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Biodiversity within ecological communities has been shown to influence plant resistance and tolerance to herbivory, and may strongly interact with climate change. However, the effects of diversity within microbial symbionts on their plant hosts’ responses to herbivores is less well documented, particularly within the context of agricultural systems. Here we examine the interactive effects of rhizobial diversity and drought in promoting soybean resistance and tolerance to insect and mammalian herbivores in an outdoor pot experiment. We demonstrate that soybean plants provided with a diverse mixture of rhizobial strains experience 30% less damage by chewing insect herbivores under both drought (reduced watering and increased temperature) and ambient weather conditions, as well as half as much colonization by aphids under drought conditions. This effect was not due to the presence of any particularly beneficial rhizobial strain (i.e., not a selection effect), but rather due to an enhanced benefit provided by the rhizobial strains in combination (i.e., a complementarity effect). No effects of rhizobial diversity were observed on the rate of defoliation by rabbits. While rhizobial diversity did affect soybean resistance to insect herbivores, these differences in insect damage did not carry through to affect soybean growth or final yield. Thus, soybean plants exhibited high tolerance to herbivory regardless of our experimentally imposed rhizobial diversity or drought treatments. With future projections for increased pest outbreaks and drought, understanding the factors that can sustainably enhance agricultural yield is critical. Our results suggest that promoting rhizobial diversity within soybean agriculture may be one nature-based solution to promote the resistance of this critical crop to insect pests.

The isoflavone irilone is found in human plasma after ingestion of red clover-based dietary supplements, but information allowing safety assessment is rare. Here, data in support of the mutagenic potential of irilone in cultured V79 cells [1] are presented. These data include (i) a quantitative assessment of irilone in the culture medium during the cell culture experiments, (ii) changes in the mutation spectrum in cDNA of the hypoxanthine-guanine phosphoribosyltransferase locus of irilone-treated V79 cells, (iii) occurrence of karyorrhexis and apoptosis as well as (iv) number of micronucleated cells containing whole chromosomes or chromosomal fragments. Also exemplary micrographs, used for the fluorescence microscopic assessment of (iii) and (iv) are presented.

Este trabajo describe cómo la evaluación formativa fue introducida en un curso de matemáticas para futuros bioingenieros. Este cambio se desarrolló en el contexto de una indagación enmarcada en los principios metodológicos de una Investigación Acción Participativa. Como resultado de la indagación el sistema tradicional de evaluación basado en exámenes parciales, evaluaciones finales y trabajos de laboratorio fue reemplazado por un nuevo sistema que incorpora nuevas actividades enfatizando el debate, la retroalimentación y la participación de los estudiantes. En este nuevo sistema se solicita a los estudiantes completar informes escritos y presentarlos oralmente en la clase, dando lugar a un intercambio enriquecido por la combinación de la evaluación entre pares, la autoevaluación y la evaluación del docente. Por otro lado también se les propone realizar entregas de borradores de los trabajos de laboratorio para recibir retroalimentación del docente, y en otra instancia de autoevaluación, se les presentan listas de cotejo y cuestionarios para reflexionar sobre su desempeño en el curso. Los primeros resultados de este nuevo sistema son alentadores, porque no sólo muestran mejoras en el desempeño de los alumnos, sino que también permiten observar un cambio de actitud beneficioso tanto en los alumnos como en los docentes.

The molecular mechanisms underpinning the formation of the large, ellipsoidal starch granules of potato tuber are poorly understood. Here, we demonstrate the distinct effects of PROTEIN TARGETING TO STARCH2b (PTST2b) and MYOSIN RESEMBLING CHLOROPLAST PROTEIN (MRC) on tuber starch granule morphology. A gene duplication event in the Solanaceae resulted in two PTST2 paralogs (PTST2a and PTST2b). PTST2b is expressed in potato tubers, and unlike PTST2a, it had no detectable interaction with STARCH SYNTHASE 4. MRC expression was detectable in leaves, but not in tubers. Using transgenic potato lines in the variety Clearwater Russet, we demonstrate that MRC overexpression leads to the formation of granules with aberrant shapes, many of which arise from multiple initiation points. Silencing PTST2b led to the production of striking near-spherical granules, each arising from a single, central initiation point. Contrary to all reported PTST2 mutants in other species, we observed no change in the number of granules per cell in these lines, suggesting PTST2b is specifically involved in the control of starch granule shape. Starch content and tuber yield per plant were not affected by PTST2b silencing, but MRC overexpression led to strong decreases in both parameters. Notably, the spherical granules in PTST2b silencing lines had a distinctively altered pasting profile, with higher peak and final viscosity than the wild type. Thus, PTST2b and MRC are promising target genes for altering starch granule size and shape in potato tubers, and can be used to create novel starches with altered physicochemical and/or functional properties., (© 2024 The Author(s). Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

The determination of starch granule morphology in plants is poorly understood. The amyloplasts of wheat endosperm contain large discoid A-type granules and small spherical B-type granules. To study the influence of amyloplast structure on these distinct morphological types, we isolated a mutant in durum wheat (Triticum turgidum) defective in the plastid division protein PARC6, which had giant plastids in both leaves and endosperm. Endosperm amyloplasts of the mutant contained more A- and B-type granules than those of the wild-type. The mutant had increased A- and B-type granule size in mature grains, and its A-type granules had a highly aberrant, lobed surface. This morphological defect was already evident at early stages of grain development and occurred without alterations in polymer structure and composition. Plant growth and grain size, number and starch content were not affected in the mutants despite the large plastid size. Interestingly, mutation of the PARC6 paralog, ARC6, did not increase plastid or starch granule size. We suggest TtPARC6 can complement disrupted TtARC6 function by interacting with PDV2, the outer plastid envelope protein that typically interacts with ARC6 to promote plastid division. We therefore reveal an important role of amyloplast structure in starch granule morphogenesis in wheat., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

MonocotJRLs are Poaceae-specific two-domain proteins that consist of a jacalin-related lectin (JRL) and a dirigent (DIR) domain which participate in multiple developmental processes, including disease resistance. For OsJAC1, a monocotJRL from rice, it has been confirmed that constitutive expression in transgenic rice or barley plants facilitates broad-spectrum disease resistance. In this process, both domains of OsJAC1 act cooperatively, as evidenced from experiments with artificially separated JRL- or DIR-domain-containing proteins. Interestingly, these chimeric proteins did not evolve in dicotyledonous plants. Instead, proteins with a single JRL domain, multiple JRL domains or JRL domains fused to domains other than DIR domains are present. In this study, we wanted to test if the cooperative function of JRL and DIR proteins leading to pathogen resistance was conserved in the dicotyledonous plant Arabidopsis thaliana. In Arabidopsis, we identified 50 JRL and 24 DIR proteins, respectively, from which seven single-domain JRL and two single-domain DIR candidates were selected. A single-cell transient gene expression assay in barley revealed that specific combinations of the Arabidopsis JRL and DIR candidates reduced the penetration success of barley powdery mildew. Strikingly, one of these pairs, AtJAX1 and AtDIR19, is encoded by genes located next to each other on chromosome one. However, when using natural variation and analyzing Arabidopsis ecotypes that express full-length or truncated versions of AtJAX1, the presence/absence of the full-length AtJAX1 protein could not be correlated with resistance to the powdery mildew fungus Golovinomyces orontii. Furthermore, an analysis of the additional JRL and DIR candidates in a bi-fluorescence complementation assay in Nicotiana benthamiana revealed no direct interaction of these JRL/DIR pairs. Since transgenic Arabidopsis plants expressing OsJAC1-GFP also did not show increased resistance to G. orontii, it was concluded that the resistance mediated by the synergistic activities of DIR and JRL proteins is specific for members of the Poaceae, at least regarding the resistance against powdery mildew. Arabidopsis lacks the essential components of the DIR-JRL-dependent resistance pathway.

Debate persists over whether animals develop innovative solutions primarily in response to needs or conversely whether they innovate more when basic needs are covered and opportunity to develop novel behaviour is offered. We sourced 746 cases of "unusual" behaviour in equids by contacting equid owners and caretakers directly and via a website (https://innovative-behaviour.org), and by searching the internet platforms YouTube and Facebook for videos. The study investigated whether differences in need or opportunity for innovation were reflected in the numbers of different types of innovations and in the frequencies of repeating a once-innovative behaviour (i) with respect to the equids' sex, age, and breed type, (ii) across behavioural categories, and whether (iii) they were affected by the equids' management (single vs group housing, access to roughage feed, access to pasture, and social contact). We found that the numbers of different types of innovation and the frequency of displaying specific innovations were not affected by individual characteristics (sex, age, breed or equid species). Few types of innovation in escape and foraging contexts were observed, whilst the comfort, play, and social contexts elicited the greatest variety of innovations. We also found higher numbers of different types of innovations in horses kept in groups rather than in individual housing, and with unlimited rather than with restricted access to pasture and roughage. Equids in permanent social contact performed high rates of once-innovative behaviour. We suggest that equids produce goal-directed innovations and repeat the behaviour at high frequency in response to urgent needs for food and free movement or when kept in conditions with social conflict. However, equids devise the greatest variety of innovations when opportunity to play and to develop comfort behaviour arises and when kept in good conditions., Competing Interests: The authors have declared that no competing interests exist.

Every animal species has particular environmental requirements that are essential for its welfare, and when these so-called "basic needs" are not fulfilled, the animals suffer. The basic needs of horses have been claimed to be social contact, social companionship, free movement and access to roughage. To assess whether horses suffer when one or more of the four proposed basic needs are restricted, we examined several studies ( n = 38) that reported behavioural and physiological reactions to these restrictions. We assigned the studies according to the four types of responses investigated: (a) Stress, (b) Active, (c) Passive, and (d) Abnormal Behaviour. Furthermore, the number of studies indicating that horses reacted to the restrictions were compared with the number of studies reporting no reaction. The limited number of studies available on single management restrictions did not allow conclusions to be drawn on the effect of each restriction separately, especially in the case of social companionship. However, when combinations of social contact, free movement and access to roughage were restricted, many of the horses had developed responses consistent with suffering. Passive Responses, indicating acute suffering, and Abnormal Behaviour, indicating suffering currently or at some time in the past, were especially clearly demonstrated. This provides further evidence of the usefulness of assessing behavioural parameters in combination with physiological measurements when evaluating horse welfare. This meta-analysis of the literature confirms that it is justified to claim that social contact, free movement and access to roughage are basic needs in horses.

Anecdotal reports of horses opening fastened doors and gates are an intriguing way of exploring the possible scope of horses' problem-solving capacities. The species' natural environment has no analogues of the mechanisms involved. Scientific studies on the topic are missing, because the rate of occurrence is too low for exploration under controlled conditions. Therefore, we compiled from lay persons case reports of horses opening closed doors and gates. Additionally, we collected video documentations at the internet platform YouTube, taking care to select raw data footage of unedited, clearly described and clearly visible cases of animals with no distinct signs of training or reduced welfare. The data included individuals opening 513 doors or gates on hinges, 49 sliding doors, and 33 barred doors and gateways; mechanisms included 260 cases of horizontal and 155 vertical bars, 43 twist locks, 42 door handles, 34 electric fence handles, 40 carabiners, and 2 locks with keys. Opening was usually for escape, but also for access to food or stable-mates, or out of curiosity or playfulness. While 56 percent of the horses opened a single mechanism at one location, 44 percent opened several types of mechanism (median = 2, min. = 1, max. = 5) at different locations (median = 2, min. = 1, max. = 4). The more complex the mechanism was, the more movements were applied, varying from median 2 for door handles to 10 for carabiners. Mechanisms requiring head- or lip-twisting needed more movements, with significant variation between individuals. 74 horses reported in the questionnaire had options for observing the behaviour in stable mates, 183 did not, which indicates that the latter learned to open doors and gates either individually or from observing humans. Experience favours opening efficiency; subjects which opened several door types applied fewer movements per lock than horses which opened only one door type. We failed to identify a level of complexity of door-fastening mechanism that was beyond the learning capacity of the horse to open. Thus, all devices in frequent use, even carabiners and electric fence handles, are potentially vulnerable to opening by horses, something which needs to be considered in relation to keeping horses safely., Competing Interests: The authors have declared that no competing interests exist.

Physical activity initiates a wide range of multi-systemic adaptations that promote mental and physical health. Recent work demonstrated that exercise triggers the release of extracellular vesicles (EVs) into the circulation, possibly contributing to exercise-associated adaptive systemic signalling. Circulating EVs comprise a heterogeneous collection of different EV-subclasses released from various cell types. So far, a comprehensive picture of the parental and target cell types, EV-subpopulation diversity and functional properties of EVs released during exercise (ExerVs) is lacking. Here, we performed a detailed EV-phenotyping analysis to explore the cellular origin and potential subtypes of ExerVs. Healthy male athletes were subjected to an incremental cycling test until exhaustion and blood was drawn before, during, and immediately after the test. Analysis of total blood plasma by EV Array suggested endothelial and leukocyte characteristics of ExerVs. We further purified ExerVs from plasma by size exclusion chromatography as well as CD9-, CD63- or CD81-immunobead isolation to examine ExerV-subclass dynamics. EV-marker analysis demonstrated increasing EV-levels during cycling exercise, with highest levels at peak exercise in all EV-subclasses analysed. Phenotyping of ExerVs using a multiplexed flow-cytometry platform revealed a pattern of cell surface markers associated with ExerVs and identified lymphocytes (CD4, CD8), monocytes (CD14), platelets (CD41, CD42, CD62P), endothelial cells (CD105, CD146) and antigen presenting cells (MHC-II) as ExerV-parental cells. We conclude that multiple cell types associated with the circulatory system contribute to a pool of heterogeneous ExerVs, which may be involved in exercise-related signalling mechanisms and tissue crosstalk.

Domesticated horses are constantly confronted with novel tasks. A recent study on anecdotal data indicates that some are innovative in dealing with such tasks. However, innovative behavior in horses has not previously been investigated under experimental conditions. In this study, we investigated whether 16 horses found an innovative solution when confronted with a novel feeder. Moreover, we investigated whether innovative behavior in horses may be affected by individual aspects such as: age, sex, size, motor and sensory laterality, fecal stress hormone concentrations (GCMs), and task-related behavior. Our study revealed evidence for 25% of the horses being capable of innovative problem solving for operating a novel feeder. Innovative horses of the present study were active, tenacious, and may be considered to have a higher inhibitory control, which was revealed by their task related behavior. Furthermore, they appeared to be emotional, reflected by high baseline GCM concentrations and a left sensory and motor laterality. These findings may contribute to the understanding of horses' cognitive capacities to deal with their environment and calls for enriched environments in sports and leisure horse management.

The use of community health workers (CHWs) has been explored as a viable option to provide home health education, counselling and basic health care, notwithstanding their challenges in training and retention. In this manuscript, we review the evidence and discuss how the digitalization affects the CHWs programmes for tackling non-communicable diseases (NCDs) in low- and middle-income countries (LMICs). We conducted a review of literature covering two databases: PubMED and Embase. A total of 97 articles were abstracted for full text review of which 26 are included in the analysis. Existing theories were used to construct a conceptual framework for understanding how digitalization affects the prospects of CHW programmes for NCDs. The results are divided into two themes: (1) the benefits of digitalization and (2) the challenges to the prospects of digitalization. We also conducted supplemental search in non-peer reviewed literature to identify and map the digital platforms currently in use in CHW programmes. We identified three benefits and three challenges of digitalization. Firstly, it will help improve the access and quality of services, notwithstanding its higher establishment and maintenance costs. Secondly, it will add efficiency in training and personnel management. Thirdly, it will leverage the use of data generated across grass-roots platforms to further research and evaluation. The challenges posed are related to funding, health literacy of CHWs and systemic challenges related to motivating CHWs. Several dozens of digital platforms were mapped, including mobile-based networking devices (used for behavioural change communication), Web-applications (used for contact tracking, reminder system, adherence tracing, data collection and decision support), videoconference (used for decision support) and mobile applications (used for reminder system, supervision, patients' management, hearing screening and tele-consultation). The digitalization efforts of CHW programmes are afflicted by many challenges, yet the rapid technological penetration and acceptability coupled with the gradual fall in costs constitute encouraging signals for the LMICs. Both CHWs interventions and digital technologies are not inexpensive, but they may provide better value for the money when applied at the right place and time., (© The Author(s) 2019. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Magnetoencephalography (MEG) and Electroencephalography (EEG) are noninvasive techniques to study the electrophysiological activity of the human brain. Thus, they are well suited for real-time monitoring and analysis of neuronal activity. Real-time MEG/EEG data processing allows adjustment of the stimuli to the subject's responses for optimizing the acquired information especially by providing dynamically changing displays to enable neurofeedback., New Method: We introduce MNE Scan, an acquisition and real-time analysis software based on the multipurpose software library MNE-CPP. MNE Scan allows the development and application of acquisition and novel real-time processing methods in both research and clinical studies. The MNE Scan development follows a strict software engineering process to enable approvals required for clinical software., Results: We tested the performance of MNE Scan in several device-independent use cases, including, a clinical epilepsy study, real-time source estimation, and Brain Computer Interface (BCI) application., Comparison With Existing Method(s): Compared to existing tools we propose a modular software considering clinical software requirements expected by certification authorities. At the same time the software is extendable and freely accessible., Conclusion: We conclude that MNE Scan is the first step in creating a device-independent open-source software to facilitate the transition from basic neuroscience research to both applied sciences and clinical applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Magnetoencephalography (MEG) and electroencephalography provide a high temporal resolution, which allows estimation of the detailed time courses of neuronal activity. However, in real-time analysis of these data two major challenges must be handled: the low signal-to-noise ratio (SNR) and the limited time available for computations. In this work, we present real-time clustered multiple signal classification (RTC-MUSIC) a real-time source localization algorithm, which can handle low SNRs and can reduce the computational effort. It provides correlation information together with sparse source estimation results, which can, e.g., be used to identify evoked responses with high sensitivity. RTC-MUSIC clusters the forward solution based on an anatomical brain atlas and optimizes the scanning process inherent to MUSIC approaches. We evaluated RTC-MUSIC by analyzing MEG auditory and somatosensory data. The results demonstrate that the proposed method localizes sources reliably. For the auditory experiment the most dominant correlated source pair was located bilaterally in the superior temporal gyri. The highest activation in the somatosensory experiment was found in the contra-lateral primary somatosensory cortex.

Plant lectins are proteins that reversibly bind carbohydrates and are assumed to play an important role in plant development and resistance. Through the binding of carbohydrate ligands, lectins are involved in the perception of environmental signals and their translation into phenotypical responses. These processes require down-stream signaling cascades, often mediated by interacting proteins. Fusing the respective genes of two interacting proteins can be a way to increase the efficiency of this process. Most recently, proteins containing jacalin-related lectin (JRL) domains became a subject of plant resistance responses research. A meta-data analysis of fusion proteins containing JRL domains across different kingdoms revealed diverse partner domains ranging from kinases to toxins. Among them, proteins containing a JRL domain and a dirigent domain occur exclusively within monocotyledonous plants and show an unexpected high range of family member expansion compared to other JRL-fusion proteins. Rice, wheat, and barley plants overexpressing OsJAC1, a member of this family, are resistant against important fungal pathogens. We discuss the possibility that JRL domains also function as a decoy in fusion proteins and help to alert plants of the presence of attacking pathogens., Competing Interests: The authors declare no conflict of interest.

Versatile controllers for accurate, fast, and real-time synchronized acquisition of large-scale data are useful in many areas of science, engineering, and technology. Here, we describe the development of a controller software based on a technique called queued state machine for controlling the data acquisition (DAQ) hardware, continuously acquiring a large amount of data synchronized across a large number of channels (>400) at a fast rate (up to 20 kHz/channel) in real time, and interfacing with applications for real-time data analysis and display of electrophysiological data. This DAQ controller was developed specifically for a 384-channel pediatric whole-head magnetoencephalography (MEG) system, but its architecture is useful for wide applications. This controller running in a LabVIEW environment interfaces with microprocessors in the MEG sensor electronics to control their real-time operation. It also interfaces with a real-time MEG analysis software via transmission control protocol/internet protocol, to control the synchronous acquisition and transfer of the data in real time from >400 channels to acquisition and analysis workstations. The successful implementation of this controller for an MEG system with a large number of channels demonstrates the feasibility of employing the present architecture in several other applications.

We developed a 375-channel, whole-head magnetoencephalography (MEG) system ("BabyMEG") for studying the electrophysiological development of human brain during the first years of life. The helmet accommodates heads up to 95% of 36-month old boys in the USA. The unique two-layer sensor array consists of: (1) 270 magnetometers (10 mm diameter, ∼15 mm coil-to-coil spacing) in the inner layer, (2) thirty-five three-axis magnetometers (20 mm × 20 mm) in the outer layer 4 cm away from the inner layer. Additionally, there are three three-axis reference magnetometers. With the help of a remotely operated position adjustment mechanism, the sensor array can be positioned to provide a uniform short spacing (mean 8.5 mm) between the sensor array and room temperature surface of the dewar. The sensors are connected to superconducting quantum interference devices (SQUIDs) operating at 4.2 K with median sensitivity levels of 7.5 fT/√Hz for the inner and 4 fT/√Hz for the outer layer sensors. SQUID outputs are digitized by a 24-bit acquisition system. A closed-cycle helium recycler provides maintenance-free continuous operation, eliminating the need for helium, with no interruption needed during MEG measurements. BabyMEG with the recycler has been fully operational from March, 2015. Ongoing spontaneous brain activity can be monitored in real time without interference from external magnetic noise sources including the recycler, using a combination of a lightly shielded two-layer magnetically shielded room, an external active shielding, a signal-space projection method, and a synthetic gradiometer approach. Evoked responses in the cortex can be clearly detected without averaging. These new design features and capabilities represent several advances in MEG, increasing the utility of this technique in basic neuroscience as well as in clinical research and patient studies.

Modular proteins are an evolutionary answer to optimize performance of proteins that physically interact with each other for functionality. Using a combination of genetic and biochemical experiments, we characterized the rice protein OsJAC1, which consists of a jacalin-related lectin (JRL) domain predicted to bind mannose-containing oligosaccharides, and a dirigent domain which might function in stereoselective coupling of monolignols. Transgenic overexpression of OsJAC1 in rice resulted in quantitative broad-spectrum resistance against different pathogens including bacteria, oomycetes, and fungi. Overexpression of this gene or its wheat ortholog TAJA1 in barley enhanced resistance against the powdery mildew fungus. Both protein domains of OsJAC1 are required to establish resistance as indicated by single or combined transient expression of individual domains. Expression of artificially separated and fluorescence-tagged protein domains showed that the JRL domain is sufficient for targeting the powdery mildew penetration site. Nevertheless, co-localization of the lectin and the dirigent domain occurred. Phylogenetic analyses revealed orthologs of OsJAC1 exclusively within the Poaceae plant family. Dicots, by contrast, only contain proteins with either JRL or dirigent domain(s). Altogether, our results identify OsJAC1 as a representative of a novel type of resistance protein derived from a plant lineage-specific gene fusion event for better function in local pathogen defense., (Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.)

Background: Recombinant protein production using Escherichia coli as expression host is highly efficient, however, it also induces strong host cell metabolic burden. Energy and biomass precursors are withdrawn from the host's metabolism as they are required for plasmid replication, heterologous gene expression and protein production. Rare codons in a heterologous gene may be a further drawback. This study aims to investigate the influence of particular silent codon exchanges within a heterologous gene on host cell metabolic activity. Silent mutations were introduced into the coding sequence of a model protein to introduce all synonymous arginine or leucine codons at two randomly defined positions, as well as substitutions leading to identical amino acid exchanges with different synonymous codons. The respective E. coli clones were compared during cultivation in a mineral autoinduction medium using specialized online and offline measuring techniques to quantitatively analyze effects on respiration, biomass and protein production, as well as on carbon source consumption, plasmid copy number, intracellular nucleobases and mRNA content of each clone., Results: Host stain metabolic burden correlates with recombinant protein production. Upon heterologous gene expression, tremendous differences in respiration, biomass and protein production were observed. According to their different respiration activity the E. coli clones could be classified into two groups, Type A and Type B. Type A clones tended to higher product formation, Type B clones showed stronger biomass formation. Whereas codon usage and intracellular nucleobases had no influence on the Type-A-Type-B-behavior, plasmid copy number, mRNA content and carbon source consumption strongly differed between the two groups., Conclusions: Particular silent codon exchanges in a heterologous gene sequence led to differences in initial growth of Type A and Type B clones. Thus, the biomass concentration at the time point of induction varied. In consequence, not only plasmid copy number and expression levels differed between the two groups, but also the kinetics of lactose and glycerol consumption. Even though the underlying molecular mechanisms are not yet identified we observed the astonishing phenomenon that particular silent codon exchanges within a heterologous gene tremendously affect host cell metabolism and recombinant protein production. This could have great impact on codon optimization of heterologous genes, screening procedures for improved variants, and biotechnological protein production processes.

Several novel therapeutic agents have demonstrated ability to improve overall survival in metastatic castration-resistant prostate cancer (mCRPC) in recent years. With as many as 5 new agents approved within the last 5 years and an ongoing lack of comparative and prospective data, strategies for patient selection and sequencing of drug treatments are urgently needed. This review will summarize current clinical evidence and relevant molecular mechanisms in mCRPC. The understanding of these mechanisms may provide valuable assistance in making therapeutic decisions, especially while robust clinical data remain sparse., (© 2014 S. Karger GmbH, Freiburg.)

Objective: Air pollution PM is associated with cardiovascular morbidity and mortality. In Appalachia, PM from mining may represent a health burden to this sensitive population that leads the nation in cardiovascular disease, among others. Cardiovascular consequences following inhalation of PM(MTM) are unclear, but must be identified to establish causal effects., Methods: PM was collected within 1 mile of an active MTM site in southern WV. The PM was extracted and was primarily <10 μm in diameter (PM10), consisting largely of sulfur (38%) and silica (24%). Adult male rats were IT with 300 μg PM(MTM) . Twenty-four hours following exposure, rats were prepared for intravital microscopy, or isolated arteriole experiments., Results: PM(MTM) exposure blunted endothelium-dependent dilation in mesenteric and coronary arterioles by 26%, and 25%, respectively, as well as endothelium-independent dilation. In vivo, PM(MTM) exposure inhibited endothelium-dependent arteriolar dilation (60% reduction). α-adrenergic receptor blockade inhibited PVNS-induced vasoconstriction in exposed animals compared with sham., Conclusions: These data suggest that PM(MTM) exposure impairs microvascular function in disparate microvascular beds, through alterations in NO-mediated dilation and sympathetic nerve influences. Microvascular dysfunction may contribute to cardiovascular disease in regions with MTM sites., (© 2012 John Wiley & Sons Ltd.)

Purpose: To determine if chronic cardiovascular disease (CVD) mortality rates are higher among residents of mountaintop mining (MTM) areas compared to mining and nonmining areas, and to examine the association between greater levels of MTM surface mining and CVD mortality., Methods: Age-adjusted chronic CVD mortality rates from 1999 to 2006 for counties in 4 Appalachian states where MTM occurs (N = 404) were linked with county coal mining data. Three groups of counties were compared: MTM, coal mining but not MTM, and nonmining. Covariates included smoking rate, rural-urban status, percent male population, primary care physician supply, obesity rate, diabetes rate, poverty rate, race/ethnicity rates, high school and college education rates, and Appalachian county. Linear regression analyses examined the association of mortality rates with mining in MTM areas and non-MTM areas and the association of mortality with quantity of surface coal mined in MTM areas., Findings: Prior to covariate adjustment, chronic CVD mortality rates were significantly higher in both mining areas compared to nonmining areas and significantly highest in MTM areas. After adjustment, mortality rates in MTM areas remained significantly higher and increased as a function of greater levels of surface mining. Higher obesity and poverty rates and lower college education rates also significantly predicted CVD mortality overall and in rural counties., Conclusions: MTM activity is significantly associated with elevated chronic CVD mortality rates. Future research is necessary to examine the socioeconomic and environmental impacts of MTM on health to reduce health disparities in rural coal mining areas., (© 2011 National Rural Health Association.)

In addition to its search for extrasolar planets, the NASA Kepler mission provides exquisite data on stellar oscillations. We report the detections of oscillations in 500 solar-type stars in the Kepler field of view, an ensemble that is large enough to allow statistical studies of intrinsic stellar properties (such as mass, radius, and age) and to test theories of stellar evolution. We find that the distribution of observed masses of these stars shows intriguing differences to predictions from models of synthetic stellar populations in the Galaxy.