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Trigonella foenum graecum (fenugreek) is traditionally used to treat disorders such as diabetes, high cholesterol, wounds, inflammation, and gastrointestinal ailments. Recent studies suggest that fenugreek and its active constituents may possess anticarcinogenic potential. We evaluated the preventive efficacy of dietary fenugreek seed and its major steroidal saponin constituent, diosgenin, on azoxymethane-induced rat colon carcinogenesis during initiation and promotion stages. Preneoplastic colonic lesions or aberrant crypt foci (ACF) were chosen as end points. In addition, we assessed the mechanism of tumor growth inhibition of diosgenin in HT-29 human colon cancer cells. To evaluate the effect of the test agent during the initiation and postinitiation stages, 7-week-old male F344 rats were fed experimental diets containing 0% or 1% fenugreek seed powder (FSP) or 0.05% or 0.1% diosgenin for 1 week and were injected with azoxymethane (15 mg/kg body weight). Effects during the promotional stage were studied by feeding 1% FSP or 0.1% diosgenin 4 weeks after the azoxymethane injections. Rats were sacrificed 8 weeks after azoxymethane injection, and their colons were evaluated for ACF. We found that, by comparison with control, continuous feeding of 1% FSP and 0.05% and 0.1% diosgenin suppressed total colonic ACF up to 32%, 24%, and 42%, respectively (P < or = 0.001 to 0.0001). Dietary FSP at 1% and diosgenin at 0.1% fed only during the promotional stage also inhibited total ACF up to 33% (P < or = 0.001) and 39% (P < or = 0.0001), respectively. Importantly, continuous feeding of 1% FSP or 0.05% or 0.1% diosgenin reduced the number of multicrypt foci by 38%, 20%, and 36% by comparison with the control assay (P < or = 0.001). In addition, 1% FSP or 0.1% diosgenin fed during the promotional stage caused a significant reduction (P < or = 0.001) of multicrypt foci compared with control. Dietary diosgenin at 0.1% and 0.05% inhibited total colonic ACF and multicrypt foci formation in a dose-dependent manner. Results from the in vitro experiments indicated that diosgenin inhibits cell growth and induces apoptosis in the HT-29 human colon cancer cell line in a dose-dependent manner. Furthermore, diosgenin induced apoptosis in HT-29 cells at least in part by inhibition of bcl-2 and by induction of caspase-3 protein expression. On the basis of these findings, the fenugreek constituent diosgenin seems to have potential as a novel colon cancer preventive agent.

The ideal of orderly family life in early modern Germany did not exclude drinking. In fact, drinks shared at the family table were closely tied to early modern notions of the marital bond and were also a necessary component of normal work relations. Drinking became a problem only when it threatened the stability of the household. The amount of alcohol involved in such cases might be as little as one drink if the circumstances were unsuitable. On the other hand, drinking that would by our standards be viewed as excessive or chronic could be considered acceptable . Even during and immediately after the period of Reformation, when polemical and prescriptive literature addressing the household was dominated by the problem of sin, drunkenness was rarely treated as a spiritual issues. The primary concern of both authorities and populace was not to protect the health or the rights of individuals but to protect the sanctity of the household and the stability of the community.

A number of important insights into the peopling of the New World have been gained through molecular genetic studies of Siberian and Native American populations. While there is no complete agreement on the interpretation of the mitochondrial DNA (mtDNA) and Y chromosome (NRY) data from these groups, several generalizations can be made. To begin with, the primary migration of ancestral Asians expanded from south-central Siberia into the New World and gave rise to ancestral Amerindians. The initial migration seems to have occurred between 20,000-15,000 calendar years before present (cal BP), i.e., before the emergence of Clovis lithic sites (13,350-12,895 cal BP) in North America. Because an interior route through northern North America was unavailable for human passage until 12,550 cal BP, after the last glacial maximum (LGM), these ancestral groups must have used a coastal route to reach South America by 14,675 cal BP, the date of the Monte Verde site in southern Chile. The initial migration appears to have brought mtDNA haplogroups A-D and NRY haplogroups P-M45a and Q-242/Q-M3 to the New World, with these genetic lineages becoming widespread in the Americas. A second expansion that perhaps coincided with the opening of the ice-free corridor probably brought mtDNA haplogroup X and NRY haplogroups P-M45b, C-M130, and R1a1-M17 to North and Central America. Finally, populations that formerly inhabited Beringia expanded into northern North America after the LGM, and gave rise to Eskimo-Aleuts and Na-Dené Indians., (Copyright 2004 Wiley-Liss, Inc.)

The cleavage of the transmembrane amyloid precursor protein (APP) by beta-secretase leaves the C-terminal fragment of APP, C99, anchored in the plasma membrane. C99 is subsequently processed by gamma-secretase, an unusual aspartyl protease activity largely dependent on presenilin (PS), generating the amyloid beta-peptide (Abeta) that accumulates in the brain of patients with Alzheimer's disease. It has been suggested that PS proteins are the catalytic core of this proteolytic activity, but a number of other proteins mandatory for gamma-secretase cleavage have also been discovered. The exact role of PS in the gamma-secretase activity remains a matter of debate, because cells devoid of PS still produce some forms of Abeta. Here, we used insect cells expressing C99 to demonstrate that the expression of presenilin 1 (PS1), which binds C99, not only increases the production of Abeta by these cells but also increases the intracellular levels of C99 to the same extent. Using pulse-chase experiments, we established that this results from an increased half-life of C99 in cells expressing PS1. In Chinese hamster ovary cells producing C99 from full-length human APP, similar results were observed. Finally, we show that a functional inhibitor of gamma-secretase does not alter the ability of PS1 to increase the intracellular levels of C99. This finding suggests that the binding of PS1 to C99 does not necessarily lead to its immediate cleavage by gamma-secretase, which could be a spatio-temporally regulated or an induced event, and provides biochemical evidence for the existence of a substrate-docking site on PS1.

Throughout the evolution of the concepts concerning the peripheral nerves, different ideas have dominated at different moments in history. The studies and demonstrations conducted in an attempt to further our knowledge of our own constitution and working at the same time enabled us to gain a better understanding of the make-up and specific functioning of the vestibular nerves, together with their central connecting elements in the brainstem: the vestibular nuclei. It may be that the first references to vestibular nerves are now lost in time, yet the Ancient Greeks already attempted to understand their functional nature by carrying out studies essentially focused on neuroanatomical aspects, but heavily influenced by philosophical concepts. It was not until the 18th century that researchers came to understand that there were differences between the vestibular nerve and the cochlear nerve --until then they were believed to be one single nerve. Another century went by before attempts were made to clarify the role it plays in balance and not in hearing. The differences between the distinct vestibular nuclei situated between the medulla oblongata and the pons were established in the 19th and 20th centuries when a number of authors, backed by previous microscopic studies, contributed to clarifying the fuzzy limits of cells separating the four classic nuclear groups and four others taken as being accessory.

A peat core from Lindow bog near Manchester, England, was precisely cut into 2 cm slices to provide a high-resolution reconstruction of atmospheric Pb deposition. Radiocarbon and (210)Pb age dates show that the peat core represents the period ca. 2000 BC to AD 1800. Eleven radiocarbon age dates of bulk peat samples reveal a linear age-depth relationship with an average temporal resolution of 18.5 years per cm, or 37 years per sample. Using the Pb/Ti ratio to calculate the rates of anthropogenic, atmospheric Pb deposition, the profile reveals Pb contamination first appearing in peat samples dating from ca. 900 BC which clearly pre-date Roman mining activities. Using TIMS, MC-ICP-MS, and SF-ICP-MS to measure the isotopic composition of Pb, the (208)Pb/(206)Pb and (206)Pb/(207)Pb data indicate that English ores were the predominant sources during the pre-Roman, Roman, and Medieval Periods. The study shows that detailed studies of peat profiles from ombrotrophic bogs, using appropriate preparatory and analytical methods, can provide new insight into the timing, intensity, and predominant sources of atmospheric Pb contamination, even in samples dating from ancient times.

Previous studies have shown that oesophageal and gastric cancers are the most common causes of cancer death in the Golestan Province, Iran. In 2001, we established Atrak Clinic, a referral clinic for gastrointestinal (GI) diseases in Gonbad, the major city of eastern Golestan, which has permitted, for the first time in this region, endoscopic localisation and histologic examination of upper GI cancers. Among the initial 682 patients seen at Atrak Clinic, 370 were confirmed histologically to have cancer, including 223 (60%) oesophageal squamous cell cancers (ESCC), 22 (6%) oesophageal adenocarcinomas (EAC), 58 (16%) gastric cardia adenocarcinomas (GCA), and 58 (16%) gastric noncardia adenocarcinomas. The proportional occurrence of these four main site-cell type subdivisions of upper GI cancers in Golestan is similar to that seen in Linxian, China, another area of high ESCC incidence, and is markedly different from the current proportions in many Western countries. Questioning of patients about exposure to some known and suspected risk factors for squamous cell oesophageal cancer confirmed a negligible history of consumption of alcohol, little use of cigarettes or nass (tobacco, lime and ash), and a low intake of opium, suggesting that the high rates of ESCC seen in northeastern Iran must have other important risk factors that remain speculative or unknown. Further studies are needed to define more precisely the patterns of upper GI cancer incidence, to test other previously suspected risk factors, and to find new significant risk factors in this high-risk area.

The discovery of the premaxillary bone (os incisivum, os intermaxillare or premaxilla) in humans has been attributed to Goethe, and it has also been named os Goethei. However, Broussonet (1779) and Vicq d'Azyr (1780) came to the same result with different methods. The first anatomists described this medial part of the upper jaw as a separate bone in the vertebrate skull, and, as we know, Coiter (1573) was the first to present an illustration of the sutura incisiva in the human. This fact, and furthermore its development from three parts:-(1) the alveolar part with the facial process, (2) the palatine process, and (3) the processus Stenonianus-can no longer be found in modern textbooks of developmental biology. At the end of the nineteenth and in the early twentieth century a vehement discussion focused on the number and position of its ossification centers and its sutures. Therefore, it is hard to believe that the elaborate work of the old embryologists is ignored and that the existence of a premaxillary bone in humans is even denied by many authors. Therefore this re-evaluation was done to demonstrate the early development of the premaxillary bone using the reconstructions of Felber (1919), Jarmer (1922) and data from our own observations on SEM micrographs and serial sections from 16 mm embryo to 68 mm fetus. Ossification of a separate premaxilla was first observed in a 16 mm embryo. We agree with Jarmer (1922), Peter (1924), and Shepherd and McCarthy (1955) that it develops from three anlagen, which are, however, not fully separated. The predominant sutura incisiva (rudimentarily seen on the facial side in a prematurely born child) and a shorter sutura intraincisiva argue in this sense. The later growth of this bone and its processes establish an important structure in the middle of the facial skull. Its architecture fits well with the functional test of others. We also focused on the relation of the developing premaxilla to the forming nasal septum moving from ventral to dorsal and the intercalation of the vomer. Thus the premaxilla acts as a stabilizing element within the facial skeleton comparable with the keystone of a Roman arch. Furthermore, the significance of the premaxillary anlage for the closure of the palatine was documented by a synopsis made from a stage 16, 10.2 mm GL embryo to a 49 mm GL fetus. Finally the growth of the premaxilla is closely related to the development of the human face. Abnormal growth may be correlated to characteristic malformations such as protrusion, closed bite and prognathism. Concerning the relation of the premaxillary bone to cleft lip and palate we agree with others that the position of the clefts is not always identical with the incisive suture. This is proved by the double anlagen of an upper-outer incisor in a 55 mm fetus and an adult.

It has been suggested that oxidative stress contributes to impaired left ventricular (LV) contractility in the setting of heart failure (HF). To test this hypothesis, we studied the effect of an antioxidant on contractility at rest and in response to dobutamine in 10 HF patients. We hypothesized that vitamin C would augment contractility in HF and that this effect would be of a greater magnitude in HF patients compared with patients with normal LV (NLV) function. Data from 10 patients with NLV function who participated in this study are included in this report and have been published elsewhere. A micromanometer-tipped catheter was introduced into the LV. In the experimental protocol, an infusion catheter was positioned in the left main coronary artery. The peak positive rate of change of LV pressure (LV +dP/dt) was measured in response to the intravenous infusion of dobutamine before and during the intracoronary infusion of vitamin C (96 mg/min). Vitamin C had no effect on basal LV +dP/dt in either HF or NLV groups. The infusion of vitamin C augmented the LV +dP/dt response to dobutamine by 22 +/- 4% in the NLV function group. In contrast, vitamin C had no effect on the inotropic response to dobutamine in the HF group. In the control protocol, without vitamin C, no differences were observed between responses to two sequential dobutamine infusions in either group (HF, n = 11; NLV, n = 9). Therefore, a positive effect of vitamin C on contractility was limited to patients with NLV function. The absence of this effect in HF patients may suggest that normal redox responsiveness is lost in this disease state.

The Lido of Venice is an island twelve kilometers long and between a hundred and one thousand meters wide. The citizans of Venice and many turists can't imagine today, what Lido was some centuries ago Initially totally sandy, it was fertilized by means of a continuous supply of Venice's garbage (the "scoasse"). In addition to the "scoasse", damaged foodstuffs and the waste of the vegetable market were also sent to the Lido. Other fertilisers originated from the dung of the cattle and sheep arriving by ship from Dalmatia, which were landed on the Lido, where they could pasture before slaughter to regain weight lost during their voyage. The sheep dung, especially, was important for the proto-industrial production of saltpetre, a material of the greatest strategic importance, like uranium at the present time. Saltpetre is the most important component of gun powder, which was the only explosive known up to the second half of 19th century. There were plans to establish an "artificial nitriary" in the Lido, making use of the garbage and of the animal waste. In all probability, the most bulky item ever buried in the Lido is the corpse of an enraged elephant, which escaped from its cage on the Riva degli Schiavoni where it was performing during the 1819 carnival, and was killed by a cannon shot in a church where it took refuge. The original title of the paper, published in Italian is: V. Giormani, II Lido di Venezia "scoassera" della città. I montoni dalmati e l'elefante del 1819, in Atti del III Convegno nazionale di storia della medicina veterinaria, Lastra a Signa (Firenze), 23-24 settembre 2000, a cura di Alba Veggetti, Brescia, 2001, pp. 333-339. Other information has been added in order to facilitate non-italians readers and articles appearing after the publication of the Proceedings of the Third National Congress for the History of Veterinary Medicine, Lastra a Signa, (Florence), Italy, have also been used. I am deeply grateful to Mrs. Mary Moors for the translation from Italian and for editorial assistance in the production of this article.

We have realized in many documents that in the Ottoman period surgeons were involved in pharmaceutics as much as physicians and herbalists. Surgeons employed by the state ordered more drugs than physicians, and it is interesting that in their order list there were mostly singular drugs instead of ready-made ones. In addition to drugs used by surgeons in preparing ointments and plasters, pans and filters were utilized in the process of production, and earthenware pots, tin and wooden boxes with various kinds of paper were ordered for the purpose of packaging. We have determined that most of the single drugs placed onto the lists of surgeons were "ointment of rust" that dries the pus, and "red ointment" that is good for all kinds of pus. The preparation of the ointments were specified in detail in books of surgery (Cerrahnames)We have observed that parallel to the Regulation of 1826, surgeons were given the title of pharmacist when they were appointed to military bodies. 100 kurus (piaster) were paid to surgeons for performing surgery and 50 kurus for preparing drugs, which is another important document indicating that surgeons were more responsible than physicians in preparing drugs.

According to Charles Frédéric Heusinger (1853), dog distemper had been imported from Peru into Spain in the course of the 17th century. The disease was well described in 1746 by Ulloa in his work Relación histórica del viaje a la América meridional. During the course of the 1760s, the disease was reported in Spain, followed by England, Italy (1764) and Russia (1770). In 1763, 900 dogs died in a single day in Madrid. In 1844, Karle succeeded in the first experimental transmission of the disease by brushing the lips of young dogs with the discharge from sick animals. The causal agent of the disease was only discovered in 1905, when the virus was isolated by Henri Carré. In the meantime, Edward Jenner, who thought that the disease was a pox-like affection, claimed that it could be prevented by inoculation of the vaccinia virus.

Parvovirus B19 (PVB19) is a non-trivial cause of morbidity and mortality in young individuals from diseases such as aplastic anemia and hydrops fetalis. Curiously, given this significant disease burden, the one genetic phenotype known to protect against PVB19 infection--the p red-cell phenotype characterized by the lack on any P group antigens on erythrocytes--is extremely rare with a prevalence of only approximately 1/200,000. One explanation is that PVB19 is a new virus to the Old World. It is pointed out in this paper that recently developed powerful genetic methods can be used to test this proposal. Confirmation that PVB19 is a new virus could shed light on the etiology of rheumatoid arthritis.

Archaeology's main contribution to the debate over the origins of modern humans has been investigating where and when modern human behavior is first recognized in the archaeological record. Most of this debate has been over the empirical record for the appearance and distribution of a set of traits that have come to be accepted as indicators of behavioral modernity. This debate has resulted in a series of competing models that we explicate here, and the traits are typically used as the test implications for these models. However, adequate tests of hypotheses and models rest on robust test implications, and we argue here that the current set of test implications suffers from three main problems: (1) Many are empirically derived from and context-specific to the richer European record, rendering them problematic for use in the primarily tropical and subtropical African continent. (2) They are ambiguous because other processes can be invoked, often with greater parsimony, to explain their character. (3) Many lack theoretical justification. In addition, there are severe taphonomic problems in the application of these test implications across differing spans of time. To provide adequate tests of these models, archaeologists must first subject these test implications to rigorous discussion, which is initiated here.

The initial interpretations of motion phenomena are often in terms of eye movements. It reflects a desire to link an objective expression of motion (of the eyes) with a subjective experience of motion. This approach is examined historically with respect to induced motion, motion aftereffects, visual vertigo, autokinetic effects and stroboscopic motion. All but one of these phenomena were initially observed in the natural environment and they have subsequently been studied under laboratory conditions. Eye movements are not correlated with induced motion, the motion aftereffect, or stroboscopic motion, but they do correspond to the direction and extent of visual vertigo. The extent of apparent visual motion in the autokinetic effect far exceeds that of involuntary eye movements but there might be a weak relation between them. If eye movements are to provide a reasonable account of motion illusions then they should apply to all the contours that are visible. This does apply to visual vertigo, but not to induced motion, the motion aftereffect and stroboscopic motion, all of which involve relative motion in a visible display. The autokinetic phenomenon involves the perception of isolated stimuli, and so interpretations in terms of some internal eye movement signals remain sustainable.

This paper explores historical backgrounds and contents of Treatise on Medicine written by King Sejo (r. 1455-1468) including his views on traditional medicine and pharmacy in the early Chosen period. The Treatise declared by King Sejo in 1463 has been considered as an important and unique manual of medicine because it was the exclusive example written by the king of Chosen. It was the King Sejo' s era when the medical milieu in both social and medical aspects was highly encouraged thanks to the previous achievements by King Sejong the Great (r.1418-1450). King Sejo, in particular, who was much interested in practical learning called 'Miscellaneous Studies', emphasized on court medicine. His writing can be understood in such historical frame. Another reason why he wrote the Treatise can be said that he felt necessary for establishing the medical ethic codes for inefficient court medicine-officials. In personal background, he tried to find available remedies since he had been suffered from some chronic diseases. The contents of the Treatise can be broadly fallen to the clinical and ethical aspects. In the former one, the Treatise focuses on treatment without hesitation through the sharp and exact diagnosis by medical doctors. In the latter one, eight categories of medical doctors are discussed according to their moral degrees: sim'eui, sik'eui, yak'eui, hon'eui, kwang eui, mang'eui, sa'eui, and sal'eui. Finally, musim' ji-eui was supplemented. Among them, sal'eui, medicine-official lacking both medical ability and ethical attitude, was classified as the lowest degree; sim'eui, medicine-official sincerely making his all efforts for patients, was thought to be a paragon of medical morality. In conclusion, the Treatise on Medicine by King Sejo played an important role as a manual for the principle of medical practice and for the instruction to enhance ethical attitude among medicine-officials.

In the medical writings of antiquity the recipe, a basic form of scientific writing, was considered a literary genre with conventions of its own. In texttype-linguistics, however, the recipe plays only a minor role; in studies on the history of literary short texts it is hardly ever mentioned and, furthermore, it has come to the conclusion that the recipe's function has lain solely in the curing of the sick. The present study focuses on its multifunctional character. A collection of widely scattered and hardly accessible recipes shows that the recipe adopted functions beyond giving technical directives. Its multifunctionality in the German literature of early modern times is manifest in medical and cooking jocular recipes, cooking recipes in minnesang, mock recipes aimed at physicians and astrologers, recipes of spiritual-religious content, recipes containing art and literary criticism as well as recipes in a moral-satirical or a political-agitative vein.

Studies generally, it is believed that the ancient 'Chinese ginseng' did exist due to the fact that it is clearly recorded in the Chinese historical and medicine-related sources. Although it is hard to deny that such 'ginseng' did exist in ancient China, the re-examination of its true nature is also necessary. In other words, certain refutation can be made against the claim that ancient 'Chinese jinseng' was in fact 'Panax jinseng' (C. A. Mey.), since the Chinese jinseng accounts do not tell that it is such. For example, when looking into its shape based on descriptions, the 'Chinese Jinseng' has black seed, hairy stem, and violet flower. ' Panax jinseng' on the other hand, has opal seed, no-hair stem, and light-green flower. In terms of cultivation centre, most of mainland China is unsuitable for Jinseng production with the exception of the Shangdang area of Shanxi province, which solely had the reputation of being the production centre of ancient 'Chinese jinseng'. However, when looking into the Chinese sources for jinseng-producing areas, they show that Hepei and Liaoning province and Jiangnan (south of the Yangtze river) areas also have had some jinseng-related history. Regardless of such instance, these regions did not cultivate Panax jinseng. As shown above, ancient 'Chinese jinseng' was far from being identical, in respect to its shape or production areas, to Panax jinseng. Hence, this study came to the conclusion that there is indeed very high skepticism about whether the true nature of 'jinseng' in ancient China was in fact Panax jinseng. On the contrary, there is higher possibility that the ancient 'Chinese jinseng' is totally different plant from Panax jinseng which is actually Codonopsis pilosula. When examining the shape and production areas of Codonopsis pilosula, it is closely matched with many parts of ancient 'Chinese jinseng' texts. In short, it is presumed that the 'Chinese jinseng' did indeed exist in ancient China but it was Codonopsis pilosula instead of Panax jinseng.

The symbolic characters of the Seven Deadly Sins can be traced from time to time in the cultural history of human mankind, being directly specified in certain artistic products. Such are, among others, the painting entitled "The Seven Deadly Sins and the Four Lost Things" by Hieronymus Bosch and the poems Divina Commedia and The Foerie Queene by Dante Alighieri and Edmund Spenser, respectively. However, there are several paragraphs referring to these behaviours of the Seven Deadly Sins in the Bible and in the dramas of William Shakespeare. The objective of the present review is to propose that dysfunctions in the central serotonergic system might be involved in the neurobiology of these 'sinful' behaviour patterns. Evidences indicate that behaviour traits such as Accidia (Sloth), Luxuria (Lust, Lechery), Superbia (Pride), Ira (Wrath, Anger), Invidia (Envy), Avaritia (Greed, Avarice), and Gula (Gluttony) can relate to the functional alterations of serotonin in the brain. Results of biochemical and molecular genetic (polymorphism) studies on the human serotonergic system (receptor, transporter, enzyme), findings of functional imaging techniques, effects of depletion (or supplementation) of the serotonin precursor tryptophan, data of challenge probe investigations directed to testing central serotonergic functions, alterations in the peripheral serotonin measures (platelet), and the changes in the CSF 5-hydroxy-indoleacetic acid content indicate such serotonergic involvement. Furthermore, results of animal experiments on behaviour change (aggressive, dominant or submissive, appetite, alcohol preference) attributed to serotonin status modification and the clinically evidenced therapeutic efficacy of pharmacological interventions, based on the modulation and perturbation of the serotonergic system (e.g. selective serotonin reuptake inhibitors), in treating the 'sinful' behaviour forms and analogous pathological states reaching the severity of psychiatric disorders (depression, sexual disturbances, social phobia, impulsivity-aggression, obsessive-compulsive and related spectrum disorders, paranoid jealousy, eating disorders) all strongly suggest the possibility that brain serotonin dysfunctions might underlie the neurophysiology of the Seven Deadly Sins.

While S4 is known as the voltage sensor in voltage-gated potassium channels, the carboxyl terminus of S3 (S3C) is of particular interest concerning the site for gating modifier toxins like hanatoxin. The thus derived helical secondary structural arrangement for S3C, as well as its surrounding environment, has since been intensively and vigorously debated. Our previous structural analysis based on molecular simulation has provided sufficient information to describe reasonable docking conformation and further experimental designs (Lou et al., 2002. J. Mol. Recognit. 15: 175-179). However, if one only relies on such information, more advanced structure-functional interpretations for the roles S3C may play in the modification of gating behavior upon toxin binding will remain unknown. In order to have better understanding of the molecular details regarding this issue, we have performed the docking simulation with the S3C sequence from the hanatoxin-insensitive K+-channel, shaker, and analyzed the conformational changes resulting from such docking. Compared with other functional data from previous studies with respect to the proximity of the S3-S4 linker region, we suggested a significant movement of drk1 S3C, but not shaker S3C, in the direction presumably towards S4, which was comprehended as a possible factor interfering with S4 translocation during drk1 gating in the presence of toxin. In combination with the discussions for structural roles of the length of the S3-S4 linker, a possible molecular mechanism to illustrate the hanatoxin binding-modified gating is proposed., (Copyright 2003 John Wiley & Sons, Ltd.)

According to textual research, the "Huci" was first recorded in ancient document, Zhenglei Bencao, not "Funiu Hua" recorded in Kaibao Bencao. Therefore, in Li Shizhen's works, Compendium of Materia Medica, incorporating "Huci" into an item of "Funiu Hua" is incorrect. The original plan of "Huci" is Damnacanthus indicus Gaertn. f. from Rubiaceae.

As has been shown and explained, the stigmata and other mortifications of the flesh can serve as survival tools for someone who has been severely traumatized, devout Christian or unbeliever alike. When Diana, Princess of Wales, was killed, this nonreligious woman came to be regarded by her admirers as a popular saint who wanted nothing more than to help and serve others. Despite her wealth, she became a waif in the popular imagination, and like many others who suffered great psychic pain, she too inflicted further pain and suffering on herself through starving herself, binging and purging, and cutting herself. This suffering was her visible stigmata, inspiring great popular devotion. When she died, millions cried, carrying candles in the streets as they listened to Elton John's song to this suffering woman whose light flickered "like a candle in the wind".

Drawing from four sixteenth-century sources, the article reports some apparent incidents of American Tegumentary Leishmaniasis within the territory of the Andes. Reinterpretation of these sources affords a look at the longstanding issue of the origin of espundia,or mucosal Leishmaniasis (ML). The study reinforces the hypothesis that ML originated in the western Amazon region, from there climbing into the high forests and later into hot inter-Andean lands via Bolivia's and Peru's borders with Brazil, above al through human migration. dating to archeological times, this process intensified during the Inca period under the social policies of the mitmaq or mitimaes. These events transpired within the historical and social context of the fall of the Inca Empire and the advent of Spanish colonization.