Single-cell-bioreactors as end of miniaturization approaches in biotechnology: progresses with characterised bioreactors and a glance into the future

Incidents with single cells and their genesis have not been the major focus of science up to now. This fact is supported by the difficulties one faces when wanting to monitor and cultivate small populations of cells in a defined compartment under controlled conditions, in vitro. Several approaches of up- and down-scaling have often led to poorly understood results which might be better elucidated by understanding the cellular genesis as a function of its microenvironment. This review of the approaches of scale-up and scale-down processes illustrates technical possibilities and shows up their limitations with regard to obtainable data for the characterisation of cellular genesis and impact of the cellular microenvironment. For example, stem cell research advances underline the lack of information about the impact of the microenvironment on cellular development. Finally, a proposal of future research efforts is given on how to overcome this lack of data via a novel bioreactor setup.     

Rotating biological contactors: a review on main factors affecting performance

Rotating biological contactors (RBCs) constitute a very unique and superior alternative for biodegradable matter and nitrogen removal on account of their feasibility, simplicity of design and operation, short start-up, low land area requirement, low energy consumption, low operating and maintenance cost and treatment efficiency. The present review of RBCs focus on parameters that affect performance like rotational speed, organic and hydraulic loading rates, retention time, biofilm support media, staging, temperature, influent wastewater characteristics, biofilm characteristics, dissolved oxygen levels, effluent and solids recirculation, step-feeding and medium submergence. Some RBCs scale-up and design considerations, operational problems and comparison with other wastewater treatment systems are also reported.     

Differential Effects of Wave form and the Subject's Possible Temporal Lobe Signs Upon Experiences During Cerebral Exposure to Weak Intensity Magnetic Fields

In three separate experiments a total of 85 male and female university students were exposed within a Ganzfeld setting to weak (1 mG, 100 nT), complex magnetic field patterns. They were applied across the temporal lobes and generated by computer software. When the patterns were rotated spatially over the temporal lobes the numbers of subjective experiences that simulate possible temporal lobe signs and symptoms were markedly increased and qualitatively more extreme than those evoked when the fields were not rotated. A 16 Hz pulsed square wave generated more experiences of thought intrusion than a 4 Hz wave. A positive-feedback ringing wave presented at 4 Hz evoked more visual memories and images than the mirror image of the same wave; the effect was only apparent when the subject's quantitative scores for possible temporal lobe signs was covaried. Only those subjects who displayed above average temporal lobe signs and were exposed to a burst-firing wave pattern for one second once every 4 seconds (a condition intended to release endogenous opiates), reported more emotional perturbations when the state was disrupted relative to subjects who were exposed continuously to the same pattern. The results indicate that a person's temporal lobe profile affects the types and intensities of experiences that are reported when very weak magnetic fields are applied through the human brain.     

Focus: Preventive Medicine: The Opportunity of Social Ecological Resilience in the Promotion of Youth Health and Wellbeing: A Narrative Review

Youth experience adversity that increases their risk for immediate and long-term health consequences. Resilience has traditionally been conceptualized as an internal disposition or trait that supports youth to overcome that risk and avoid the negative impact on their health and wellbeing. However, this model of resilience overemphasizes the role of the individual and their capacity to control their environment, while minimizing the integral role of relational, social, structural, and cultural contexts in which they live. Instead, social ecological resilience (SER) emphasizes the influence of social and environmental factors on individual processes and outcomes and offers different pathways for preventive interventions to promote youth health and wellbeing. Within preventive medicine, it is important for researchers and practitioners to understand the processes that support or impede SER, particularly in youth when adversity can impact health throughout the lifespan. The purpose of this review was to examine the contributions and scope of the SER model in research on youth, with the goal of advancing SER-informed research and interventions within preventive medicine. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach as a guiding framework, we conducted a narrative review of the literature. The review characterizes 37 existing studies across the fields of education, psychology, and social work in terms of topic, focal population, methods, use of SER, and implications. We conclude with recommendations for future applications of SER to promote the health and wellbeing of youth.     

Analysis of particle strain in stirred bioreactors by drop breakage investigations

Understanding of particle strain and drop breakage is relevant for various technical applications. To analyze it, single drop experiments in a breakage cell and evolving drop size distributions in an agitated system are studied. The mechanisms for particle strain and drop breakage are assumed to be comparable for the investigated turbulent flow regime. The agitation process is simulated using a population balance model. This model provides transient prediction capacities at different scales and can be used for scale-up/down projects. The number and the size distributions of daughter fragments for single drops have been studied. The results clearly support the assumption of binary breakage. The most common assumption of a Gaussian distribution for the daughter drop size distribution could not be supported. The evolution of a breakage-dominated toluene/water system was then simulated using different daughter drop size distributions from literature. The computational results were compared with experimental values. All simulations were able to predict the transient Sauter mean diameter excellently but varied strongly in the results on the shape of the distribution. In agreement with the experimental single drop results, the use of a bimodal or a very broad bell-shaped distribution of the daughter drops is proposed for the simulations. Although these results were obtained in a particular vessel for a specific phase system, it can be applied to simulate transient multiphase systems at different scales. We would expect that the general trends observed in this study are comparable to various applications in multiphase bioreactors.     

Comparison of Cell Growth and Alkaloid Production of Catharanthus roseus Cells Cultured in Shake Flask and in Bioreactor

The cell growth and alkaloid production of Catharanthus roseus (L.) G. Don cells cultured in the shake flasks with different volumes and in the stirred tank bioreactor (10 L) were compared. Cell dry weight and alkaloid production showed no significant difference in the small volume scale-up shake flasks. When more broths were added to a certain volume in the shake flask, both cell weight and alkaloid production were decreased. The maximum cell dry weight was similar between the cell cultures in the shake flask and the bioreactor, but the alkaloid production of cells was much less in the bioreactor. Gas regime and shear stress were recognized to be the main factors contributing the important effect on alkaloid production during the scale-up processes.     

Revisiting the influence of learning in predator functional response,how it can lead to shapes different from type III

Predator/parasitoid functional response is one of the main tools used to study predation behavior, and in assessing the potential of biological control candidates. It is generally accepted that predator learning in prey searching and manipulation can produce the appearance of a type III functional response. Holling proposed that in the presence of alternative prey, at some point the predator would shift the preferred prey, leading to the appearance of a sigmoid function that characterized that functional response. This is supported by the analogy between enzyme kinetics and functional response that Holling used as the basis for developing this theory. However, after several decades, sigmoidal functional responses appear in the absence of alternative prey in most of the biological taxa studied. Here, we propose modeling the effect of learning on the functional response by using the explicit incorporation of learning curves in the parameters of the Holling functional response, the attack rate (a), and the manipulation time (h). We then study how the variation in the parameters of the learning curves causes variations in the shape of the functional response curve. We found that the functional response product of learning can be either type I, II, or III, depending on what parameters act on the organism, and how much it can learn throughout the length of the study. Therefore, the presence of other types of curves should not be automatically associated with the absence of learning. These results are important from an ecological point of view because when type III functional response is associated with learning, it is generally accepted that it can operate as a stabilizing factor in population dynamics. Our results, to the contrary, suggest that depending on how it acts, it may even be destabilizing by generating the appearance of functional responses close to type I.     

Persistence of psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort: a prospective two‐year follow‐up

Prospective evaluation of youths with early psychotic‐like experiences can enrich our knowledge of clinical, biobehavioral and environmental risk and protective factors associated with the development of psychotic disorders. We aimed to investigate the predictors of persistence or worsening of psychosis spectrum features among US youth through the first large systematic study to evaluate subclinical symptoms in the community. Based on Time 1 screen of 9,498 youth (age 8‐21) from the Philadelphia Neurodevelopmental Cohort, a subsample of participants was enrolled based on the presence (N=249) or absence (N=254) of baseline psychosis spectrum symptoms, prior participation in neuroimaging, and current neuroimaging eligibility. They were invited to participate in a Time 2 assessment two years on average following Time 1. Participants were administered the Structured Interview for Prodromal Syndromes, conducted blind to initial screen status, along with the Schizotypal Personality Questionnaire and other clinical measures, computerized neurocognitive testing, and neuroimaging. Clinical and demographic predictors of symptom persistence were examined using logistic regression. At Time 2, psychosis spectrum features persisted or worsened in 51.4% of youths. Symptom persistence was predicted by higher severity of subclinical psychosis, lower global functioning, and prior psychiatric medication at baseline. Youths classified as having psychosis spectrum symptoms at baseline but not at follow‐up nonetheless exhibited comparatively higher symptom levels and lower functioning at both baseline and follow‐up than typically developing youths. In addition, psychosis spectrum features emerged in a small number of young people who previously had not reported significant symptoms but who had exhibited early clinical warning signs. Together, our findings indicate that varying courses of psychosis spectrum symptoms are evident early in US youth, supporting the importance of investigating psychosis risk as a dynamic developmental process. Neurocognition, brain structure and function, and genomics may be integrated with clinical data to provide early indices of symptom persistence and worsening in youths at risk for psychosis.     

Lessons and recommendations from three decades as an NSF REU site: A call for systems‐based assessment

For more than 30 years, the US National Science Foundation's Research Experiences for Undergraduates (REU) program has supported thousands of undergraduate researchers annually and provides many students with their first research experiences in field ecology or evolution. REUs embed students in scientific communities where they apprentice with experienced researchers, build networks with their peers, and help students understand research cultures and how to work within them. REUs are thought to provide formative experiences for developing researchers that differ from experiences in a college classrooms, laboratories, or field trips. REU assessments have improved through time but they are largely ungrounded in educational theory. Thus, evaluation of long‐term impacts of REUs remains limited and best practices for using REUs to enhance student learning are repeatedly re‐invented. We describe how one sociocultural learning framework, cultural–historical activity theory (CHAT), could be used to guide data collection to characterize the effects of REU programs on participant's learning in an educationally meaningful context. CHAT embodies a systems approach to assessment that accounts for social and cultural factors that influence learning. We illustrate how CHAT has guided assessment of the Harvard Forest Summer Research Program in Ecology (HF‐SRPE), one of the longest‐running REU sites in the United States. Characterizing HF‐SRPE using CHAT helped formalize thoughts and language for the program evaluation, reflect on potential barriers to success, identify assessment priorities, and revealed important oversights in data collection.     

Optimization of culture conditions and scale-up to pilot and plant scales for vancomycin production by <Emphasis Type="Italic">Amycolatopsis orientalis</Emphasis>

This report describes the optimization of culture conditions for vancomycin production by Amycolatopsis orientalis KCCM-10836P, an identified high-vancomycin-producing strain (US11/712,494). Among the conditions tested, pH and the dissolved oxygen tension (DOT) were key factors affecting vancomycin production. When the pH and DOT were controlled at 7.0 and 20–30%, respectively, a dry-cell weight (DCW) of 62.0 g l⁻¹ and a vancomycin production of 11.5 g l⁻¹ were obtained after 120 h of batch culture, corresponding to a specific vancomycin content of 185.4 mg g-DCW⁻¹. Vancomycin production was scaled up from a laboratory scale (7-l fermentor) to a pilot scale (300 l) and a plant scale (5,000 l) using the impeller tip velocity (V _tip) as a scale-up parameter. Vancomycin production at the laboratory scale was similar to those at the pilot and plant scales.