Biosecurity in the age of Big Data: a conversation with the FBI

New scientific frontiers and emerging technologies within the life sciences pose many global challenges to society. Big Data is a premier example, especially with respect to individual, national, and international security. Here a Special Agent of the Federal Bureau of Investigation discusses the security implications of Big Data and the need for security in the life sciences.     

Finite elements/Taguchi method based procedure for the identification of the geometrical parameters significantly affecting the biomechanical behavior of a lumbar disc

The aim of this work is to show a quick and simple procedure able to identify the geometrical parameters of the intervertebral disc that strongly affect the behavior of the FEM model. First, we allocated a selection criterion for the minimum number of geometrical parameters that describe, with a good degree of approximation, a healthy human vertebra. Next, we carried out a sensitivity analysis using the ‘Taguchi orthogonal array’ to arrive at a quick identification of the parameters that strongly affect the behavior of the Fem model.     

Morphological variation among the inner ears of extinct and extant baleen whales (Cetacea: Mysticeti)

Living mysticetes (baleen whales) and odontocetes (toothed whales) differ significantly in auditory function in that toothed whales are sensitive to high‐frequency and ultrasonic sound vibrations and mysticetes to low‐frequency and infrasonic noises. Our knowledge of the evolution and phylogeny of cetaceans, and mysticetes in particular, is at a point at which we can explore morphological and physiological changes within the baleen whale inner ear. Traditional comparative anatomy and landmark‐based 3D‐geometric morphometric analyses were performed to investigate the anatomical diversity of the inner ears of extinct and extant mysticetes in comparison with other cetaceans. Principal component analyses (PCAs) show that the cochlear morphospace of odontocetes is tangential to that of mysticetes, but odontocetes are completely separated from mysticetes when semicircular canal landmarks are combined with the cochlear data. The cochlea of the archaeocete Zygorhiza kochii and early diverging extinct mysticetes plot within the morphospace of crown mysticetes, suggesting that mysticetes possess ancestral cochlear morphology and physiology. The PCA results indicate variation among mysticete species, although no major patterns are recovered to suggest separate hearing or locomotor regimes. Phylogenetic signal was detected for several clades, including crown Cetacea and crown Mysticeti, with the most clades expressing phylogenetic signal in the semicircular canal dataset. Brownian motion could not be excluded as an explanation for the signal, except for analyses combining cochlea and semicircular canal datasets for Balaenopteridae. J. Morphol. 277:1599–1615, 2016. © 2016 Wiley Periodicals, Inc.     

Caspase 3 activation and PARP cleavage in lymphocytes from newborn babies of diabetic mothers with unbalanced glycaemic control

Several epidemiological studies showed that gestational diabetes mellitus is the most frequent metabolic disorder of pregnancy, the pathogenesis of which has yet to be completely clarified. The aim of this study was to investigate the presence and processing of caspase 3 (Casp3) and poly(ADP‐ribose) polymerase 1 (PARP1) in cord blood lymphocytes as markers of apoptosis in relation to glycaemic control during intrauterine life. Our results showed a specific positive correlation between the levels of active Casp3 (17–19 kDa) and the inactive form of PARP1 (89 kDa) in lymphocytes isolated from newborn babies of diabetic women with unbalanced glycaemic control, with a direct correlation between the activation of casp3 and the inactivation of PARP1, that makes lymphocytes unresponsive towards lipopolysaccharide stimulation, highlighting an altered functional response. Besides more studies are required to fully correlate the activation of the apoptotic process during the intrauterine life with the foetal health later in life, our study indicates that a cord blood lymphocyte, an easily accessible source, is informative about the activation of apoptotic stimuli in circulating cells of newborn babies in relation to the glycaemic control reached by the mother during pregnancy. Copyright © 2013 John Wiley & Sons, Ltd.     

A speculative model of affective illness cyclicity based on patterns of drug tolerance observed in amygdala-kindled seizures

In this article, we discuss molecular mechanisms involved in the evolution of amygdala kindling and the episodic loss of response to pharmacological treatments during tolerance development. These phenomena allow us to consider how similar principles (in different neurochemical systems) could account for illness progression, cyclicity, and drug tolerance in affective disorders. We describe the phenomenon of amygdala-kindled seizures episodically breaking through effective daily pharmacotherapy with carbamazepine and valproate, suggesting that these observations could reflect the balance of pathological vs compensatory illness-induced changes in gene expression. Under certain circumstances, amygdala-kindled animals that were initially drug responsive can develop highly individualized patterns of seizure breakthroughs progressing toward a complete loss of drug efficacy. This initial drug efficacy may reflect the combination of drug-related exogenous neurochemical mechanisms and illness-induced endogenous compensatory mechanisms. However, we postulate that when seizures are inhibited, the endogenous illness-induced adaptations dissipate (the “time-off seizure” effect), leading to the re-emergence of seizures, a re-induction of a new, but diminished, set of endogenous compensatory mechanisms, and a temporary period of renewed drug efficacy. As this pattern repeats, an intermittent or cyclic response to the anticonvulsant treatment emerges, leading toward complete drug tolerance. We also postulate that the cyclic pattern accelerates over time because of both the failure of robust illness-induced endogenous adaptations to emerge and the progression in pathophysiological mechanisms (mediated by long-lasting changes in gene expression and their downstream consequences) as a result of repeated occurrences of seizures. In this seizure model, this pattern can be inhibited and drug responsivity can be temporarily reinstated by several manipulations, including lowering illness drive (decreasing the stimulation current.), increasing drug dosage, switching to a new drug that does not show crosstolerance to the original medication, or temporarily discontinuing treatment, allowing the illness to re-emerge in an unmedicated animal. Each of these variables is discussed in relation to the potential relevance to the emergence, progression, and suppression of individual patterns of episodic cyclicity in the recurrent affective disorders. A variety of clinical studies are outlined that specifically test the hypotheses derived from this formulation. Data from animal studies suggest that illness cyclicity can develop from the relative ratio between primary pathological processes and secondary endogenous adaptations (assisted by exogenous medications). If this proposition is verified, it further suggests that illness cyclicity is inherent to the neurobiological processes of episode emergence and amelioration, and one does not need to postulate a separate defect in the biological clock. The formulation predicts that early and aggressive long-term interventions may be optimal in order to prevent illness emergence and progression and its associated accumulating neurobiological, vulnerability factors.