Bioscience hypotheses最新文献

A characteristic feature of the life history of humans and some other species of social mammals is a long post-reproductive period. This condition is of a physiological nature in females (menopause), whereas in males it is largely of a behavioral nature. We discuss the hypothesis that old, post-reproductive individuals in these species may act as repositories of acquired knowledge, thereby providing an evolutionary benefit for their group. According to this view, the group's investment into the care for their older members is overcompensated by the benefits gained from the experience of these individuals (“senators”). This phenomenon is suggested to be largely independent from the degree of genetic relatedness within the group. We put forward a list of several necessary preconditions for the senator phenomenon to evolve. The presence or absence of these preconditions can be studied empirically.

Studies have shown that the more iron in a given population, the more that population is vulnerable to intracellular opportunistic infections (OIs) in AIDS, mainly because these microbes make use of the intracellular iron to proliferate, and could render infections deadly. In contrast, macrophages that lack iron are effective in preventing an establishment of infection. We propose that reduction in total body iron could be a valuable treatment option for some intracellular infections, including OIs. We suggest two options to deprive pathogens of using intracellular iron (i) to practice regular blood-letting, an ancient treatment option, and (ii) to down-regulate hepcidin, the key hormone involved in the regulation of iron balance and recycling. This could also deprive transformed cells of metabolizing iron for survival. Whether or these methods serve to curb the onset of OIs/cancers to prolong HIV disease progression remains to be investigated.

Autoimmune disorders are connected with the actions of sex hormones. Clinical observations have shown that especially estrogens are involved in these phenomena. In some cases the administration of estrogens can increase the pathological symptoms of a disorder, while in others they can cause disease remission. In multiple autoimmune diseases, type I interferons, a family of cytokines acting through the common receptor IFNAR1/IFNAR2, seem to have action convergent with that of estrogens. We hypothesize that this coincidence is not accidental and type I interferons can regulate the level of estrogen receptor alpha (ERα) and consequently change the sensitivity of immune cells to estrogen's action. There is evidence that ERα is responsible for the effects exerted by estrogens and that this phenomenon mainly involves antigen-presenting cells. On the other hand, research on IFN-tau, a type I interferon family members, showed that this cytokine can modulate ERα levels in ovine endometrium. Because of the common receptor for these interferons, we suspect that other type I interferons can act in this way not only in endometrial cells, but also in immune cells. If there is such a mechanism, it can be exploited in the therapy of immune disorders, especially autoimmune disease, for example through simultaneous administration of less toxic interferons and estrogens.

The brain's wrong-sidedness, or contralaterality, is one of life's great mysteries. Unlike invertebrates, all vertebrates from fish to mammals possess a forebrain with hemispheres innervated from sense organs on the body's opposite side. The vertebrate chambered eye has long been implicated as the cause for this paradox but no credible or testable theory had previously been postulated to support such an idea. Ramon y Cajal, the founder of neurobiology, made such a claim in the early 1900s but failed to provide adequate evidence. Here we show that the eye indeed appears to be the inverting culprit based on this author's entirely original, but untested, concept of a cyclopean origin to vertebrates at a time when single-eyed chordates were evolving to double-eyed agnathan fish.

This framework of evidence has been entitled The Inversion Hypothesis and was originally based on the author's observation that the primary cortical sensorimotor map in mammals appears to unfold from a prior longitudinal position which was inverted in all three dimensions to the body itself. It postulates a four-stage development of the vertebrate forebrain from primitive to modern whereby a longitudinal primary bodymap (Protomap) unfolds in a predictable caudal direction. As proposed, the initial establishment of the map in the contralateral hemispheres was consequent on the inverting effect of a single frontal imaging eye as it developed in tandem with the early forebrain in ancient fish.

The most conspicuous evidence today of these cyclopean origins is the common fetal abnormality in all vertebrates of cyclopia, the default developmental condition when cyclopia-nulling genes fail to activate. Further, the most exciting and convincing evidence of these origins promises to come from a change in paradigm for explaining the bizarre single circular stain at the anterior snout of primitive agnathan fossils. This circular stain is presently causing much consternation amongst palaeontologists. Unable to ascribe two eyes to these primitive fossils, mainstream palaeontology is bereft of a weltanschauung that allows the interpretation of the circular stain as a single frontal eye. The Inversion Hypothesis offers a very credible solution.

The kidney is a major source of systemic erythropoietin, despite itself showing little angiogenesis. Based on paper by Schumacher VA et-al. [J Am Soc Nephrol 2007;18:719–29] that renal synthesis of an inhibitory VEGF variant (VEGF165b) blocks local angiogenesis, we hypothesise that the chronic hypoxia in the renal medulla, due to limited perfusion through vasa recta stimulates continuous renal erythropoietin secretion.

Because human mesenchymal stem cells (hMSCs) can proliferate indefinitely in an undifferentiated state and differentiate into various cell types, hMSCs are expected to be useful for cell replacement therapy. But the clinic application is limited by its differentiation efficiency of hMSCs. It has been proved that cells can be geometrically switched between gene programs for growth, apoptosis and differentiation. Previous studies showed that hMSCs started showing round when exposed to modeled microgravity (MMG), while their differentiation capability seemed enhanced simultaneously. Thus, this article briefly reviews such studies, and hypothesizes that “spherical shape” could be a potential predictor of hMSCs with potentiated differentiation capability.

Myocardial infarction and stroke are two of the leading causes of death and primarily triggered by destabilization of atherosclerotic plaques. Fatty streaks are known to develop at sites in the arterial wall where shear stress is low. These fatty streaks can develop into more advanced plaques that are prone to rupture. Rupture leads to thrombus formation, which may subsequently result in a myocardial infarction or stroke. The relation between shear stress on the inner (endothelial) layer of the arterial wall in relation to plaque development has been studied extensively. However, a causal relation between adventitial shear forces and atherosclerosis development has never been considered.

Arterial stiffening increases with age and may facilitate an increase in shear strain in the adventitial layer, an axial shear between artery and surrounding tissue. In the adventitial layer, a large number of inflammatory cells and perivascular structures are present that are subjected to shear strain. Cyclic strain applied to endothelial cells stimulates neovascularisation via different pathways. The conduit arteries in the human body (e.g. coronary and carotid artery) have their own nutrition supply: the vasa vasorum, which is located in the adventitial layer and sprouts into the intimal layer when atherosclerotic plaque develops. Increased plaque neovascularisation makes the plaques more prone to rupture. Therefore we hypothesize that increased shear strain facilitates the development of vulnerable plaques by stimulation of atherosclerotic plaque neovascularisation that sprouts from the adventitial vasa vasorum. Validation of this hypothesis paves the road to the use of adventitial shear strain (measured using a noninvasive ultrasound technique) as risk assessment in plaque.