also across geographical regions

A targeted gene panel that covers coding, non-coding and short tandem repeat regions improves the diagnosis of patients with neurodegenerative diseases

Genetic testing for neurodegenerative diseases (NDs) is highly challenging because of genetic heterogeneity and overlapping manifestations. Targeted-gene panels (TGPs), coupled with next-generation sequencing (NGS), can facilitate the profiling of a large repertoire of ND-related genes. Due to the technical limitations inherent in NGS and TGPs, short tandem repeat (STR) variations are often ignored. However, STR expansions are known to cause such NDs as Huntington\u27s disease and spinocerebellar ataxias type 3 (SCA3). Here, we studied the clinical utility of a custom-made TGP that targets 199 NDs and 311 ND-associated genes on 118 undiagnosed patients. At least one known or likely pathogenic variation was found in 54 patients; 27 patients demonstrated clinical profiles that matched the variants; and 16 patients whose original diagnosis were refined. A high concordance of variant calling were observed when comparing the results from TGP and whole-exome sequencing of four patients. Our in-house STR detection algorithm has reached a specificity of 0.88 and a sensitivity of 0.82 in our SCA3 cohort. This study also uncovered a trove of novel and recurrent variants that may enrich the repertoire of ND-related genetic markers. We propose that a combined comprehensive TGPs-bioinformatics pipeline can improve the clinical diagnosis of NDs

Tuning the Magnetic Anisotropy at a Molecule-Metal Interface

International audienceWe demonstrate that a C 60 overlayer enhances the perpendicular magnetic anisotropy of a Co thin film, inducing an inverse spin reorientation transition from in plane to out of plane. The driving force is the C 60 =Co interfacial magnetic anisotropy that we have measured quantitatively in situ as a function of the C 60 coverage. Comparison with state-of-the-art ab initio calculations show that this interfacial anisotropy mainly arises from the local hybridization between C 60 p z and Co d z 2 orbitals. By generalizing these arguments, we also demonstrate that the hybridization of C 60 with a Fe(110) surface decreases the perpendicular magnetic anisotropy. These results open the way to tailor the interfacial magnetic anisotropy in organic-material–ferromagnet systems

Exact first-passage exponents of 1D domain growth: relation to a reaction diffusion model

In the zero temperature Glauber dynamics of the ferromagnetic Ising or $q$-state Potts model, the size of domains is known to grow like $t^{1/2}$. Recent simulations have shown that the fraction $r(q,t)$ of spins which have never flipped up to time $t$ decays like a power law $r(q,t) \sim t^{-\theta(q)}$ with a non-trivial dependence of the exponent $\theta(q)$ on $q$ and on space dimension. By mapping the problem on an exactly soluble one-species coagulation model ($A+A\rightarrow A$), we obtain the exact expression of $\theta(q)$ in dimension one.Comment: latex,no figure

Altered purinergic signaling in uridine adenosine tetraphosphate-induced coronary relaxation in swine with metabolic derangement

We previously demonstrated that uridine adenosine tetraphosphate (Up4A) induces potent and partially endothelium-dependent relaxation in the healthy porcine coronary microvasculature. We subsequently showed that Up4A-induced porcine coronary relaxation was impaired via downregulation of P1 receptors

Recreational Exposure to Low Concentrations of Microcystins During an Algal Bloom in a Small Lake

We measured microcystins in blood from people at risk for swallowing water or inhaling spray while swimming, water skiing, jet skiing, or boating during an algal bloom. We monitored water samples from a small lake as a Microcystis aeruginosa bloom developed. We recruited 97 people planning recreational activities in that lake and seven others who volunteered to recreate in a nearby bloom-free lake. We conducted our field study within a week of finding a 10-μg/L microcystin concentration. We analyzed water, air, and human blood samples for water quality, potential human pathogens, algal taxonomy, and microcystin concentrations. We interviewed study participants for demographic and current health symptom information. Water samples were assayed for potential respiratory viruses (adenoviruses and enteroviruses), but none were detected. We did find low concentrations of Escherichia coli, indicating fecal contamination. We found low levels of microcystins (2 μg/L to 5 μg/L) in the water and (<0.1 ng/m3) in the aerosol samples. Blood levels of microcystins for all participants were below the limit of detection (0.147μg/L). Given this low exposure level, study participants reported no symptom increases following recreational exposure to microcystins. This is the first study to report that water-based recreational activities can expose people to very low concentrations of aerosol-borne microcystins; we recently conducted another field study to assess exposures to higher concentrations of these algal toxins

Vorticity alignment results for the three-dimensional Euler and Navier-Stokes equations

We address the problem in Navier-Stokes isotropic turbulence of why the vorticity accumulates on thin sets such as quasi-one-dimensional tubes and quasi-two-dimensional sheets. Taking our motivation from the work of Ashurst, Kerstein, Kerr and Gibson, who observed that the vorticity vector {\boldmath\omega} aligns with the intermediate eigenvector of the strain matrix $S$, we study this problem in the context of both the three-dimensional Euler and Navier-Stokes equations using the variables \alpha = \hat{{\boldmath\xi}}\cdot S\hat{{\boldmath\xi}} and {\boldmath\chi} = \hat{{\boldmath\xi}}\times S\hat{{\boldmath\xi}} where \hat{{\boldmath\xi}} = {\boldmath\omega}/\omega. This introduces the dynamic angle $\phi (x,t) = \arctan(\frac{\chi}{\alpha})$, which lies between {\boldmath\omega} and S{\boldmath\omega}. For the Euler equations a closed set of differential equations for $\alpha$ and {\boldmath\chi} is derived in terms of the Hessian matrix of the pressure $P = \{p_{,ij}\}$. For the Navier-Stokes equations, the Burgers vortex and shear layer solutions turn out to be the Lagrangian fixed point solutions of the equivalent (\alpha,{\boldmath\chi}) equations with a corresponding angle $\phi = 0$. Under certain assumptions for more general flows it is shown that there is an attracting fixed point of the (\alpha,\bchi) equations which corresponds to positive vortex stretching and for which the cosine of the corresponding angle is close to unity. This indicates that near alignment is an attracting state of the system and is consistent with the formation of Burgers-like structures.Comment: To appear in Nonlinearity Nov. 199

A novel long non-coding natural antisense RNA is a negative regulator of Nos1 gene expression

Long non-coding natural antisense transcripts (NATs) are widespread in eukaryotic species. Although recent studies indicate that long NATs are engaged in the regulation of gene expression, the precise functional roles of the vast majority of them are unknown. Here we report that a long NAT (Mm-antiNos1 RNA) complementary to mRNA encoding the neuronal isoform of nitric oxide synthase (Nos1) is expressed in the mouse brain and is transcribed from the non-template strand of the Nos1 locus. Nos1 produces nitric oxide (NO), a major signaling molecule in the CNS implicated in many important functions including neuronal differentiation and memory formation. We show that the newly discovered NAT negatively regulates Nos1 gene expression. Moreover, our quantitative studies of the temporal expression profiles of Mm-antiNos1 RNA in the mouse brain during embryonic development and postnatal life indicate that it may be involved in the regulation of NO-dependent neurogenesis