Does the occurrence of Harris lines affect the morphology of human long bones?

The purpose of the study is to check the relationship between the occurrence of Harris lines and the morphological differentiation of the long bones of the human skeleton as an indicator of living conditions. The bone material (233 adult individuals, including 120 males and 113 females) was collected at a mediaeval burial ground in Cedynia, Poland. Recommended methods were applied to estimate the sex and age of the individuals (Ferembach et al 1979; Buikstra & Ubelaker 1994). The results obtained indicate that there is no clear relationship between metric characteristics of the studied long bones and the occurrence of Harris lines. Adverse environmental factors, which triggered the occurrence of Harris lines did not strongly affect the growth of long bones and did not change their morphology. Regardless of the phase of ontogenetic development in which the arrested growth lines (HL) formed, no effect of this fact on the final length of bones was observed. Similarly, no statistically significant differences were found in the proportions of bones between individuals reacting to adverse living conditions with the formation of Harris lines and those, whose bones were free of Harris lines. One may assume that Harris lines are of significance in epidemiological research and when assessing the general health profile of a population, but they are less useful in research on morphological reactions of individuals to living conditions.     

What is unique about the human eye? Comparative image analysis on the external eye morphology of human and nonhuman great apes

The gaze-signaling hypothesis and the related cooperative-eye hypothesis posit that humans have evolved special external eye morphology, including exposed white sclera (the white of the eye), to enhance the visibility of eye-gaze direction and thereby facilitate conspecific communication through joint-attentional interaction and ostensive communication. However, recent quantitative studies questioned these hypotheses based on new findings that certain features of human eyes are not necessarily unique among great ape species. Accordingly, there is currently a heated debate over whether external eye features of humans are distinct from those of other apes and how such distinguishable features contribute to the visibility of eye-gaze direction. The present study leveraged updated image analysis techniques to test the uniqueness of human eye features in facial images of great apes. Although many eye features were similar between humans and other great apes, a key difference was that humans have uniformly white sclera which creates clear visibility of both the eye outline and iris—the two essential features contributing to the visibility of eye-gaze direction. We then tested the robustness of the visibility of these features against visual noise, such as shading and distancing, and found that both eye features remain detectable in the human eye, while eye outline becomes barely detectable in other species under these visually challenging conditions. Overall, we identified that humans have unique external eye morphology among other great apes, which ensures the robustness of eye-gaze signals in various visual conditions. Our results support and also critically update the central premises of the gaze-signaling hypothesis.     

Patents and the human genome project--new claims for old?

The development and application of genomics is set to revolutionize the life sciences. Commercial exploitation of this research will allow the development of novel therapies and diagnostic assays. However, some argue that a 'gold rush' is underway and conflicts have already arisen over the question of filing patents and sharing data. In this article we consider some of the issues that relate to patenting genomic inventions.     

Disease-related versus polymorphic mutations in human mitochondrial tRNAs: Where is the difference?

A number of point mutations in human mitochondrial (mt) tRNA genes are correlated with a variety of neuromuscular and other severe disorders including encephalopathies, myopathies, cardiopathies and diabetes. The complexity of the genotype/phenotype relationships, the diversity of possible molecular impacts of the different mutations at the tRNA structure/function levels, and the exponential discovery of new mutations call for the search for unifying features. Here, the basic features (at the levels of primary and secondary structure) of 68 ‘pathogenic’ mutations are compared with those of 64 ‘polymorphic’ neutral mutations, revealing that these standard parameters for mutant analysis are not sufficient to predict the pathogenicity of mt tRNA mutations. Thus, case by case molecular investigation remains the only means of assessing the growing family of pathogenic mutations in mt tRNAs. New lines of research are suggested.     

How informative is the mouse for human gut microbiota research?

The microbiota of the human gut is gaining broad attention owing to its association with a wide range of diseases, ranging from metabolic disorders (e.g. obesity and type 2 diabetes) to autoimmune diseases (such as inflammatory bowel disease and type 1 diabetes), cancer and even neurodevelopmental disorders (e.g. autism). Having been increasingly used in biomedical research, mice have become the model of choice for most studies in this emerging field. Mouse models allow perturbations in gut microbiota to be studied in a controlled experimental setup, and thus help in assessing causality of the complex host-microbiota interactions and in developing mechanistic hypotheses. However, pitfalls should be considered when translating gut microbiome research results from mouse models to humans. In this Special Article, we discuss the intrinsic similarities and differences that exist between the two systems, and compare the human and murine core gut microbiota based on a meta-analysis of currently available datasets. Finally, we discuss the external factors that influence the capability of mouse models to recapitulate the gut microbiota shifts associated with human diseases, and investigate which alternative model systems exist for gut microbiota research.KEY WORDS: Gut microbiota, Humanized mouse models, Mouse core gut microbiota, Mouse models, Mouse pan-gut microbiota     

High Affinity Not in the Vicinity?

Functional interactions between the p75 neurotrophin receptor (p75NTR) and the Trk receptors were demonstrated several years ago, but their mechanistic basis remains uncertain. In this issue of Neuron, Wehrman et al. provide a three-dimensional structure of the full TrkA ectodomain complexed to NGF and examine the possibility of a ternary p75NTR-NGF-TrkA complex.     

The morphology of the gluteus maximus during human evolution: Prerequisite or consequence of the upright bipedal posture?

The human gluteus maximus differs from that of the other hominoids because of its size and bony attachments. These differences raise questions concerning their sequence of appearance in human evolution. Given that humans practice a unique locomotor style, one wonders if the human gluteus maximus morphology is a prerequisite or a consequence of upright bipedal locomotion. This question is addressed using a computer model that evaluates muscle leverage in a variety of locomotor postures. In this model, the human-like, or ape-like, muscular pattern is imposed upon a representative hindlimb of each of the five extant hominoids. Shapes of the skeletal elements (i.e. ilium and ischium lengths) are adjusted in the computer to simulate an evolutionary progression from an ape to a human skeletal morphology. Changes in the leverage of different parts of the gluteus maximus (measured as moment arms) are monitored during this transition. The results show how the mechanical leverages of the gluteus maximus would have changed in a variety of hypothetical evolutionary sequences that describe an ape to human transition. Although the hominoid models exhibit minor differences in these simulations, they all show that the postural and locomotor functions of the gluteus maximus would become more difficult if musculoskeletal morphology changed to the human-like pattern before erect bipedal posture was adopted. Conversely, small adjustments in the ape-like musculoskeletal condition support an erect bipedal posture. These results suggest that a human like posture would have preceded the appearance of the human-like musculoskeletal morphology. Human gluteal morphology, therefore, is a consequence and not a prerequisite of the upright bipedal posture.     

Molecules of choice?

Transmembrane proteins with seven helices, whether they are in the insect ‘nose'' or the mammalian eye, are the molecule of choice for detecting the world. No matter the kingdom, evolution seems to settle on the optimal solution time and time again.How best to describe evolution? A drunkard''s walk; a shambling billion-year spree punctuated with prat-falls, accompanied by a Beckettian mumbling? Or a sleek greyhound rippling with suppressed energy, racing along the narrow highways of the Darwinian landscape? “Mumble and shuffle” would be the answer of most biologists, but perhaps next time we open our Darwin we should also turn up The Ride of the Valkyries.When reviewing the evolution of eyes, Russell Fernald hit the nail on the head when he remarked how the opsins have “proven irresistible for use in eyes” [1]. Indeed they have; not only do they belong to the vast family of G-protein-coupled receptors (GPCRs), but it is no accident that, in ears and noses, related transmembrane proteins with the canonical seven helices are also poised to transduce noise and smells into electrical signals and ultimately awareness.There is a comforting congruity in all this. Just as our eyes register the world through the opsins, in the compound eyes of insects the same proteins wait in attendance. But let us turn to the insect ‘nose''. Here, despite a radically different anatomy replete with antennal and maxillary sensilla, the arrangement turns out to be strikingly convergent in terms of operation with the mammalian schnozzle [2], but when we look at the molecular machinery something curious seems to be going on. One component, concentrated in the coeloconic sensilla, is tasked with detecting molecules such as alcohol and ammonia. Here, the machinery depends on the ionotropic glutamate receptors. This appears to be a classic case of co-option because not only are these receptors ancient [3], they also show fascinating links to synaptic receptors [4]. However, the bulk of the olfactory capacity looks to a series of transmembrane proteins. At first glance, complete with their seven helices spanning the sensory membrane, they look reassuringly like the ever-reliable GPCRs. Except they aren''t! Blink twice and then notice that these proteins are back to front so that the amino-terminal is cytoplasmic and the carboxy-terminal extracellular. This is completely opposite to the GPCRs [5], but surely it represents a trivial difference? On the contrary. Lurking in the insect ‘nose'' is a ligand-gated cation channel that at first sight looks practically identical to a GPCR but is completely unrelated [6].Maybe I am a bear of little brain, but is this not all a little peculiar? Why throw away a perfectly acceptable GPCR—which after all other ecdysozoans such as nematodes use—and install what is effectively a near-perfect mimic? A little trick to keep us on our Darwinian toes? Maybe a clue comes from the choanoflagellates. Central to their life is nitrogen metabolism, but rather oddly the genes they employ have been recruited from algae. “If it ain''t broke, don''t fix it”, except that Aurora Nedelcu and colleagues [7] suggest these imports turned out to be a notch better than the incumbent machinery. Spitfire versus Messerschmitt if you like; both superb aircraft, but the former had the edge.Perhaps a parallel argument applies to the insects. Their ‘noses'' might be functionally equivalent to those of mammals but insects live in a different world, zooming through the air at high speed and encountering smells in the form of narrow odour plumes separated by ‘clear'' air. Rather different from the leisurely inhalations of a large mammal; on the insect scale of things, time is of the essence [8]. This might also explain why there are a variety of transduction cascades, some linked to tried and tested methods but others evidently novel. We should, however, not lose sight of the central point. Be it in terms of fundamental configurations of olfactory design or the molecular machinery behind it, insects do indeed replay the tape of life, but with end results that are very much the same. With respect to the receptor protein, frankly who cares if it is a GPCR or a ligand-gated ion channel protein? They are completely unrelated, but the far more remarkable fact is that, in terms of transduction, the system evidently has no alternative. The molecule must be a seven-helix transmembrane protein; this is the molecule of choice. Evolution meets design: Darwin and Plato embrace.Irresistibly, evolution will navigate to this solution. Rest assured that on Threga IX—that charming little planet just to the left of Arcturus—eyes will flicker and noses will swivel beneath an alien sun. We can save ourselves all the fuss of an extremely expensive extraterrestrial excursion. In those alien eyes and noses, we can be quite certain that a seven-helix transmembrane protein will be busy telling its owner that the sunset is red and dinner is almost ready. Gin and tonic anybody?     

Not all the same after all? Superdiversity as a lens for the study of past migrations

Due to its claim of contemporary exceptionalism, the notion of superdiversity raises suspicion among historians. However, historians would do well to not dismiss the entire superdiversity debate as more hype that does not concern them. As a multidimensional perspective on diversity, encouraging researchers to examine the interplay of many different factors that condition people's lives and to move beyond an ethno-focal perspective, superdiversity could be of interest to historians as well. This article shows how the notion can help historians debunk some of the homogenizing categories that tend to characterize the representation of past immigrant populations. The paper uses a superdiversity lens to examine migration to the city of Ghent from 1960 to 1980. It is an open invitation to historians to accept the challenges that superdiversity poses and to provide a proper historicization of the concept, thus furthering its theoretical development.     

“Neutral theory” and the dynamics of the evolution of “Modern” human morphology

There is a widespread assumption, even among those who reject the Synthetic Theory of Evolution, that the form of “modern”Homo sapiens is somehow superior to that of archaicHomo sapiens (Tattersall 2000). Those who accept the general outlook of evolutionary biology also tend to assume that “modern” form emerged because it was selected for, which also implies that it was better than that which preceded it. However, after years of using craniofacial measurements to compare human populations, I finally came to realize that, with only a few exceptions, the dimensions measured have no relation to differences in adaptation (Brace 1989, 1996, 2000; Brace et al., 1993). Elsewhere the conclusion has been supported that what is shown by craniometrics is selectively neutral on the average (Relethford 2002). With the documentation that approximately 95% of the genome is not functional, molecular genetics has proved to be useful in documenting the length of time of separation of related human populations by investigating the differences that have accumulated in the neutral parts of the genome. Not surprisingly, the picture revealed by the study of genetic differences is very similar to the one revealed by the study of craniometric differences (Brace et al., 2001). For this reason, the logic behind the “neutral theory” in molecular genetics is very similar to that applied to what happens to morphological characteristics when selection ceases (Brace 1963; Kimura 1968). The difference is that random changes in the neutral part of the genome have no other consequences. However, random changes in the genes that produce specific aspects of morphology will be visible even when selection is no longer controlling the particular trait in question. From an assessment of what random changes in genes controlling morphological traits are likely to do, it follows that the most likely change will probably be a reduction in the trait in question, i.e. the Probable Mutation Effect will produce structural reduction. When survival in the temperate zone during the last glaciation dependend on “obligatory cooking”, one of the unintended consequences was a reduction in the selective pressures maintaining a Middle Pleistocene-sized dentition. The result was a gradual reduction in tooth size and a conversion, of a Neanderthal-sized face into one of “modern” dimensions. The manufacture and use of string for snares and nets similarly reduced the selective pressures maintaining post-cranial levels of robustness and muscularity. The reduction in the latter resulted in the emergence of moderm post-cranial robustness out of what had been a Neanderthal level,in situ wherever the technology can be documented and without any need for invasions and replacements.     

Apoptosis in human disease: a new skin for the old ceremony?

Naturally occurring cell death or apoptosis is essential for the maintenance of tissue homeostasis and serves to remove extraneous or dangerous cells in a swift and unobtrusive manner. Recent studies have indicated a role for apoptosis in a plethora of human diseases. Hence, dysregulation of apoptosis has been implicated in autoimmune disease, acquired immune deficiency syndrome, and other viral (and bacterial) infections, as well as in neurodegenerative disorders and cancer. Furthermore, dysregulated apoptosis signaling may impinge on other age-related disorders such as osteoporosis and atherosclerosis and perhaps on the process of aging itself. The present review provides an overview of human diseases, which are associated with defective or inadvertent apoptosis, with examples of pathological conditions in which putative apoptosis defects have been elucidated at the molecular level. Novel apoptosis-modulating therapeutic strategies are also discussed.     

Is aromaticity essential for trapping the catalytic histidine 447 in human acetylcholinesterase?

Replacement of both the acyl pocket residue Phe295 as well as residue Phe338, adjacent to the catalytic His447 in human acetylcholinesterase (HuAChE), resulted in a 680-fold decline in catalytic activity due to conformational destabilization of the histidine side chain [Barak et al. (2002) Biochemistry 41, 8245]. A possible restriction of this catalytically nonproductive mobility of His447 in a series of F295X/F338A HuAChEs was examined in silico followed by site-directed mutagenesis. Simulations suggested that of the 12 aliphatic residues substituted at position 295, including hydrophobic and polar amino acids, only methionine was capable of maintaining the catalytically viable conformation of His447. Examination of the reactivities of the actual F295X/F338A HuAChEs showed that indeed the F295M/F338A enzyme was only 2-fold less reactive than the F338A mutant toward acetylthiocholine, while enzymes substituted by the similarly bulky residues leucine and isoleucine were catalytically impaired. Furthermore, only the F295M/F338A enzyme exhibited wild-type-like reactivity toward covalent modifiers of the catalytic Ser203 including the methylphosphonate soman and transition state analogue m-(N,N,N-trimethylammonio)trifluoroacetophenone (TMTFA), as well as a facile dealkylation of the F295M/F338A-soman adduct. A different behavior was observed for bulkier ligands which introduce a deformation in the acyl pocket, and therefore their activity seems only marginally affected by the positioning of His447. The findings emphasize the importance of the precise positioning of His447 for catalysis and indicate that, in the absence of aromatic "trapping", restriction of the histidine mobility in F295X/F338A HuAChEs requires a combination of steric interference and a specific polar interaction. The results also underscore the role of the acyl pocket subsite of cholinesterases in maintaining the catalytically viable conformation of the catalytic histidine.     

Is the human trophoblast in vitro an adaptive tissue for immunological influences?

The role of the extra-embryonic organs (e.g. placenta) in the feto-maternal immunological interactions is not clear. Trophoblast cells of human placenta were studied in vitro in relation to their adaptive capacities under the immunological influence of allogeneic leucocytes of pregnant women. It was shown that after an 18-h interaction some trophoblastic cells were still viable, they were rich in glycoproteins and RNA, and elicited a prominent activity of some enzymes. Mitosis was often seen. The authors suppose that the trophoblast is highly adaptable to some immunological influences in vitro.