Determination of biokinetic parameters for ingestion of radionuclides of zirconium in animals using stable tracers

Exposure to the radioactive isotope ⁹⁵Zr, as in nuclear accidents, and to stable zirconium, due to its use in industry, has increased the interest in the biokinetics of this element. Information has been derived mainly from tests performed on animals by means of radioactive tracers. Due to the fact that extrapolation from animals to humans is always open to question, there is an increasing need of a methodology which allows data to be obtained directly from humans. The use of stable tracers, being ethically justifiable, is a powerful tool for providing this information. As two tracers of the same element must be utilized in order to evaluate gut absorption, an analytical technique which is capable of distinguishing and measuring simultaneously different isotopes of zirconium in biological samples is required. Preliminary tests on laboratory animals were performed in order to assess the feasibility of the double tracer technique combined with proton activation analysis. Received: 7 April 1999 / Accepted in revised form: 4 November 1999     

A biogeochemical cycle for aluminium?

The elaboration of biogeochemical cycles for elements which are known to be essential for life has enabled a broad appreciation of the homeostatic mechanisms which underlie element essentiality. In particular they can be used effectively to identify any part played by human activities in element cycling and to predict how such activities might impact upon the lithospheric and biospheric availability of an element in the future. The same criteria were the driving force behind the construction of a biogeochemical cycle for aluminium, a non-essential element which is a known ecotoxicant and a suspected health risk in humans. The purpose of this exercise was to examine the concept of a biogeochemical cycle for aluminium and not to review the biogeochemistry of this element. The cycle as presented is rudimentary and qualitative though, even in this nascent form, it is informative and predictive and, for these reasons alone, it is deserving of future quantification. A fully fledged biogeochemical cycle for aluminium should explain the biospheric abundance of this element and whether we should expect its (continued) active involvement in biochemical evolution.     

Characterization of Soymar1, a mariner element in soybean.

Mariner elements, a family of DNA-mediated transposable elements with short, inverted terminal repeats, have been reported in a wide variety of arthropods, as well as planarians, nematodes, and humans. No such element has been reported in a plant. Here we report a mariner element in the plant soybean (Glycine max (L.) Merr.). Although this sequence belongs to the mariner family, it is clearly distinct from previously reported mariner-like elements, as well as from the Tc1 transposon family. Novel aspects of its sequence could be useful as a starting point to identify mariner-like elements in new organisms, and it may prove useful in creating a transformation vector for plants.     

The influence of lactoferrin, orally administered, on systemic iron homeostasis in pregnant women suffering of iron deficiency and iron deficiency anaemia

Iron is a fundamental element for humans as it represents an essential component of many proteins and enzymes. However, this element can also be toxic when present in excess because of its ability to generate reactive oxygen species. This dual nature imposes a tight regulation of iron concentration in the body. In humans, systemic iron homeostasis is mainly regulated at the level of intestinal absorption and, until now, no regulated pathways for the excretion of iron have been found. The regulation and maintenance of systemic iron homeostasis is critical to human health. Excessive iron absorption leads to iron-overload in parenchyma, while low iron absorption leads to plasma iron deficiency, which manifests as hypoferremia (iron deficiency, ID) and ID anaemia (IDA). ID and IDA are still a major health problem in pregnant women. To cure ID and IDA, iron supplements are routinely prescribed. The preferred treatment of ID/IDA, consisting in oral administration of iron as ferrous sulphate, often fails to exert significant effects on hypoferremia and may also cause adverse effects. Lactoferrin (Lf), an iron-binding glycoprotein abundantly found in exocrine secretions of mammals, is emerging as an important regulator of systemic iron homeostasis. Recent data suggest that this natural compound, capable of interacting with the most important components of iron homeostasis, may represent a valuable alternative to iron supplements in the prevention and cure of pregnancy-associated ID and IDA. In this review, recent advances in the molecular circuits involved in the complex cellular and systemic iron homeostasis will be summarised. The role of Lf in curing ID and IDA in pregnancy and in the maintenance of iron homeostasis will also be discussed. Understanding these mechanisms will provide the rationale for the development of novel therapeutic alternatives to ferrous sulphate oral administration in the prevention and cure of ID and IDA.     

Vertebrae numbers of the early hominid lumbar spine

General doctrine holds that early hominids possessed a long lumbar spine with six segments. This is mainly based on Robinson's (1972) interpretation of a single partial Australopithecus africanus skeleton, Sts 14, from Sterkfontein, South Africa. As its sixth last presacral vertebra exhibits both thoracic and lumbar characteristics, current definitions of lumbar vertebrae and lumbar ribs are discussed in the present study. A re-analysis of its entire preserved vertebral column and comparison with Stw 431, another partial A. africanus skeleton from Sterkfontein, and the Homo erectus skeleton KNM-WT 15000 from Nariokotome, Kenya, did not provide strong evidence for the presence of six lumbar vertebrae in either of these early hominids. Thus, in Sts 14 the sixth last presacral vertebra has on one side a movable rib. In Stw 431, the corresponding vertebra shows indications for a rib facet. In KNM-WT, 15000 the same element is very fragmentary, but the neighbouring vertebrae do not support the view that it is L1. Although in all three fossils the transitional vertebra at which the articular facets change orientation seems to be at Th11, this is equal to a large percentage of modern humans. Indeed, a modal number of five lumbar vertebrae, as in modern humans, is more compatible with evolutionary principles. For example, six lumbar vertebrae would require repetitive shortening and lengthening not only of the lumbar, but also of the entire precaudal spine. Furthermore, six lumbar vertebrae are claimed to be biomechanically advantageous for early hominid bipedalism, yet an explanation is lacking as to why the lumbar region should have shortened in later humans. All this raises doubts about previous conclusions for the presence of six lumbar vertebrae in early hominids. The most parsimonious explanation is that they did not differ from modern humans in the segmentation of the vertebral column.     

A motion-dependent distortion of retinotopy in area V4

When one element in an apparent motion sequence differs in color from the others, it is perceived as shifted along the motion trajectory. We examined whether V4 neurons encode the physical or perceived location of this "flashed" element by recording neuronal responses while monkeys viewed these stimuli. The retinotopic locus of V4 activity evoked by the flashed element shifted along the motion trajectory. The magnitude of the shift is consistent with the perceptual shift in humans viewing identical stimuli. This retinotopic distortion depended on the presence of a flashed element but was observed for both color-selective and non-color-selective neurons. The distortion was undiminished when the flashed element terminated the sequence, a condition that reduced the perceptual shift in humans. These findings are consistent with a Bayesian model of localization in which perceived location is derived from position signals optimally integrated across visual areas.     

The 'problem' with automation: inappropriate feedback and interaction, not 'over-automation'

As automation increasingly takes its place in industry, especially high risk industry, it is often blamed for causing harm and increasing the chance of human error when failures do occur. I propose that the problem is not the presence of automation, but rather its inappropriate design. The problem is that the operations under normal operating conditions are performed appropriately, but there is inadequate feedback and interaction with the humans who must control the overall conduct of the task. When the situations exceed the capabilities of the automatic equipment, then the inadequate feedback leads to difficulties for the human controllers. The problem, I suggest, is that the automation is at an intermediate level of intelligence, powerful enough to take over control that used to be done by people, but not powerful enough to handle all abnormalities. Moreover, its level of intelligence is insufficient to provide the continual, appropriate feedback that occurs naturally among human operators. This is the source of the current difficulties. To solve this problem, the automation should either be made less intelligent or more so, but the current level is quite inappropriate. The overall message is that it is possible to reduce error through appropriate design considerations. Appropriate design should assume the existence of error, it should continually provide feedback, it should continually interact with operators in an effective manner, and it should allow for the worst situations possible. What is needed is a soft, compliant technology, not a rigid, formal one.     

Olduvai Hominid 7 trapezial metacarpal 1 articular morphology: contrasts with recent humans

A consideration of the metacarpal 1 articulation of the Olduvai Hominid 7 trapezium shows that, although it is generally similar to those of recent humans, it is considerably flatter radioulnarly and dorsopalmarly than those of modern humans and similar in its degree of dorsopalmar flattening to those of Upper Pleistocene late archaic humans. Even though this flattening may have slightly limited flexion-extension at the pollical carpometacarpal joint, it is most likely related to the apparently elevated levels of axial joint reaction force through the thumbs of archaic members of the genus Homo. It also documents the continuation of human carpometacarpal articular evolution through the Pleistocene.     

Is metronidazole carcinogenic?

Metronidazole (MTZ, 1-[2-hydroxyethyl]-2-methyl-5-nitroimidazole), an antiparasitic and antibacterial compound, is one of the world’s most used drugs. MTZ is potentially carcinogenic to humans due to the following facts: it is a proven mutagen in bacterial systems, it is genotoxic to human cells and also, it is carcinogenic to animals. However, due to inadequate epidemiological evidence, it is not considered as a risk factor for cancer in humans. As it will be discussed here, the existing population studies are deficient since they have not included sufficient sample size, the follow-up time has not been long enough, and the individual sensitivity to the drug might have been acting as a confounding factor. Due to the increasing use of this drug, more and improved studies are needed to elucidate its mechanism of genotoxicity and its carcinogenic potential.     

Is metronidazole carcinogenic?

Metronidazole (MTZ, 1-[2-hydroxyethyl]-2-methyl-5-nitroimidazole), an antiparasitic and antibacterial compound, is one of the world's most used drugs. MTZ is potentially carcinogenic to humans due to the following facts: it is a proven mutagen in bacterial systems, it is genotoxic to human cells and also, it is carcinogenic to animals. However, due to inadequate epidemiological evidence, it is not considered as a risk factor for cancer in humans. As it will be discussed here, the existing population studies are deficient since they have not included sufficient sample size, the follow-up time has not been long enough, and the individual sensitivity to the drug might have been acting as a confounding factor. Due to the increasing use of this drug, more and improved studies are needed to elucidate its mechanism of genotoxicity and its carcinogenic potential.     

New tools for engineering tomorrow's forests

It is difficult to overstate the role of wood in the story of humanity. In times that predate recorded history it provided shelter from the elements, light and warmth when burned, and a supple material with which early humans could craft their first tools. Today, it is still one of our chief building materials and an emerging industry is extending its applications through the development of novel biomaterials, such as cellulose fiber‐derived nanocomposites. An article in this issue of Physiologia Plantarum (Johnsson et al. 2019) describes the influence the phytohormones auxin and gibberellic acid (GA) have on the process of wood formation, and reveals possible targets for optimizing cell wall properties in fiber cells.     

宿主限制LINE-1转座活性的机制

转座子约占了人类基因组的45%,对基因组的结构与功能造成了重大的影响. 一部分转座子现在仍然具有活性,它们的转座能引发疾病. LINE-1（long interspersed element-1）是现今在人类基因组中发现的唯一具有活性并能自主转座的转座子,并能介导非自主转座的元件进行转座. 近年来LINE-1的研究有新的突破,本文简述了LINE-1的结构、转座机制及对基因组的影响,重点总结和分析宿主对LINE-1的限制机制. 由于LINE-1的生活周期与逆转录病毒有相似之处,也希望能够为宿主抗病毒的研究提供线索.     

Huperzine A from <Emphasis Type="Italic">Huperzia serrata:</Emphasis> a review of its sources,chemistry, pharmacology and toxicology

The use and popularity of herbal medicines has been increasing worldwide. In fact, today, the traditional Chinese medicine offers a vast repertory for pharmaceutical research, as is the case of Huperzia serrata, a member of Huperziaceae family. This review reports the Lycopodium alkaloids that have been isolated from this plant. However, it was mainly focused on the huperzine A (HupA), a promising therapeutic option in several acute and chronic disorders. The major therapeutic interest described for HupA has been directed to the treatment of acetylcholine-deficit dementia, including Alzheimer’s disease. However, HupA was also shown to be effective on cerebrovascular dementia and other neurodegenerative disorders with an ischemic component, as well as on other kind of cognitive impairments; the value of HupA on myasthenia gravis, organophosphate poisoning and schizophrenia has also been described. In addition, many other pharmacological properties have been ascribed to HupA, namely its anti-inflammatory, antinociceptive and anticonvulsant properties, which was recently identified, promoting a growing interest on HupA research. Furthermore, its particular chemical structure and the fact that HupA is well tolerated in humans, even at doses well above those clinically required, along with its favorable pharmacokinetics, also boosted an intense research in the pharmaceutical industry. Therefore, several HupA-related features are addressed in this review, including not only its therapeutic properties, but also its chemistry, biological and chemical sources, structure–activity relationship, pharmacokinetics and toxicology, which are discussed in detail covering the literature published from 1962 to 2014.     

肉毒毒素及其检测方法研究进展

肉毒毒素是自然界中毒性极强的一类神经麻痹毒素,可引起人类和动物肉毒中毒。因其制备简单、毒性强,已被列为最具威胁的生物恐怖剂之一,同时也是重要的毒素战剂。其感染剂量极低,每个人都易感。肉毒中毒后,病情严重者一般2-3 d内即可能死亡。如采取正确及时的治疗,可使肉毒中毒死亡率降低,而快速检测方法的建立无疑是成功治疗的前提。本文就肉毒毒素及其检测方法做一综述。     

Genotype-dependent Molecular Evolution of Sheep Bovine Spongiform Encephalopathy (BSE) Prions in Vitro Affects Their Zoonotic Potential

Prion diseases are rare fatal neurological conditions of humans and animals, one of which (variant Creutzfeldt-Jakob disease) is known to be a zoonotic form of the cattle disease bovine spongiform encephalopathy (BSE). What makes one animal prion disease zoonotic and others not is poorly understood, but it appears to involve compatibility between the prion strain and the host prion protein sequence. Concerns have been raised that the United Kingdom sheep flock may have been exposed to BSE early in the cattle BSE epidemic and that serial BSE transmission in sheep might have resulted in adaptation of the agent, which may have come to phenotypically resemble scrapie while maintaining its pathogenicity for humans. We have modeled this scenario in vitro. Extrapolation from our results suggests that if BSE were to infect sheep in the field it may, with time and in some sheep genotypes, become scrapie-like at the molecular level. However, the results also suggest that if BSE in sheep were to come to resemble scrapie it would lose its ability to affect humans.     

Biochemical mechanisms of chromium action in the human and animal organism

Modern data concerning biologic characteristics of chromium (Cr3+) its placement in nature, accessibility and metabolic action of its different forms in humans and animals is presented in this survey. Essentiality of chromium for humans is emphasized, data about consumption norms of this microelement and its use for curing different diseases especially diabetes mellitus and atherosclerosis of vessels are presented. The biochemical mechanisms of Cr3+ effect on the metabolism in the human and animal organism are analyzed. It is shown that the organism reacts to chrome additions by the change of some metabolism links. Chrome influences positively growth and development of foetus, stimulates metabolism of glucose and insulin in the humans and animals. However, at the set chromium requirements it is necessary to take into account its low availability in food, high release of Cr3+ from the organism under the influence of stress factors, considerable decline of its level with age, and also in the period of pregnancy and lactation. Therefore experimental researches of introduction of Cr3+ additions to the diet of people and forage of animals taking into account their body mass, age and clinical state, can explain the biochemical mechanisms of biological action of this microelement.     

Ghosts of the past I: some muscles and fasciae in the head domain

Humans alone among primates lack a superficial head of the temporalis muscle, although a complete superficial muscle is present in 1% of humans and an incomplete one in 8%. Yet the temporal fascia of normal humans contains all the fascial sheets associated with that head even though it is absent. The implication is that humans have lost the superficial temporal muscle, that this is evident from the retention of the fascial sheets, and that the muscular variations represent situations where the muscle has persisted to some degree. Molecular factors in the head domain that are responsible for the development of the muscles of mastication (myosin heavy chain 16) are likewise different in humans than in all non-human species and seem to be responsible for the reduction of those muscles in humans. Could the loss of the superficial portion of the temporalis muscle be a component of this reduction? Could the uncommon muscular variations result from some slight persistence of the prior molecular situation? Could the persistence of the fascial sheets, even when the muscle is absent, be because the molecular factors responsible for connective tissues are not the same as those responsible for muscles? How much of all this can be visualised in the fossil record? Skeletal dimensions of the temporal fossa, partly related to the temporal muscle size, imply that it may be possible to determine in which fossils temporal muscle reduction has occurred. Likewise, surface features of the bone in modern humans without a superficial muscular component but with a strong complex fibrous element suggest that it might be possible to determine, in any fossil in which the surface preservation is good enough, how far back this situation may have persisted. It is already known that myosin heavy chain molecular dating suggests that the muscle reduction may have occurred about 2.4 million years ago.     

Evaluation of the spontaneous reversibility of carbon tetrachloride-induced liver cirrhosis in rabbits

There is a general consensus that liver fibrosis in humans is potentially reversible, while scepticism prevails on the concept that cirrhosis can be truly reversed. The availability of suitable experimental models is fundamental for disease research. The experimental murine model of liver cirrhosis induced by carbon tetrachloride (CCl(4)) reproduces both the histological picture of the postnecrotic cirrhosis and its biochemical and clinical parameters. Normal hepatic structure is modified by formation of regeneration nodules. Fibrosis represents a morphological element of disease and an effect of hepatocyte necrosis. However, the relevance for research of this well-established model of liver cirrhosis is hampered by some spontaneous cirrhosis regression reported in mice and rats. It has been reported that CCl(4) also induces experimental liver cirrhosis in rabbits, but it is not known whether the process is reversible in this species. The aim of our study was to investigate this question. Male New Zealand White rabbits were treated intragastrically with CCl(4) or the vehicle only for 19 weeks and groups were sacrificed three and five months after treatment interruption. Cirrhotic and control livers were processed for routine light microscopy and for morphometric study of fibrosis by semiquantitative evaluation. The degree of fibrosis was based on the Knodell's scoring system.     

Use of a mammalian interspersed repetitive (MIR) element in the coding and processing sequences of mammalian genes.

The mammalian interspersed repetitive (MIR) element was amplified in mammals 130 million years ago. The MIR element is at least 260 bp in length and is found in approximately 105 copies in the mammalian genome. We analyzed copies of the MIR element in the DNA of various mammals to determine its relationship to the structure and function of genes, in an attempt to identify specific uses of the MIR element within the mammalian genome. We found that alternative splicing within the acetylcholine receptor gene in humans takes place within the MIR element and results in the incorporation of part of the MIR element into the coding sequence of this gene. Furthermore, the polyadenylation signal (AATAAA) at the 3' end of four different mammalian genes is derived from the MIR element. These uses of the MIR element suggest that other regulatory sequences found within the mammalian genome originated from ancient transposable elements, many of which may no longer be recognizable.