Chondrodystrophic mice with coincidental agnathia: evidence for the tongue obstruction hypothesis in cleft palate

Mice homozygous for either of two mutations, chondrodysplasia (cho) or cartilage matrix deficiency (cmd), have short-limbed chondrodystrophy. This phenotype includes retrognathia, relative macroglossia, and cleft palate. It has been postulated that the cleft palate in these mice is the result of tongue obstruction during palatogenesis. Agnathia associated with microglossia is an independent spontaneously occurring defect in the strains bearing these mutations. The coincidental occurrence of agnathia-microglossia with chondrodystrophy lends itself to the study of the mechanism of cleft palate formation. We examined approximate midsagittal histological sections of normal and chondrodystrophic newborn mice, both with and without agnathia. Mandibular measurements and examinations of palate closure and tongue structure were made from photographic prints. Typical chondrodystrophic mutants with cleft palates had a mean mandibular length that was 66% of normal and a tongue that appeared large relative to the shortened mandible. Chondrodystrophic mutants with agnathia and microglossia had a mean mandibular length that was further reduced to 30% of normal, yet had a closed palate. We also observed two nonagnathic chondrodystrophic mutants that had slightly decreased mandibular lengths, microglossia, and closed palates. These observations suggest that tongue obstruction during palatogenesis is the pathogenetic mechanism of cleft palate in chondrodystrophic mice. A similar tongue obstruction hypothesis has been proposed as the mechanism of cleft palate formation in the human Pierre Robin sequence, which consists of retrognathia, glossoptosis, and cleft palate. This mechanistic hypothesis has been challenged, but our findings support the tongue obstruction hypothesis in the Robin cleft.     

Aquatic feeding in a terrestrial turtle: a functional-morphological study of the feeding apparatus in the Indochinese box turtle Cuora galbinifrons (Testudines, Geoemydidae)

The Indochinese box turtle Cuora galbinifrons is regarded as a purely terrestrial species, but our results demonstrate that it can feed both on land and in water. The inverse relationship between the relative development of the hyoid apparatus and the tongue found in the most investigated chelonians is not valid in the Indochinese box turtle. Our morphological analysis of the feeding apparatus reveals that the palate shape and the design of the tongue are consistent with terrestrial feeders, but the construction of the hyoid complex is more characteristic of aquatic feeders. Previous studies have demonstrated that tongue enlargement negatively impacts the capacity of the turtles to suction feed. The present study focuses on the aquatic intraoral prey transport kinematic patterns. Our analysis is based on high-speed films with 250 fr/s and high-speed cineradiography with 50 fr/s. The aquatic intraoral food transport mechanisms differ depending on prey size: small items are transported predominantly by “inertial suction”, whereas larger items are moved by the tongue—normally a clear terrestrial strategy. As the genus Cuora is ancestrally aquatic, the use of lingual food transport in the aquatic environment is presumably an aberrant modus typical only for the most terrestrial among the Asian box turtles.     

Tongue evolution in lungless salamanders, family plethodontidae. III. Patterns of peripheral innervation

Innervation of the tongue and associated musculature in plethodontid salamanders was studied using Palmgren stained sectioned materials, fresh dissection, and whole mounts of experimental specimens treated with horseradish peroxidase (HRP). Species studied were chosen to represent modes of tongue projection recognized by Lombard and Wake ('77). Special attention was given to species of the genera Plethodon, Batrachoseps, Pseudoeurycea, and Hydromantes, but representatives of other genera were investigated. As expected we found that cranial nerves IX and X and spinal nerve 1 supplied the muscles involved in tongue movement. The peripheral courses of the nerves were traced, and both functionally related and phylogenetically determined routes were found. As relative projection length increases, the nerves supplying the tongue tip also increase in length. When the tongue is at rest the long nerves are stored in coils. The coil of ramus lingualis lies between the ceratobranchials, but that of ramus hypoglossus is more variable, although constant within a species. Ramus hypoglossus bifurcates into separate branches to tongue and anterior musculature of the floor of the mouth. In generalized, presumably primitive, modes the bifurcation and coiling are far anterior. In most of the tongue projection modes bifurcation is relatively posterior, but in one, bifurcation is anterior, but coiling is relatively posterior in position. The most unusual condition is in Hydromantes, in which bifurcation is relatively posterior and a coiled ramus hypoglossus joins a coiled ramus lingualis to form a unique, coiled common ramus to the tongue tip. Hydromantes has the greatest projection distance of any salamander.     

Genetic linkage of hereditary gingival fibromatosis to chromosome 2p21.

Gingival fibromatosis is characterized by a slowly progressive benign enlargement of the oral gingival tissues. The condition results in the teeth being partially or totally engulfed by keratinized gingiva, causing aesthetic and functional problems. Both genetic and pharmacologically induced forms of gingival fibromatosis are known. The most common genetic form, hereditary gingival fibromatosis (HGF), is usually transmitted as an autosomal dominant trait, although sporadic cases are common and autosomal recessive inheritance has been reported. The genetic basis of gingival fibromatosis is unknown. We identified an extended family (n=32) segregating an autosomal dominant form of isolated gingival fibromatosis. Using a genomewide search strategy, we identified genetic linkage (Zmax=5.05, straight theta=.00) for the HGF phenotype to polymorphic markers in the genetic region of chromosome 2p21 bounded by the loci D2S1788 and D2S441. This is the first report of linkage for isolated HGF, and the findings have implications for identification of the underlying genetic basis of gingival fibromatosis.     

Developments in social terminology: semantic battles in a conceptual war

The problems posed by the evolution of the diverse forms of animal sociality are among the most important and fascinating in evolutionary biology. The conceptual and terminological framework guiding studies of social evolution has been based on a particular insect model, namely, that of highly derived family-structured societies. Virtually all other social systems have been categorized as 'less social' relative to these societies. Recently, the ambiguities and constraints inherent in this hierarchical classification have led to numerous proposals to amend social terminology. What is the best framework for studying social evolution? Should the traditional classification be expanded, narrowed or abandoned altogether? In an important respect, most recent proposals present the same wine in a different bottle by retaining and recasting key terms of the traditional social-evolutionary classification.     

Developing a systematic approach to the diagnosis and classification of mitochondrial disease

The accurate diagnosis and classification of mitochondrial diseases are essential first steps in understanding the natural history and true health care burden imposed by these protean and devastating disorders. Epidemiologic studies place the incidence of genetic forms of mitochondrial disease between 1 in 2000 and 1 in 5000 live births. Symptoms may not appear for years after birth, even when inherited. Once they occur, however, the course is often relentlessly progressive. Diagnosis requires a combination of clinical and laboratory studies that are applied systematically. DNA analysis and respiratory chain studies remain the mainstays of diagnosis, but several other disciplines may contribute to achieving diagnostic confidence when a single study is suggestive but inconclusive. A comprehensive classification system for mitochondrial diseases has not yet been developed. The current International Classification of Diseases, 10th Revision (ICD-10) includes just 10 codes for mitochondrial disorders. Supplementary data of 347 proposed ICD-10 codes is included to assist with the development of a more comprehensive system for the diagnosis and classification of mitochondrial disease.     

The conjunctival lymphoid follicle in mucosal immunology

The conjunctiva forms a continuous mucosal surface from the eyelid margin to the cornea, and makes contact with airborne antigens and those on the adjacent eyelid skin and preocular tear film. Conjunctival lymphoid follicles (CLF) undergo hyperplasia upon conjunctival infection by a specific array of pathogens; infection-associated enlargement of draining preauricular lymph nodes suggests that CLF participate in the afferent limb of acquired immune responses for the ocular surface. In this review, we examine the evidence for classification of CLF as part of the common mucosal immune system, and explore the possible therapeutic implications.     

Comparative gross anatomy of ratites

The four most common ratites kept in captivity, emus, rheas, ostriches, and cassowaries, share similar musculoskeletal features based on their common evolution to a flightless form. However, they differ in body size and coloration, wing size relative to entire body size, extent of leg feathering, and number of toes. During necropsies we observed the differences among the birds, which include the shape of tongue and tonsils, a tracheal cleft found only in emus, varied shapes of the thymus, spleen, bursa of Fabricius, proventriculus, duodenal loop, and ceca, different lengths of colon and ceca relative to the entire intestinal length, and different coloration of the gonads. Several of the structural differences reflect the phylogeny of the ratites. Rheas and ostriches share common features in relatively large wings, kidney-bean shaped spleen, tan gonads, and long ceca, whereas emus and cassowaries have relatively small wings, short ceca, and similar proventriculi. The anatomical variations may reflect their varied diets in the wild and the different behaviors among the groups such as their characteristic vocalizations. Knowledge of the differences may be useful in formulating proper diets for captive birds and is important for the recognition of clinically normal structures in the ratites.     

On comparing biological shapes: detection of influential landmarks.

For problems of classification and comparison in biological research, the primary focus is on the similarity of forms. A biological form consists of size and shape. Several approaches for comparing biological forms using landmark data are available. If the two biological forms are demonstrated to be different, the next important issue is to localize the differences by identifying those areas which differ most between the two objects. In this paper we suggest a technique to detect influential landmarks, those which contribute most to the difference between forms. We study the effectiveness of the technique using three-dimensional simulated data sets and two examples. Results suggest that the technique is useful in the study of biological form and its variation.     

生长型分类方案不同导致森林生态系统植物功能性状的统计偏差

将植物划分为不同的生长型来统计植物功能性状特征，是当前植物性状研究中常用的方法；但生长型分类方案的不同很可能造成植物功能性状统计分析的偏差，对此偏差的评估却尚未见报道。根据植物志描述及野外调查实际情况，将生长型划分为3种不同的分类方案：分类1：根据植物志信息划分为传统意义的乔木和灌木；分类2：根据树高和胸径划分乔木、小乔木和灌木；分类3：仅根据树高划分乔木层与灌木层的乔木和灌木。以东部亚热带常绿阔叶林区域的浙江金华北山35种优势阔叶木本植物的枝叶性状为研究对象，比较不同生长型分类对植物枝叶性状统计数据的影响。结果表明：（1）与传统的分类1相比，分类2对乔木植物枝叶性状影响的显著程度要高于分类3，而对灌木植物枝叶性状的影响程度低于分类3；但不同生长型分类方案中乔木和灌木的枝叶性状总体差异不显著。而与分类2小乔木相比，分类1以及分类2内部的乔木和灌木生长型的性状与分类2小乔木差异非常明显；（2）将不同生长型植物再划分为不同生活型后，不同生长型分类方案对性状统计的影响增大。无论是常绿还是落叶生活型的小乔木，其与不同生活型乔木和灌木的性状差异仍然显著。可见，不同的生长型分类方案可造成植物功能性状统计的差异；把小乔木植物这一功能类群划分出来，能更好地反映森林生态系统性状特征的差异性。     

Disorders of attention: a frontier in neuropsychology

There is an extensive behavioural neurological literature on so-called unilateral attentional disorders, but a striking paucity of papers on global disorders of attention, i.e. confusional states. However, confusional states are distinctive because: (1) they are the most common disturbance of the higher functions in clinical practice, by orders of magnitude; (2)they are the only disturbance of the higher functions from which all normal subjects have suffered; (3) they have characteristic clinical manifestations; (4) they are frequently misdiagnosed as progressive dementias, aphasia, memory disorders, and psychoses; (5) they are the only disturbance of the higher functions that commonly cause patients to produce statement that appear to be extremely witty; (6) they can be readily studied experimentally; (7) they are the most common cause of unconcern with or denial of illness. There are almost certainly several different forms of confusional state depending on the aetiology, the rate of development, the age, and the anatomical systems involved, but little classification has yet been carried on. Confusional states are most simply defined as disorders in which there is a loss of the normal coherence of thought or action. Among the striking clinical features are: (1) failure to pay attention, excessive distractibility, or failure to shift attention; (2) paramnesias, i.e. distortions of memory; (3) reduplicative phenomena, 'wild' paraphasias with 'propagation' of error, alterations of mood in many different directions; (4) isolated or predominant disturbance of writing (the most common cause of pur agraphia); (5) unconcern with or denial of illness; (6) apparently playful behaviour. While confusional states are usually attributed to 'global involvement of the brain' as a result of metabolic or toxic disorder, there are in fact many cases produced by focal infarctions inthe right hemisphere, which, in the experience of my department, is one of the commonest effects of cerebrovascular disease. Brief reference is made to the prognosis, and to the theoretical significance for cerebral dominance and the evolutionary development of cerebral dominance in non-human species.     

To shape a cell: an inquiry into the causes of morphogenesis of microorganisms.

We recognize organisms first and foremost by their forms, but how they grow and shape themselves still largely passes understanding. The objective of this article is to survey what has been learned of morphogenesis of walled eucaryotic microorganisms as a set of problems in cellular heredity, biochemistry, physiology, and organization. Despite the diversity of microbial forms and habits, some common principles can be discerned. (i) That the form of each organism represents the expression of a genetic program is almost universally taken for granted. However, reflection on the findings with morphologically aberrant mutants suggests that the metaphor of a genetic program is misleading. Cellular form is generated by a web of interacting chemical and physical processes, whose every strand is woven of multiple gene products. The relationship between genes and form is indirect and cumulative; therefore, morphogenesis must be addressed as a problem not of molecular genetics but of cellular physiology. (ii) The shape of walled cells is determined by the manner in which the wall is laid down during growth and development. Turgor pressure commonly, perhaps always, supplies the driving force for surface enlargement. Cells yield to this scalar force by localized, controlled wall synthesis; their forms represent variations on the theme of local compliance with global force. (iii) Growth and division in bacteria display most immediately the interplay of hydrostatic pressure, localized wall synthesis, and structural constraints. Koch's surface stress theory provides a comprehensive and quantitative framework for understanding bacterial shapes. (iv) In the larger and more versatile eucaryotic cells, expansion is mediated by the secretion of vesicles. Secretion and ancillary processes, such as cytoplasmic transport, are spatially organized on the micrometer scale. The diversity of vectorial physiology and of the forms it generates is illustrated by examples: apical growth of fungal hyphae, bud formation in yeasts, germination of fucoid zygotes, and development of cells of Nitella, Closterium, and other unicellular algae. (v) Unicellular organisms, no less than embryos, have a remarkable capacity to impose spatial order upon themselves with or without the help of directional cues. Self-organization is reviewed here from two perspectives: the theoretical exploration of morphogens, gradients, and fields, and experimental study of polarization in Fucus cells, extension of hyphal tips, and pattern formation in ciliates. Here is the heart of the matter, yet self-organization remains nearly as mysterious as it was a century ago, a subject in search of a paradigm.     

Purification and kinetic characterization of a phenol-sulfating form of phenol sulfotransferase from human brain

The identification of three forms of phenol sulfotransferase (PST) in human brain and the subsequent purification and kinetic characterization of a phenol-sulfating form of the enzyme are described. Two forms of PST which were capable of conjugating phenol and a third form which sulfated dopamine were resolved from one another using DEAE-cellulose chromatography. One of the phenol-sulfating forms (P1-PST) was subsequently purified on Affi-Gel blue and Sephacryl S-200, giving a final purification of almost 390-fold, with an overall yield of approximately 5%. The purified enzyme was sensitive to NaCl and showed an optimum for phenol conjugation at pH 8.5. Kinetic analysis demonstrated that sulfation by P1-PST proceeds via a sequential ordered, bi-substrate reaction mechanism, where 3'-phosphoadenosine-5'-phosphosulfate (PAPS) is the leading substrate. The true Km and Kia values for PAPS were both 0.35 microM, while the true Km value for phenol was 2.8 microM.     

Immunochemistry of the surface carbohydrate antigens of Bacteroides fragilis and definition of a common antigen

The components extracted by aqueous phenol from whole cells of Bacteroides fragilis were analysed by SDS-PAGE and immunoblotting and shown to consist of a series of strain-specific, cross-reactive and common antigens. Regularly-spaced ladder patterns on silver-stained gels indicated that in most strains the LPS was present as a predominantly smooth type, but with chain lengths of varying molecular mass, ranging within each particular strain from essentially rough forms to long chain-length smooth forms. The rough form of the LPS at the gel front possessed an antigen common to most of the strains investigated. Another antigen, which migrated behind the rough LPS on SDS gels, was common to all strains of the species. The smooth LPS forms and the other high molecular mass components were strain-specific antigens. Previously published methods are not capable of producing pure LPS or capsular polysaccharide for this organism.     

Molecular Forms of Acetylcholinesterase: Regulation in a Testosterone-Sensitive Nerve-Muscle Axis

We measured the distribution of molecular forms of acetylcholinesterase (AChE) in muscles of a song bird, the zebra finch, and found a pattern similar to those reported in other vertebrates. As in other species, the most rapidly sedimenting form of the enzyme decreases to barely detectable levels following denervation. In the muscles of the syrinx, castration causes a large decrease in AChE activity, but has little or no effect on the relative abundance of AChE forms. This suggests that the number of AChE catalytic sites is changing without affecting the distribution of catalytic sites among the molecular forms. This is in marked contrast with the effect of denervation in the syrinx, which causes changes in the distribution of activity, as well as in total activity.     

On assessing surrogacy in a single trial setting using a semicompeting risks paradigm

Summary .  There has been a recent emphasis on the identification of biomarkers and other biologic measures that may be potentially used as surrogate endpoints in clinical trials. We focus on the setting of data from a single clinical trial. In this article, we consider a framework in which the surrogate must occur before the true endpoint. This suggests viewing the surrogate and true endpoints as semicompeting risks data; this approach is new to the literature on surrogate endpoints and leads to an asymmetrical treatment of the surrogate and true endpoints. However, such a data structure also conceptually complicates many of the previously considered measures of surrogacy in the literature. We propose novel estimation and inferential procedures for the relative effect and adjusted association quantities proposed by Buyse and Molenberghs (1998, Biometrics 54, 1014–1029). The proposed methodology is illustrated with application to simulated data, as well as to data from a leukemia study.     

植物硒及其含硒蛋白的研究

硒是植物的有益元素,植物对硒的吸收与外源硒的有效性、硒的形态、植物的种类等有关;硒在植物中主要以有机硒形态存在,HPLC-ICP-MS联用已成为植物体内硒形态鉴定的最常用手段;含硒蛋白是植物体内最主要的有机大分子硒,具有抗肿瘤、抗氧化等多种生物活性。在环境安全和人类健康等方面,富硒植物具有很好的应用价值,所以利用分子生物学手段分析富硒植物的富硒机制,可以为富硒基因的筛选和利用提供理论依据。     

Emerging strategies to treat rare and intractable subtypes of melanoma

Melanoma is the deadliest form of skin cancer, possessing a diverse landscape of subtypes with distinct molecular signatures and levels of aggressiveness. Although immense progress has been achieved therapeutically for patients with the most common forms of this disease, little is known of how to effectively treat patients with rarer subtypes of melanoma. These subtypes include acral lentiginous (the rarest form of cutaneous melanoma; AL), uveal, and mucosal melanomas, which display variations in distribution across (a) the world, (b) patient age‐groups, and (c) anatomic sites. Unfortunately, patients with these relatively rare subtypes of melanoma typically respond worse to therapies approved for the more common, non‐AL cutaneous melanoma and do not have effective alternatives, and thus consequently have worse overall survival rates. Achieving durable therapeutic responses in these high‐risk melanoma subtypes represents one of the greatest challenges of the field. This review aims to collate and highlight effective preclinical and/or clinical strategies against these rare forms of melanoma.