Diagnosis of human sleeping sickness: sense and sensitivity

In 1997 the World Health Organization (WHO) advocated increased access to diagnosis and treatment, as well as reinforcement of surveillance, for the control of sleeping sickness (human African trypanosomiasis, HAT). This coincided with the end of decades of civil conflicts in several endemic regions and negotiation of a sustainable supply of 'free' curative drugs and, as a result, HAT is at its lowest level in 50 years. However, reported cases underestimate prevalence and downplay HAT when compared with data generated by advanced diagnostic capacity for human immunodeficiency virus (HIV), tuberculosis (TB) and malaria, and, because HAT case numbers fall between epidemics, diagnostics become less commercially appealing. Here recent trends in the development of diagnostics for sleeping sickness are considered and progress towards a much-needed sensitive, specific and affordable point-of-care diagnostic is assessed.     

Carbon isotopes and water use efficiency: sense and sensitivity

We revisit the relationship between plant water use efficiency and carbon isotope signatures (δ¹³C) of plant material. Based on the definitions of intrinsic, instantaneous and integrated water use efficiency, we discuss the implications for interpreting δ¹³C data from leaf to landscape levels, and across diurnal to decadal timescales. Previous studies have often applied a simplified, linear relationship between δ¹³C, ratios of intercellular to ambient CO₂ mole fraction (C _i/C _a), and water use efficiency. In contrast, photosynthetic ¹³C discrimination (Δ) is sensitive to the ratio of the chloroplast to ambient CO₂ mole fraction, C _c/C _a (rather than C _i/C _a) and, consequently, to mesophyll conductance. Because mesophyll conductance may differ between species and over time, it is not possible to determine C _c/C _a from the same gas exchange measurements as C _i/C _a. On the other hand, water use efficiency at the leaf level depends on evaporative demand, which does not directly affect Δ. Water use efficiency and Δ can thus vary independently, making it difficult to obtain trends in water use efficiency from δ¹³C data. As an alternative approach, we offer a model available at to explore how water use efficiency and ¹³C discrimination are related across leaf and canopy scales. The model provides a tool to investigate whether trends in Δ indicate changes in leaf functional traits and/or environmental conditions during leaf growth, and how they are associated with trends in plant water use efficiency. The model can be used, for example, to examine whether trends in δ¹³C signatures obtained from tree rings imply changes in tree water use efficiency in response to atmospheric CO₂ increase. This is crucial for predicting how plants may respond to future climate change. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Directional sensitivity of velocity sense in the lumbar spine

Regulating spinal motion requires proprioceptive feedback. While studies have investigated the sensing of static lumbar postures, few have investigated sensing lumbar movement speed. In this study, proprioceptive contributions to lateral trunk motion were examined during paraspinal muscle vibration. Seventeen healthy subjects performed lateral trunk flexion movements while lying prone with pelvis fixed. A 44.5-Hz vibratory stimulus was applied to the paraspinal muscles at the L3 level. Subjects attempted to match target paces of 9.5, 13.5, and 17.5 deg/s with and without paraspinal muscle vibration. Vibration of the paraspinal musculature was found to result in slower overall lateral flexion. This effect was found to have a greater influence in the difference of directional velocities with vibration applied to the left musculature. These changes reflect the sensitivity of lumbar velocity sense to applied vibration leading to the perception of faster muscle lengthening and ultimately resulting in slower movement velocities. This suggests that muscle spindle organs modulate the ability to sense velocity of motion and are important in the control of dynamic motion of the spine.     

Consciousness enigma: the "hard problem"--binding problem entanglement, "extra ingredient" and field principle

The "Hard problem" of consciousness relates to the perplexing emergence of consciousness as a result of the brain activity. The binding problem concerns separate processing of perceived data in functionally and topographically segregated cortical areas and functional integration of such locally disjoined operations into coherently perceived images and events. The existing field-grounded theories of consciousness fall into two groups: (i) those based on the physical (electromagnetic) field, and (ii) those grounded on autonomous fields irreducible to the established physical fundamentals. The critical analysis of the existing theories results in formulation of the extra ingredient and a novel irreducible field-based theory of consciousness.     

Receptor sensitivity: when T cells lose their sense of self

The T-cell antigen receptor binds to self-MHC molecules with low affinity. Recent reports disagree as to whether this interaction sensitizes or desensitizes the receptor. Here we discuss how these findings might be reconciled.     

The problem of "benign macrocephaly"

24 families of probands with a high head circumference/height ratio greater than the 97th percentile were investigated for head circumference and height. It is concluded that "benign macrocephaly" represents rather the upper extreme of the normal distribution of head circumference than--as has been suggested by some authors--a discrete and autosomal dominant entity.     

The problem with the species problem

When Charles Darwin convinced the scientific community that species evolve, the long-held essentialist view of each species as fixed was rejected and a clear conceptual understanding of the term was lost. For the next century, a real species problem existed that became culturally entrenched within the scientific community. Although largely solved decades ago, the species problem remains entrenched today due to a suite of factors. Most of the factors that help maintain its perceived intractability have been revealed and logically dismissed; yet this is not widely known so those factors continue to be influential. It is time to recognize this false foundation and relegate the species problem to history.     

Skipping the co-expression problem: the new 2A "CHYSEL" technology

The rapid progress in the field of genomics is increasing our knowledge of multi-gene diseases. However, any realistic hope of gene therapy treatment for those diseases needs first to address the problem of co-ordinately co-expressing several transgenes. Currently, the use of internal ribosomal entry sites (IRESs) is the strategy chosen by many researchers to ensure co-expression. The large sizes of the IRESs (~0.5 kb), and the difficulties of ensuring a well-balanced co-expression, have prompted several researchers to imitate a co-expression strategy used by many viruses: to express several proteins as a polyprotein. A small peptide of 18 amino acids (2A) from the foot-and-mouth disease virus (FMDV) is being used to avoid the need of proteinases to process the polyprotein. FMDV 2A is introduced as a linker between two proteins to allow autonomous intra-ribosomal self-processing of polyproteins. Recent reports have shown that this sequence is compatible with different sub-cellular targeting signals and can be used to co-express up to four proteins from a single retroviral vector. This short peptide provides a tool to allow the co-expression of multiple proteins from a single vector, a useful technology for those working with heteromultimeric proteins, biochemical pathways or combined/synergistic phenomena.     

The philosophical "mind-body problem" and its relevance for the relationship between psychiatry and the neurosciences

Parallel to psychiatry, "philosophy of mind" investigates the relationship between mind (mental domain) and body/brain (physical domain). Unlike older forms of philosophy of mind, contemporary analytical philosophy is not exclusively based on introspection and conceptual analysis, but also draws upon the empirical methods and findings of the sciences. This article outlines the conceptual framework of the "mind-body problem" as formulated in contemporary analytical philosophy and argues that this philosophical debate has potentially far-reaching implications for psychiatry as a clinical-scientific discipline, especially for its own autonomy and its relationship to neurology/neuroscience. This point is illustrated by a conceptual analysis of the five principles formulated in Kandel's 1998 article "A New Intellectual Framework for Psychiatry." Kandel's position in the philosophical mind-body debate is ambiguous, ranging from reductive physicalism (psychophysical identity theory) to non-reductive physicalism (in which the mental "supervenes" on the physical) to epiphenomenalist dualism or even emergent dualism. We illustrate how these diverging interpretations result in radically different views on the identity of psychiatry and its relationship with the rapidly expanding domain of neurology/neuroscience.