Mobility and kinship in the world's first village societies.

Around 10,000 y ago in southwest Asia, the cessation of a mobile lifestyle and the emergence of the first village communities during the Neolithic marked a fundamental change in human history. The first communities were small (tens to hundreds of individuals) but remained semisedentary. So-called megasites appeared soon after, occupied by thousands of more sedentary inhabitants. Accompanying this shift, the material culture and ancient ecological data indicate profound changes in economic and social behavior. A shift from residential to logistical mobility and increasing population size are clear and can be explained by either changes in fertility and/or aggregation of local groups. However, as sedentism increased, small early communities likely risked inbreeding without maintaining or establishing exogamous relationships typical of hunter-gatherers. Megasites, where large populations would have made endogamy sustainable, could have avoided this risk. To examine the role of kinship practices in the rise of megasites, we measured strontium and oxygen isotopes in tooth enamel from 99 individuals buried at Pinarbasi, Boncuklu, and Çatalhöyük (Turkey) over 7,000 y. These sites are geographically proximate and, critically, span both early sedentary behaviors (Pinarbasi and Boncuklu) and the rise of a local megasite (Çatalhöyük). Our data are consistent with the presence of only local individuals at Pinarbasi and Boncuklu, whereas at Çatalhöyük, several nonlocals are present. The Çatalhöyük data stand in contrast to other megasites where bioarchaeological evidence has pointed to strict endogamy. These different kinship behaviors suggest that megasites may have arisen by employing unique, community-specific kinship practices.

Historic and bioarchaeological evidence supports late onset of post-Columbian epidemics in Native California.

Catastrophic decline of Indigenous populations in the Americas following European contact is one of the most severe demographic events in the history of humanity, but uncertainty persists about the timing and scale of the collapse, which has implications for not only Indigenous history but also the understanding of historical ecology. A long-standing hypothesis that a continent-wide pandemic broke out immediately upon the arrival of Spanish seafarers has been challenged in recent years by a model of regional epidemics erupting asynchronously, causing different rates of population decline in different areas. Some researchers have suggested that, in California, significant depopulation occurred during the first two centuries of the post-Columbus era, which led to a "rebound" in native flora and fauna by the time of sustained European contact after 1769. Here, we combine a comprehensive prehistoric osteological dataset (n = 10,256 individuals) with historic mission mortuary records (n = 23,459 individuals) that together span from 3050 cal BC to AD 1870 to systematically evaluate changes in mortality over time by constructing life tables and conducting survival analysis of age-at-death records. Results show that a dramatic shift in the shape of mortality risk consistent with a plague-like population structure began only after sustained contact with European invaders, when permanent Spanish settlements and missions were established ca. AD 1770. These declines reflect the syndemic effects of newly introduced diseases and the severe cultural disruption of Indigenous lifeways by the Spanish colonial system.

Bioarchaeology of Neolithic Çatalhöyük reveals fundamental transitions in health, mobility, and lifestyle in early farmers.

The transition from a human diet based exclusively on wild plants and animals to one involving dependence on domesticated plants and animals beginning 10,000 to 11,000 y ago in Southwest Asia set into motion a series of profound health, lifestyle, social, and economic changes affecting human populations throughout most of the world. However, the social, cultural, behavioral, and other factors surrounding health and lifestyle associated with the foraging-to-farming transition are vague, owing to an incomplete or poorly understood contextual archaeological record of living conditions. Bioarchaeological investigation of the extraordinary record of human remains and their context from Neolithic Çatalhöyük (7100-5950 cal BCE), a massive archaeological site in south-central Anatolia (Turkey), provides important perspectives on population dynamics, health outcomes, behavioral adaptations, interpersonal conflict, and a record of community resilience over the life of this single early farming settlement having the attributes of a protocity. Study of Çatalhöyük human biology reveals increasing costs to members of the settlement, including elevated exposure to disease and labor demands in response to community dependence on and production of domesticated plant carbohydrates, growing population size and density fueled by elevated fertility, and increasing stresses due to heightened workload and greater mobility required for caprine herding and other resource acquisition activities over the nearly 12 centuries of settlement occupation. These changes in life conditions foreshadow developments that would take place worldwide over the millennia following the abandonment of Neolithic Çatalhöyük, including health challenges, adaptive patterns, physical activity, and emerging social behaviors involving interpersonal violence.

Relapse rate and renal prognosis in ANCA-associated vasculitis according to long-term ANCA patterns.

Long-term observation of patients with ANCA-associated vasculitis (AAV) allows the identification of different longitudinal patterns of ANCA levels during follow-up. This study aimed to characterize these patterns and to determine their prognostic significance. All ANCA determinations performed in two university hospitals during a 2-year period were retrospectively reviewed. Patients were included in the analysis if they had high titers of anti-myeloperoxidase (anti-MPO) or anti-proteinase 3 (anti-PR3) antibodies at least once, ≥ 5 serial ANCA determinations and AAV diagnosed by biopsy or American College of Rheumatology (ACR) classification criteria. Patients' time-course ANCA patterns were classified as monophasic, remitting, recurrent or persistent. Associations between ANCA patterns and prognostic variables (relapse rate and renal outcome) were analysed by univariate and multivariate statistics. A total of 99 patients [55 with microscopic polyangiitis (MPA), 36 with granulomatosis with polyangiitis (GPA) and eight with eosinophilic granulomatosis with polyangiitis (EGPA)] were included. Median follow-up was 9 years. Among patients diagnosed with MPA or GPA, recurrent or persistent ANCA patterns were associated with a higher risk of clinical relapse [hazard ratio (HR) = 3·7, 95% confidence interval (CI) = 1·5-9·1 and HR = 2·9, 95% CI = 1·1-8·0, respectively], independently of clinical diagnosis or ANCA specificity. In patients with anti-MPO antibodies, the recurrent ANCA pattern was associated with worsening renal function [odds ratio (OR) = 5·7, 95% CI = 1·2-26·0]. Recurrent or persistent ANCA patterns are associated with a higher risk of clinical relapse. A recurrent ANCA pattern was associated with worsening renal function in anti-MPO-associated vasculitis.

Perceptions of Race and Ancestry in Teaching, Research, and Public Engagement in Biological Anthropology.

The concept of race has a complex history in the field of biological anthropology. Despite increased recognition of the racist origins of the discipline, there remains little agreement about what the concept means, how it is used, or how it is discussed. This study presents the results of a survey of biological anthropologists to investigate the relationship of biological anthropologists with race and ancestry. The survey focuses on the areas of research, public engagement, and teaching as related to these concepts. Results indicate that a large majority of biological anthropologists agree that race (as a social not biological concept) is separate from ancestry. The majority of respondents agreed that ancestry categories should be based on geography (e.g., Asian, European, and African), and more anthropologists thought the terms "Hispanic" and "Latino" were inappropriate ancestry categories. While most respondents felt that discussions of these terms were not matters of "political correctness," nearly a quarter of respondents suggested that concerns over the moral and ethical implications of research (e.g., photos, terminology, and ancestry) result in the silencing of anthropological research. Overwhelmingly, respondents felt that anthropologists have a responsibility to ensure the avoidance of misappropriation of their work by race science and by white nationalists/supremacists. Some differences in survey responses were found relating to respondents' subdiscipline, educational level, location, age, self-identified racial/ethnic categories, and gender. In regard to teaching, survey results indicate that these concepts are minimally covered in university classrooms. When taught, topics focus on the colonialist/racist history of anthropology, the presence of white privilege/supremacy, and racism. Based on the results of this survey, the authors argue for greater public engagement on these concepts, a standardized system of teaching race and ancestry, and a disciplinary conversation about practice and terminology. In this way, biological anthropologists can best place themselves to combat racism in a socially responsible way.

A comparison of subadult skeletal and dental development based on living and deceased samples.

OBJECTIVES: A fundamental assumption in biological anthropology is that living individuals will present with different growth than non-survivors of the same population. The aim is to address the question of whether growth and development data of non-survivors are reflective of the biological consequences of selective mortality and/or stress. MATERIALS AND METHODS: The study compares dental development and skeletal growth collected from radiographic images of contemporary samples of living and deceased individuals from the United States (birth to 20 years) and South Africa (birth to 12 years). Further evaluation of deceased individuals is used to explore differential patterns among manners of death (MOD). RESULTS: Results do not show any significant differences in skeletal growth or dental development between living and deceased individuals. However, in the South African deceased sample the youngest individuals exhibited substantially smaller diaphyseal lengths than the living sample, but by 2 years of age the differences were negligible. In the US sample, neither significant nor substantial differences were found in dental development or diaphyseal length according to MOD and age (>2 years of age), though some long bones in individuals <2 years of age did show significant differences. No significant differences were noted in diaphyseal length according to MOD and age in the SA sample. DISCUSSION: The current findings refute the idea that contemporary deceased and living individuals would present with differential growth and development patterns through all of ontogeny as well as the assumptions linking short stature, poor environments, and MOD.

Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk.

Because of the ubiquitous adaptability of our material culture, some human populations have occupied extreme environments that intensified selection on existing genomic variation. By 32,000 years ago, people were living in Arctic Beringia, and during the Last Glacial Maximum (LGM; 28,000-18,000 y ago), they likely persisted in the Beringian refugium. Such high latitudes provide only very low levels of UV radiation, and can thereby lead to dangerously low levels of biosynthesized vitamin D. The physiological effects of vitamin D deficiency range from reduced dietary absorption of calcium to a compromised immune system and modified adipose tissue function. The ectodysplasin A receptor (EDAR) gene has a range of pleiotropic effects, including sweat gland density, incisor shoveling, and mammary gland ductal branching. The frequency of the human-specific EDAR V370A allele appears to be uniquely elevated in North and East Asian and New World populations due to a bout of positive selection likely to have occurred circa 20,000 y ago. The dental pleiotropic effects of this allele suggest an even higher occurrence among indigenous people in the Western Hemisphere before European colonization. We hypothesize that selection on EDAR V370A occurred in the Beringian refugium because it increases mammary ductal branching, and thereby may amplify the transfer of critical nutrients in vitamin D-deficient conditions to infants via mothers' milk. This hypothesized selective context for EDAR V370A was likely intertwined with selection on the fatty acid desaturase (FADS) gene cluster because it is known to modulate lipid profiles transmitted to milk from a vitamin D-rich diet high in omega-3 fatty acids.

Implementation of an Enhanced Recovery After Surgery (ERAS) protocol for acute complicated and uncomplicated appendicitis.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) protocols are well-documented logistic programs in elective surgery but it is still uncertain whether ERAS can benefit emergency patients, because of significant challenges facing its application to emergency surgery. The aim of this study was to evaluate the implementation of an ERAS protocol for patients with acute appendicitis (AA), both complicated and uncomplicated. METHODS: A prospective observational study was performed at two university hospitals in Spain, between January 2012 and December 2019. Inclusion criteria were patients with diagnosis of AA, undergoing appendectomy following an ERAS protocol of perioperative care. The different items of the ERAS protocol were recorded and their implementation was separately evaluated. Analyzed variables also included postoperative complications, hospital stay and readmission rate. Levels of acute phase reactants were assessed as predictors of implementation for the ERAS protocol. RESULTS: Eight hundred fifty patients were included; 498 males (58.5%) and 302 females (41.5%), with a mean age of 34.95 ± 17 years. The implementation of all the items of the protocol was achieved in 770 patients (90.6%), 86.8% of patients with complicated AA and 93.1% of patients with uncomplicated AA (p = 0.02). Higher preoperative C-reactive protein (CRP) levels were significantly associated with the impossibility of implementing all the items of the ERAS protocol (p < 0.001), establishing a cut-off point at CRP = 13.5 mg/dl. CONCLUSIONS: The implementation of ERAS protocols is safe and feasible in patients with AA. Although the implementation rate of all the items is lower in patients with complicated AA, it can be completed in 86.8% of these patients. CRP levels over 13.5 mg/dl are predictors of difficulties in the implementation of all the items of ERAS protocols.

Clinical outcomes after tricuspid surgery : The role of previous cardiac surgery.

BACKGROUND: The aim of our study was to assess the outcomes of surgical treatment for severe tricuspid regurgitation according to whether cardiac surgery had been performed before the tricuspid valve intervention. METHODS: Between 1996 and 2013, 201 consecutive patients with severe tricuspid regurgitation underwent tricuspid surgery at our center. Patients were classified according to whether or not they had undergone previous cardiac surgery, which 33% of the sample had. Perioperative as well as long-term morbidity and mortality were analyzed. RESULTS: Mean patient age was 62.3 years. 32.8% underwent suture annuloplasty, 41.3% underwent ring annuloplasty, 15.4% received a bioprosthesis, and 10.4% received a mechanical prosthesis. There were no significant differences in perioperative mortality between the group that had not undergone previous cardiac surgery and the group that had (12.7% vs. 17.9%, respectively; p = 0.32). The long-term mortality rate (median follow-up time: 53 months) was 43.3%. Long-term survival curves showed no significant differences between the two groups (p = 0.884), and previous cardiac surgery was not a predictive factor for long-term mortality (hazard ratio = 1.211; p = 0.521). CONCLUSION: In a series of patients who underwent tricuspid valve surgery, no significant differences were observed in perioperative mortality or in long-term survival according to whether or not subjects had undergone previous cardiac surgery.

Turning Drops into Bubbles: Cavitation by Vapor Diffusion through Elastic Networks.

Some members of the vegetal kingdom can achieve surprisingly fast movements making use of a clever combination of evaporation, elasticity, and cavitation. In this process, enthalpic energy is transformed into elastic energy and suddenly released in a cavitation event which produces kinetic energy. Here, we study this unusual energy transformation by a model system: A droplet in an elastic medium shrinks slowly by diffusion and eventually transforms into a bubble by a rapid cavitation event. The experiments reveal the cavity dynamics over the extremely disparate timescales of the process, spanning 9 orders of magnitude. We model the initial shrinkage as a classical diffusive process, while the sudden bubble growth and oscillations are described using an inertial-(visco)elastic model, in excellent agreement with the experiments. Such a model system could serve as a new paradigm for motile synthetic materials.

Observer error and its impact on ancestry estimation using dental morphology.

Dental morphology is becoming increasingly visible in forensic anthropology as part of the estimation of ancestry. As methods are developed based on these data, it is important to understand the role of observer error in data collection and method application. In this study, 10 observers collected dental morphological data on 19 traits on the same set of nine plaques. Various measures of interrater reliability were calculated to assess observer error. Data were then input into one of three ancestry estimation methods based on dental morphology to understand the role of observer error in these methods. Results show low rater reliability for all dental morphological traits when all 10 observers are compared. Rater reliability increases when only experienced observers are compared and traits are dichotomized. Further, differences in trait scores by observers resulted in disparate estimations of ancestry in each of the methods. While observer error appears to be an issue in dental morphological methods of ancestry estimation, these problems can be addressed. An argument is made for advanced training in dental anthropology in laboratories and in graduate programs. Further, methods need to test for and employ traits with high rater agreement.

Multifractal analysis of diurnal temperature range over Southern Spain using validated datasets.

Multifractal properties of diurnal temperature range (DTR) have been analyzed in this work, using validated data of maximum and minimum temperature from 197 weather stations in Southern Spain (Andalusia region). DTR is a crucial factor to characterize the regional climate, providing more information than the average daily temperature. Apart from climate change studies, one of the most important applications of DTR in Agrometeorology is as an input variable in the solar radiation or reference evapotranspiration estimation models based on the temperature. With the aim of obtaining a detailed information for different time scales, different multifractal approaches have been applied. Different quality control methods such as range/limits or persistence tests were previously applied in order to detect incorrect and anomalous values, being discarded in the subsequent analysis. The DTR scaling of moments has been analyzed and the moment scaling exponent function K(q) has been obtained, finding some differences between weather stations. In addition, multifractal dimension (D1) and multifractal degree (MD) were also estimated, revealing differences at coastal and inland locations that show heterogeneity across the region, including its multifractal nature and its invariance for a range of scales. The nonlinear characterization carried out in this work improves the understanding of DTR as an indicator of climate changes, and it can have a very positive impact on the calibration of regional models for estimating solar radiation or reference evapotranspiration based on the temperature. This multifractal characterization can be used to group stations with similar nonlinear dynamics, regardless of their geographical features, in such a way that more accurate coefficients than conventional ones are used.

Multifractal analysis to study break points in temperature data sets.

Since the last century, the air surface temperature has increased at a global scale, showing trends and inhomogeneities that vary from place to place. Many statistical methods can be used to analyze whether or not an inhomogeneity or break point exists in a meteorological data series, and even to detect the time of the break. Sometimes, there is no agreement in the year at which the inhomogeneity occurs detected by different tests. The scale invariance of a process can be studied through its multifractal properties that can be related to the existence of break points in it. In this work, the multifractal properties of monthly temperature data series are used to test what is the right break point year in those situations at which different dates are found by two different tests: the Pettitt and the Standard Normal Homogeneity tests. The comparison of the fractal dimension function Dq and the multifractal spectrum obtained by the box counting method for both the original data sets and for those obtained by splitting the original into two considering the break point years was made. When different multifractal functions and parameters were obtained, a break point was confirmed. Whereas, if equal values appeared, the break point year was discarded. These results let to select the most suitable test to be applied to detect inhomogeneities in a certain data set that will be very useful for climate change studies.

Patterns in Forensic Decapitations: A Review of the Literature and Case Report.

Separation of the head from the body can occur for a variety of reasons and in various locations across the neck. This study presents a review of the literature to identify the patterns of decapitations in forensic cases in relation to manner of death, age, and anatomical location (n = 88). The most common manner of death was suicide, followed by homicide and then accident. Ages ranged from 32 weeks prenatal to 85 years. Decapitation is reported at higher rates for individuals between 19 and 65. The majority of decapitations occurred at the midneck (second to fifth cervical vertebrae), followed by the upper neck and then the lower neck. This pattern holds true for all manners of death; however, in homicides, the percentage occurring at the midneck decreases. The findings of this study indicate some patterns in terms of manner of death, age, and location of decapitation, which could aid the medicolegal community in interpreting neck trauma. A case study is also briefly presented to illustrate findings.

Bis(dioxaborine) Dyes with Variable π-Bridges: Towards Two-Photon Absorbing Fluorophores with Very High Brightness.

Bis(dioxaborine) dyes of the A-π-A format (A: acceptor, π: conjugated bridge) were prepared and photophysically characterized. The best performing dyes feature (a) visible-light absorption (>400 nm), (b) high molar absorption coefficients (up to 70000 m-1  cm-1 ), (c) Stokes shifts in the range of ca. 2500-5800 cm-1 , and (d) strong fluorescence emission with quantum yields of up to 0.74. This yields very bright-emitting dyes for one-photon excitation. However, the most intriguing feature of the dyes is their strong two-photon absorption. This was achieved by means of increased π-conjugation in the phenylene or phenylene-thiophene bridges through the variation of the conjugation length and rigidity. This provided two-photon absorption cross sections of up to 2800 GM (1 Goeppert-Mayer (GM)=10-50  cm4 s photon-1 ). Considering the mentioned high fluorescence quantum yields, exceptionally bright-emitting A-π-A two-photon absorbing dyes with low molecular mass are obtained. Time-dependent density-functional theory calculations corroborated the experimental results.

Unmasking of intracranial metastatic melanoma during ipilimumab/nivolumab therapy: case report and literature review.

BACKGROUND: While data from several studies over the last decade has demonstrated that introduction of immunologic checkpoint blockage therapy with anti-CTLA-4/PD-1 drugs leads to improved survival in metastatic melanoma patients, relatively little is known about brain-specific therapeutic response and adverse events in the context of immunotherapeutic treatment of intracranial disease. Here we report two independent cases of new intracranial metastases presenting after initiation of combined checkpoint blockade Ipilimumab and Nivolumab for recurrent metastatic melanoma in the context of positive systemic disease response. CASE PRESENTATION: Case #1: A 43-year-old Caucasian male with Stage III melanoma of the left knee had subsequent nodal, hepatic and osseous metastases and was started on ipilimumab/nivolumab. He developed an intractable headache one week later. MRI revealed new enhancing and hemorrhagic brain metastases. After 6 weeks of immunotherapy, there was interval hemorrhage of a dominant intracranial lesion but substantial improvement in systemic metastatic disease. Durable, near complete intracranial and systemic response was achieved after completion of both induction and maintenance immunotherapy. Case #2: A 58-year old Caucasian woman with stage II melanoma of the right index finger developed cutaneous, pulmonary and hepatic metastases within 4 months of adjuvant radiation. Although combined checkpoint blockade resulted in improvement in both cutaneous and systemic disease, brain MR performed for eye discomfort demonstrated new enhancing and hemorrhagic brain metastases. Serial MR imaging five months later revealed only a solitary focus of brain enhancement with continued improved systemic disease. CONCLUSIONS: These cases raise the question of whether the initial immune activation and modulation of the blood brain barrier by Ipilimumab/Nivolumab somehow "unmasks" previously clinically silent metastatic disease, rather than representing new or progressive metastatic disease. An overview of currently available literature discussing the role of immune checkpoint blockade in the treatment of intracranial metastatic melanoma will be provided, as well as discussion highlighting the need for future work elucidating the response of brain metastases to anti-CTLA/PD-1 drugs and documentation of brain-specific adverse events.

Birth-weight differences at term are explained by placental dysfunction and not by maternal ethnicity.

OBJECTIVE: To investigate the influence of ethnicity, fetal gender and placental dysfunction on birth weight (BW) in term fetuses of South Asian and Caucasian origin. METHODS: This was a retrospective study of 627 term pregnancies assessed at two public tertiary hospitals in Spain and Sri Lanka. All fetuses underwent biometry and Doppler examinations within 2 weeks of delivery. The influences of fetal gender and ethnicity, gestational age (GA) at delivery, cerebroplacental ratio (CPR) and maternal age, height, weight and parity on BW were evaluated by multivariable regression analysis. RESULTS: Fetuses born in Sri Lanka were smaller than those born in Spain (mean BW = 3026 ± 449 g vs 3295 ± 444 g; P < 0.001). Multivariable regression analysis demonstrated that GA at delivery, maternal weight, CPR, maternal height and fetal gender (estimates = 0.168, P < 0.001; 0.006, P < 0.001; 0.092, P = 0.003; 0.009, P = 0.002; 0.081, P = 0.01, respectively) were associated significantly with BW. Conversely, no significant association was noted for maternal ethnicity, age or parity (estimates = -0.010, P = 0.831; 0.005, P = 0.127; 0.035, P = 0.086, respectively). The findings were unchanged when the analysis was repeated using INTERGROWTH-21st fetal weight centiles instead of BW (log odds, -0.175, P = 0.170 and 0.321, P < 0.001, respectively for ethnicity and CPR). CONCLUSION: Fetal BW variation at term is less dependent on ethnic origin and better explained by placental dysfunction. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Key actors in driving behavioural change in relation to on-farm biosecurity; a Northern Ireland perspective.

BACKGROUND: Agriculture and farming are valued contributors to local economy in Northern Ireland (NI). There is limited knowledge about farmers' behaviours and attitudes towards disease biosecurity measures. As part of a larger project, a scenario-based workshop with key stakeholders was organised by the Agri-Food and Biosciences Institute (AFBI)-NI in December 2015. RESULTS: A total of 22 participants belonging to 12 different institutions took part in the workshop. Participants were presented with an overview of previously conducted biosecurity research in NI and England. In small groups, participants were subsequently asked to discuss and give their opinions about a series of questions across four key areas in a semi-structured approach with an external facilitator. The key areas were 1- disease risk perception at the farm level; 2-perceived barriers to implementing on farm biosecurity measures; 3- avenues to successful behaviour change and 4-key industry responsibilities and roles. The discussion showed that training in biosecurity for farmers is important and necessary. Training was recommended to be provided by veterinary surgeons, preferably via a face-to-face format. The discussion addressing disease disclosure proved particularly challenging between those who were prospective buyers of cattle, and those who sold cattle. CONCLUSIONS: This workshop provided a unique and invaluable insight into key issues regarding farm level biosecurity activities. From a policy perspective, delivering improved on-farm biosecurity must be addressed via a multidisciplinary approach. This can only be achieved with active involvement, commitment and support of a number of key industry and government stakeholders.

A NodD-like protein activates transcription of genes involved with naringenin degradation in a flavonoid-dependent manner in Herbaspirillum seropedicae.

Herbaspirillum seropedicae is an associative, endophytic non-nodulating diazotrophic bacterium that colonises several grasses. An ORF encoding a LysR-type transcriptional regulator, very similar to NodD proteins of rhizobia, was identified in its genome. This nodD-like gene, named fdeR, is divergently transcribed from an operon encoding enzymes involved in flavonoid degradation (fde operon). Apigenin, chrysin, luteolin and naringenin strongly induce transcription of the fde operon, but not that of the fdeR, in an FdeR-dependent manner. The intergenic region between fdeR and fdeA contains several generic LysR consensus sequences (T-N11 -A) and we propose a binding site for FdeR, which is conserved in other bacteria. DNase I foot-printing revealed that the interaction with the FdeR binding site is modified by the four flavonoids that stimulate transcription of the fde operon. Moreover, FdeR binds naringenin and chrysin as shown by isothermal titration calorimetry. Interestingly, FdeR also binds in vitro to the nod-box from the nodABC operon of Rhizobium sp. NGR234 and is able to activate its transcription in vivo. These results show that FdeR exhibits two features of rhizobial NodD proteins: nod-box recognition and flavonoid-dependent transcription activation, but its role in H. seropedicae and related organisms seems to have evolved to control flavonoid metabolism.

Buchnera has changed flatmate but the repeated replacement of co-obligate symbionts is not associated with the ecological expansions of their aphid hosts.

Symbiotic associations with bacteria have facilitated important evolutionary transitions in insects and resulted in long-term obligate interactions. Recent evidence suggests that these associations are not always evolutionarily stable and that symbiont replacement, and/or supplementation of an obligate symbiosis by an additional bacterium, has occurred during the history of many insect groups. Yet, the factors favouring one symbiont over another in this evolutionary dynamic are not well understood; progress has been hindered by our incomplete understanding of the distribution of symbionts across phylogenetic and ecological contexts. While many aphids are engaged into an obligate symbiosis with a single Gammaproteobacterium, Buchnera aphidicola, in species of the Lachninae subfamily, this relationship has evolved into a 'ménage à trois', in which Buchnera is complemented by a cosymbiont, usually Serratia symbiotica. Using deep sequencing of 16S rRNA bacterial genes from 128 species of Cinara (the most diverse Lachninae genus), we reveal a highly dynamic dual symbiotic system in this aphid lineage. Most species host both Serratia and Buchnera but, in several clades, endosymbionts related to Sodalis, Erwinia or an unnamed member of the Enterobacteriaceae have replaced Serratia. Endosymbiont genome sequences from four aphid species confirm that these coresident symbionts fulfil essential metabolic functions not ensured by Buchnera. We further demonstrate through comparative phylogenetic analyses that cosymbiont replacement is not associated with the adaptation of aphids to new ecological conditions. We propose that symbiont succession was driven by factors intrinsic to the phenomenon of endosymbiosis, such as rapid genome deterioration or competitive interactions between bacteria with similar metabolic capabilities.