Role of melanocortin signaling in the regulation of the hypothalamic-pituitary-thyroid (HPT) axis

The melanocortin signaling system is orchestrated by two, independent groups of neurons in the hypothalamic arcuate nucleus with opposing functions that synthesize either alpha-melanocyte stimulating hormone (alpha-MSH) or agouti-related protein (AGRP). These neurons exert regulatory control over hypophysiotropic TRH neurons in the hypothalamic paraventricular nucleus (PVN) at least in part through direct, overlapping, monosynaptic projections to the PVN. Alpha-MSH has an activating effect on hypophysiotropic TRH neurons via the phosphorylation of CREB, and when administered exogenously, can completely reverse fasting-induced suppression of TRH mRNA in the PVN. AGRP has a potent inhibitory effect on the hypothalamic-pituitary-thyroid axis in normally fed animals, mediated through actions at melanocortin 4 receptors. Inhibition of the HPT axis by fasting may be explained by inhibition of melanocortin signaling as a result of a reduction in alpha-MSH and increase in AGRP. Neuropeptide Y may also modulate the effects of the melanocortin signaling system during fasting by potentiating the inhibitory actions of AGRP on hypophysiotropic TRH neurons to prevent the phosphorylation of CREB and through direct inhibitory effects on alpha-MSH-producing neurons in the arcuate nucleus.     

Pituitary-adrenal mediation of bombesin-induced inhibition of gastrointestinal transit in rats

Centrally administered bombesin (0.1-3.5 micrograms, i.c.v.) inhibits gastrointestinal transit of a charcoal meal in a dose-related manner in rats. The roles of pituitary and adrenal glands in the mediation of this effect were assessed. The inhibition of gastrointestinal transit associated with bombesin (0.5 microgram, i.c.v.) was prevented by either hypophysectomy or adrenalectomy. Bombesin-induced inhibition of gastrointestinal transit is therefore mediated through the pituitary-adrenal axis. This is in contrast to bombesin-induced scratching and inhibition of gastric acid secretion which are not markedly influenced by either hypophysectomy or adrenalectomy.     

Respiratory pathways in aged soybean seeds

Respiratory activities in soybean seeds (Glvcine max (L.) Merr. cv. Chippewa 64) have been examined in the first minutes after water imbibition and after three hours of imbibition, using either particles or intact axes. Cyanide and azide were utilized as inhibitors of the cytochrome oxidase pathway of respiration, and SHAM inhibitions were interpreted as effects on the alternative pathway, since in unaged axes inhibitions by SHAM were obtained only when respiratory activity had either been restricted with inhibitors of the cytochrome oxidase pathway or expanded by an uncoupler (CCCP). From the experiments with these inhibitors, it is suggested that unaged seeds utilize both respiration pathways in the cotyledon but only the cytochrome pathway in the axis. Accelerated aging causes a marked deterioration of respiration, especially that through the cytochrome pathway, and there is an associated engagement of the alternative pathway in the seed axis. It is suggested that the lowering of respiratory activity and the shift in respiratory pathways may play a major role in the decline of germinability and vigor.     

Is the anterior-posterior axis of the fetus specified before implantation in the mouse?

The mouse conceptus is generally held to be radially symmetrical about its embryonic-abembryonic axis from the blastocyst stage until the primitive streak appears at the beginning of gastrulation. However, this notion has been challenged by recent observations on conceptuses sectioned in utero which suggest that the blastocyst is already bilaterally symmetrical when it begins to implant. Accordingly, the blastocyst has been assigned an anterior-posterior axis which appears to persist through gastrulation and is claimed to coincide with the anterior-posterior axis of the future fetus in both orientation and polarity. In the present investigation the relationship between these two axes was examined in conceptuses dissected from the uterus early in gastrulation so that it could be determined more accurately than is possible in situ. The anterior-posterior axis of the conceptus and nascent fetus were found to be either parallel or antiparallel to each other, suggesting that while the orientation of the fetal axis may be specified at the blastocyst stage its polarity is not.     

Animal and vegetal poles of the mouse egg predict the polarity of the embryonic axis, yet are nonessential for development

Recent studies suggest early (preimplantation) events might be important in the development of polarity in mammalian embryos. We report here lineage tracing experiments with green fluorescent protein showing that cells located either near to or opposite the polar body at the 8-cell stage of the mouse embryo retain their same relative positions in the blastocyst. Thus they come to lie on either end of an axis of symmetry of the blastocyst that has recently been shown to correlate with the anterior-posterior axis of the postimplantation embryo (see R. J. Weber, R. A. Pedersen, F. Wianny, M. J. Evans and M. Zernicka-Goetz (1999). Development 126, 5591-5598). The embryonic axes of the mouse can therefore be related to the position of the polar body at the 8-cell stage, and by implication, to the animal-vegetal axis of the zygote. However, we also show that chimeric embryos constructed from 2-cell stage blastomeres from which the animal or the vegetal poles have been removed can develop into normal blastocysts and become fertile adult mice. This is also true of chimeras composed of animal or vegetal pole cells derived through normal cleavage to the 8-cell stage. We discuss that although polarity of the postimplantation embryo can be traced back to the 8-cell stage and in turn to the organisation of the egg, it is not absolutely fixed by this time.     

Directional cell migration establishes the axes of planar polarity in the posterior lateral-line organ of the zebrafish

The proper orientation of mechanosensory hair cells along the lateral-line organ of a fish or amphibian is essential for the animal's ability to sense directional water movements. Within the sensory epithelium, hair cells are polarized in a stereotyped manner, but the mechanisms that control their alignment relative to the body axes are unknown. We have found, however, that neuromasts can be oriented either parallel or perpendicular to the anteroposterior body axis. By characterizing the strauss mutant zebrafish line and by tracking labeled cells, we have demonstrated that neuromasts of these two orientations originate from, respectively, the first and second primordia. Furthermore, altering the migratory pathway of a primordium reorients a neuromast's axis of planar polarity. We propose that the global orientation of hair cells relative to the body axes is established through an interaction between directional movement by primordial cells and the timing of neuromast maturation.     

A review of fossil cycad megasporophylls, with new evidence of Crossozamia pomel and its associated leaves from the lower permian of Taiyuan, China

Four species of cycad megasporophyll from the Lower Permian of Taiyuan, China, are described as Crossozamia chinensis (Zhu and Du) comb. nov., C. minor sp. nov., C. spadicia sp. nov. and C. cucullata comb. nov. together with the associated leaves Tianbaolinia circinalis gen. et sp. nov., Yuania chinensis Zhu and Du and Taeniopteris taiyuanensis Halle. An axis bearing megasporophylls in organic connection is described for the first time. Two possible evolutionary pathways from this structure to those of the female reproductive organs of extant cycads are proposed, involving either the reduction of the megasporophylls and their compaction on the axis, or the reduction of the “strobilus” axis. It is suggested that migration of cycads from North China to Europe might have occurred through transportation of their buoyant seeds by the palaeoceanic currents of the Tethys sea.     

Bifunctional action of ephrin-B1 as a repellent and attractant to control bidirectional branch extension in dorsal-ventral retinotopic mapping

We report that the EphB receptor ligand, ephrin-B1, may act bifunctionally as both a branch repellent and attractant to control the unique mechanisms in mapping the dorsal-ventral (DV) retinal axis along the lateral-medial (LM) axis of the optic tectum. EphB receptors are expressed in a low to high DV gradient by retinal ganglion cells (RGCs), and ephrin-B1 is expressed in a low to high LM gradient in the tectum. RGC axons lack DV ordering along the LM tectal axis, but directionally extend interstitial branches that establish retinotopically ordered arbors. Recent studies show that ephrin-B1 acts as an attractant in DV mapping and in controlling directional branch extension. Modeling indicates that proper DV mapping requires that this attractant activity cooperates with a repellent activity in a gradient that mimics ephrin-B1. We show that ectopic domains of high, graded ephrin-B1 expression created by retroviral transfection repel interstitial branches of RGC axons and redirect their extension along the LM tectal axis, away from their proper termination zones (TZs). In contrast, the primary RGC axons are unaffected and extend through the ectopic domains of ephrin-B1 and arborize at the topographically correct site. However, when the location of a TZ is coincident with ectopic domains of ephrin-B1, the domains appear to inhibit arborization and shape the distribution of arbors. Our findings indicate that ephrin-B1 selectively controls, through either attraction or repulsion, the directional extension and arborization of interstitial branches extended by RGC axons arising from the same DV position: branches that arise from axons positioned lateral to the correct TZ are attracted up the gradient of ephrin-B1 and branches that arise from axons positioned medial to the same TZ are repelled down the ephrin-B1 gradient. Alternatively, EphB receptor signaling may act as a 'ligand-density sensor' and titrate signaling pathways that promote branch extension toward an optimal ephrin-B1 concentration found at the TZ; branches located either medial or lateral to the TZ would encounter a gradient of increasingly favored attachment in the direction of the TZ.     

Morphogenetic interactions between rotated skin cuffs and underlying stump tissues in regenerating axolotl forelimbs

Rotation of skin cuffs 180° around the longitudinal axis of the underlying tissues in the axolotl forelimb results in a high percentage of multiple regenerates after amputation through the rotated skin. Similar results occur after rotation of only the anteroposterior (A-P) axis of the skin. Rotation of only the proximodistal (Pr-Ds) axis of the skin results in normal regenerates whereas dorsoventral (D-V) axial skin rotation results in single regenerates with some disturbances in symmetry. Rotation of anterior or posterior half cuffs of skin produces results similar to those obtained after A-P rotation of full skin cuffs, and rotation of dorsal or ventral skin halves duplicates the results obtained by rotating full skin cuffs about the D-V axis. Skin cuffs rotated for periods from 6 months to over 2 years before amputation are also capable of causing multiple regenerates to form. No significant difference in the percentage of multiple regenerates was seen after skin rotation and limb amputation through shoulder, upper arm, and forearm levels. X-Radiation (4000 r) of either the skin or underlying tissues before skin rotation resulted in single regenerates after amputation. If a strip of normal skin was turned perpendicularly to the long axis of the irradiated underlying stump tissues, the regenerative response was blocked. In some of the above experiments, regenerates with longitudinally duplicated upper arm and forearm segments appeared. It is postulated that normally both the skin and the underlying limb tissues can influence morphogenesis during regeneration and that they work in harmony. In contrast, rotated skin and the underlying tissues each exert a morphogenetic influence upon the regenerating limb, and the regenerate is not able to integrate these disharmonious influences. This is reflected in the highly abnormal morphology of the regenerates. The nature of the morphogenetic influence disrupted by skin rotation is not yet known.     

Cross-tolerance between ethanol and levorphanol with respect to stimulation of plasma corticosterone

Male rats chronically intoxicated with ethanol for at least two days were tolerant to the ethanol-induced stimulation of hypothalamic-pituitary-adrenal axis. Chronically intoxicated rats also were tolerant to stimulation of this axis by levorphanol but not by amphetamine or ether. In a similar manner, animals treated with levorphanol for two days were tolerant to stimulation of the hypothalamic-pituitary-adrenal axis by either levorphanol or ethanol. These observations provide further support for the hypothesis that endogenous opioids may be involved in the development of tolerance to ethanol.     

The role of the GH/IGF-I axis for cardiac function and structure.

There is ample evidence to support a role for the GH/IGF-I axis in regulation of cardiac growth, structure and function. GH may act directly on the heart or through circulating IGF-I (Fig. 1). Moreover, GH has been found to regulate local production of IGF-I in the heart. Both the GH-R and IGF-I-R are expressed in cardiac tissue. Hence, the IGF-I-R receptor can theoretically be activated through locally produced IGF-I acting via autocrine/paracrine mechanisms, or via circulating IGF-I exerting its effects as an endocrine agent. During conditions of pressure and volume overload, an increased systolic wall stress triggers an induction of gene expression of IGF-I GH-R and possibly IGF-J-R implying a potential role for the GH/IGF-I axis in the development of adaptive hypertrophy of the heart and vessels. Cardiovascular effects of GH in clinical studies include beneficial effects on contractility, exercise performance and TPR, and experimental studies suggest an increased Ca2+ responsiveness as one possible underlying cause, although effects of GH and IGF-I on apoptosis may possibly also play a role. The GH secretagogue hexarelin improves cardiac function after experimental myocardial infarction either through an increased GH secretion or possibly through a cardiac GHS receptor, although this needs further investigation. Moreover, it is clear that further basic and clinical studies are required to gain insight into the GH and IGF-I mechanisms of action and to monitor long-term effects when GH is administered as substitution therapy or as an agent in the treatment of congestive heart failure.     

Plasmodium berghei: Architectural analysis by freeze-fracturing of the intraoocyst sporozoite's pellicular system

The technique of freeze-fracturing has been used to study the architecture of the pellicular complex of the intraoocyst sporozoite of Plasmodium berghei. The sporozoite is surrounded by three plasma membranes and a layer of subpellicular microtubules. During freeze-fracturing, each of the three membranes can split along its hydrophobic interior to yield a total of six fracture faces. The most obvious feature of each fracture face is the presence of globular intramembranous particles on the surface. The six fracture faces differ from one another in arrangement, size, and density of these intramembranous particles. Two of the fracture faces exhibit a unique arrangement of particles in well-organized parallel rows along the long axis of the sporozoite. This arrangement has not been reported in either the erythrocytic or the exoerythrocytic forms of Plasmodium spp. Another unique feature in the sporozoite revealed through freeze-fracturing is a single suture line that traverses the long axis of the inner two membranes of the parasite.     

Combining classical and molecular approaches elaborates on the complexity of mechanisms underpinning anterior regeneration

The current model of planarian anterior regeneration evokes the establishment of low levels of Wnt signalling at anterior wounds, promoting anterior polarity and subsequent elaboration of anterior fate through the action of the TALE class homeodomain PREP. The classical observation that decapitations positioned anteriorly will regenerate heads more rapidly than posteriorly positioned decapitations was among the first to lead to the proposal of gradients along an anteroposterior (AP) axis in a developmental context. An explicit understanding of this phenomenon is not included in the current model of anterior regeneration. This raises the question what the underlying molecular and cellular basis of this temporal gradient is, whether it can be explained by current models and whether understanding the gradient will shed light on regenerative events. Differences in anterior regeneration rate are established very early after amputation and this gradient is dependent on the activity of Hedgehog (Hh) signalling. Animals induced to produce two tails by either Smed-APC-1(RNAi) or Smed-ptc(RNAi) lose anterior fate but form previously described ectopic anterior brain structures. Later these animals form peri-pharyngeal brain structures, which in Smed-ptc(RNAi) grow out of the body establishing a new A/P axis. Combining double amputation and hydroxyurea treatment with RNAi experiments indicates that early ectopic brain structures are formed by uncommitted stem cells that have progressed through S-phase of the cell cycle at the time of amputation. Our results elaborate on the current simplistic model of both AP axis and brain regeneration. We find evidence of a gradient of hedgehog signalling that promotes posterior fate and temporarily inhibits anterior regeneration. Our data supports a model for anterior brain regeneration with distinct early and later phases of regeneration. Together these insights start to delineate the interplay between discrete existing, new, and then later homeostatic signals in AP axis regeneration.     

Visual position stabilization in the hummingbird hawk moth, Macroglossum stellatarum L. II. Electrophysiological analysis of neurons sensitive to wide-field image motion

Response properties of neurons in the cervical connectives of the hummingbird hawk moth, Macroglossum stellatarum L., were determined. All neurons described in this account respond directionally selectively to motion in large parts of the visual field of either eye. They respond maximally to bilateral stimulation, preferring either motion as induced on the eyes during translatory movements of the animal or when it turns around one of its body axes. Cells most sensitive to rotational motion either respond best to rotation of the patterns around the vertical axis of the animal or around its longitudinal body axis. Neurons most sensitive to translational pattern motion respond best to either simulated translations of the animal along its vertical or along an oblique axis. Most types of neurons respond tonically and do not habituate. The sensitivity to motion stimuli is not evenly distributed within the receptive field of any investigated neuron. Part of these neurons might play a role in visual position and course stabilization. Accepted: 13 August 1997     

An interactive modeling program for DNA

An interactive program for modeling A-, B- and Z-DNA in a schematic and nonatomic representation has been developed for the Evans and Sutherland PS300. The program lets users display several molecules for which parameters determining the three-dimensional structure can be calculated either on the basis of theoretical models or inferred from experimental data. The calculation of the curvature and torsion of the helical axis, by a method based on Frenet's equations, makes it possible to quantify the effects of the parameters on the helical axis.     

A STUDY OF Si DEPOSITION SYNCHRONY IN RHIZOSOLENIA (BACILLARIOPHYCEAE) MATS USING A NOVEL 32Si AUTORADIOGRAPHIC METHOD

A ³²Si autoradiographic technique using a liquid photographic emulsion was developed for the study of diatom silica deposition in culture or in natural water samples. The method was used in the Central North Pacific to study silica deposition by diatoms of the genus Rhizosolenia. The species examined form centimeter-sized aggregates commonly referred to as mats. The Rhizosolenia mats examined were composed of a matrix of R. fallax Sundström chains, embedded with chains of larger cells, either R. debyana H. Peragallo or R. acuminata H. Peragallo. The autoradiographs revealed distinct rings of labeled intercalary bands and/or labeled valves. A greater proportion of the frustule of the larger species was labeled during the incubations with ³²Si, implying higher rates of silicification by R. debyana and R. accuminata compared to R. fallax. A quantitative consideration of these differences in species-specific Si production combined with abundance and surface area estimates for each species indicates that cells of the larger species carry out the majority of silica production in Rhizosolenia mats. The large cell size (pervalvar axis 240 to 3000 μm) and elongate frustule morphology of Rhizosolenia cells enabled us to localize the deposition of silica along the pervalvar axis. Positions of labeled bands along this axis indicate progress through the Si deposition cycle, and the results suggest that cell division is phased, with either a bimodal or unimodal age distribution of cells within the cell cycle for all species in a mat. Species-specific doubling times from 25 to 60 h were implied by the mean fractions of frustule that were labeled. ³²Si autoradiography revealed unique species-specific differences in diel patterns of cell division and silica deposition and has potential for studies of Si deposition by other diatom species and assemblages.     

Can axes conventions of the trunk reference frame influence breast displacement calculation during running?

To obtain breast motion relative to the trunk, skin markers are used to define a local coordinate system (trunk), with respect to the global reference frame. This study aimed to quantify any differences in multiplanar breast displacement relative to the trunk using the first axis of rotation as either the mediolateral or longitudinal axis. Ten female participants ran on a treadmill (10 kph) in three different breast supports (no bra, everyday bra, sports bra). Four reflective markers placed on the trunk and right nipple were tracked using eight infrared cameras (200 Hz) during five running gait cycles in each breast support condition. Following marker identification, right breast multiplanar displacements were calculated relative to the trunk using either the mediolateral axis or the longitudinal axis as the first rotational axis to define the orthogonal local coordinate system. Results showed that there was a significant difference (8.2%) in superioinferior breast displacement in the sports bra condition when calculated using different axes conventions for the trunk segment. Furthermore, the greatest magnitude of breast displacement occurred in a different direction depending upon the selection of the first rotational axis. The definition of the primary reference axis of the trunk significantly alters the magnitude of superioinferior breast displacement and therefore it is recommended that the previously reported ‘stable’ longitudinal axis should be defined as the first rotational axis during running. Caution should also be used as the axes convention influences the magnitude and direction of breast support requirements, which has important implications for bra design.     

猪流行性腹泻病毒诱导的猪肠道-乳腺-sIgA轴以及免疫机制探讨

猪的“肠道-乳腺-sIgA轴”免疫通路是指侵染猪的胃肠道病原通过胃肠道免疫可以激发乳腺产生sIgA;sIgA被初生仔猪摄取可以获得针对胃肠道病原的被动免疫保护。该免疫通路的反应动力模式涉及病原侵染、抗原提呈、淋巴细胞活化、淋巴细胞的肠道和乳腺归巢以及抗体分泌等诸多环节,受到病原毒力、母猪的妊娠阶段及免疫生理状态等众多因素影响。目前,猪流行性腹泻病毒（Porcine Epidemic Diarrhea Virus,PEDV）诱发的“肠道-乳腺-sIgA轴”的理论可以解释自然感染状态下哺乳仔猪获得的被动免疫保护,但根据这一概念所设计的疫苗和免疫方案并未取得满意效果。本文综述了PEDV感染和宿主免疫各个环节的研究现状,分析了影响PEDV免疫和肠道-乳腺-sIgA轴系反应的关键病原和宿主因素,提出了在轴系理论基础上应重视PEDV灭活疫苗以及特异IgG作用的建议。