The phylogeny of the red panda (Ailurus fulgens): evidence from the forelimb

Within the order Carnivora, the phylogeny of the red panda (Ailurus fulgens) is contentious, with morphological and molecular studies supporting a wide range of possible relationships, including close ties to procyonids, ursids, mustelids and mephitids. This study provides additional morphological data, including muscle maps, for the forelimb of Ailurus, based on the dissection of four cadavers from the National Zoological Park, Washington, DC, USA. The red panda forelimb is characterized by a number of primitive features, including the lack of m. rhomboideus profundus, a humeral insertion for m. cleidobrachialis, the presence of mm. brachioradialis, articularis humeri and coracobrachialis, a single muscle belly for m. extensor digitorum lateralis with tendons to digits III–V, four mm. lumbricales, and the presence of mm. flexor digitorum brevis manus, adductores digiti I, II and V, and abductor digiti I and V. Red pandas resemble Ailuropoda, mustelids and some procyonids in possessing a soft tissue origin of m. flexor digitorum superficialis. In addition, red pandas are similar to ursids and procyonids in having a variable presence of m. biceps brachii caput breve. Furthermore, Ailurus and some ursids lack m. rhomboideus capitis. The forelimb muscle maps from this study represent a valuable resource for analyzing the functional anatomy of fossil ailurids and some notes on the Miocene ailurid, Simocyon batalleri, are presented.     

The phylogeny of the red panda (Ailurus fulgens): evidence from the hindlimb

The red panda (Ailurus fulgens) is an endangered carnivore living in the temperate forests of the Himalayas and southern China. The phylogeny of the red panda has been the subject of much debate. Morphological and molecular studies have supported a wide range of possible relationships, including close ties to procyonids, ursids, mustelids, and mephitids. This study provides additional morphological data, including muscle maps, for Ailurus. The hindlimbs of four cadavers from the National Zoological Park were dissected. Red pandas retain a number of muscles lost in other carnivore groups, including muscles and tendons related to their robust and weight‐bearing hallux. Three features, including a single‐bellied m. sartorius, a proximal insertion for m. abductor digiti V, and an absent m. articularis coxae, are found in all terrestrial arctoids, including Ailurus. In addition, red pandas are similar to ursids and canids in lacking a caudal belly of m. semitendinosus, while they resemble procyonids and mustelids in the degree of fusion observed between mm. gluteus medius and piriformis. Furthermore, Ailurus and procyonids are characterized by numerous subdivisions within the adductor compartment, while red pandas and raccoons share a variable m. semimembranosus, composed of one, two, or three bellies. Lastly, a deep plantar muscle inserting onto the metatarsophalangeal joint of the hallux is described for Ailurus. This muscle has not been previously described and is given the name m. flexor hallucis profundus. Additional dissections of the forelimb and axial musculature of red pandas may shed further light on the phylogeny of this species. In addition, the muscle maps presented here offer a valuable resource for interpreting the functional anatomy of fossil ailurids.     

CT examination of the manipulation system in the giant panda (Ailuropoda melanoleuca)

The manipulation mechanism of the giant panda ( Ailuropida melanoleuca ) was examined by means of CT (computed tomography) and 3-dimensional (3-D) Volume Rendering techniques. In the 3-D images of the giant panda hand, not only the bones but also the muscular system was visualised. Sections of the articulated skeleton were obtained. It was demonstrated that the hand of the panda is equipped with separately moulded manipulation units as follows: (1) the radial sesamoid (RS), the radial carpal, and the first metacarpal (R–R–M) complex; and (2) the accessory carpal (AC) and the ulnar (A–U) complex. When the giant panda grasps anything, the R–R–M complex strongly flexes at the wrist joint, the RS becomes parallel with the AC, and the phalanges bend and hold the object. It is shown that the well-developed opponens pollicis and abductor pollicis brevis muscles envelop and fix the objects between the R–R–M complex and the phalanges during grasping.     

Carpal bone movements in gripping action of the giant panda (Ailuropoda melanoleuca)

The movement of the carpal bones in gripping was clarified in the giant panda ( Ailuropoda melanoleuca ) by means of macroscopic anatomy, computed tomography (CT) and related 3-dimensional (3-D) volume rendering techniques. In the gripping action, 3-D CT images demonstrated that the radial and 4th carpal bones largely rotate or flex to the radial and ulnar sides respectively. This indicates that these carpal bones on both sides enable the panda to flex the palm from the forearm and to grasp objects by the manipulation mechanism that includes the radial sesamoid. In the macroscopic observations, we found that the smooth articulation surfaces are enlarged between the radial carpal and the radius on the radial side, and between the 4th and ulnar carpals on the ulnar side. The panda skilfully grasps using a double pincer-like apparatus with the huge radial sesamoid and accessory carpal.     

Sequence analysis of a canine parvovirus isolated from a red panda (<Emphasis Type="Italic">Ailurus fulgens</Emphasis>) in China

Canine parvovirus (CPV) was first recognized in the late 1970 s in dogs and has mutated and spread throughout the world in canid and felid species since then. In this study, a novel CPV was isolated from the endangered red panda (Ailurus fulgens) in China. Nucleotide and phylogenetic analysis of the capsid protein VP2 gene classified the red panda parvovirus (RPPV) as a CPV-2a type. Substitution of Val for Gly at the conserved 300 residue in RPPV presents an unusual variation in the CPV-2a amino acid sequence and is further evidence for the continuing evolution of the virus. The 300 residue is important in distinguishing the antigenicity and host range of CPVs. The clinical significance and population impact of RPPV infection in captive red pandas in China is unknown and is an important topic for future research.     

Congenital absence of the lateral metatarso-phalangeal sesamoid bone of the human hallux: a case report

A case of congenital absence of the lateral metatarsophalangeal sesamoid bone of the hallux is reported. in a 47-year-old woman. The lateral sesamoid bone was absent on the right hallux, and extremely reduced on the left hallux. The normal intersesamoidean crest and both sesamoidean grooves of the metatarsal head were absent. Physical examination was normal, and no functional disturbance resulted from this variant. Only two previous cases have been found in the literature. It must be distinguished from a total resorption due to an infectious process, or from an absence due to surgical excision. This absence can be related to the general tendency of disappearance of the sesamoid bones within hominoid primates.     

Bioengineering: the advent of metabiology (part I).

The ability to modify or replace organs or functions and to intervene in the transmission of hereditary characteristics is a fundamental turning point in the development of living organisms and of bioengineering. The history of bioengineering leading to this stage is briefly reviewed and reinterpreted. The view is proposed that bioengineering is the instrument by which metabiology - the continuance of biology with other means - is brought about. Metabiology deals with the study of living organisms as they can be modified by outside interventions on their functions, organs or sub-organs. Some of the fundamental questions raised by interventions from the outside on the organism - such as the loss of validity of the concept of homeostasis and the destruction of any vestige of orthogenesis - are briefly explored. Part II of this paper will appear in the next issue of this Journal.     

Bioengineering: the advent of metabiology (part II).

The ability to modify or replace organs or functions and to intervene in the transmission of hereditary characteristics is a fundamental turning point in the development of living organisms and of bioengineering. The theoretical potential of metabiology--the intervention from the outside on functions, organs and sub-organs through artificial organs as well as genetic engineering-- is briefly reviewed. Specific goals are proposed and engineering capabilities needed to achieve them are assessed. The impact on engineering and bioengineering of metabiology is examined and some fundamental issues of public policy concerning metabiology and bioengineering are proposed. (Part I of this paper was published in the July-Sept. 1981 issue of the Journal of Clinical Engineering.).     

The function of the gallbladder as a lesser biliary circulation

The function of the gallbladder is questioned in a hypothesis postulating that all bile which enters this reservoir is totally absorbed to the liver and none of it flows back to the cystic duct and duodenum. Cholecystokinesis is believed to increase and maintain a gradient of intravesical pressure which increases the filtration pressure necessary for the absorption of bile to the liver. The absorption is through the tributaries of the cystic veins, the ducts of Luschka and Rokitansky-Aschoff sinuses. Although the hypothesis lacks experimental support, it is based on a number of anatomical, histological, physiological, radiological and surgical observations.     

Human biological variation in sesamoid bone prevalence: the curious case of the fabella

The fabella is a sesamoid bone located in the gastrocnemius behind the lateral femoral condyle. In humans, fabellae are 3.5 times more common today than they were 100 years ago, with prevalence rates varying between and within populations. In particular, fabellae have been assumed to be more common in Asians than non-Asians, equally common in men and women, potentially more common in older individuals, and bilateral cases (one per knee) appear to be more common than unilateral ones. The roles of genetic and environmental factors in this phenotypic variation have been hypothesized, but not rigorously investigated. Given its clinical and evolutionary significance (i.e. being associated with several knee ailments, causing medical issues on its own, interfering with medical devices, and being less common in humans than in other mammals), it is important comprehensively to understand prevalence rate variation, and the roles of genetics and environmental factors in that variation. To address these questions, we performed a meta-analysis on data from studies published from 1875 to 2018 to investigate possible variation in sexual dimorphic (n = 22 studies, 7911 knees), ontogenetic (n = 10 studies, 4391 knees), and global (n = 65 studies, 21 626 knees) fabella prevalence rates. In addition, we investigated what proportion of cases are bilateral (n = 37 studies, 900 individuals), and among unilateral cases (n = 20 studies, 204 individuals), if fabellae are more common in the left or right knee. Our results show that, today, fabellae are 2.47–2.60% more common in men than women, and prevalence rates increase ontogenetically in old age (i.e. 70 years old), implying that fabellae can ossify early (i.e. 12 years old) or late in life. Approximately 72.94% of cases are bilateral, and among unilateral ones, fabellae are equally common in right and left knees. There is marked regional variation in fabella prevalence rates, with rates being highest in Asia, followed by Oceania, South America, Europe, Middle East, and North America, and lowest in Africa. Worldwide, an average of 36.80% of knees has ossified fabellae detectable by dissection. These results imply that, while the ability to form a fabella may be genetically controlled, the mechanisms that trigger fabella ossification may be environmentally controlled. What these environmental factors are, can only be speculated.     

The immunologic properties of epidermal Langerhans cells as a part of the dendritic cell system

Summary Dendritic cells form a system of antigen-presenting cells that is widely distributed in the body. They constitute trace populations in lymphoid and nonlymphoid tissues and in the circulation. They are characterized by their typical dendritic and veiled morphology, by their constitutive expression of high levels of major histocompatibility complex class II molecules on their surface, and by their outstanding capacity to initiate primary immune responses. Dendritic cells occur in two states of differentiation. In the immature state they are highly specialized for processing foreign protein antigens; in the mature state they efficiently stimulate resting antigen-specific T cells. Dendritic cells can migrate from the non-lymphoid tissues, where they reside in the immature state, via the afferent lymphatics or the blood to the T cell-dependent areas of the lymphoid organs (lymph nodes, spleen). There, they appear as mature dendritic cells. Therefore, dendritic cells are ideally suited to mediate important aspects of immunogenicity: they can acquire antigens in the tissues and process them in an immunogenic form; they can carry the immunogen to the lymphoid organs; and they can find and efficiently activate antigen-specific T cell clones and thus generate an immune response. Studies of epidermal Langerhans cells have greatly helped in establishing this concept. They can be investigated freshly isolated from the epidermis where they represent immature (tissue) dendritic cells. After 2–3 days in culture they develop into mature dendritic cells. The mechanisms of dendritic cell maturation, which can be studied best using epidermal Langerhans cells, and the specific functions of Langerhans cells in immunogenicity are discussed.     

Gonadoblastoma in the ovaries of a lesser galago (Galago senegalensis braccatus)

An enlarged right ovary was removed from a 14-year-old lesser galago (Galago senegalensis braccatus). Cytological preparations consisted of a heterogeneous population of neoplastic cells admixed with extracellular hyaline structures and cell-free nuclei. Microscopically, the ovary was replaced with gonadoblastoma and was composed of nests of germinal cells, including large oocyte-like cells, and sex cord-stromal cells arranged in palisading patterns around the germinal cells, the periphery of the nests and around extracellular hyaline material. The animal died 2 years after initial diagnosis. Necropsy examination revealed gonadoblastoma in the left ovary. The germinal cells of the tumour in the right and left ovaries were immunoreactive for calretinin, OCT3/4, PGP 9.5, Ki67 and/or faintly for cytokeratins. Sex cord-stromal cells were immunoreactive for calretinin, OCT3/4, GATA-4, E-cadherin and vimentin. Luteinized sex cord-stromal cells were immunoreactive for inhibin-alpha. The extracellular hyaline material was immunoreactive for laminin. This is the first case of gonadoblastoma in a non-human primate.     

Cultivation of porcine hepatocytes in polyurethane nonwovens as part of a biohybrid liver support system

Many patients suffering from end-stage liver disease cannot be transplanted within reasonable time due to the shortage of donor organs. Bioartificial liver support systems may contribute to the liver regeneration or bridging the time until a liver graft for transplantation becomes available. Nonwovens with integrated oxygenation capacity have been developed and manufactured by melt blow technology using thermoplastic polyurethane. Capillary membranes for oxygenation were integrated into the nonwoven during the processing. The polyurethane nonwoven structures with adapted pore size and high pore volume allow high cell densities in the hepatocyte culture. The three-dimensional cell culture was housed by a flow bioreactor system and was integrated in a closed loop circulation with monitoring possibilities for pressure, pH, temperature, ammonia, and oxygen. Hepatocytes were isolated from rats or pigs by collagenase perfusion and infused into the medium-perfused circulation. Cells showed high viability and hepatocyte specific cytochrome P450-dependent metabolic function in culture (MEGX test).     

Mechanical properties of hydroxyapatite-reinforced gelatin as a model system of bone

The elastic Young's modulus of hydroxyapatite-reinforced gelatin as a mechanical model system of bone was measured as a function of the volume fraction of hydroxyapatite, phi h. Initially, the Young's modulus gradually increased with an increase in phi h and then increased rapidly in the vicinity of phi h approximately 0.2. The phi h dependence of the Young's modulus was analysed by means of the theory of composite materials. It was found that with the increase in phi h the initial uniform stress deformation mode of the sample changed to the uniform strain deformation mode. The non-linear character in phi h dependence of the Young's modulus of this system was considered to reproduce well the novel behaviour of the mechanical properties of bone as a function of the mineral fraction. The situation was considered to be similar to a percolation problem. A preliminary analysis revealed that the critical exponent about the viscosity of the system accorded with the theoretically expected value. The result may present the evidence that the discontinuous point in mechanical properties of bone would be originated from an interaction such as a percolation of mineral particles on a matrix protein.     

CaMKII plays a part in the chondrogenesis of bone marrow-derived mesenchymal stem cells

Aims: The purpose of the study is to observe the functions of calcium/calmodulin dependent protein kinase II (CaMKII) in the induced chondrogenic differentiation of bone marrow derived mesenchymal stem cells (BMSCs). Methods: BMSCs was in vitro isolated and cultured for induced chondrogenesis. Western blot was used to ascertain the expression of CaMKII and phosphorylated CaMKII (PCaMKII, activatory CaMKII) in chondrogenic induced BMSCs. MTT method was utilized to observe the impact of CaMKII on the proliferation of BMSCs. The generation of cartilage matrix in BMSCs cells was detected by toluidine blue staining. The levels of cartilage marker genes COL2A1, Aggrecan and SOX9 in BMSCs were gained by real-time fluorescence quantitative polymerase chain reaction (RT-QPCR). Finally, BMSCs proliferation, cartilage matrix generation and the changes of COL2A1, Aggrecan and SOX9 were surveyed after CaMKII being blocked by CaMKII inhibitor KN93. Results: Expression of CaMKII and PCaMKII could be found in chondrogenic induced BMSCs. CaMKII had no significant influence on BMSCs proliferation, but the toluidine blue staining was obviously lighter, indicating a significant decline in the expression of COL2A1, Aggrecan and SOX9. Conclusion: As one of the factors influencing the chondrogenic capacity of BMSCs, CaMKII does not impact on BMSCs proliferation, but it can inhibit the chondrogenic ability of BMSCs by influencing its differentiation.     

Macrophages as a source of tumoricidal activity (tumor-necrotizing factor).

Macrophage-enriched peritoneal exudate cells from mice infected with Mycobacterium bovis BCG, macrophage-like tumor cells (PU 5-1.8), and peritoneal macrophages propagated in vitro with macrophage growth factor released tumoricidal activity into the culture medium within 2 to 3 h after stimulation with nanogram quantities of bacterial lipopolysaccharide. The cytotoxic activities from each of the macrophage culture supernatants eluted from diethylaminoethyl-Sephacel columns at a sodium chloride concentration of 200 mM exhibited a molecular weight of 50,000 to 60,000 as estimated by gel filtration, were stable at 56 degrees C for 30 min, and were active at a pH range of 6 to 10. A rabbit antiserum directed against serum-derived cytotoxic activity (tumor-necrotizing factor) from BCG-infected and lipopolysaccharide-challenged mice inhibited all of the cytotoxic activities generated in vitro. This suggests that the macrophage-derived cytotoxins are identical with serum-derived cytotoxic factor, which further implies that the macrophage is the cellular source of tumor-necrotizing factor.     

Genetic manipulation of the renin-angiotensin system in the kidney.

Over the past 5 years, genetic manipulation has revolutionized the way we examine physiological processes by providing a targeted specificity that was not possible previously. The application of transgenesis and gene targeting has been applied to numerous physiological pathways; and both will remain important tools as we reach the completion of the human genome project and begin to assess the function of newly identified genes. The renin-angiotensin system (RAS) has been the target of numerous transgenic and gene targeting studies designed to help uncover its role in cardiovascular regulation and organ development. Each gene of the system has now been both over-expressed and knocked out. It will be discussed as to how new advances in tissue-specific gene targeting by both over-expression and gene ablation can be used as powerful tools to dissect the role of the RAS in individual tissues.