PlasmaCap EBA: An innovative method of isolating plasma proteins from human plasma.

BACKGROUND AND OBJECTIVES: The growing demand for immunoglobulin (IG) requires development of improved plasma fractionation methods to provide higher yields in a cost effective, scalable manner without compromising product purity and efficacy. A novel protein extraction method, utilizing expanded bed adsorption (EBA) chromatography, has been developed. PlasmaCap IG (10% liquid formulation intravenous IG [IVIG]) is the first plasma-derived product manufactured using PlasmaCap EBA technology. MATERIALS AND METHODS: The PlasmaCap EBA platform consists of a series of consecutive columns which bind a target protein, or group of proteins, in their native state directly from cryo-poor plasma. EBA chromatography includes five key steps: (1) expand, (2) sanitize and equilibrate, (3) load, (4) wash and (5) elute. These steps are made possible using high-density tungsten-carbide agarose beads, suspended by upward flow. The PlasmaCap EBA process was evaluated during Evolve's clinical campaign for scalability, product quality and yield. RESULTS: PlasmaCap EBA technology can be predictably scaled by maintaining the minimum residence time and residence time distribution for EBA columns of different diameters. Scalability of the manufacturing process was demonstrated by the 50-fold volumetric increase from laboratory-scale lots to clinical-scale lots. The process is also associated with enhanced product purity, such as lower aggregates. The PlasmaCap EBA process is expected to have the same or better yield and purity at commercial scale production compared to the clinical campaign. CONCLUSION: The PlasmaCap EBA platform was used to successfully develop PlasmaCap IG (10% liquid formulation IVIG) with proven scalability, product quality and yield.

Words matter: Reflections on language projects with chimpanzees and their implications.

Beginning in the 1960s the first systematic projects dedicated to testing whether great apes could acquire some aspects of human language were conducted. The ape subjects demonstrated remarkable capacities to learn and use elements of either sign language or an artificial language. The results from research across several laboratories drew a mixture of excitement and skepticism, and critiques and debates have ensued since the earliest reports were published. This continues today. Terrace (2019, Nim: A chimpanzee who learned sign language. New York, NY: Columbia University Press) repeats many of the same points made decades earlier, and has added some additional critiques. That scientists hold different perspectives on what to conclude from ape language studies is expected. However, any conclusion one draws should be based upon available evidence, which we outline in this review. We also address the critiques offered by Terrace (2019), including the stance that apes cannot understand or use words. Focusing on symbol use by chimpanzees and bonobos we describe evidence that argues for understanding of words, including capacities for declarative communication and intersubjectivity found in these apes. We conclude that the many decades of research using a variety of symbol systems challenges the absolutist position that chimpanzees and bonobos cannot learn language or understand the concept of a word.

Animal pointing: Changing trends and findings from 30 years of research.

The past 30 years have witnessed a continued and growing interest in the production and comprehension of manual pointing gestures in nonhuman animals. Captive primates with diverse rearing histories have shown evidence of both pointing production and comprehension, though there certainly are individual and species differences, as well as substantive critiques of how to interpret pointing or "pointing-like" gestures in animals. Early literature primarily addressed basic questions about whether captive apes point, understand pointing, and use the gesture in a way that communicates intent (declarative) rather than motivational states (imperative). Interest in these questions continues, but more recently there has been a dramatic increase in the number of articles examining pointing in a diverse array of species, with an especially large literature on canids. This proliferation of research on pointing and the diversification of species studied has brought new and exciting questions about the evolution of social cognition, and the effects of rearing history and domestication on pointing production and, more prolifically, comprehension. A review of this work is in order. In this article, we examine trends in the literature on pointing in nonhumans. Specifically, we examine publication frequencies of different study species from 1987 to 2016. We also review data on the form and function of pointing, and evidence either supporting or refuting the conclusion that various nonhuman species comprehend the meaning of pointing gestures. (PsycINFO Database Record

Evolutionary perspectives on learning: conceptual and methodological issues in the study of adaptive specializations.

Inquiry into evolutionary adaptations has flourished since the modern synthesis of evolutionary biology. Comparative methods, genetic techniques, and various experimental and modeling approaches are used to test adaptive hypotheses. In psychology, the concept of adaptation is broadly applied and is central to comparative psychology and cognition. The concept of an adaptive specialization of learning is a proposed account for exceptions to general learning processes, as seen in studies of Pavlovian conditioning of taste aversions, sexual responses, and fear. The evidence generally consists of selective associations forming between biologically relevant conditioned and unconditioned stimuli, with conditioned responses differing in magnitude, persistence, or other measures relative to non-biologically relevant stimuli. Selective associations for biologically relevant stimuli may suggest adaptive specializations of learning, but do not necessarily confirm adaptive hypotheses as conceived of in evolutionary biology. Exceptions to general learning processes do not necessarily default to an adaptive specialization explanation, even if experimental results "make biological sense". This paper examines the degree to which hypotheses of adaptive specializations of learning in sexual and fear response systems have been tested using methodologies developed in evolutionary biology (e.g., comparative methods, quantitative and molecular genetics, survival experiments). A broader aim is to offer perspectives from evolutionary biology for testing adaptive hypotheses in psychological science.

Cognitive and locomotor/exploratory behavior after chronic exercise in the olfactory bulbectomy animal model of depression.

Despite the evidence that exercise improves cognitive behavior in animal models, little is known about these beneficial effects in animal models of pathology. We examined the effects of activity wheel (AW) running on contextual fear conditioning (CFC) and locomotor/exploratory behavior in the olfactory bulbectomy (OBX) model of depression, which is characterized by hyperactivity and changes in cognitive function. Twenty-four hours after the conditioning session of the CFC protocol, the animals were tested for the conditioned response in a conditioned and a novel context to test for the effects of both AW and OBX on CFC, but also the context specificity of the effect. OBX reduced overall AW running behavior throughout the experiment, but increased locomotor/exploratory behavior during CFC, thus demonstrating a context-dependent effect. OBX animals, however, displayed normal CFC behavior that was context-specific, indicating that aversively conditioned memory is preserved in this model. AW running increased freezing behavior during the testing session of the CFC protocol in the control animals but only in the conditioned context, supporting the hypothesis that AW running improves cognitive function in a context-specific manner that does not generalize to an animal model of pathology. Blood corticosterone levels were increased in all animals at the conclusion of the testing sessions, but levels were higher in AW compared to sedentary groups indicating an effect of exercise on neuroendocrine function. Given the differential results of AW running on behavior and neuroendocrine function after OBX, further exploration of the beneficial effects of exercise in animal models of neuropathology is warranted.

Learning with arbitrary versus ecological conditioned stimuli: evidence from sexual conditioning.

Laboratory investigations of Pavlovian conditioning typically involve the association of an arbitrary conditioned stimulus (CS) with an unconditioned stimulus (US) that has no inherent relation to the CS. However, arbitrary CSs are unlikely to become conditioned outside the laboratory, because they do not occur often enough with the US to result in an association. Learning under natural circumstances is likely only if the CS has a preexisting relation to the US. Recent studies of sexual conditioning have shown that in contrast to an arbitrary CS, an ecologically relevant CS is resistant to blocking, extinction, and increases in the CS-US interval and results in sensitized responding and stronger second-order conditioning. Although the mechanisms of these effects are not fully understood, these findings have shown that signature learning phenomena are significantly altered when the kinds of stimuli that are likely to become conditioned under natural circumstances are used. The implications of these findings for an ecological approach to the study of learning are discussed.

Extinction of conditioned sexual responses in male Japanese quail (Coturnix japonica): role of species-typical cues.

The authors examined how a conditioned stimulus (CS) that included species-typical cues affected the acquisition and extinction of conditioned sexual responses in male quail (Coturnix japonica). Some subjects were conditioned with a CS that supported sexual responses and included a taxidermic head of a female quail. Others were conditioned with a similar CS that lacked species-typical cues. Pairing the CSs with access to live females increased CS-directed behavior, with the head CS eliciting significantly more responding than the no-head CS. Responding to the head CS persisted during the 42-day, 126-trial extinction phase; responses to the no-head CS extinguished. Responding declined when the cues were removed or the subjects were sexually satiated. Possible functions and mechanisms of these effects are discussed.

Research productivity in animal learning from 1953 to 2000.

Searches conducted with Medline and PsycInfo showed that the number of publications dealing with learning in animals increased between 1975 and 2000 and that the increase was substantially greater in Medline than in PsycInfo. An examination of major journals dealing with behavioral studies of conditioning and learning for the years 1953, 1963, 1973, 1983, 1993, and 2000 revealed a different pattern of results. The number of papers published in these journals increased from 1953 to 1973 but has been declining steadily since then. However, this decline was partially offset by an increase in the number of experiments published in each paper. Substantially more experiments were published in 2000 than in 1963 or 1953. The number of core authors in the field also peaked in 1973 and has been declining since. However, there were only seven fewer core authors in 2000 than in 1983, and 1983 had as many core authors as 1963. These data suggest that pessimism about the status of behavioral studies of learning is not warranted if research activity is considered over a 40-year period. Furthermore, increased interest in the neural and biological mechanisms of learning should bode well for the status of behavioral research, because one cannot examine the physiological mechanisms of a behavioral process without first clearly understanding the phenomenon at the behavioral level.

There is more to biological behavior than causation and control.

Biorobots may model the causation of relatively simple behaviors, but many animal behaviorists are concerned with complex cognitive traits and their evolution. Biorobotics seems limited in its ability to model cognition and to provide evolutionary explanations. Also, if robots could model complex traits, such as theory of mind, underdetermination could be problematic. Underdetermination is also a challenge for comparative psychologists.