Emergence of robust growth laws from optimal regulation of ribosome synthesis

Bacteria must constantly adapt their growth to changes in nutrient availability; yet despite large‐scale changes in protein expression associated with sensing, adaptation, and processing different environmental nutrients, simple growth laws connect the ribosome abundance and the growth rate. Here, we investigate the origin of these growth laws by analyzing the features of ribosomal regulation that coordinate proteome‐wide expression changes with cell growth in a variety of nutrient conditions in the model organism Escherichia coli. We identify supply‐driven feedforward activation of ribosomal protein synthesis as the key regulatory motif maximizing amino acid flux, and autonomously guiding a cell to achieve optimal growth in different environments. The growth laws emerge naturally from the robust regulatory strategy underlying growth rate control, irrespective of the details of the molecular implementation. The study highlights the interplay between phenomenological modeling and molecular mechanisms in uncovering fundamental operating constraints, with implications for endogenous and synthetic design of microorganisms.ISSN:1744-429

Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host´s cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that processFil: Salinas Ojeda, Romina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ortiz Flores, Rodolfo Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Distel, Jesús Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Aguilera, Milton Osmar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Beron, Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Social participation for older people with aphasia: The impact of communication disability on friendships

Purpose: The language changes experienced by a person with aphasia following a stroke often have sudden and long-lasting negative impact on friendships. Friendship relationships are core to social engagement, quality of life, and emotional well-being. The aims of this study were to describe everyday communication with friends for older people with and without aphasia and to examine the nature of actual friendship conversations involving a person with aphasia. Method: This naturalistic inquiry drew data from two phases of research: a participant observation study of 30 older Australians, 15 of whom had aphasia following a stroke, and a collective case study using stimulated recall to examine friendship conversations involving an older person with aphasia. Results: People with aphasia communicated with fewer friends and had smaller social networks. "Friendship" was a core domain of communication for older people and participation in leisure and educational activities was focal in everyday communication with friends. Case study data of conversations between three older people with aphasia and their friends illuminated features of "time," the role of humour, and friends having shared interests. Conclusion: Aphasia has been found to impact on friendships. A need exists for research and intervention programs to address communication with friends for older people with aphasia

Spinning strings and integrable spin chains in the AdS/CFT correspondence

In this introductory review we discuss dynamical tests of the AdS_5 x S^5 string/N=4 super Yang-Mills duality. After a brief introduction to AdS/CFT we argue that semiclassical string energies yield information on the quantum spectrum of the string in the limit of large angular momenta on the S^5. The energies of the folded and circular spinning string solutions rotating on a S^3 within the S^5 are derived, which yield all loop predictions for the dual gauge theory scaling dimensions. These follow from the eigenvalues of the dilatation operator of N=4 super Yang-Mills in a minimal SU(2) subsector and we display its reformulation in terms of a Heisenberg s=1/2 spin chain along with the coordinate Bethe ansatz for its explicit diagonalization. In order to make contact to the spinning string energies we then study the thermodynamic limit of the one-loop gauge theory Bethe equations and demonstrate the matching with the folded and closed string result at this loop order. Finally the known gauge theory results at higher-loop orders are reviewed and the associated long-range spin chain Bethe ansatz is introduced, leading to an asymptotic all-loop conjecture for the gauge theory Bethe equations. This uncovers discrepancies at the three-loop order between gauge theory scaling dimensions and string theory energies and the implications of this are discussed. Along the way we comment on further developments and generalizations of the subject and point to the relevant literature.Comment: 40 pages, invited contribution to Living Reviews in Relativity. v2: improvements in the text and references adde

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Higher derivative type II string effective actions, automorphic forms and E11

By dimensionally reducing the ten-dimensional higher derivative type IIA string theory effective action we place constraints on the automorphic forms that appear in the effective action in lower dimensions. We propose a number of properties of such automorphic forms and consider the prospects that E11 can play a role in the formulation of the higher derivative string theory effective action.Comment: 34 page

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Modelling the public health impact of male circumcision for HIV prevention in high prevalence areas in Africa

Background: Recent clinical trials in Africa, in combination with several observational epidemiological studies, have provided evidence that male circumcision can reduce HIV female-to-male transmission risk by 60% or more. However, the public health impact of large-scale male circumcision programs for HIV prevention is unclear. Methods: Two mathematical models were examined to explore this issue: a random mixing model and a compartmental model that distinguishes risk groups associated with sex work. In the compartmental model, two scenarios were developed, one calculating HIV transmission and prevalence in a context similar to the country of Botswana, and one similar to Nyanza Province, in western Kenya. Results: In both models, male circumcision programs resulted in large and sustained declines in HIV prevalence over time among both men and women. Men benefited somewhat more than women, but prevalence among women was also reduced substantially. With 80% male circumcision uptake, the reductions in prevalence ranged from 45% to 67% in the two "countries", and with 50% uptake, from 25% to 41%. It would take over a decade for the intervention to reach its full effect. Conclusion: Large-scale uptake of male circumcision services in African countries with high HIV prevalence, and where male circumcision is not now routinely practised, could lead to substantial reductions in HIV transmission and prevalence over time among both men and women

Plant ecology meets animal cognition: impacts of animal memory on seed dispersal

We propose that an understanding of animal learning and memory is critical to predicting the impacts of animals on plant populations through processes such as seed dispersal, pollination and herbivory. Focussing on endozoochory, we review the evidence that animal memory plays a role in seed dispersal, and present a model which allows us to explore the fundamental consequences of memory for this process. We demonstrate that decision-making by animals based on their previous experiences has the potential to determine which plants are visited, which fruits are selected to be eaten from the plant and where seeds are subsequently deposited, as well as being an important determinant of animal survival. Collectively, these results suggest that the impact of animal learning and memory on seed dispersal is likely to be extremely important, although to date our understanding of these processes suffers from a conspicuous lack of empirical support. This is partly because of the difficulty of conducting appropriate experiments but is also the result of limited interaction between plant ecologists and those who work on animal cognition

Host plant range of a fruit fly community (Diptera: Tephritidae): Does fruit composition influence larval performance?

Background: Phytophagous insects differ in their degree of specialisation on host plants, and range from strictly monophagous species that can develop on only one host plant to extremely polyphagous species that can develop on hundreds of plant species in many families. Nutritional compounds in host fruits affect several larval traits that may be related to adult fitness. In this study, we determined the relationship between fruit nutrient composition and the degree of host specialisation of seven of the eight tephritid species present in La Réunion; these species are known to have very different host ranges in natura. In the laboratory, larval survival, larval developmental time, and pupal weight were assessed on 22 fruit species occurring in La Réunion. In addition, data on fruit nutritional composition were obtained from existing databases. Results: For each tephritid, the three larval traits were significantly affected by fruit species and the effects of fruits on larval traits differed among tephritids. As expected, the polyphagous species Bactrocera zonata, Ceratitis catoirii, C. rosa, and C. capitata were able to survive on a larger range of fruits than the oligophagous species Zeugodacus cucurbitae, Dacus demmerezi, and Neoceratitis cyanescens. Pupal weight was positively correlated with larval survival and was negatively correlated with developmental time for polyphagous species. Canonical correspondence analysis of the relationship between fruit nutrient composition and tephritid survival showed that polyphagous species survived better than oligophagous ones in fruits containing higher concentrations of carbohydrate, fibre, and lipid. Conclusion: Nutrient composition of host fruit at least partly explains the suitability of host fruits for larvae. Completed with female preferences experiments these results will increase our understanding of factors affecting tephritid host range. (Résumé d'auteur