Properties of fractionated chondroitin sulphate from ox nasal septa

1. Chondroitin sulphate was isolated from bovine nasal septa by precipitation with cetylpyridinium chloride after digestion of the tissue with papain. 2. The material was divided into two portions, one of which was partially degraded with testicular hyaluronidase. 3. Untreated and hyaluronidase-digested material were fractionated into a total of eleven subfractions by gel chromatography on Sephadex G-200 and Sephadex G-100 respectively. 4. Chemical analyses indicated that the composition of all the fractions was similar to that of chondroitin sulphate. However, electrophoresis revealed a charge-inhomogeneity in the low-molecular-weight fractions obtained after hyaluronidase digestion. 5. The physicochemical properties of the subfractions were investigated by sedimentation-velocity, diffusion and sedimentation-equilibrium studies, osmometry, viscometry and gel chromatography. The individual fractions were essentially monodisperse and showed molecular weights ranging from 2400 to 36000. 6. The relationship between the intrinsic viscosity and the molecular weight was [eta]=5.0x10(-6)xM(1.14), indicating that the chondroitin sulphate molecules assume a shape intermediate between that of a random coil and a stiff rod. 7. The relationship between the sedimentation constant and the molecular weight (>10(4)) was s(0) (20,w)=2.3x10(-2)xM(0.44).     

Murine nasal septa for respiratory epithelial air-liquid interface cultures

Air-liquid interface models using murine tracheal respiratory epithelium have revolutionized the in vitro study of pulmonary diseases. This model is often impractical because of the small number of respiratory epithelial cells that can be isolated from the mouse trachea. We describe a simple technique to harvest the murine nasal septum and grow the epithelial cells in an air-liquid interface. The degree of ciliation of mouse trachea, nasal septum, and their respective cultured epithelium at an air-liquid interface were compared by scanning electron microscopy (SEM). Immunocytochemistry for type IV beta-tubulin and zona occludens-1 (Zo-1) are performed to determine differentiation and confluence, respectively. To rule out contamination with olfactory epithelium (OE), immunocytochemistry for olfactory marker protein (OMP) was performed. Transepithelial resistance and potential measurements were determined using a modified vertical Ussing chamber SEM reveals approximately 90% ciliated respiratory epithelium in the nasal septum as compared with 35% in the mouse trachea. The septal air-liquid interface culture demonstrates comparable ciliated respiratory epithelium to the nasal septum. Immunocytochemistry demonstrates an intact monolayer and diffuse differentiated ciliated epithelium. These cultures exhibit a transepithelial resistance and potential confirming a confluent monolayer with electrically active airway epitheliumn containing both a sodium-absorptive pathway and a chloride-secretory pathway. To increase the yield of respiratory epithelial cells harvested from mice, we have found the nasal septum is a superior source when compared with the trachea. The nasal septum increases the yield of respiratory epithelial cells up to 8-fold.     

Possible cases of relaxed selection in civilized populations

Summary Genetic traits which are disadvantageous or deleterious in primitive cultures, of hunters and food gatherers, have very low frequencies in almost all cases. There are a few special exceptions, such as the sickle cell trait. Some deleterious traits under genetic control are rare in primitive populations but have fairly high frequencies in populations with long histories or prehistories of civilization, such as Chinese, Japanese or European populations. The Darwinist might suggest that these traits have less selective disadvantage, that is, lower rates of selective elimination, in civilized habitats; i.e. that the various changes in habitat accompanying civilization have caused the rigor of natural selection to relax, in part or perhaps completely.Several cases are discussed of traits under genetic control or genetic influence which demonstrate this phenomenal contrast, between low frequencies among primitive populations and high frequencies among civilized populations. Population data are presented for 4 such cases: colorblindness, myopia, abnormality of the nasal septum and abnormally small external opening of the tear duct.

---

Zusammenfassung Mit einigen bekannten Ausnahmen, z. B. Sichelzellanämie, kommen genetische Merkmale, die bei den Urvölkern von Jägern und Sammlern ungünstig oder sogar schädlich wirkten, mit niedriger Häufigkeit vor. Genetisch bedingte schädliche Merkmale, die selten unter Urvölkern gefunden werden, kommen jedoch häufiger vor bei Bevölkerungen, die eine lange Geschichte bzw. Vorgeschichte der Zivilisation besitzen, wie z. B. in China, Japan oder Europa. Ein Darwinist würde behaupten, daß bei zivilisierten Wohnorten solche Merkmale selektiv weniger nachteilig wirken, d. h., daß die selektive Ausscheidung langsamer vorgeht. Anders gesagt: der mit der Zivilisation verbundene Wechsel des Wohnortes bildet einen Grund für eine Milderung der Strenge der natürlichen Auslese.Es werden einige genetisch bestimmte oder genetisch beeinflußte Merkmale besprochen, die den Unterschied zwischen den Häufigkeiten (niedrig bei Urvölkern, hoch bei zivilisierten Völkern) aufzeigen,. Für 4 solcher Fälle: Farbensinnstörungen, Kurzsichtigkeit, Nasenscheidenwand-Deformitäten und anomale kleine Außenöffnungen der Tränenwege werden die Befunde aus den Bevölkerungen dargestellt.

     

Human testis-specific genes are under relaxed negative selection

Recent studies have suggested that selective forces and constraints acting on genes varied during human evolution depending on the organ in which they are expressed. To gain insight into the evolution of organ determined negative selection forces, we compared the non-synonymous SNP diversity of genes expressed in different organs. Based on a HAPMAP dataset, we determined for each SNP its frequency in 11 human populations and, in each case, predicted whether or not the change it produces is deleterious. We have shown that, for all organs under study, SNPs predicted to be deleterious are present at a significantly lower frequency than SNPs predicted to be tolerated. However, testis-specific genes contain a higher proportion of deleterious SNPs than other organs. This study shows that negative selection is acting on the whole human genome, but that the action of negative selection is relaxed on testis-specific genes. This result adds to and expands the hypothesis of a recent evolutionary change in the human male reproductive system and its behavior.     

Down syndrome rates and relaxed selection at older maternal ages.

Preferential survival in older mothers of fetuses with Down syndrome has been proposed as contributing to the maternal-age effect of this condition. If correct, this provocative hypothesis, which may be termed "relaxed selection," has major implications for approaches to prevention of Down syndrome live births in older women. Several predictions of this hypothesis are examined here by comparisons of parental ages among various populations. These revealed that: (1) mean maternal age of Down syndrome live births is slightly lower than that of Down syndrome spontaneous fetal deaths; (2) mean maternal age of those with mutant D/21 translocation Down syndrome is about the same as that of controls; (3) the ages of Down syndrome mothers who have Down syndrome live births is slightly lower than ages of Down syndrome mothers who have unaffected live births; and (4) in recent data on 47, +21 cases in which the extra chromosome 21 is of paternal origin, the mean maternal ages are 4-5 years lower than the maternal ages of cases of maternal origin (in contrast to earlier reports). All of these observations are contrary to the hypothesis that relaxed selection contributes significantly to the maternal-age association of Down syndrome. If there is any effect of relaxed selection, it is likely to be very weak and/or act primarily upon abortions that occur before recognition of pregnancy.     

Life history trade-offs and relaxed selection can decrease bacterial virulence in environmental reservoirs

Pathogen virulence is usually thought to evolve in reciprocal selection with the host. While this might be true for obligate pathogens, the life histories of opportunistic pathogens typically alternate between within-host and outside-host environments during the infection-transmission cycle. As a result, opportunistic pathogens are likely to experience conflicting selection pressures across different environments, and this could affect their virulence through life-history trait correlations. We studied these correlations experimentally by exposing an opportunistic bacterial pathogen Serratia marcescens to its natural protist predator Tetrahymena thermophila for 13 weeks, after which we measured changes in bacterial traits related to both anti-predator defence and virulence. We found that anti-predator adaptation (producing predator-resistant biofilm) caused a correlative attenuation in virulence. Even though the direct mechanism was not found, reduction in virulence was most clearly connected to a predator-driven loss of a red bacterial pigment, prodigiosin. Moreover, life-history trait evolution was more divergent among replicate populations in the absence of predation, leading also to lowered virulence in some of the 'predator absent' selection lines. Together these findings suggest that the virulence of non-obligatory, opportunistic bacterial pathogens can decrease in environmental reservoirs through life history trade-offs, or random accumulation of mutations that impair virulence traits under relaxed selection.     

Effectiveness of sexual selection in preventing fitness deterioration in bulb mite populations under relaxed natural selection

Under the 'good genes' mechanism of sexual selection (SS), females benefit from mate choice indirectly: their offspring inherit genes of the preferred, high quality fathers. Recent models assume that the genetic variance for male quality is maintained by deleterious mutations. Consequently, SS can be predicted to remove deleterious mutations from populations. We tested this prediction by relaxing selection in populations of the bulb mite, thus increasing their rate of accumulation of deleterious mutation. SS, allowed to operate in half of these populations, did not prevent the fitness decline observed in the other half of the relaxed selection lines. After 11 generations of relaxed selection, female fecundity in lines in which males were allowed to compete for females declined compared with control populations by similar amount as in monogamous lines (17.5 and 14.5%, respectively), whereas other fitness components (viability, longevity, male reproductive success) did not differ significantly between both types of lines and control populations.     

Possible genetic consequences of relaxed selection against common disorders with complex inheritance

Summary With increasing success in medical treatment for many common disorders with complex inheritance, it is expected that the incidence of patients requiring treatment will gradually rise from generation to generation. While this is theoretically true for a long range of future, the pattern of possible increase in the frequency of a disorder resulting from complete cure has been examined with special reference to the next few generations. It was shown that the maximum possible increment will take place in the first generation, with additional increment repidly diminishing with subsequent generations. For congenital heart disease, for example, the restoration of full fertility to all of the patients would incur an increase in the frequency at birth of the disease by about 10% after 5 to 10 generations.     

On the fate of seasonally plastic traits in a rainforest butterfly under relaxed selection

Many organisms display phenotypic plasticity as adaptation to seasonal environmental fluctuations. Often, such seasonal responses entails plasticity of a whole suite of morphological and life‐history traits that together contribute to the adaptive phenotypes in the alternative environments. While phenotypic plasticity in general is a well‐studied phenomenon, little is known about the evolutionary fate of plastic responses if natural selection on plasticity is relaxed. Here, we study whether the presumed ancestral seasonal plasticity of the rainforest butterfly Bicyclus sanaos (Fabricius, 1793) is still retained despite the fact that this species inhabits an environmentally stable habitat. Being exposed to an atypical range of temperatures in the laboratory revealed hidden reaction norms for several traits, including wing pattern. In contrast, reproductive body allocation has lost the plastic response. In the savannah butterfly, B. anynana (Butler, 1879), these traits show strong developmental plasticity as an adaptation to the contrasting environments of its seasonal habitat and they are coordinated via a common developmental hormonal system. Our results for B. sanaos indicate that such integration of plastic traits – as a result of past selection on expressing a coordinated environmental response – can be broken when the optimal reaction norms for those traits diverge in a new environment.     

Controlling incision-induced distortion of nasal septal cartilage: a model to predict the effect of scoring of rabbit septa

Cartilage can be shaped by scoring. In an exploratory study in living adult animals, this phenomenon was demonstrated in cartilage of the nasal septum. Bending was observed immediately after superficial scoring of the cartilage surface, and the cartilage always warped in the direction away from the scored side. The scored piece of cartilage still showed its initially distorted shape 10 weeks after primary surgery. In ex vivo experiments, a clear relation between incision depth and bending of septal cartilage was observed. Under these controlled conditions, the variation between different septa was small. Deformation of the septal specimens was increased by introducing single superficial incisions deepening to half the thickness of the cartilage. A positive correlation between incision depth and bending was demonstrated. A model was used to accurately predict the degree of bending of the cartilage after making an incision of a particular depth. Hence, the effect of cartilage scoring can be predicted. Because the results of this controlled study showed excellent reproducibility for different septa, it is expected that this model can be extrapolated to human nasal septum cartilage. This would enable the surgeon to better predict the result of cartilage scoring, either preoperatively or perioperatively.     

Ultrastructure of septa in Blastobotrys and Sporothrix

Transmission electron micrographs of septa in Blastobotrys species invariably showed central micropores. Septa of species of Sporothrix, however, exhibited three types of pores: (a) micropores which were central if single, or scattered; (b) central simple pores with Woronin bodies; (c) dolopores. The results confirm the heterogeneity of the genus Sporothrix.     

Morphogenesis and ultrastructure of Geotrichum candidum septa

The ultrastructure and mode of formation of septa of Geotrichum candidum were investigated by light and electron microscopy. The invaginations of the lateral membrane and wall appear to initiate at multiple points around the circumference of the cell; the immature septum subsequently assumes a cart-wheel shape, with branched spokes radiating from the center of the septum. Each face of the septum is covered with a membrane possessing hitherto undescribed structural differentiation; the membrane substructures are comprised of two central subunits encircled by 12 identical subunits. The diameter of the entire 12 plus 2 structure is 24 to 25 nm, and the diameter of each individual subunit is approximately 4 nm. The maturation of the septum appears to occur by further deposition of material along the branched skeletal regions. Numerous small openings (micropores), formed as a result of incomplete deposition, ultimately give rise to plasmodesmata. During arthrospore formation, the plasmodesmal canals and associated micropores are occluded by electron-dense materials, rendering each segment of the hyphae completely independent of the rest of the hyphae.     

The cognitive and speech genes are jointly shaped by both positive and relaxed selection in the human lineage

The emergence of a coordinated network of cognitive and speech genes in the human lineage performing overlapping functions is a great evolutionary puzzle. Prior studies on the speech gene FOXP2 are inconclusive on the nature of selection operating on this gene in the human lineage. Here, I show that the evolution of FOXP2 is accelerated in the human lineage due to relaxation of purifying selection (relaxed selection). Five potential genes associated with human-specific intelligence and speech genes have evolved under the impact of positive selection and three genes including FOXP2 have undergone relaxation of purifying selection in the human lineage. Overall, three evolutionary processes namely positive selection, relaxation of purifying selection and neutral evolution have contributed for the genomic evolution of extraordinary cognitive ability and speech in the hominin lineage. The cognitive and speech genes subjected to natural selection in the human lineage have demonstrated a coevolutionary trend.     

The structure and development of septa inNeurospora crassa

Summary Electron microscopy of septa ofNeurospora crassa has shown that microfibrillar material is a major structural component. These microfibrils are arranged in a predominantly tangential orientation and in young (24 hours) mycelium can often be seen in unextracted septal preparations. In older (5 days) mycelium they are overlain with amorphous material, which can be removed by treatment with Pronase, or by chemical extractions. The structure of septa is described and compared with that of the lateral hyphal wall.Developing septa are typically surrounded by vesicles, and sometimes by alignments of cytoplasmic tubules. Electron and light microscopic autoradiography have shown that N-acetylglucosamine is quickly and specifically incorporated into developing septa, and there is no evidence for its prior incorporation into any cytoplasmic site. Glucose is also incorporated into septa, but less specifically. From the autoradiographic results and from experiments with chemical and enzymic extractions it is suggested that chitin is a major component of the septum. A model of the septum is constructed from these data.     

The re-emergence of felid camouflage with the decay of predator recognition in deer under relaxed selection

When a previously common predator disappears owing to local extinction, the strong source of natural selection on prey to visually recognize that predator becomes relaxed. At present, we do not know the extent to which recognition of a specific predator is generalized to similar looking predators or how a specific predator-recognition cue, such as coat pattern, degrades under prolonged relaxed selection. Using predator models, we show that deer exhibit a more rapid and stronger antipredator response to their current predator, the puma, than to a leopard displaying primitive rosettes similar to a locally extinct predator, an early jaguar. Presentation of a novel tiger with a striped coat engendered an intermediate speed of predator recognition and strength of antipredator behaviour. Responses to the leopard model slightly exceeded responses to a non-threatening deer model, suggesting that thousands of years of relaxed selection have led to the loss of recognition of the spotted coat as a jaguar-recognition cue, and that the spotted coat has regained its ability to camouflage the felid form. Our results shed light on the evolutionary arms race between adoption of camouflage to facilitate hunting and the ability of prey to quickly recognize predators by their formerly camouflaging patterns.     

Deformed wing virus

Deformed wing virus (DWV; Iflaviridae) is one of many viruses infecting honeybees and one of the most heavily investigated due to its close association with honeybee colony collapse induced by Varroa destructor. In the absence of V. destructor DWV infection does not result in visible symptoms or any apparent negative impact on host fitness. However, for reasons that are still not fully understood, the transmission of DWV by V. destructor to the developing pupae causes clinical symptoms, including pupal death and adult bees emerging with deformed wings, a bloated, shortened abdomen and discolouration. These bees are not viable and die soon after emergence. In this review we will summarize the historical and recent data on DWV and its relatives, covering the genetics, pathobiology, and transmission of this important viral honeybee pathogen, and discuss these within the wider theoretical concepts relating to the genetic variability and population structure of RNA viruses, the evolution of virulence and the development of disease symptoms.