Discovery of adrenomedullin in rat ischemic cortex and evidence for its role in exacerbating focal brain ischemic damage.

Focal brain ischemia is the most common event leading to stroke in humans. To understand the molecular mechanisms associated with brain ischemia, we applied the technique of mRNA differential display and isolated a gene that encodes a recently discovered peptide, adrenomedullin (AM), which is a member of the calcitonin gene-related peptide (CGRP) family. Using the rat focal stroke model of middle cerebral artery occlusion (MCAO), we determined that AM mRNA expression was significantly increased in the ischemic cortex up to 17.4-fold at 3 h post-MCAO (P < 0.05) and 21.7-fold at 6 h post-MCAO (P < 0.05) and remained elevated for up to 15 days (9.6-fold increase; P < 0.05). Immunohistochemical studies localized AM to ischemic neuronal processes, and radioligand (125I-labeled CGRP) displacement revealed high-affinity (IC50 = 80.3 nmol) binding of AM to CGRP receptors in brain cortex. The cerebrovascular function of AM was studied using synthetic AM microinjected onto rat pial vessels using a cranial window or applied to canine basilar arteries in vitro. AM, applied abluminally, produced dose-dependent relaxation of preconstricted pial vessels (P < 0.05). Intracerebroventricular (but not systemic) AM administration at a high dose (8 nmol), prior to and after MCAO, increased the degree of focal ischemic injury (P < 0.05). The ischemia-induced expression of both AM mRNA and peptide in ischemic cortical neurons, the demonstration of the direct vasodilating effects of the peptide on cerebral vessels, and the ability of AM to exacerbate ischemic brain damage suggests that AM plays a significant role in focal ischemic brain injury.

Nitric oxide mediates the increase in local cerebral blood flow during focal seizures.

The role of nitric oxide (NO) in the increase in local cerebral blood flow (LCBF) elicited by focal cortical epileptic seizures was investigated in anesthetized adult rats. Seizures were induced by topical bicuculline methiodide applied through two cranial windows drilled over homotopic sites of the frontal cortex, and LCBF was measured by quantitative autoradiography by using 4-iodo[N-methyl-14C]antipyrine. Superfusion of an inhibitor of NO synthase, N omega-nitro-L-arginine (NA; 1 mM), for 45 min abolished the increase of LCBF induced by topical bicuculline methiodide (10 mM) [164 +/- 18 ml/100 g per min in the artificial cerebrospinal fluid (aCSF)-superfused side and 104 +/- 12 ml/100 g per ml in the NA-superfused side; P < 0.005]. This effect was reversed by coapplication of an excess of L-arginine substrate (10 mM) (218 +/- 22 ml/100 g per min in the aCSF-superfused side and 183 +/- 31 ml/100 g per min in the NA + L-Arg-superfused side) but not by 10 mM D-arginine, a stereoisomer with poor affinity for NO synthase (193 +/- 17 ml/100 g per min in the aCSF-superfused side and 139 +/- 21 ml/100 g per min in the NA + D-Arg-superfused side; P < 0.005). Superfusion of the guanylyl cyclase inhibitor methylene blue attenuated the LCBF increase elicited by topical bicuculline methiodide by 25% +/- 16% (P < 0.05). The present findings suggest that NO is the mediator of the vasodilation in response to focal epileptic seizures.

Proprotein convertases in amphioxus: predicted structure and expression of proteases SPC2 and SPC3.

SPC2 and SPC3 are two members of a family of subtilisin-related proteases which play essential roles in the processing of prohormones into their mature forms in the pancreatic B cell and many other neuroendocrine cells. To investigate the phylogenetic origins and evolutionary functions of SPC2 and SPC3 we have identified and cloned cDNAs encoding these enzymes from amphioxus (Branchiostoma californiensis), a primitive chordate. The amino acid sequence of preproSPC2 contains 689 aa and is 71% identical to human SPC2. In contrast, amphioxus prproSPC3 consists of 774 aa and exhibits 55% identity to human SPC3. These results suggest that the primary structure of SPC2 has been more highly conserved during evolution than that of SPC3. To further investigate the function(s) of SPC2 and SPC3 in amphioxus, we have determined the regional expression of these genes by using a reverse transcriptase-linked polymerase chain reaction (RT-PCR) assay. Whole amphioxus was dissected longitudinally into four equal-length segments and RNA was extracted. Using RT-PCR to simultaneously amplify SPC2 and SPC3 DNA fragments, we found that the cranial region (section 1) expressed equal amounts of SPC2 and SPC3 mRNAs, whereas in the caudal region (section 4) the SPC2-to-SPC3 ratio was 5:1. In the mid-body sections 2 and 3 the SPC2-to-SPC3 ratio was 1:5. By RT-PCR we also determined that amphioxus ILP, a homologue of mammalian insulin/insulin-like growth factor, was expressed predominately in section 3. These results suggest that the relative levels of SPC2 and SPC3 mRNAs are specifically regulated in various amphioxus tissues. Furthermore, the ubiquitous expression of these mRNAs in the organism indicates that they are involved in the processing of other precursor proteins in addition to proILP.

Relações filogenéticas das espécies de Crenicichla Heckel, 1840 e Teleocichla Kullander, 1988 (Teleostei: Cichlidae)

São reconhecidos 90 nomes específicos válidos de Crenicichla e oito de Teleocichla. Juntos, os dois gêneros-alvo do presente estudo compreendem quase 1/5 da diversidade total de Cichlinae, subfamília neotropical de Cichlidae. Apesar das espécies de Crenicichla e Teleocichla formarem um clado bem corroborado através de filogenias baseadas tanto em dados morfológicos quanto em dados moleculares, as relações entre as suas espécies foram ainda pouco estudadas. Os dois estudos filogenéticos de Crenicichla conhecidos são parcialmente discordantes entre si e incorporaram apenas uma parcela da diversidade do grupo. Baseados apenas em dados moleculares, não foram acompanhados por um estudo de caracteres morfológicos que indicariam as sinapomorfias ou características diagnósticas para identificação dos grupos monofiléticos delimitados. No presente estudo, os principais objetivos consistem em testar o monofiletismo do grupo formado pelas espécies de Crenicichla e Teleocichla e identificar e definir unidades monofiléticas dentro desse grupo, com base na análise cladística de caracteres morfológicos. Como objetivo secundário, são testadas as recentes hipóteses de relações filogenéticas dessas espécies com as demais espécies de ciclídeos neotropicais. Foram incluídas todas as espécies válidas de Teleocichla e 54 espécies válidas de Crenicichla (60% das espécies válidas), além de uma espécie nova de Teleocichla e cinco prováveis espécies novas de Crenicichla. 20 representantes de diferentes linhagens de Cichlinae foram incluídos, totalizando 88 táxons terminais. As análises cladísticas foram realizadas a partir de uma matriz com 211 caracteres provenientes do estudo comparado de morfologia externa, incluindo padrões de colorido e osteologia. Além da análise com pesagens igualitárias, foram explorados também os resultados das análises com pesagem implícita utilizando diferentes valores da variável k e com pesagem sucessiva. A partir da comparação e discussão dos resultados obtidos a partir das diferentes análises, a topologia obtida através da análise com pesagem implícita utilizando o valor de k=3 foi escolhida para obtenção das inferências filogenéticas. Duas classificações alternativas foram discutidas e, a fim de minimizar mudanças nomenclaturais, aquela baseada no reconhecimento de subgêneros de Crenicichla correspondendo aos grupos monofiléticos encontrados foi preferida em detrimento da proposta baseada no reconhecimento de vários gêneros. Isso porque o posicionamento de Crenicichla macrophthalma (espécie-tipo de Crenicichla) continua sendo considerado instável. O gênero Crenicichla é corroborado como um grande clado formado por todas as espécies de Crenicichla e Teleocichla incluídas e é sustentado por 40 sinapomorfias não-ambíguas. Um complexo cenário foi encontrado quanto às relações entre as espécies de Crenicichla, com várias linhagens dentro desse grande grupo, assim como era previsto de acordo com estudos filogenéticos prévios. As relações entre essas linhagens, por outro lado, são ainda instáveis, podendo variar de acordo com os diferentes tipos de pesagem aplicados e apresentam algumas divergências em relação aos estudos prévios, que também divergem entre si. Teleocichla é um grupo monofilético dentro de Crenicichla e foi considerado como um de seus oito subgêneros. O subgênero Crenicichla é constituído apenas por Crenicichla macrophthalma. Os seis subgêneros restantes (Wallaciia, Batrachops, Hemeraia, Saxatilia, Lugubria e Lacustria) correspondem totalmente ou parcialmente a grupos de espécies de Crenicichla previamente existentes na literatura. Em Lacustria, quatro complexos de espécies foram delimitados: C. missioneira, C. scotti, C. jaguarensis e C. lacustris sensu stricto. Foram listadas as espécies nominais de cada subgênero e uma diagnose para auxiliar a identificação dos mesmos foi elaborada. Uma nova hipótese de relações de Crenicichla em Cichlinae é inferida a partir da análise realizada, na qual Crenicichla é grupo-irmão de um clado formado por Chaetobranchus flavescens e todos os representantes de Cichlasomatini e Geophagini incluídos

Descrição de um fóssil de Eira barbara (Carnivora, Mustelidae) do Pleistoceno final (Bacia do Acre) e morfologia comparada do sincrânio de E. barbara recente: implicações paleobiogeográficas, geográficas e taxonômicas

A espécie recente Eira barbara (Mustelidae, Carnivora) possui uma distribuição geográfica desde o México até o norte da Argentina. É um importante táxon a ser estudado como modelo anatômico dentre os mustelídeos, assim como um importante modelo para uma melhor compreensão e entendimento sobre a diversificação dos Mustelidae. Atualmente, os registros fósseis de E. barbara na América do Sul são bastante escassos e restritos às idades pleistocênicas, sendo que os estudos destes fósseis são frequentemente desprovidos de maiores esforços para realização de descrições morfológicas detalhadas e de estudos paleobiogeográficos. Assim como os estudos dos fósseis de E. barbara são limitados, constatou-se que o mesmo cenário é observado quanto aos estudos sobre a morfologia e biogeografia da espécie. Desta forma, o presente trabalho se propôs a: realizar uma revisão de todos os registros da espécie e de uma forma geral, contribuir para um melhor conhecimento sobre a morfologia sincraniana e sobre a história biogeográfica e paleobiogeográfica de E. barbara. Para tanto, os seguintes objetivos foram propostos: estudo e redescrição detalhada do fóssil UFAC-PV 036, proveniente do Pleistoceno final do Alto Rio Juruá do sudoeste da Amazônia Brasileira; descrição sincraniana comparada de estruturas morfológicas externas e internas, analisando caracteres intraespecíficos da espécie E. barbara; realização de análises multivariadas a fim de investigar variações geográficas sob o uso de caracteres craniométricos de E. barbara entre os diferentes biomas brasileiros. A revisão dos registros fósseis foi de grande importância para o estabelecimento dos verdadeiros registros de Eira na América do Sul e a redescrição de UFAC-PV 36 contribui para o melhor conhecimento morfológico e paleobiogeográfico da espécie. A descrição morfológica comparada do sincrânio de E. barbara contribui de forma significativa para o conhecimento sobre a morfologia da espécie bem como, a descrição de caracteres intraespecíficos proporcionam caracteres mais apropriados em matrizes morfológicas, fornecendo maior robustez nas análises filogenéticas futuras. Este trabalho propõe que E. barbara não possui diferenças craniométricas estatisticamente significativas entre os biomas brasileiros, porém, E. barbara caracteriza-se aqui como uma espécie dimórfica, na qual os machos possuem estruturas cranianas relativamente maiores do que as fêmeas.

Ethnogenesis and Craniofacial Change in Japan from the Perspective of Nonmetric Traits

To examine population affinities in light of the ‘dual structure model’, frequencies of 21 nonmetric cranial traits were analyzed in 17 prehistoric to recent samples from Japan and five from continental northeast Asia. Eight bivariate plots, each representing a different bone or region of the skull, as well as cluster analysis of 21-trait mean measures of divergence using multidimensional scaling and additive tree techniques, revealed good discrimination between the Jomon-Ainu indigenous lineage and that of the immigrants who arrived from continental Asia after 300 BC. In Hokkaido, in agreement with historical records, Ainu villages of Hidaka province were least, and those close to the Japan Sea coast were most, hybridized with Wajin. In the central islands, clines were identified among Wajin skeletal samples whereby those from Kyushu most resembled continental northeast Asians, while those from the northernmost prefectures of Tohoku apparently retained the strongest indigenous heritage. In the more southerly prefectures of Tohoku, stronger traces of Jomon ancestry prevailed in the cohort born during the latest Edo period than in the one born after 1870. Thus, it seems that increased inter-regional mobility and gene flow following the Meiji Restoration initiated the most recent episode in the long process of demic diffusion that has helped to shape craniofacial change in Japan.

Mandibular Torus : A Synthesis of New and Previously Reported Data and a Discusssion of its Cause

Usinig original data on 1,5000 mandibles, but mainly previously published data, I present a overview of the distribution characteristics of mandibular torus and a hypothesis concerning its cause. Pedigree studies have established that genetic factors influence torus development. Extrinsic factors are strongly implicated by other evidence: prevalence among Arctic peoples, effect of dietary change, age regression, preponderance in males and on the right side, effect of cranial deformation, concurrence with palatine torus and maxillary alveolar exostoses, and clinical evidence. I propose that the primary factor is masticatory stress. According to a mechanism suggested by orthodontic research, the horizontal component of bite force tips the lower canine, premolars and first molar so that their root apices exert pressure on the periodontal membrane, causing formation of new bone on the lingual cortical plate of the alveolar process. Thus formed, the hyperostosis is vulnerable to trauma and its periosteal covering becomes bruised causing additional deposition of bone. Genes influence torus indirectly through their effect on occlusion. A patern of increased expressivity with incidence suggests that a quasicontinuous model may provide a better fit to pedigree data than single locus models previously tested.

Tratamento endoscópico endonasal de tumores nasossinusais malignos : resseção e reconstrução

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

A Wormian Bone, Mimicking an Entry Gunshot Wound of the Skull, in an Anthropological Specimen

Wormian bones (WB) are irregular small cranial ossicles found along suture lines and fontanels. In Brazil, gunshot wounds to the skull are quite common in young individuals. Nevertheless, as far as we know, this is the first report of a WB giving an erroneous aspect of gunshot entrance due to its displacement position. The present manuscript describes the case of a Brazilian young man who died due to ballistic trauma, where a gaping bony defect on the right side of the skull was thought to be the exit wound of an injury related to the destruction found on the left side, highly suggestive of firearm injury. Thus, this case study has brought to light similarities between a traumatic lesion and an orifice of a WB, with emphasis on differential diagnosis during routine anthropological examinations.

Morris's Human anatomy; a complete systematic treatise by English and American authors,

pt. 1. General morphogeny. Osteology. Articulations.--pt. 2. The musculature. The organs of circulation. The lymphatics.--pt. 3. The nervous system. Organs of special sense.--pt. 4. The organs of digestion. The respitory organs. The urinary and reproductive organs. The ductless glands. The skin and mammary gland.--pt.5. Surgical and topographical anatomy.

Physical anthropology of the Lenape or Delawares, and of the eastern Indians in general,

Contributions from the Museum of the American Indian, Heye Foundation, vol. 3.

Speciation of Antechinus stuartii and A. subtropicus (Marsupialia : Dasyuridae) in eastern Australia: molecular and morphological evidence

This paper evaluates the systematic status of the Antechinus populations of northern New South Wales and southern Queensland, using a combined morphological and molecular (allozymes and mitochondrial DNA) approach. Analysis of the d-loop section of the mitochondrial DNA control region revealed two highly supported clades within A. stuartii sensu lato that were sympatric in the Border Ranges of northern New South Wales. However, genetic distances between these clades were small ( approximately 3%), indicating that time of divergence was probably relatively recent. Allozyme electrophoresis also showed very small differences between clades/ species. Analyses of cranial and dental characters showed that the members of each of these clades differed morphologically and that the clades corresponded to A. stuartii and the recently described A. subtropicus. The combined results support the species status of A. stuartii and A. subtropicus, and suggest that speciation was likely a result of a recent vicariant event.

Anatomy of the pharyngeal jaw apparatus of Zenarchopterus (Gill) (Teleostei : Beloniformes)

The structure of the pharyngeal jaw apparatus (PJA) of Zenarchopterus dispar and Z. buffonis, carnivorous estuarine and freshwater West-Pacific halfbeaks, was investigated using dissection, light, and scanning electron microscopy as part of a comparison with estuarine and marine herbivorous confamilials. The Zenarchopterus PJA differs from published descriptions of hemiramphid PJAs in that the otic capsules are less pronounced; the pharyngocranial articulation facet is trough-like; the third pharyngobranchials are ankylosed; the second pharyngobranchial anterior processes are relatively hypotrophied; all pharyngeal teeth except the posterior teeth in the fifth ceratobranchial face posteriorly; the muscularis craniopharyngobranchialis 2 posterior is short; the muscularis craniopharyngobranchialis 2 anterior is lacking, as is its insertion site, the inferior parasphenoid apophysis; the protractor pectoralis is well developed; the pharyngocleithralis internus originates dorsal to the level of the fifth ceratobranchial bony process; the fifth ceratobranchial bony processes are directed ventrolaterally; the opposing upper and lower tooth fields appear not to occlude erosively; and the muscular portion of the pharyngohyoideus is well developed anteriorly. The extent of these differences and their implications for the function of the PJA support recent molecular studies that suggest that the Hemiramphidae is polyphyletic. (C) 2004 Wiley-Liss, Inc.

Archaeology and age of a new hominin from Flores in eastern Indonesia

Excavations at Liang Bua, a large limestone cave on the island of Flores in eastern Indonesia, have yielded evidence for a population of tiny hominins, sufficiently distinct anatomically to be assigned to a new species, Homo floresiensis(1). The finds comprise the cranial and some post-cranial remains of one individual, as well as a premolar from another individual in older deposits. Here we describe their context, implications and the remaining archaeological uncertainties. Dating by radiocarbon (C-14), luminescence, uranium-series and electron spin resonance (ESR) methods indicates that H. floresiensis existed from before 38,000 years ago (kyr) until at least 18 kyr. Associated deposits contain stone artefacts and animal remains, including Komodo dragon and an endemic, dwarfed species of Stegodon. H. floresiensis originated from an early dispersal of Homo erectus ( including specimens referred to as Homo ergaster and Homo georgicus)(1) that reached Flores, and then survived on this island refuge until relatively recently. It overlapped significantly in time with Homo sapiens in the region(2,3), but we do not know if or how the two species interacted.