Critical behavior and Griffiths effects in the disordered contact process

We study the nonequilibrium phase transition in the one-dimensional contact process with quenched spatial disorder by means of large-scale Monte-Carlo simulations for times up to $10^9$ and system sizes up to $10^7$ sites. In agreement with recent predictions of an infinite-randomness fixed point, our simulations demonstrate activated (exponential) dynamical scaling at the critical point. The critical behavior turns out to be universal, even for weak disorder. However, the approach to this asymptotic behavior is extremely slow, with crossover times of the order of $10^4$ or larger. In the Griffiths region between the clean and the dirty critical points, we find power-law dynamical behavior with continuously varying exponents. We discuss the generality of our findings and relate them to a broader theory of rare region effects at phase transitions with quenched disorder.Comment: 10 pages, 8 eps figures, final version as publishe

Ariel - Volume 2 Number 5

Editors Delvyn C. Case, Jr. Paul M. Fernhoff News Editors Richard Bonanno Robin A. Edwards Features Editors Stephen P. Flynn Steven A. Ager Lay-Out Editor Carol Dolinskas Contributing Editors Michael J. Blecker W. Cherry Light Eugenia Miller Lin Sey Edwards Jack Guralnik Tom Williams James Noco

PucC and LhaA direct efficient assembly of the light-harvesting complexes in <i>Rhodobacter sphaeroides</i>

The mature architecture of the photosynthetic membrane of the purple phototroph Rhodobacter sphaeroides has been characterised to a level where an atomic-level membrane model is available, but the roles of the putative assembly proteins LhaA and PucC in establishing this architecture are unknown. Here we investigate the assembly of light-harvesting LH2 and reaction centre-light-harvesting1-PufX (RC-LH1-PufX) photosystem complexes using spectroscopy, pull-downs, native gel electrophoresis, quantitative mass spectrometry and fluorescence lifetime microscopy to characterise a series of lhaA and pucC mutants. LhaA and PucC are important for specific assembly of LH1 or LH2 complexes, respectively, but they are not essential; the few LH1 subunits found in ΔlhaA mutants assemble to form normal RC-LH1-PufX core complexes showing that, once initiated, LH1 assembly round the RC is cooperative and proceeds to completion. LhaA and PucC form oligomers at sites of initiation of membrane invagination; LhaA associates with RCs, bacteriochlorophyll synthase (BchG), the protein translocase subunit YajC and the YidC membrane protein insertase. These associations within membrane nanodomains likely maximise interactions between pigments newly arriving from BchG and nascent proteins within the SecYEG-SecDF-YajC-YidC assembly machinery, thereby co-ordinating pigment delivery, the co-translational insertion of LH polypeptides and their folding and assembly to form photosynthetic complexes. LhaA and PucC form oligomers at the sites where invagination of the cytoplasmic membranes is initiated, and they play important roles in photosystem assembly in the purple phototrophic bacterium Rhodobacter sphaeroides. Establishing the architecture of the photosynthetic membrane involves interplay between LhaA, reaction centre complexes, bacteriochlorophyll synthase, the protein translocase subunit YajC, and the YidC membrane protein insertase. These associations likely coordinate the delivery of pigments and the membrane insertion, folding and assembly of photosystem polypeptides

Depletion of the FtsH1/3 proteolytic complex suppresses the nutrient stress response in the cyanobacterium synechocystis sp strain PCC 6803

The membrane-embedded FtsH proteases found in bacteria, chloroplasts, and mitochondria are involved in diverse cellular processes including protein quality control and regulation. The genome of the model cyanobacterium Synechocystis sp PCC 6803 encodes four FtsH homologs designated FtsH1 to FtsH4. The FtsH3 homolog is present in two hetero-oligomeric complexes: FtsH2/3, which is responsible for photosystem II quality control, and the essential FtsH1/3 complex, which helps maintain Fe homeostasis by regulating the level of the transcription factor Fur. To gain a more comprehensive insight into the physiological roles of FtsH hetero-complexes, we performed genome-wide expression profiling and global proteomic analyses of Synechocystis mutants conditionally depleted of FtsH3 or FtsH1 grown under various nutrient conditions. We show that the lack of FtsH1/3 leads to a drastic reduction in the transcriptional response to nutrient stress of not only Fur but also the Pho, NdhR, and NtcA regulons. In addition, this effect is accompanied by the accumulation of the respective transcription factors. Thus, the FtsH1/3 complex is of critical importance for acclimation to iron, phosphate, carbon, and nitrogen starvation in Synechocystis.Germany Federal Ministry of Education and Research [031L0106B]Grant Agency of the Czech RepublicGrant Agency of the Czech Republic [P501-12-G055]Czech Ministry of Education Ministry of Education, Youth & Sports - Czech Republic [LO1416]Portuguese Fundacao para a Ciencia e a Tecnologia (Foundation for Science and Technology) [PTDC/BIA-MIC/4418/2012, IF/00881/2013, UID/Multi/04326/2013]United Kingdom Biotechnology and Biological Sciences Research Council (BBSRC)Biotechnology and Biological Sciences Research Council (BBSRC) [BB/M012166/1, BB/M000265/1]European Research CouncilEuropean Research Council (ERC) [338895

In vitro reconstitution of Cascade-mediated CRISPR immunity in Streptococcus thermophilus

Clustered regularly interspaced short palindromic repeats (CRISPR)-encoded immunity in Type I systems relies on the Cascade (CRISPR-associated complex for antiviral defence) ribonucleoprotein complex, which triggers foreign DNA degradation by an accessory Cas3 protein. To establish the mechanism for adaptive immunity provided by the Streptococcus thermophilus CRISPR4-Cas (CRISPR-associated) system (St-CRISPR4-Cas), we isolated an effector complex (St-Cascade) containing 61-nucleotide CRISPR RNA (crRNA). We show that St-Cascade, guided by crRNA, binds in vitro to a matching proto-spacer if a proto-spacer adjacent motif (PAM) is present. Surprisingly, the PAM sequence determined from binding analysis is promiscuous and limited to a single nucleotide (A or T) immediately upstream (-1 position) of the proto-spacer. In the presence of a correct PAM, St-Cascade binding to the target DNA generates an R-loop that serves as a landing site for the Cas3 ATPase/nuclease. We show that Cas3 binding to the displaced strand in the R-loop triggers DNA cleavage, and if ATP is present, Cas3 further degrades DNA in a unidirectional manner. These findings establish a molecular basis for CRISPR immunity in St-CRISPR4-Cas and other Type I systems

COVID-19 vaccine uptake, confidence and hesitancy in rural KwaZulu-Natal, South Africa between April 2021 and April 2022: A continuous cross-sectional surveillance study

High COVID-19 vaccine hesitancy in South Africa limits protection against future epidemic waves. We evaluated how vaccine hesitancy and its correlates evolved April 2021-April 2022 in a well-characterized rural KwaZulu-Natal setting. All residents aged >15 in the Africa Health Research Institute's surveillance area were invited to complete a home-based, in-person interview. We described vaccine uptake and hesitancy trends, then evaluated associations with pre-existing personal factors, dynamic environmental context, and cues to action using ordinal logistic regression. Among 10,011 respondents, vaccine uptake rose as age-cohorts became vaccine-eligible before levelling off three months post-eligibility; younger age-groups had slower uptake and plateaued faster. Lifetime receipt of any COVID-19 vaccine rose from 3.0% in April-July 2021 to 32.9% in January-April 2022. Among 7,445 unvaccinated respondents, 47.7% said they would definitely take a free vaccine today in the first quarter of the study time period, falling to 32.0% in the last. By March/April 2022 only 48.0% of respondents were vaccinated or said they would definitely would take a vaccine. Predictors of lower vaccine hesitancy included being male (adjusted odds ratio [aOR]: 0.70, 95% confidence interval [CI]: 0.65-0.76), living with vaccinated household members (aOR:0.65, 95%CI: 0.59-0.71) and knowing someone who had had COVID-19 (aOR: 0.69, 95%CI: 0.59-0.80). Mistrust in government predicted greater hesitancy (aOR: 1.47, 95%CI: 1.42-1.53). Despite several COVID-19 waves, vaccine hesitancy was common in rural South Africa, rising over time and closely tied to mistrust in government. However, interpersonal experiences countered hesitancy and may be entry-points for interventions

Effect of COVID-19 lockdown on hospital admissions and mortality in rural KwaZulu-Natal, South Africa: interrupted time series analysis.

OBJECTIVE: To assess the effect of lockdown during the 2020 COVID-19 pandemic on daily all-cause admissions, and by age and diagnosis subgroups, and the odds of all-cause mortality in a hospital in rural KwaZulu-Natal (KZN). DESIGN: Observational cohort. SETTING: Referral hospital for 17 primary care clinics in uMkhanyakude District. PARTICIPANTS: Data collected by the Africa Health Research Institute on all admissions from 1 January to 20 October: 5848 patients contributed to 6173 admissions. EXPOSURE: Five levels of national lockdown in South Africa from 27 March 2020, with restrictions decreasing from levels 5 to 1, respectively. OUTCOME MEASURES: Changes and trends in daily all-cause admissions and risk of in-hospital mortality before and at each stage of lockdown, estimated by Poisson and logistic interrupted time series regression, with stratification for age, sex and diagnosis. RESULTS: Daily admissions decreased during level 5 lockdown for infants (incidence rate ratio (IRR) compared with prelockdown 0.63, 95% CI 0.44 to 0.90), children aged 1-5 years old (IRR 0.43, 95% CI 028 to 0.65) and respiratory diagnoses (IRR 0.57, 95% CI 0.36 to 0.90). From level 4 to level 3, total admissions increased (IRR 1.17, 95% CI 1.06 to 1.28), as well as for men >19 years (IRR 1.50, 95% CI 1.17 to 1.92) and respiratory diagnoses (IRR 4.26, 95% CI 2.36 to 7.70). Among patients admitted to hospital, the odds of death decreased during level 5 compared with prelockdown (adjusted OR 0.48, 95% CI 0.28 to 0.83) and then increased in later stages. CONCLUSIONS: Level 5 lockdown is likely to have prevented the most vulnerable population, children under 5 years and those more severely ill from accessing hospital care in rural KZN, as reflected by the drop in admissions and odds of mortality. Subsequent increases in admissions and in odds of death in the hospital could be due to improved and delayed access to hospital as restrictions were eased

Biosynthesis of Chlorophyll a in a Purple Bacterial Phototroph and Assembly into a Plant Chlorophyll-Protein Complex

Improvements to photosynthetic efficiency could be achieved by manipulating pigment biosynthetic pathways of photosynthetic organisms in order to increase the spectral coverage for light absorption. The development of organisms that can produce both bacteriochlorophylls and chlorophylls is one way to achieve this aim, and accordingly we have engineered the bacteriochlorophyll-utilizing anoxygenic phototroph Rhodobacter sphaeroides to make chlorophyll a. Bacteriochlorophyll and chlorophyll share a common biosynthetic pathway up to the precursor chlorophyllide. Deletion of genes responsible for the bacteriochlorophyll-specific modifications of chlorophyllide and replacement of the native bacteriochlorophyll synthase with a cyanobacterial chlorophyll synthase resulted in the production of chlorophyll a. This pigment could be assembled in vivo into the plant water-soluble chlorophyll protein, heterologously produced in Rhodobacter sphaeroides, which represents a proof-of-principle for the engineering of novel antenna complexes that enhance the spectral range of photosynthesis

Structural basis for CRISPR RNA-guided DNA recognition by Cascade

The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and low-resolution structure of Cascade and show how it recognizes double-stranded DNA (dsDNA) targets in a sequence-specific manner. Cascade is a 405-kDa complex comprising five functionally essential CRISPR-associated (Cas) proteins (CasA1B2C6D1E1) and a 61-nucleotide CRISPR RNA (crRNA) with 5′-hydroxyl and 2′,3′-cyclic phosphate termini. The crRNA guides Cascade to dsDNA target sequences by forming base pairs with the complementary DNA strand while displacing the noncomplementary strand to form an R-loop. Cascade recognizes target DNA without consuming ATP, which suggests that continuous invader DNA surveillance takes place without energy investment. The structure of Cascade shows an unusual seahorse shape that undergoes conformational changes when it binds target DNA.